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    You are here : Home » MS Research News » New Discoveries » Medical Imaging

    Medical Imaging

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    Scientists get £164k to test future MS treatments

    MS MRIScientists at the University of Nottingham have been awarded £164,000 to test future treatments for people with multiple sclerosis (MS).

    A team at the university will use the grant from the MS Society to look at areas of the brain, known as grey matter, that have previously been very difficult to study.

    MS is a neurological condition, causing lesions in the brain and spinal cord, which lead to a range of symptoms – including severe fatigue, and problems with mobility and eyesight.

    The study will use advanced MRI technology at the university to monitor the grey matter, which has increasingly been shown to be important in MS.

    This new information will help researchers to more effectively identify and test new methods for treating damage caused by the condition.

    Dr Nikos Evangelou, clinical associate professor of neurology at the university, said: "This study will really advance our understanding of the damage caused in MS and how we might be able to treat it."

    Forty people with MS and ten people without the condition who live in Nottingham will be recruited to the trial, due to start in the next few months.

    Findings of the study are due to be published in the next two to three years.

    Dorothy Sutton, of the Nottingham Branch of the MS Society, said: "Anything that can speed up the discovery of new effective treatments for people with MS – especially those newly diagnosed – is really positive."

    Source: This Is Nottingham Copyright © 2012 Northcliffe Media Limited. (29/02/12)

    7T MRI depicts Multiple Sclerosis lesions

    MRIUltrahigh-field strength, T1-weighted magnetization-prepared rapid acquisition and multiple gradient echoes (MPRAGE) is highly sensitive for detecting multiple sclerosis (MS) plaques within the white and gray brain parenchyma, according to a study published online Feb. 20 in Archives of Neurology, one of the JAMA/Archives journals.

    In current clinical practice, T2-weighted MRI is commonly used to quantify the accumulated MS lesion load in the brain, whereas T1-weighted sequences are used to differentiate irreversible brain tissue damage, hyperintense lesions commonly called “black holes.” Black holes are associated with clinical worsening and cerebral atrophy. On spin-echo T1-weighted images, a proportion of T2 hyperintense lesions appears hypointense to the surrounding normal-appearing white matter for a long time, the researchers noted.

    Tim Sinnecker, of the NeuroCure Clinical Research Center, Charite University Medicine, Berlin, and colleagues enrolled 20 patients with relapsing-remitting MS and 14 healthy controls to undergo 7T MRI. A subgroup of 18 patients with MS also underwent 1.5T MRI.

    “Against the background of the unresolved dispute over the clinical significance of black holes, and the increasing appreciation of gray matter pathology in MS, we investigated whether the visibility of T1 and T2 lesions in both gray and white matter would be influenced by the improved signal-to-noise ratio at 7T,” the authors wrote. “In particular, we hypothesized that the application of MPRAGE would facilitate the detection of hypointense lesions in comparison with conventional MRI.”

    The 7T MPRAGE sequences detected a total number of 728 lesions, depicting more lesions than 7T FLASH (fast low-angle shot) and almost twice as much as 1.5T MPRAGE. Each of the 217 T1 hypointense lesions detected by the 7T MPRAGE sequences in the longitudinal subgroup persisted without major change in formation or size for at least one year and could thus be classified as a black hole, according to Sinnecker and colleagues.

    Because the lesions did not change appearance over one year, the researchers suggested that they may express brain parenchymal destruction rather than temporary edema.

    The researchers noted that the lesions were visualized with greater distinction concerning shape and appearance on the 7T MPRAGE images than via the 7T FLASH.

    “To our knowledge, the present study is the first to demonstrate that, at ultrahigh-field strength, every T2 hyperintense lesion detected on T2-weighted FLASH sequences directly corresponds to a T1 hypointense lesion on a MPRAGE sequence,” the researchers concluded.

    Source: Healthy Imaging © ©2012 TriMed Media Group (21/02/12)

    Studying communication within the brain with cutting-edge MRI techniques

    NeuronsInnovative magnetic resonance imaging (MRI) techniques that can measure changes in the microstructure of the white matter likely to affect brain function and the ability of different regions of the brain to communicate are presented in an article in the groundbreaking new neuroscience journal Brain Connectivity, a bimonthly peer-reviewed publication from Mary Ann Liebert, Inc.. The article is available free online.*

    Brain function depends on the ability of different brain regions to communicate through signaling networks that travel along white matter tracts. Using different types and amounts of tissue staining to measure how water molecules interact with the surrounding brain tissue, researchers can quantify changes in the density, orientation, and organization of white matter. They can then use this information to generate image maps of these signaling networks, a method called tractography.

    Andrew Alexander and colleagues from University of Wisconsin, Madison, describe three quantitative MRI (qMRI) techniques that are enabling the characterization of the microstructural properties of white matter: diffusion MRI, magnetization transfer imaging, and relaxometry. This approach can be used to study and compare the properties of brain tissue across populations and to shed light on mechanisms underlying aging, disease, and gender differences in brain function, for example. The authors present their findings in the article "Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains."

    "White matter is the material that provides for the wiring and connectivity between brain regions. This exciting paper describes three new methodologies to measure the integrity of white matter in normal and diseased brain. These methods show promise in multiple sclerosis, depression, aging, and human development," says Bharat Biswal, PhD, Co-Editor-in-Chief of Brain Connectivity and Associate Professor, University of Medicine and Dentistry of New Jersey.

    *Article Abstract

    Source: Medical News Today © MediLexicon International Ltd 2004-2012 (10/02/12)

    Early MRI predicts 5-year response in MS

    MS MRIMRI scans taken one year after starting disease-modifying therapy in relapsing-remitting multiple sclerosis were strongly predictive of outcomes after five years, an Italian researcher said here.

    The nonresponder rate at five years was nearly twice as high among patients in a retrospective study whose one-year MRI scans showed more than two gadolinium-enhancing T1 lesions (32% versus 18%, P=0.009), according to Marzia Romeo, MD, of the San Raffaele Hospital in Milan.

    Other significant early predictors of nonresponse in the 668-patient study included being a woman, having high disability scores, and having multifocal brain lesions, Romeo reported at the joint meeting of the European and American Committees for Treatment and Research in Multiple Sclerosis.

    Romeo and her colleagues pulled records for all patients with relapsing-remitting MS treated at San Raffaele from 1996 to 2005. To be included in the study, patients must have received beta-interferon or glatiramer acetate (Copaxone) as first-line therapy.

    Patients who completed five years of follow-up -- there were 668 in all -- were included. However, only 396 had MRI scans taken at the one-year mark after starting treatment.

    Romeo and colleagues classified those patients' five-year outcomes into three categories: responders, nonresponders, and partial responders. They defined those categories as follows:

    Responders: EDSS disability score progression of less than 1.5 and no relapse during treatment (n=223)
    Partial responders: EDSS score progression less than 1.5 but at least one relapse during treatment (n=299)
    Nonresponders: EDSS score progression of 1.5 or more over a six-month period and persisting at the five-year evaluation, or switched to a second-line therapy such as mitoxantrone (n=146)
    Just over half of patients (51%) remained on the same disease-modifying therapy throughout follow-up. Of the remainder, three-quarters switched to the other first-line disease-modifying drug and the rest were put on a second-line agent.

    Some 44% of nonresponders had moved to a second-line drug and 39% to the other first-line treatment.

    Among full and partial responders, none were switched to second-line drugs; 22% of full responders and 52% of partial responders, however, had changed first-line treatments.

    Among the 396 patients with one-year MRI scans, the number of active lesions was a powerful predictor of long-term response.

    The odds ratio for nonresponse at five years for patients with more than two active lesions at one year was 5.7 (95% CI, 2.5 to 13.2), Romeo indicated.

    She said the findings indicated that multifocal onset, a high EDSS score, and an "active MRI presentation" together were powerful indicators of nonresponse.

    "In this population, an induction therapy should be considered," she said.

    Session co-moderator Heinz Wiendl, MD, of the University of Muenster in Germany, commented afterward that the "topography" of MS lesions was also an issue and asked Romeo if her group had looked into it.

    "I would be more worried about multiple fulminant brainstem lesions" than lesions in less sensitive areas of the brain, he said.

    Romeo acknowledged that this was an important consideration that the study had not addressed.

    No external funding for the study was reported.

    Romeo had no disclosures. Some co-authors reported relationships with Bayer Schering, Merck Serono, sanofi-aventis, Biogen Dompe, Novartis, and Teva.

    Wiendl reported relationships with Biogen Idec, Novartis, Bayer Healthcare, sanofi-aventis, Serono, TEVA, Medac, Lundbeck, and Novo Nordisk.

    Primary source: ECTRIMS/ACTRIMS Triennial Meeting

    Source reference:
    Romeo M, et al "Brain MRI activity after disease-modifying treatment may predict disability progression after 5 years in relapsing-remitting multiple sclerosis patients" ECTRIMS/ACTRIMS 2011; Abstract 29.#

    Source: MedPage Today © 2011 Everyday Health, Inc.(21/10/11)

    Diagnostic breakthrough in MS achieved with advanced Fonar Upright® MRI

    Upright MRIIn a newly published paper, medical researchers at FONAR Corporation (NASDAQ-FONR) report a diagnostic breakthrough in multiple sclerosis (MS), based on observations made possible by the company's unique FONAR UPRIGHT® Multi-Position™ MRI.

    The findings reveal that the cause of multiple sclerosis may be biomechanical and related to earlier trauma to the neck, which can result in obstruction of the flow of cerebrospinal fluid (CSF), which is produced and stored in the central anatomic structures of the brain known as the ventricles. Since the ventricles produce a large volume of CSF each day (500 cc), the obstruction can result in a build up of pressure within the ventricles, resulting in leakage of the CSF into the surrounding brain tissue. This leakage could be responsible for generating the brain lesions of multiple sclerosis.

    The paper, titled "The Possible Role of Cranio-Cervical Trauma and Abnormal CSF Hydrodynamics in the Genesis of Multiple Sclerosis," has just been published and appears in the latest issue of the journal Physiological Chemistry and Physics and Medical NMR (Sept. 20, 2011, 41: 1-17). It is co-authored by MRI researchers Raymond V. Damadian and David Chu.

    Commenting on the study, the lead researcher and president of FONAR, Raymond V. Damadian stated, "These new observations have uncovered biomechanical barriers that appear to give rise to multiple sclerosis, and, even more excitingly, these barriers may be therapeutically addressable." Damadian is the medical doctor who discovered the abnormal signals from tissue that are the basis of every MRI image made today and who went on to invent the MRI and build the world's first MRI by hand at New York's Downstate Medical Center.

    The findings are based on viewing the real-time flow of cerebrospinal fluid in a series of eight randomly chosen patients with multiple sclerosis.

    The cerebrospinal fluid, known as CSF, lubricates the brain and spinal cord. Utilizing FONAR's patented Advanced UPRIGHT® Multi-Position™ MRI technology, the team was able to view the flow of cerebrospinal fluid in and out of the brain with the patients lying down and upright. These invaluable dual observations have only been possible since the invention of an MRI capable of imaging the patient upright.

    Damadian and co-researcher, Chu, discovered obstructions of the CSF flow in all eight patients in the study and, in seven out of eight patients, the obstruction was more pronounced when the patient was in the upright position. The UPRIGHT® MRI also revealed that these obstructions were the result of structural deformities of the cervical spine, induced by trauma earlier in life.

    The research was initiated when Damadian and Chu scanned a patient with multiple sclerosis. In reviewing the MRI scans, Damadian noted that one of the MS lesions in the patient's brain was directly connected with the CSF within the ventricles of the brain, which are the structures in which the body continuously produces CSF fluid. It does so through a network of blood vessels within the ventricles known as the choroid plexus. This network generates a large volume of CSF daily, approximately 500 cc.

    Damadian knew that in multiple sclerosis the lesions are typically concentrated adjacent to the ventricles and are peri-ventricular in distribution (i.e. surrounding the ventricle). He had also determined that the patient had a history of severe trauma to the cervical spine. When a careful history of subsequent patients in the study was taken, it revealed that all but one had also experienced some form of serious traumatic injury to the cervical spine.

    When viewing MRI scans of the first patient, Damadian hypothesized that any obstructions of the continuous circulation of the daily volume of CSF out of the brain to the spinal cord and back could cause increased pressure within the ventricles, which could result in leakage of the fluid into the brain tissue surrounding the ventricles.

    Damadian knew that CSF fluid contains proteins, which are made up of polypeptides, in fact, that the fluid contains more than 300 polypeptides. Nine of the proteins they form are known to be antigens that stimulate the production of antibodies. He wondered if these proteins, leaking into the brain tissue, could be initiating the antigen-antibody complexes in the brain that cause the pathology and symptoms of multiple sclerosis.

    The disease results in the destruction of the coverings, or myelin sheaths, that insulate the nerve fibers of the brain. The destruction prevents the nerves from functioning normally and produces the symptoms of multiple sclerosis. The destruction is the origin of the multiple sclerosis lesions seen on the MRI images.

    But, unlike nerve tissue, the myelin sheaths can regenerate – once the cause of their destruction is eliminated. The paper suggests that surgical or biomechanical remediation of the obstruction of the flow of CSF in the cervical spine could relieve the increased CSF pressure within the ventricles and eliminate the resultant leakage of fluid into the surrounding brain tissue and the inflammation of the myelin sheaths that it generates. Once the leakage has been stopped, the myelin sheaths could be repaired by the body's myelogenesis process with the prospect of a return to normal nerve function for these nerves.

    Images in the recumbent and upright positions of one of the MS patients from the study follow. Note the presence of ventral CSF flow when the patient (MS patient #6) is recumbent but the loss of ventral CSF flow when the patient is upright.

    Unlike traditional lie-down MRIs, patients walk into the UPRIGHT™ MRI and sit in the scanner. In the diagnosis of usual spine problems such as back pain, the patients are asked to place themselves in the position that causes their back symptoms. Then an upright MRI image is generated. As a result, the spinal pathology that is causing the patient's back pain can be more accurately and more completely identified and defined. Since the seat in the MRI can be tilted to any position and also flattened into a bed in the horizontal position, the researchers were able to view the patients in the MS study in both the recumbent and upright positions.

    The study was part of ongoing research at the UPRIGHT® MRI CENTER at FONAR Corporation, which invented the UPRIGHT® MRI scanner. Research at the center, which is located in Melville, New York, has already provided unique diagnostic views of the upright spine with the weight of the body on it, including the spine with the patient bending forward and backward, radiation-free monitoring of scoliosis, upright imaging of pelvic floor problems in women, such as a prolapsed bladder or uterus, sit-down imaging of the prostate without the usual endorectal coil, and a walk-in, sit-down 10-minute scan that allows for cost-effective MRI scanning of patients undergoing chemotherapy to monitor tumor responses biweekly.

    The complete study that led to the diagnostic breakthrough in multiple sclerosis can be accessed at the company website at

    About the Researchers

    Raymond V. Damadian is the medical doctor who first proposed scanning medical patients by NMR (nuclear magnetic resonance, the original name of the MRI) based on his discovery of the principle on which all modern MRI is based – the different NMR signals that tissues emit in a magnetic field. The amplitude of these signals accounts for the pixel brightness in every MRI image. He discovered that the NMR signal amplitudes of cancer tissue differ markedly from the NMR signal amplitudes of the normal tissues because of the differences in their rate of decay. He simultaneously discovered that the NMR signal amplitudes also differ markedly among the normal tissues themselves because of the differences in their rates of decay. These signal amplitude differences enabled cancer tissues and other tissues to be visualized in MRI images because the signal differences generate the needed brightness differences (contrast) in the picture elements (pixels) needed to visualize detail in the MRI image. The contrast in pixel brightness allows the cancer pixels in the image to be distinguished from the surrounding normal pixels. It also allows the different normal tissues to be distinguished from each other and achieve the exceptional anatomic detail MRI pictures are known for.

    Damadian went on to build the first MRI scanner by hand, assisted by two post-doctoral students, at New York's Downstate Medical Center and achieved the first MRI scan of a healthy human body in 1977 and a human body with cancer in 1978. For these discoveries he received the National Medal of Technology from President Reagan in 1988, was inducted into the National Inventors Hall of Fame in 1989 as the inventor of the MRI and was named Inventor of the Year in 2007 for his invention of the FONAR UPRIGHT® Multi-Position™ MRI. He founded FONAR to bring MRI diagnosis to patients. The company manufactured and installed the world's first commercial MRI in 1980. Damadian is currently FONAR's president and chief research officer.

    David Chu is the head MRI scientist at FONAR who specializes in the imaging of the cerebrospinal fluid with advanced cines, or movies, which allow for observation of CSF flow in real time. The technology, which the company calls TrueFlow™ Imaging, made the diagnostic breakthrough in multiple sclerosis possible.

    Source: FONAR Corporation (06/10/11)

    MS-related disorders ID’d by proteomic pattern analysis

    Proteomic Pattern AnalysisProteomic pattern analysis of cerebrospinal fluid (CSF) analysis using matrix-assisted laser desorption/ionization time-of-flight (MALDI) mass spectrometry distinguishes between similar multiple sclerosis (MS)-related disorders, according to a study published online Sept. 12 in the Annals of Neurology.

    Mika Komori, M.D., from the Kyoto University in Japan, and colleagues analyzed CSF proteomic patterns from 107 patients with MS-related disorders, including relapsing remitting-MS (RRMS), primary progressive-MS (PPMS), anti-aquaporin4 antibody seropositive-neuromyelitis optica spectrum disorder (SP-NMOSD), seronegative-NMOSD with long cord lesions of spinal magnetic resonance imaging (SN-NMOSD), amyotrophic lateral sclerosis, and non-MS inflammatory neurological control diseases, using a new, unbiased biomarker discovery strategy. Magnetic bead-based enrichment of CSF peptides and proteins was followed by MALDI mass spectrometry. Multivariate statistics and pattern-matching algorithms were used to analyze the obtained spectra. These analyses were duplicated in an independent sample of 84 patients with MS-related disorders or with other neurological diseases.

    The investigators found that MS-related disorders differed considerably with respect to CSF protein profiles. The support vector machine classifier distinguished SP-NMOSD and SN-NMOSD from RRMS with high cross-validation accuracy, especially in relapse phases. Some peaks derived from SP-NMOSD were able to discriminate RRMS with high area under the curve scores, and these results were also replicated in the second cohort. Pattern matching analysis revealed some similarity between proteomic patterns in selected neurological diseases. RRMS and PPMS had larger spectral differences than PPMS and amyotrophic lateral sclerosis.

    "Our applied proteomic pattern analysis facilitated the effective distinction of similar MS-related disorders, and revealed a possibility that these patterns, themselves, can be used as biomarkers for each disorder," the authors write.

    Full Article

    Source: Doctors Lounge © 2001-2011 Doctors Lounge. (20/09/11)

    New imaging technique evaluates nerve damage
    A new imaging technique could help doctors and researchers more accurately assess the extent of nerve damage and healing in a live patient.

    Researchers at Laval University in Québec and Harvard Medical School in Boston aimed lasers at rats' damaged sciatic nerves to create images of the individual neurons' insulating sheath called myelin. Physical trauma, repetitive stress, bacterial infections, genetic mutations, and neurodegenerative disorders such as multiple sclerosis can all cause neurons to lose myelin. The loss slows or halts the nerve's transmission of electrical impulses and can result in symptoms such as numbness, pain, or poor muscle control.

    Using their images of neurons, the researchers measured the thickness of the myelin at different locations and times after the rats' sciatic nerve was damaged. Two weeks after injury the nerve's myelin covering had thinned considerably, but at four weeks the nerve had begun to heal.

    Traditionally, researchers could only obtain such myelin measurements by removing the nerve and slicing it into thin layers, a technique whose destructive nature prevented it from being used to evaluate nerve injuries in living patients. The new imaging method, described in the September issue of the Optical Society's (OSA) open-access journal Biomedical Optics Express, holds promise as a diagnostic tool for doctors treating nerve damage or degenerative diseases, the researchers write.

    Source: Science Daily Copyright © 1995-2011 ScienceDaily LLC (13/09/11)

    Grey matter damage and overall cognitive impairment in PPMS

    MS MRISummary: This cross-sectional study of patients with primary progressive multiple sclerosis (PPMS) investigates the association between imaging measures and domain specific cognitive impairment.

    In patients, a lower grey matter (GM) peak location magnetization transfer ratio (MTR) - reductions in which are associated with demyelination and axonal loss - was associated with worse overall cognitive performance and GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline. The volume of normal appearing white matter was associated with attention/speed of visual information processing, while T2 lesion load was associated with delayed verbal memory.

    The authors have suggested that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both grey matter and white matter.

    Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS).

    Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported.

    Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55).

    Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

    Tur C, Penny S, Khaleeli Z, Altmann D, Cipolotti L, Ron M, Thompson A, Ciccarelli O.

    Dept. of Brain Repair & Rehab., Inst. Neurology, London, UK/Clinical Neuroimmunology Unit, MS Centre of Catalonia (CEM-Cat), Dept of Med., Barcelona, Spain.

    Source: Pubmed PMID: 21803874 (03/08/11)

    New nanoscale imaging may lead to new treatments for MS

    MyelinLaboratory studies by chemical engineers at UC Santa Barbara may lead to new experimental methods for early detection and diagnosis –– and to possible treatments –– for pathological tissues that are precursors to multiple sclerosis and similar diseases.

    Achieving a new method of nanoscopic imaging, the scientific team studied the myelin sheath, the membrane surrounding nerves that is compromised in patients with multiple sclerosis (MS). The study is published in this week's online edition of the Proceedings of the National Academy of Sciences (PNAS).

    "Myelin membranes are a class of biological membranes that are only two molecules thick, less than one millionth of a millimeter," said Jacob Israelachvili, one of the senior authors and professor of chemical engineering and of materials at UCSB. "The membranes wrap around the nerve axons to form the myelin sheath."

    He explained that the way different parts of the central nervous system, including the brain, communicate with each other throughout the body is via the transmission of electric impulses, or signals, along the fibrous myelin sheaths. The sheaths act like electric cables or transmission lines.

    "Defects in the molecular or structural organization of myelin membranes lead to reduced transmission efficiency," said Israelachvilli. "This results in various sensory and motor disorders or disabilities, and neurological diseases such as multiple sclerosis."

    At the microscopic level and the macroscopic level, which is visible to the eye, MS is characterized by the appearance of lesions or vacuoles in the myelin, and eventually results in the complete disintegration of the myelin sheath. This progressive disintegration is called demyelination.

    The researchers focused on what happens at the molecular level, commonly referred to as the nanoscopic level. This requires highly sensitive visualization and characterization techniques.

    The article describes fluorescence imaging and other measurements of domains, which are small heterogeneous clusters of lipid molecules –– the main constituents of myelin membranes –– that are likely to be responsible for the formation of lesions. They did this using model molecular layers in compositions that mimic both healthy and diseased myelin membranes.

    They observed differences in the appearance, size, and sensitivity to pressure, of domains in the healthy and diseased monolayers. Next, they developed a theoretical model, in terms of certain molecular properties, that appears to account quantitatively for their observations.

    "The discovery and characterization of micron-sized domains that are different in healthy and diseased lipid assemblies have important implications for the way these membranes interact with each other," said Israelachvili. "And this leads to new understanding of demyelination at the molecular level."

    The findings pave the way for new experimental methods for early detection, diagnosis, staging, and possible treatment of pathological tissues that are precursors to MS and other membrane-associated diseases, according to the authors.

    All of the work reported in the paper was completed at UCSB, although some of the authors have moved to other institutions. In addition to Israelachvili, the other authors are Dong Woog Lee, graduate student in UCSB's Department of Chemical Engineering; Younjin Min, now a postdoctoral fellow in the Department of Chemical Engineering at the Massachusetts Institute of Engineering; Prajnaparamitra Dhar, now assistant professor in the Department of Chemical Engineering at the University of Kansas; Arun Ramachandran, now assistant professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto; and Joseph A. Zasadzinski, now professor in the Department of Chemical Engineering and Materials Science at the University of Minnesota.

    Source: Eureka Alert (24/05/11)

    Multiple Sclerosis atrophy seen on brain and spine MRI

    MS MRIBrain and spinal cord atrophy in patients with multiple sclerosis (MS) correlates with the phenotype of the disease and the degree of disability, according to 2 magnetic resonance imaging (MRI) studies presented here at the International Society for Magnetic Resonance in Medicine 19th Annual Meeting and Exhibition.

    Both imaging studies point to the future value of MRI in monitoring disease progression and treatment response, suggest the authors.

    In the first long-term follow-up of MS patients, conducted over a 10-year period, researchers showed an average loss in brain volume of 5% in 47 patients, compared with a 3% loss in 11 control subjects, reported Antonio Giorgio, MD, from the Department of Neurological and Behavioral Sciences at the University of Siena, Italy.

    The mean age of the patients was 37 years; the mean age of the control subjects was 42 years. Mean disease duration was 4.7 years. The majority of patients (n = 40) had the relapsing-remitting phenotype of the disease, 5 had the secondary-progressive phenotype, and 2 had the primary-progressive phenotype.

    Conventional MRI performed at baseline and again after 10 years measured global brain volume, normalized white matter (nWM) volume, normalized grey matter (nGM) volume, and ventricular cerebrospinal fluid (vCSF). The researchers assessed the association between phenotype and disability, which was measured on the Expanded Disability Status Scale (EDSS).

    At baseline, MS patients had an EDSS score of 2.5, which increased to 3.4 at follow-up (P < .001). The mean number of relapses over 10 years was 3.8, with 3 relapsing-remitting subjects converting to secondary progressive during that period.

    Change in nGM volume was significantly higher in MS patients than in control subjects. There were no statistical differences between groups in nWM volume or vCSF, reported Dr. Giorgio.

    MS patients were categorized by relapse rate: high, defined as 5 or more relapses in the 10 years; or low, defined as fewer than 5 relapses in the 10 years. Those with a high relapse rate had statistically significantly more global volume loss, nGM loss, and nWM loss than those with a low relapse rate, he said. There were no significant differences in vCSF.

    The researchers found that MRI changes correlated with the degree of EDSS and relapse rate. "This suggests that long-term brain atrophy change may provide a valuable outcome of longstanding disability and progression in patients with MS," they conclude.

    A separate multicenter study used a semiautomated MRI approach to measure cervical cord atrophy in 333 MS patients and 143 control subjects.

    The study showed that cervical cord cross-sectional area differs significantly among the different forms of MS. "In line with previous studies, cervical cord atrophy is not present in patients with clinically isolated syndromes and relapsing-remitting MS, while it is present and extremely pronounced in patients with the progressive form of the disease," reported Maria Assunta Rocca, MD, from the neuroimaging research unit and the Department of Neurology at the Scientific Institute and University Hospital San Raffaele, Milan, Italy.

    Additionally, compared with patients with secondary-progressive MS, those with benign MS tended to have "a relative preservation of cord integrity," she said.

    The MRI findings were significantly associated with the EDSS disability scale, suggesting that "this measure should be included at least in trials involving patients with progressive forms of the disease," said Dr. Rocca.

    MRI measurement of brain and spinal cord atrophy is not clinically applicable at the moment, but might be a useful tool for monitoring treatment in the future, said Douglas Arnold, MD, a neurologist specializing in MS at the Montreal Neurological Institute and Hospital, McGill University, in Montreal, Quebec, Canada, who was comoderator of the session.

    "What the drug companies are looking for is a medication to stop neurodegeneration. I think the single most representative and most reliable biomarker of that would be atrophy. I think all this holds potential, but those treatments are still not here," he told Medscape Medical News.

    Using atrophy as a measure of treatment response is a complicated proposal, because a reduction or even arrest of atrophy might not be immediately apparent, he said.

    After starting treatment, "you'd have to wait for all the damaged tissue that's already there to be cleared out before you could actually see the real effect — and that has a long lag. Axons take time to degenerate, and myelin takes years, probably, to completely degenerate and to be phagocytized and completely disappear. Even if you were to stop the inflammation today, your atrophy rate might slow over several years before it actually was reduced to the normal aging rate."

    The speakers and the commentator have disclosed no relevant financial relationships.

    International Society for Magnetic Resonance in Medicine (ISMRM) 19th Annual Meeting and Exhibition: Abstract 403, presented May 11, 2011; Abstract 606, presented May 12, 2011.

    Source: MedScape Today Copyright © 1994-2011 by WebMD LLC (19/05/11)

    Improved understanding of brain disorders with new x-ray method

    Brain 3-d x-raysResearchers including members from the Niels Bohr Institute at the University of Copenhagen have developed a new method for making detailed X-ray images of brain cells. The method, called SAXS-CT, can map the myelin sheaths of nerve cells, which are important for conditions such as multiple sclerosis and Alzheimer's disease. The results have been published in the scientific journal, NeuroImage.

    The myelin sheaths of nerve cells are lamellar membranes surrounding the neuronal axons. The myelin layers are important to the central nervous system as they ensure the rapid and uninterrupted communication of signals along the neuronal axons. Changes in the myelin layers are associated with a number of neurodegenerative disorders such as cerebral malaria, multiple sclerosis, and Alzheimer's disease.

    The development of these diseases are still not fully understood, but are thought to be related to the damage of the myelin layers, so that messages from the brain reach the various parts of the body poorly or not at all. It is like an electric cord where the insulating material has been damaged and the current short circuits. In order to find methods to prevent or treat the diseases it is important to understand the connection between the diseases and the changes in the myelin.

    Getting 3-D X-ray images

    "We have combined two well-known medical examination methods: SAXS (Small-Angle X-ray Scattering) and CT-scanning (computed tomography scanning). Combined with a specially developed programme for data processing, we have been able to examine the variations of the myelin sheaths in a rat brain all the way down to the molecular level without surgery", explains PhD Torben Haugaard Jensen, Niels Bohr Institute at the University of Copenhagen. The method is called 'Molecular X-ray CT', because you use X-ray CT to study myelin at the molecular level.

    The research has been carried out in collaboration with researchers in Switzerland, France and Germany. The experiments took place at the Paul Scherrer Institute in Switzerland, where they have a powerful X-ray source that can measure Small-Angle X-Ray Scattering, SAXS at a high resolution. Normally such experiments would give two-dimensional X-ray images that are sharp and precise, but without information on depth. But by incorporating the method from CT-scanning, where you image from different angles, the researchers have managed to get 3D X-ray images.

    This has not only required the development of new X-ray methods and experiments, but has also required the development of new methods for processing data. The extremely detailed measurements of cross sections from different angles meant that there were 800,000 images to be analysed. So the researchers have also developed an image-processing programme for the SAXS-CT method. The result is that they can see all of the detailed information from SAXS in spatially resolved.

    From point samples to total samples

    "We can see the myelin sheaths of the neuronal axons and we can distinguish the layers which have a thickness of 17.6 nanometers", explains Torben Haugaard Jensen. "Up until now, you had to cut out a little sample in order to examine the layers in one area and get a single measuring point. With the new method we can examine 250,000 points at once without cutting into the sample. We can get a complete overview over the concentration and thickness of the myelin and this gives of the ability to determine whether the destruction of the myelin is occurring in spots or across the entire sample", he explains.

    The research provides new opportunities for collaboration with doctors at Copenhagen University Hospital and the Panum Institute, who they already have close contact with. The method cannot be used to diagnose living persons. But the doctors can obtain new knowledge about the diseases, what kind of damage is taking place? - and where? They will be able to follow the development of the diseases and find out how the brain is being attacked. This knowledge could perhaps be used to develop a treatment.

    Source: Medical News Today © MediLexicon International Ltd 2004-2011 (16/05/11)

    Identification and clinical impact of MS cortical lesions as assessed by routine 3T MR imaging

    MS MRIAbstract

    BACKGROUND AND PURPOSE: Histopathologic studies have reported widespread cortical lesions in MS; however, in vivo detection by using routinely available pulse sequences is challenging. We investigated the relative frequency and subtypes of cortical lesions and their relationships to white matter lesions and cognitive and physical disability.

    MATERIALS AND METHODS: Cortical lesions were identified and classified on the basis of concurrent review of 3D FLAIR and 3D T1-weighted IR-SPGR 3T MR images in 26 patients with MS. Twenty-five patients completed the MACFIMS battery. White matter lesion volume, cortical lesion number, and cortical lesion volume were assessed.

    RESULTS: Overall, 249 cortical lesions were detected. Cortical lesions were present in 24/26 patients (92.3%) (range per patient, 0–30; mean, 9.6 ± 8.8). Most (94.4%, n = 235) cortical lesions were classified as mixed cortical-subcortical (type I); the remaining 5.6% (n = 14) were classified as purely intracortical (type II). Subpial cortical lesions (type III) were not detected. White matter lesion volume correlated with cortical lesion number and cortical lesion volume (rS = 0.652, rS = 0.705, respectively; both P < .001). After controlling for age, depression, and premorbid intelligence, we found that all MR imaging variables (cortical lesion number, cortical lesion volume, white matter lesion volume) correlated with the SDMT score (R2 = 0.513, R2 = 0.449, R2 = 0.418, respectively; P < .014); cortical lesion number also correlated with the CVLT-II scores (R2 = 0.542–0.461, P < .043). The EDSS scores correlated with cortical lesion number and cortical lesion volume (rS = 0.472, rS = 0.404, respectively; P < .05), but not with white matter lesion volume.

    CONCLUSIONS: Our routinely available imaging method detected many cortical lesions in patients with MS and was useful in their precise topographic characterization in the context of the gray matter–white matter junction. Routinely detectable cortical lesions were related to physical disability and cognitive impairment.

    A. Mike, B.I. Glanz, P. Hildenbrand, D. Meier, K. Bolden, M. Liguori, E. Dell'Oglio, B.C. Healy, R. Bakshi and C.R.G. Guttmann

    From the Center for Neurological Imaging (A.M., P.H., D.M., K.B., M.L., E.D., C.R.G.G.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Partners Multiple Sclerosis Center (B.I.G., B.C.H., R.B.), Brigham and Women's Hospital, Harvard Medical School, Brookline, Massachusetts; Department of Radiology (P.H.), Lahey Clinic, Burlington, Massachusetts; Institute of Neurological Sciences (M.L.), National Research Council, Mangone, Cosenza, Italy; and the Biostatistics Center (B.C.H.), Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.

    Source: Journal of the American Society of Neuroradiology Copyright (c) 2011 by the American Society of Neuroradiology. (17/02/11)

    New MRI criteria have high efficiency in MS

    MRINew criteria for diagnosing multiple sclerosis with a single MRI have a sensitivity of up to 86% and a specificity of up to 75%, researchers said here.

    Their study is one of the first by an independent group to test the criteria developed by MAGNIMS (Magnetic Imaging in Multiple Sclerosis), a consortium of European academic researchers.

    "The goal of the new criteria is to save time, to allow treatment to be started earlier," Mayra Gomez-Moreno, MD, of the Infanta Leonor Hospital in Madrid, Spain, told attendees at the European Committee for Treatment and Research in Multiple Sclerosis meeting.

    Standard practice has been to obtain sequential images over a month or more, looking for progression, before arriving at the definitive diagnosis.

    In contrast, the new criteria make the diagnosis from a single scan obtained within three months of symptom onset.

    "Until now, you could not make the diagnosis with a single scan," Gomez-Moreno said. "Our data show that with the new criteria, you are going to make the correct diagnosis in 80% of patients, and will only need to wait for another MRI in 20%."

    Dissemination in space is proven by one or more asymptomatic T2 lesions in at least two of four characteristic locations: juxtacortical, periventricular, infratentorial, or spinal cord. Evidence of dissemination in time comes from the kinds of lesions found, with the requirement that there should be one or more gadolinium-enhancing lesions, plus non-enhancing lesions.

    Gomez-Moreno and colleagues enrolled 67 patients with a mean age at clinical onset of 30.7 years; 64% were female, 54 had enhancing lesions, and 42 met the full criteria for MS according to the new guidelines.

    After imaging, patients were followed for a minimum of 24 months (median 59). During this period, 49 patients (73%) received a diagnosis of MS according to standard clinical criteria.

    The group found that the disseminated-in-space criteria alone gave a sensitivity of 86% and a specificity of 65%, for a combined global efficiency of 80%, Gomez-Moreno said.

    The disseminated-in-time criteria alone gave a sensitivity of 53% and a specificity of 75%, for a global efficiency of 59%.

    The sensitivity and specificity obtained in this study are similar to those from other groups, she said, including the relatively low sensitivity of DIT criteria alone, a result that reflects "the stringency of these MRI diagnostic criteria for DIT."

    The new criteria have the potential to save both time and money, Gomez-Moreno said, especially important since early treatment is now considered the standard of care in MS.

    However, she cautioned, all of this must be done in the proper clinical setting. "The MRI is very important, but finally, we treat patients, not images. If you don't use the information correctly in a clinical setting, probably you are going to make a wrong diagnosis."

    The utility of the MAGNIMS criteria is still an open question, according to Franz Fazekas, MD, of the Medical University of Graz, Austria. Sounding a note of caution, he said the work published to date are valuable, "but we need a more general consensus that this is the direction to go" for early diagnosis of MS.

    Source: MedPage Today © 2004-2010 MedPage Today, LLC (16/10/10)

    Imaging cortical lesions in MS with ultra–high-field MRI

    MRIObjective:  To determine the sensitivity of T2*-weighted gradient-echo (T2*GRE) and inversion recovery turbo-field-echo (TFE) sequences for cortical multiple sclerosis lesions at 7 T.

    Design, Setting, and Participants:  Autopsied brain tissue from individuals with multiple sclerosis was scanned with 3-dimensional T2*GRE and 3-dimensional inversion recovery white matter–attenuated TFE sequences at 7 T. Cortical lesions visible with either sequence were scored for each anatomical lesion type. Imaged brain tissue was then processed for immunohistochemical analysis, and cortical lesions were identified by labeling with antibody against myelin basic protein and CD68 for microglia. Magnetic resonance images were matched with corresponding histological sections and scored retrospectively to determine the sensitivity for each cortical lesion type.

    Main Outcome Measure:  Cortical lesion detection by 3-dimensional T2*GRE and white matter–attenuated TFE sequences.

    Results:  The 3-dimensional T2*GRE and white matter–attenuated TFE sequences retrospectively detected 93% and 82% of all cortical lesions, respectively (with varying sensitivities for different lesion types). Lesion visibility was primarily determined by size as all undetected lesions were smaller than 1.1 mm at their smallest diameter. The T2*GRE images showed hypointense rings in some cortical lesions that corresponded with increased density of activated microglia.

    Conclusions:  Three-dimensional T2*GRE and white matter–attenuated TFE sequences at a 7-T field strength detect most cortical lesions in postmortem multiple sclerosis tissue. This study indicates the potential of T2*GRE and white matter–attenuated TFE sequences in ultra–high-field magnetic resonance imaging for cortical lesion detection in patients with multiple sclerosis.

    Author Affiliations: Departments of Neurology (Drs Pitt, Boster, Pei, and Rammohan and Messrs Wohleb and Jasne) and Radiology (Mr Zachariah and Drs Knopp and Schmalbrock), The Ohio State University, Columbus.

    David Pitt, MD; Aaron Boster, MD; Wei Pei, MD; Eric Wohleb, BS; Adam Jasne, BS; Cherian R. Zachariah, BS; Kottil Rammohan, MD; Michael V. Knopp, MD, PhD; Petra Schmalbrock, PhD

    Source: Arch Neurol. 2010;67(7):812-818. doi:10.1001/archneurol.2010.148 © 2010 American Medical Association. (19/07/10)

    Increased diffusivity in acute MS lesions predicts risk of black hole

    MS MRIAbstract
    OBJECTIVE: Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. Inflammation leads to tissue injury, resulting in increased diffusivity and decreased directionality.

    We hypothesize that DTI can quantify the damage within acute multiple sclerosis (MS) white matter lesions to predict gadolinium (Gd)-enhancing lesions that will persist 12 months later as T1 hypointensities.

    METHODS: A cohort of 22 individuals underwent 7 brain MRI scans over 15 months. DTI parameters were temporally quantified within regions of Gd enhancement. Comparison to the homologous region in the hemisphere contralateral to the Gd-enhancing lesion was also performed to standardize individual lesion DTI parameters.

    RESULTS: After classifying each Gd-enhancing region as to black hole outcome, radial diffusivity, mean diffusivity, and fractional anisotropy, along with their standardized values, were significantly altered for persistent black holes (PBHs), and remained elevated throughout the study. A Gd-enhancing region with a 40% elevation in radial diffusivity had a 5.4-fold (95% confidence interval [CI]: 2.1, 13.8) increased risk of becoming a PBH, with 70% (95% CI: 51%, 85%) sensitivity and 69% (95% CI: 57%, 80%) specificity. A model of radial diffusivity, with volume and length of Gd enhancement, was associated with a risk of becoming a PBH of 5.0 (95% CI: 2.6, 9.9). Altered DTI parameters displayed a dose relationship to duration of black hole persistence.

    CONCLUSIONS: Elevated radial diffusivity during gadolinium enhancement was associated with increased risk for development of a persistent black hole, a surrogate of severe demyelination and axonal injury. An elevated radial diffusivity within active multiple sclerosis lesions may be indicative of more severe tissue injury.

    Naismith RT, Xu J, Tutlam NT, Scully PT, Trinkaus K, Snyder AZ, Song SK, Cross AH.

    Neurology, Washington University, St. Louis, MO 63110, USA.

    Source: Neurology. 2010 May 25;74(21):1694-701. - Pubmed PMID: 20498437 (02/06/10)

    A longitudinal study of MRI-detected atrophy in secondary progressive multiple sclerosis

    MS MRIAbstract
    MRI measures of tissue atrophy within the central nervous system may reflect the neurodegenerative process which underpins the progressive phase of multiple sclerosis (MS).

    There has been limited longitudinal investigation of MRI-detected atrophy in secondary progressive MS.

    This study includes 56 subjects with secondary progressive MS.

    Subjects were followed up for 2 years and MRI analysis was conducted at 12 month intervals using the following measures: (1) whole brain (WB) volume change; (2) grey and white matter (WM) volumes; (3) central brain volume; (4) upper cervical spinal cord (SC) area; (5) T2 lesion volumes.

    Clinical measures included the Expanded Disability Status Scale and the MS Functional Composite. All volumetric MRI measures were assessed for sensitivity, responsiveness, reliability and correlation with disability.

    The mean annual atrophy rate of WB was 0.59% per year and this was the most responsive atrophy measure assessed. Grey matter (GM) atrophy (-1.18% per year) was greater and more responsive than WM atrophy (0.12% per year). The SC demonstrated the highest atrophy rate at 1.63% per year. WB, GM and SC atrophy all correlated with change in the Multiple Sclerosis Functional Composite z score (r = 0.35, 0.42, 0.34), and GM atrophy was the only correlate of change in the 9 Hole Peg Test and Paced Auditory Serial Addition Test performance. None of the MRI measures correlated with Expanded Disability Status Score progression.

    Measures of WB, GM and SC atrophy all have attributes for use as surrogate markers in secondary progressive MS trials and improvement in the reliability of the GM and SC volume measurements may enhance these further.

    Furby J, Hayton T, Altmann D, Brenner R, Chataway J, Smith KJ, Miller DH, Kapoor R.

    Department of Neuroinflammation, Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Source: Pubmed PMID: 20437181 (12/05/10)

    Diffusion tensor imaging sheds light on multiple sclerosis

    Diffusion Tensor Imaging & Multiple SclerosisA safe, noninvasive method for looking inside patients with MS offers promise for treating this complex disease.

    More than a century after multiple sclerosis (MS) was first recognized as a distinct pathologic disorder, its hallmark continues to be its frustrating unpredictability. Francis Clark, diagnosed with the autoimmune condition in high school, has learned to live with it. According to Clark, “MS is simply a fact of life.”

    MS symptoms — inflammation of the optic nerve, loss of muscle strength and balance problems, to name just a few — can cause a wide range of problems. No two people have the same experience with MS and, as Clark points out, a flare-up of one or more symptoms can happen at any time, with varying recovery times.

    “It seems to happen in a three-year cycle or close to it,” she says of her own disease. “Sometimes I get better very quickly, and sometimes it takes a long time. It can be very frustrating, not just for me, but also for my family. ”

    But the veil of unpredictability is finally starting to give way. Neurologists, radiologists and others at the School of Medicine have teamed up to show that an imaging technique, diffusion tensor imaging (DTI), can help assess damage to the optic nerves from MS. Now they are working to apply the same technique to other MS lesions that lead to symptoms affecting a broad range of the body. The questions they are posing about MS may one day allow better prognostic information and contribute to identifying more effective treatments.

    Scientists believe that MS, which affects an estimated 500,000 Americans, results from misdirected immune system attacks against the central nervous system.

    “For many years prior to the advent of MR imaging, MS was a disease of exclusion,” says Anne H. Cross, MD, the Manny and Rosalyn Rosenthal–Dr. John L. Trotter chair in neuroimmunology and director of the John L. Trotter MS Clinic at Barnes-Jewish Hospital. “The doctor would first rule out a list of other potential diagnoses until MS was the only thing left. This would sometimes lead to misdiagnoses that made it harder to understand MS.”

    MRI has revolutionized the care of MS patients by allowing early and accurate diagnosis. However, standard MR imaging techniques didn’t help researchers  reliably make a critical distinction for understanding, predicting and treating MS: When was MS damaging axons, the fibers leaving nerve cells that carry impulses from one nerve cell to another? And when was it harming only myelin, the protective sheath around the axons?

    “When an axon loses its myelin, it can still carry information,” Cross explains. “It may not be able to transmit it as effectively, but it can still work. And there’s evidence that many people with MS may be able to regenerate their myelin.”

    When an axon is lost, however, the prognosis is grim. No messages can be conveyed, and there is little evidence that the axon can regenerate.

    Using a mouse model of MS, Cross collaborated with Sheng-Kwei (Victor) Song, PhD, associate professor of radiology, to see whether an experimental imaging technique using the MRI scanner, known as diffusion tensor imaging (DTI) could help to distinguish between myelin damage and axon loss. DTI uses MRI to track water diffusion in tissue.

    Diffusion Tensor Imaging

    The diffusion tensor imaging technique measures neurons within a three-dimensional picture element called a voxel. About half a million neurons occupy the space captured in one voxel.

    Song and Cross reasoned that MS inflammation and the damage it causes would likely alter water diffusion in the affected tissues. Song thought a new approach to interpreting the DTI results could be particularly useful: analyze water diffusion both down the length of a nerve axon (axial diffusion) and across the insulating myelin (radial diffusion).

    “We were able to show that a decrease in axial diffusion was a very good bio-marker for axonal injury, and an increase in radial diffusion was a good marker for myelin damage,” says Song. “And we were able to correlate axonal injury with axon damage and increased likelihood of permanent disability.”

    Next, Robert T. Naismith, MD, assistant professor of neurology, led an effort to apply the approach to human MS patients with inflammation of the optic nerve, which causes loss of vision, blurring or fogginess and pain in the affected eye. They found that DTI could be used to predict both the severity and permanence of damage from these episodes.

    Now, with support from a new National Institutes of Neurological Disorders and Stroke grant, these scientists are applying DTI to other MS questions. “The optic nerve was our proof of concept, because it’s structurally a very simple tract with all the nerves going one direction, like a one-way street,” says Naismith. “Now we’re taking the technique into the brain and spinal cord, where there are numerous streets, including many that cross. Measuring damage and correlating it to dysfunction will be more complex as a result.”

    Cross, Song and others are trying to use DTI to learn more about a phenomenon informally known as “black holes”: large, MS-induced lesions in the central nervous system that show up as dark spots on MRI scans.

    “There’s so much tissue damage that the black holes can look almost like strokes,” Cross explains. “We’re trying to use DTI to help us predict which lesions, at early stages, will eventually develop into black holes. Patients with that type of MS lesion may need more aggressive treatments.”

    Some data for the project will come from a recently completed clinical trial of a potential MS treatment that Cross conducted at Barnes-Jewish Hospital. The team is currently writing up their findings.

    DTI also may help researchers understand MS at a more basic level. Robyn S. Klein, MD, associate professor of medicine, is using DTI to study a molecule her lab has linked to myelin regrowth. Her lab will block this molecule to see whether disabling the nerve cell’s ability to regrow the myelin sheath leads to axonal damage. She also plans to block individual molecules involved in inflammatory processes to see whether they can prevent the initial damage that occurs during MS flares.

    “Being able to study these processes in live animals with DTI is extremely powerful,” Klein says. “By doing so, we can determine whether preventing early axonal injury with a drug is directly linked to eventual recovery from the flare-up.”

    The same principle may work in clinical trials of new drug treatments in humans. Currently, such studies must wait weeks, months or longer to determine whether a new treatment has prevented permanent disability. If DTI provides quicker and more conclusive results, it will accelerate the drug development process.

    Such knowledge is power, says MS sufferer Clark, recalling the days when her disease first began to manifest and she had yet to be diagnosed. “To have the right people working to find out what’s going on and to find the right way to treat MS is very helpful.”

    Source: Washington University in St. Louis Copyright 2010 (01/04/10)

    Advanced MRI may speed diagnosis of multiple sclerosis

    MS MRIMRI has become central to the diagnosis of multiple sclerosis, a complex disease of the central nervous system that affects over 400,000 people in Europe. Around 90% of all MS diagnoses are now based on MRI findings, owing to the modality’s high sensitivity to inflammation and demyelinating plaques.

    Trials have shown that an early diagnosis can make a big difference to the efficacy of MS drug treatments. Familiarity with the optimum diagnostic strategy is consequently crucial. Work is also under way to identify imaging biomarkers that could show whether a selected treatment is working, well before that same conclusion can be drawn from clinical findings.

    Members of the European Magnetic Imaging in Multiple Sclerosis (MAGNIMS) network shared with ECR delegates their expertise on MS diagnosis and management. The state-of-the-art session included practical tips for general radiologists who are faced with a potential case of MS, as well as details about research that will appeal to specialists in neuroradiology.

    “From a practical point of view, the most important message is to be familiar with the diagnostic criteria,” said Dr. Alex Rovira, head of the MRI unit at the Vall d’Hebron University Hospital, Barcelona, Spain, and the session chair. “In most European countries, the criteria required to start treatment for MS is to establish the diagnosis, and this is done with MRI. To avoid a wrong diagnosis, we have to know about the typical features of this disease and how we should apply imaging criteria.”

    An imaging-led diagnosis of MS is typically based on conventional MRI techniques. T2-weighted imaging can reveal lesions that indicate the presence of inflammation, demyelination, gliosis, axonal loss, and even remyelination. This information may be used by radiologists to estimate the overall burden of MS disease. Contrast-enhanced T1-weighted MRI can also be used to detect lesions that are currently active.

    A firm diagnosis is not usually made until the disease has been identified clinically in a separate part of the central nervous system some time after the initial onset of symptoms. It may take a couple of years for this criterion to be met. Repeated MRI, on the other hand, may identify new “silent” lesions and speed up the diagnosis. Alternatively, and of equal importance, imaging may be able to exclude MS and identify another cause of the patient’s symptoms.

    Once the diagnosis has been made, the value of MRI to MS patients begins to waver. Radiologists would like to use MRI to track progression of the disease, and perhaps even forecast periods of remission and relapse, but it is difficult to predict the outcome of treatment based on conventional MRI findings alone. What you see on imaging does not necessarily reflect what benefit the patient will get.

    The main reason for this clinical-radiological paradox is the complexity of MS. A number of factors contribute to disease severity, and not all of this information can be captured from T2- and T1-weighted imaging alone. Conventional MRI techniques may be able to spot MS lesions, but they say little about changes occurring within those lesions or about damage to brain tissue that has a “normal” appearance. More sophisticated techniques, such as MR spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI) are needed to complete the picture.

    “MS is not just focal inflammatory demyelination, as we used to think. There are a lot of additional things going on,” said Prof. Massimo Filippi, director of the Neuroimaging Research Unit at San Raffaele University in Milan, and one of the session’s three invited speakers. “It is a more complex puzzle that we still need to define.”

    This process would be aided if the application of these nonconventional MRI techniques could be standardized, according to Filippi. Clear criteria for the diagnosis of MS based on conventional MRI approaches have already been established, but as yet, there is no common language covering MRS, DTI, and/or fMRI findings.

    Nonconventional MRI techniques are becoming increasingly important in preclinical and clinical trials as companies move forward in developing neuroprotective drugs, as well as anti-inflammatory agents. The development of internationally acceptable guidelines relating to MRI-based monitoring of MS would help researchers from different institutions to compare their results.

    “We are lucky to have MRI, which is not a single technique but a set of techniques. We should not be using the same technique in all scenarios, but tailoring our approach to MRI when addressing different research questions,” Filippi said.

    Source: © 1996 - 2010 UBM Medica LLC (15/03/10)

    Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis

    MS MRI BACKGROUND: Cognitive impairment in primary progressive multiple sclerosis (PPMS) is common and correlates modestly with contemporary lesion burden and brain volume. Using a cohort/case control methodology, we explore the ability of MRI abnormalities, including those in the normal-appearing brain tissue, to predict future cognitive dysfunction in PPMS.

    METHODS: Thirty-one patients recruited into a longitudinal study within 5 years of onset of PPMS were assessed neuropsychologically on average 5.5 years later along with 31 matched healthy controls. MRI data obtained at entry into the study (lesion metrics, brain volumes, magnetization transfer ratio histogram metrics, and magnetic resonance spectroscopy metabolite concentrations) were used to predict cognitive impairment at follow-up.

    RESULTS: Twenty-nine percent of patients were categorized as cognitively impaired. T2 lesion volume was the best MRI predictor of overall cognitive function and performance on tests of verbal memory and attention/speed of information processing. Low gray matter magnetization transfer ratio was the best predictor of poor performance on a further test of attention/speed of information processing and an executive function test. Low gray and white matter volumes were independent predictors of poor performance on a second test of executive function.

    CONCLUSIONS: MRI abnormalities observed in early primary progressive multiple sclerosis can predict cognitive impairment 5 years later. While focal damage disrupting white matter tracts appears to be the most important predictor of subsequent cognitive dysfunction, gray matter pathology also plays a role.

    Penny S, Khaleeli Z, Cipolotti L, Thompson A, Ron M.

    Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Source: Pubmed PMID: 20157157 (23/02/10)

    New diagnostic criteria for Multiple Sclerosis published

    MS MRIInvestigators are proposing new diagnostic standards for multiple sclerosis in clinically isolated syndromes. Their criteria are less stringent than other proposals and are designed to improve sensitivity to promote early diagnosis.

    The authors report they wanted to simplify existing diagnostic criteria for multiple sclerosis. The group, led by Xavier Montalban, MD, from the Hospital Universitari Vall d'Hebron, in Barcelona, Spain, suggests current recommendations are complex and that "a good working knowledge of them is not always evident even among neurologists and neuroradiologists."

    They point out that multiple magnetic resonance imaging (MRI) examinations are often needed to achieve an accurate diagnosis.

    "This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome," they note.

    The new criteria appeared in the February 2 issue of Neurology.


    •Clinically definite multiple sclerosis can be confirmed if a MRI is performed at any time demonstrating dissemination in space and showing at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions.
    •Patients without any enhancing or with all enhancing lesions would require a new MRI to demonstrate new T2 or gadolinium-enhancing lesions.
    •Patients with an abnormal MRI performed at any time, but not showing dissemination in space or time, would require follow-up imaging.

    "We recommend 1 dissemination in space criterion," the authors note. This would represent 1 or more asymptomatic T2 lesions in 2 or more of 4 locations considered characteristic for multiple sclerosis in previous MRI criteria — juxtacortical, periventricular, infratentorial, and spinal cord.

    "We recommend 2 dissemination in time criteria," they add, and call for the presence of at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions irrespective of the time of the scan and the presence of a new T2 or gadolinium-enhancing lesion compared with a previous scan.

    Asked by Medscape Neurology to comment on the new criteria, Gary Birnbaum, MD, from the Minneapolis Clinic of Neurology in Golden Valley, Minnesota, raised some concerns about the effect these recommendations could have.

    "The proposed criteria are less stringent than other criteria, possibly increasing the sensitivity of detecting conversion to clinically definite multiple sclerosis, but possibly decreasing the specificity of the changes," he said. "This will need to be monitored carefully."

    Increasing the Risk for Misdiagnosis

    Dr. Birnbaum says the data supporting early treatment of multiple sclerosis are good; however, he suggests that not all patients with clinically isolated syndrome need, or necessarily benefit from, treatment with disease-modifying therapies.

    "Indeed, recent long-term data show that more than 30% of persons with 'high-risk' MRI changes do not have significant disease after 20 years of follow-up," he said. "There may not be a great urgency for establishing a diagnosis of clinically definite multiple sclerosis in a significant proportion of individuals with clinically isolated syndrome, especially if the specificity of criteria are less stringent — increasing the risk of misdiagnosis."

    Dr. Birnbaum points out there are many disease-modifying therapies already approved for the treatment of patients with clinically isolated syndrome. "If a physician feels there is a need to begin treatment early, conversion to clinically definite multiple sclerosis is not necessary to prescribe such agents," he said.

    More Study Needed

    Dr. Birnbaum emphasizes that having less stringent MRI criteria for establishing disease progression may not be necessary and could increase the risk of treating people with diseases other than multiple sclerosis.

    Ben Thrower, MD, a neurologist and senior medical advisor for the Multiple Sclerosis Foundation, said he agrees there are risks involved in early diagnosis. This could lead to inaccurate diagnosis or patients starting therapy with expensive and inconvenient medications, he suggests.

    However, Dr. Thrower also acknowledges the benefits of early diagnosis, including peace of mind for patients and families dealing with unexplained symptoms. He points to data suggesting fewer relapses and new MRI lesions in those who start therapy sooner.

    "These new proposed guidelines offer the possibility of using a single MRI to fulfil diagnostic criteria," Dr. Thrower said. "If the brain MRI shows lesions with and without active inflammation, this would demonstrate dissemination in time and space."

    Dr. Thrower says the new criteria will need to be studied further and compared with existing McDonald criteria to determine whether they are sufficient.

    Dr. Montalban and his team acknowledge that testing these criteria in new, prospectively followed clinically isolated syndrome cohorts is needed.

    They also point out that scans in most studies have been performed on 1.5-Tesla or lower field-strength scanners using conventional T2-weighted spin echo or fluid-attenuated inversion recovery sequences.

    They note, "The impact of 3 Tesla or higher field MRI findings or other MRI sequences on diagnosis will have to be considered in the future."

    Dr. Xavier Montalban has received support from Novartis, Teva, Merck, Biogen Idec, Bayer, Schering Pharma, Sanofi-Aventis, Almirall, Eli Lilly, Genentech, Genzyme, Wyeth, and Fundació Esclerosi Multiple.

    Source: Medscape Today © 1994-2010 by WebMD LLC (15/02/10)

    MRI study evaluates dynamic causal model to assess interactions of brain regions during motor task in Multiple Sclerosis patients

    MS MRIThe use of functional MRI to assess patterns of brain activation in adults and children with multiple sclerosis (MS) may offer insight into disease progression among these groups, according to research published in the February issue of Radiology.

    Maria A. Rocca, M.D., of the University Hospital San Raffaele in Milan, Italy, and colleagues analyzed data from five small groups: healthy pediatric and adult controls, pediatric and adult patients with relapsing-remitting MS, and adults with clinically isolated syndromes. Patients underwent MRI during a simple motor task. Also, a dynamic causal model approach was used to assess interactions between different regions during the task.

    The researcher's findings suggest that the brain pattern of cortical activation is relatively preserved in pediatric relapsing-remitting patients, and additional areas of the network are progressively recruited in adult relapsing-remitting patients. The relatively preserved adaptive properties of the cerebral cortex in pediatric patients may inhibit clinical disability in the short to medium term.

    "The preservation of brain adaptive properties might explain the favorable medium-term clinical outcome of pediatric MS patients," the authors write. "The progressive recruitment of cortical networks over time in patients with the adult relapsing-remitting forms of the disease might result in a loss of their plastic reservoir, thus possibly contributing to subsequent disease evolution."


    Source: Modern Medicine © 2010 HealthDay. (29/01/10)

    Magnetic resonance imaging predictors of conversion to Multiple Sclerosis in the BENEFIT study

    MS MRIBackground:  Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance (MR) imaging variables for conversion to clinically definite multiple sclerosis (CDMS), depending on the population, follow-up duration, and treatment intervention. However, the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation.

    Objectives:  To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and (2) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging.

    Design:  Cohort study.

    Setting:  Multicenter randomized clinical trial.

    Patients:  Four hundred sixty-eight patients with a clinically isolated syndrome who had an initial clinical demyelinating event within the past 60 days who received early treatment (3 years of interferon beta-1b) or delayed treatment (placebo first, followed by 1 year of interferon beta-1b).

    Intervention:  Magnetic resonance imaging.

    Main Outcome Measure:  Time to CDMS.

    Results:  The overall conversion rate to CDMS was 42%. Barkhof criteria with the strongest prognostic value were the presence at baseline of at least 9 T2-weighted lesions (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.15-2.33; P = .006) and at least 3 periventricular lesions (1.66; 1.14-2.41; P = .009). No specific advantage was noted in using a fixed cutoff of at least 3 Barkhof criteria (HR, 1.31; 95% CI, 0.95-1.79; P = .10). The prognostic value of all MR imaging criteria was unaffected by treatment intervention (P  .20 for all). Dissemination in time resulted in increased risk for CDMS only in patients without dissemination in space at baseline and was most informative at the 9-month MR imaging (HR, 2.72; 95% CI, 1.26-5.87; P = .01).

    Conclusions:  The modified Barkhof criteria showed moderate predictive value for conversion to CDMS, although all patients had received interferon beta-1b therapy for at least 1 year. The predictive value was unaffected by treatment intervention. Follow-up MR imaging was most informative after 9 months in patients without dissemination in space at baseline.

    Author Affiliations: Departments of Diagnostic Radiology (Drs Moraal and Barkhof), Clinical Epidemiology and Biostatistics (Dr Uitdehaag), and Neurology (Drs Uitdehaag and Polman), Multiple Sclerosis Center Amsterdam, Vrije University Medical Center, Amsterdam, the Netherlands; Bayer Schering Pharma AG, Berlin (Drs Pohl, Lanius, and Sandbrink), Department of Neurology, University Hospital of Bonn, Bonn (Dr Pohl), and Heinrich-Heine University, Düsseldorf (Drs Hartung and Sandbrink), Germany; Department of Neurology, Centre Hospitalier Universitaire, Rennes, France (Dr Edan); Multiple Sclerosis Research Unit, The Ottawa Hospital, Ottawa, Ontario, Canada (Dr Freedman); Departments of Neurology and Neurosurgery, University Hospital Basel, Basel, Switzerland (Dr Kappos); Institute of Neurology, University College London, London, England (Dr Miller); and Unit of Clinica Neuroimmunology, Hospital Vall d’Hebron, Barcelona, Spain (Dr Montalban).

    Bastiaan Moraal, MD; Christoph Pohl, MD; Bernard M. J. Uitdehaag, MD, PhD; Chris H. Polman, MD, PhD; Gilles Edan, MD; Mark S. Freedman, MD; Hans-Peter Hartung, MD; Ludwig Kappos, MD; David H. Miller, MD; Xavier Montalban, MD; Vivian Lanius, PhD; Rupert Sandbrink, MD, PhD; Frederik Barkhof, MD, PhD

    Source: Arch Neurol. 2009;66(11):1345-1352. (10/11/09)

    New software to detect multiple sclerosis before brain damage occurs

    3D Fractal Of Brain
    Researchers of the Unit for Systems Biology of the University of Jaén, led by Francisco J. Esteban, are developing a software for clinical use to detect multiple sclerosis even before the typical brain damage of this neurodegenerative disease appear. In order to do so, this scientific multidisciplinary team is calculating the fractal dimension of the brain images registered on magnetic resonance imaging. They are starting to implement this technique also to other neurodegenerative diseases, and therefore it could be a tool for the early diagnosis of these type of diseases. Centre for Applied Medical Research of the University of Navarra and Hospital Clínico of Barcelona are collaborating in this research.

    Multiple sclerosis is a degenerative disease of the nervous system that cannot be cured and whose exact causes are unknown. When the first symptoms appear, one of the tests that is usually carried out is an MRI to find out if the brain suffers the typical damage of this disease. In the early stages of the disease it may be that no damage has been caused yet or that the damage caused is under the resolution limit of the MRI. In such cases the brain of an ill person is said to be 'apparently normal' as it shows the same features than that of a healthy person. However a group of Jaen scientists has applied an analysis by calculating the fractal dimension of an ill person's brain and they have proven that the result of that -shown with this parameter- is different from a healthy person's brain.

    Unlike the Euclidean dimension (a point has a dimension of zero, a line has a dimension of one, a plane has a dimension of 2, and a volume has a dimension of 3), the fractal dimension is a parameter that allows to obtain dimensions ranging between 1 and 2 (2-D fractal dimension) and 2 and 3 (3-D fractal dimension). The fractal dimension is the dimension of irregular digitalized curves, and for some years now it has been applied to different biological structures, but the application to the brain was scarce. For the first time, this group of biologists, computing engineers, mathematicians, neurologists, neurosurgeons, psychologists and statisticians are carrying out this type of calculations on 3D magnetic resonance imaging of brains to try to solve clinical problems.

    What the eye cannot see

    This team is developing software that allows calculating the 3D fractal dimension of the brain. 'It is a tool for clinical use to try to see if persons suffering the early symptoms of multiple sclerosis, with an apparently normal brain, can suffer this disease. It could be a very useful tool for the early diagnosis of brain-related diseases' Esteban said.

    With the currently carried out tests, you can calculate the volume, size or circumvolutions of the brain, but it was difficult to calculate its complexity, which is something that can be done with the fractal dimension. Jaen-based scientists are using different computer algorithms for image processing and are applying the theory of fractal dimension both on nuclear magnetic resonance of healthy people and on persons with certain neurodegenerative diseases such as multiple sclerosis. 'When fractal dimension is applied to the brain, we are able to detect certain alterations in the brain structures that cannot be observed with any other method used so far. By using this new technique, we can detect alterations that the eye cannot see' Professor Esteban Ruiz stressed.

    So far this study has been carried out in patients with multiple sclerosis, but the aim is to apply it to other neurodegenerative diseases. 'We are using this method, in collaboration with Hospital Clínico of Barcelona, to detect possible changes in the brain of children that can develop learning difficulties. An early diagnosis can minimise such problems by applying a suitable treatment', the main researcher pointed out.

    'The next step in our study consists of seeking the collaboration of Andalusian hospitals to see if there are successful results in different groups of patients' he added. If all the results are positive, 'this could be a good clinical tool, available straight away', the researcher ended.

    The research conclusions have been published in prestigious medical journals such as Neuroimage and Journal of the Neurological Sciences, and they are been revolutionary in this field.

    Source: University of Jaén (01/10/09)

    Imaging outcomes for neuroprotection and repair in multiple sclerosis trials

    MS Brain Image

    Multiple sclerosis (MS) is commonly regarded as an inflammatory disease, but it also has a neurodegenerative component, which represents an additional target for treatment.

    The use of MRI to evaluate the inflammatory disease component in 'proof-of concept' clinical trials is well established, but no systematic assessment of imaging outcomes to evaluate neuroprotection or repair in MS has been performed.

    In this Review, we examine the potential of traditional and novel imaging parameters to serve as primary outcomes in phase II clinical trials of neuroprotective and reparative strategies in MS.

    We present the conclusions of an international meeting of imaging, clinical and statistical experts, as well as a review of relevant literature.

    The available imaging techniques are appraised in five categories of performance: pathological specificity, reproducibility, sensitivity to change, clinical relevance, and response to treatment. At present, the three most promising primary outcomes in phase II trials of neuroprotective and/or reparative strategies in MS are: changes in whole-brain volume to gauge general cerebral atrophy; T1 hypointensity and magnetization transfer ratio to monitor the evolution of lesion damage; and optical coherence tomography findings to evaluate the anterior visual pathway. Power calculations show that these outcome measures can be applied with attainable sample sizes.

    Frederik Barkhof1, Peter A. Calabresi2, David H. Miller3 & Stephen C. Reingold4

    1Department of Radiology and Amsterdam MS Center, VU University Medical Center, Amsterdam, The Netherlands.
    2Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
    3Department of Neuroinflammation and NMR Research Unit, Institute of Neurology, University College London, London, UK.
    4National MS Society and Scientific and Clinical Review Associates, LLC, New York, NY, USA.

    Source: Nature Reviews Neurology © 2009 Nature Publishing Group (11/05/09)

    MRI scans can predict effects of Multiple Sclerosis flare-ups on optic nerve

    MS Brain MRI

    One of the most pernicious aspects of multiple sclerosis (MS) — its sheer unpredictability — may finally be starting to yield to advanced medical imaging techniques.

    Researchers from Washington University School of Medicine in St. Louis report online in the journal Neurology that an approach known as magnetic resonance diffusion tensor imaging (DTI) allowed them to estimate three months in advance the chronic effects of inflammation of the optic nerve. The condition occurs most often as a result of MS, a neurodegenerative disorder that can present with an extremely broad variety of symptoms that range from vision loss and other sensory damage to muscle weakness, spasticity or paralysis to depression, sleep loss or incontinence. MS affects an estimated 500,000 Americans.

    "We see this as part of a battery of tests we hope to give patients within the next decade to help our clinical assessment and tailor it to an optimal treatment," says lead author Robert T. Naismith, M.D., assistant professor of neurology and a staff physician at Barnes-Jewish Hospital. "It may also help further refine our basic understanding of MS in terms of expanding our insights into where and how damage occurs and why it can affect patients differently."

    Scientists believe MS results from misdirected immune system attacks against the nervous system. Symptoms occur in bouts that vary unpredictably in nature, severity, duration and frequency. Symptoms of optic nerve inflammation, known as optic neuritis, include loss of vision, blurring or fogginess and pain in the affected eye.

    Regular MRI scans can detect optic neuritis but offer no information on its severity and potential lasting consequences for a patient's vision.

    Currently in use clinically to detect and follow up on strokes, DTI uses a rapid series of MRI scans to track water diffusion in tissue. Noting that inflammation and the cell damage it causes would likely alter water diffusion in the affected tissues, Naismith and his colleagues hypothesized that this information might allow them to assess the severity and potential for lasting damage of MS flare-ups. Over the past five years, the new paper's senior authors, Sheng-Kwei Song, Ph.D., associate professor of radiology, and Anne Cross, M.D., professor of radiology, did much of the quantitative work in animal models of MS. The new data, based upon this successful collaborative history, are the first to show that DTI can produce potentially useful predictive information in humans.

    For the study, researchers used DTI to image the optic nerves of 12 healthy volunteers, 12 patients who had begun to suffer from optic neuritis within the past month and 28 patients with a history of earlier outbreaks. They gave participants with optic neuritis or a history of it detailed assessments of their visual health, including tests of visual acuity and the thickness and conductivity of their optic nerves.

    In the healthy subjects, DTI scans showed that the water diffusion along the length of the subjects' optic nerves, a characteristic known as axial diffusivity, averaged about 1.66 micrometers squared per millisecond. In three patients with acute optic neuritis, those levels went down as much as 0.45 micrometers squared per millisecond.

    "As the inflammation breaks down the structure of the axons or branches of the optic nerves, the normal water diffusion in this direction is impeded," Naismith explains. "After several months, though, the debris is cleared away, and this value and another characteristic known as radial diffusivity then start to increase."

    In acute patients, the initial decrease in axial diffusivity brought on by optic neuritis correlated with decreased sensitivity to visual contrast one month and three months later. In patients with a history of optic neuritis, the increase in radial diffusivity was a good predictor of lower scores on several tests of visual health. Scientists plan to assess the acute patients again one year after the onset of symptoms to see if the scan results continue to be predictive.

    Researchers are currently working to expand the approach to assess MS attacks in the brain and spinal cord.

    "The optic nerve was our proof of concept, because it's structurally a very simple tract with all the nerves going one way, like a one-way street," he says. "The next step is taking the technique into the brain and spinal cord, where there are many different streets crossing. Measuring damage and correlating it to dysfunction will be more complex as a result."

    Source: Science Daily © 1995-2008 ScienceDaily LLC (17/12/08)

    Demyelinating pathology on MRI may precede MS symptoms

    MS Brain MRI

    Patients with incidental MRI anomalies resembling demyelinated lesions that are not due to another disease process are at increased risk for multiple sclerosis (MS), researchers in San Francisco report in Neurology.

    “Some observed changes (on MRI) are highly suggestive of demyelinating pathology based both upon their location and morphology in the CNS (i.e., periventricular geography, involvement of the corpus callosum, ovoid, well-circumscribed, homogeneous),” Dr. Darin T. Okuda and co-authors note. They call such lesions in the absence of symptoms “radiologically isolated syndrome.”

    The research team at the UCSF Multiple Sclerosis Center studied the natural history of radiologically isolated syndrome in 44 patients ages 16 to 67 years. Thirty patients were followed clinically; longitudinal MRI data were available for 41 patients.

    Except for one patient with a history of stroke and two with asymmetric reflexes, initial neurologic examinations were normal. However, cerebrospinal fluid profiles obtained from 27 subjects were suggestive of MS in 18 (67%).

    During a median follow-up of 2.7 years (maximum 26 years), 24 of 41 patients (59%) exhibited radiologic progression.

    Of 30 patients who were followed clinically, 10 (30%) converted to clinically isolated syndromes or clinically defined MS. Median time to the first clinical event was 5.4 years (maximum 9.8 years). No other disease entity has been identified in this cohort.

    Dr. Okuda’s team cautions that “these data should not be generally applied in those cases with nonspecific brain MRI anomalies, leukoariosis, or those who fail to meet validated dissemination in space criteria.”

    Noting that “MS remains a clinicopathologic entity and patients must have symptoms to receive a diagnosis,” authors of an accompanying editorial point out that some patients with demyelinating lesions remain permanently asymptomatic.

    Drs. Dennis Bourdette and Jack Simon at the Oregon Health & Science University in Portland therefore advise that physicians “not tell patients with radiologically isolated syndrome that they have MS (or) treat them with disease-modifying therapies.”

    Source: Neurology 2008. (11/12/08)

    MRI can now predict Multiple Sclerosis progression

    MS MRI

    A new study published in Journal of Neuroimaging shows that MRI scans used on multiple sclerosis (MS) patients to determine if the disease has affected gray matter in the brain can identify those at-risk for progression of disability.

    MS affects approximately 400,000 people in the United States and as many as 2.5 million worldwide. It is the most common cause of progressive disability in young adults. While the cause of the disease remains unknown, it is characterized by damage to the covering over the nerve fibers in the brain and spinal cord, or to the nerve fiber itself.

    In an attempt to understand the causes of disease progression, researchers at the Partners MS Center, led by Dr. Rohit Bakshi and his team, have developed new ways to detect gray matter damage.

    Dr. Bakshi, Director of the Laboratory for Neuroimaging Research and an Associate Professor of Neurology and Radiology at the Brigham and Women's Hospital and Harvard Medical School, led a four year follow-up study, which found that patients with unnatural darkness of gray matter structures as seen on MRI pictures carried a higher risk for progression of physical disability. This abnormal darkness is referred to as T2 hypointensity, and is suggestive of excessive iron deposits. In addition, the researchers found that the new marker of gray matter damage showed closer correlations with patients' clinical status than other established MRI markers of disease severity, including lesions, also known as "plaques," and shrinkage of the brain, also know as "atrophy."

    "MRI scans obtained from patients with MS are being used to develop measures and techniques that can accurately measure the visible and hidden damage to the brain, especially in gray matter areas and can more accurately predict the course of the disease," says Bakshi.

    As a result of the findings, MRI-based measurement of gray matter damage may be used as a surrogate marker of disease progression. Physicians may therefore be able to more accurately identify patients at risk for developing this progressive disease.

    MS has been traditionally viewed as a disease affecting the white matter of the brain, where messages are transferred between the brains gray matter sections, which control the processing of information. While prior research has shown that the brain's gray matter is also affected, studies detailing its effects have been limited. In addition, current therapies for MS are incomplete, raising the need to better understand disease mechanisms and the biomarkers of disease progression. If excessive iron in gray matter contributes to damage, this would open a new avenue for developing better therapies.

    Source: ScienceDaily © 1995-2008 ScienceDaily (06/11/08)

    Magnetic resonance imaging can predict who will develop Multiple Sclerosis

    Specific magnetic resonance imaging (MRI) scans can predict which patients will develop multiple sclerosis (MS), according to retrospective research presented at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRMS).

    The Betaferon/Betaseron in Newly Emerging MS for Initial Treatment (BENEFIT) study is a randomised, double-blind, placebo-controlled, parallel-group clinical trial that was carried out among 468 patients whose first clinical event suggestive of MS happened within 60 days of trial entry. The study found that treatment with interferon (INF) beta-1b 250 mcg prevented the onset of clinically definite multiple sclerosis (CDMS) by 1 year.

    Patients in the BENEFIT study were assigned to either early treatment, which was IFN beta-1b from the start of the trial, or delayed treatment, which was initial placebo followed by IFN beta-1b therapy after conversion to CDMS or upon completing 2-year follow-up.

    Principal investigator Bastiaan Moraal, MD, VU Medical Center, Amsterdam, Netherlands, speaking at an oral session, said that this analysis examined radiological rather than clinical endpoints.

    "We were looking at which type of lesions measured at baseline would predict conversion to clinically definite multiple sclerosis or McDonald multiple sclerosis," said Dr. Moraal.

    In this analysis, blinded raters assessed baseline MRI parameters using T2-weighted and postcontrast T1-weighted sequences. Statistical analysis was employed to assess the predictive value of each baseline MRI parameter and treatment interaction.

    Investigators found overall conversion to CDMS was 42%, with factors such as the presence of =>9 T2 lesions and =>3 periventricular lesions demonstrating predictive value. They found that conversion rose with the cumulative number of positive criteria. No specific advantage was demonstrated for a threshold of =>3 Barkhof criteria.

    "Patients whose treatment was delayed and had 4 positive Barkhof criteria had a higher chance of conversion to CDMS and McDonald MS compared to those with early treatment and fewer positive Barkhof criteria at baseline," explained Dr. Moraal.

    Investigators found that prognostic value was affected by treatment (P = .002) for 4 positive Barkhof criteria. The prognostic value was not influenced by therapy for CDMS.

    "We saw that, with one exception, the predictive value of MRI values was not affected by treatment," said Dr. Moraal.

    Future analysis will examine the predictive value of MRI variables at 3, 6, and 9 months to assess the impact of those variables on conversion to either CDMS or McDonald MS.

    Source: Doctor's Guide Channels (c) 1995-2008 Doctor's Guide Publishing Limited (25/09/08)

    MRI findings predict evolution of preclinical multiple sclerosis

    Patients with subclinical demyelinating lesions fulfilling MRI Barkhof-Tintoré criteria with a normal neurological examination are likely to develop multiple sclerosis (MS), according to a report in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

    "Patients who fulfill the Barkhof and Tintoré MRI criteria, combined with CSF study, can be considered high risk for MS and have early treatment," Dr. Christine Lebrun-Frenay from CHU de Nice, France told Reuters Health.

    Dr. Lebrun-Frenay and colleagues note that the concept of preclinical MS is now recognized. Silent brain T2 lesions are often seen on incidental MRI, they point out, but patients fulfilling Barkhof-Tintoré criteria are relatively uncommon.

    The researchers report clinical and MRI findings after a five-year follow-up in 30 patients with subclinical demyelinating lesions fulfilling Barkhof criteria seen on MRI performed for medical complaints such as headache or trauma.
    All patients had a normal examination and biological screening, the authors report, but all patients had increased CSF immunoglobulin levels (including nine with oligoclonal bands) and eight patients had abnormal asymptomatic visual evoked potentials.

    Eleven patients clinically converted, including five with optic neuritis, three with diplopia or internuclear ophthalmoplegia, two with paresthesias in the lower limbs, and one with cognitive deterioration.

    Four of these patients had their first clinical events during the first year after the first abnormal MRI, three during the second year, three during the third year, and one at five years. The mean time between the abnormal MRI and the clinically isolated syndrome was 2.3 years.

    All 17 patients who underwent a second MRI during the first year showed MRI dissemination, the researchers note, as did eight of 12 patients whose second MRI was done between 12 and 24 months.

    "For the pre-MS patient, without clinical events but with evidence of dissemination to time and space, medical discussion on the therapeutic options of immunomodulatory agents for reducing the risk of MS should be conducted, with the knowledge that subclinical MS can evolve into relapsing remitting MS in the majority of cases or more rarely into progressive MS," the investigators advise.

    "Physicians and especially neurologists must really know Barkhof and McDonald criteria to not overestimate the diagnosis of MS," Dr. Lebrun-Frenay said. "A lot of abnormal MRI with T hyperintensities are classified MS, but a lot of physicians forget what Barkhof and Tintoré said in their principal publications on the way to interpret brain MRI."

    If the patient does fulfill the Barkhof-Tintoré criteria, "then a simple workup for other inflammatory conditions would seem to be in order," writes Dr. Jeremy Chataway from St. Mary's Hospital, London, UK in a related editorial. "From there on, time and clinical evaluation would perhaps guide subsequent investigation."

    Source: © 2008 Medicexchange PLC (20/02/08)

    Stronger MRI's Speed Multiple Sclerosis Diagnosis
    U.S. scientists say ultra-high-field MRIs allow for earlier diagnosis of multiple sclerosis.

    Ultra-high-field -- or 7T -- MRI can detect multiple sclerosis lesions better than 3T MRI, researchers from Ohio State University and New York's Columbia University said in a release.

    "The greater sensitivity of 7T MRI for multiple sclerosis can delay disease conversion, and may lead to improved monitoring of neurological deficits in multiple sclerosis," said lead author Dr. Steffen Sammet.

    Sammet said MRI at 7T can also give additional information about the lesion microstructure to help doctors better understand the disease.

    Source: (18/01/08)

    Cervical Spinal Cord Lesions in Multiple Sclerosis: T1-weighted Inversion-Recovery MR Imaging with Phase-Sensitive Reconstruction.
    This magnetic resonance (MR) imaging study was approved by the institutional review board and was HIPAA compliant.

    Written informed consent was obtained from all participants.

    The purpose of the study was to prospectively compare T1-weighted inversion recovery with short inversion time inversion recovery (STIR) and dual fast spin echo (FSE) for imaging cervical spinal cord lesions in patients with multiple sclerosis (MS).

    Twelve patients (eight men, four women; median age, 44 years) were imaged by using T1-weighted inversion recovery, STIR, and FSE. Contrast between lesions and normal cervical cord was measured for each sequence, and generalized estimating equation analysis was used to test statistical significance of the results.

    Normalized contrast between lesion and normal-appearing spinal cord was significantly higher for T1-weighted inversion recovery than for the other sequences (P < .0001).

    Use of phase-sensitive reconstruction improved lesion localization and boundary definition. These advantages of T1-weighted inversion recovery over STIR and dual-echo FSE suggest that it has potential in cervical spinal cord imaging of MS.

    Poonawalla AH, Hou P, Nelson FA, Wolinsky JS, Narayana PA. Department of Diagnostic and Interventional Radiology and Department of Neurology, The University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030. the 2006 RSNA Annual Meeting.

    Source: Radiology (c) RSNA, 2007. (09/01/08)

    MR Imaging Intensity Modeling of Damage and Repair In Multiple Sclerosis: Relationship of Short-Term Lesion Recovery to Progression and Disability
    BACKGROUND AND PURPOSE: Formation of lesions in multiple sclerosis (MS) shows pronounced short-term fluctuation of MR imaging hyperintensity and size, a qualitatively known but poorly characterized phenomenon. With the use of time-series modeling of MR imaging intensity, our study relates the short-term dynamics of new T2 lesion formation to those of contrast enhancement and markers of long-term progression of disease.

    MATERIALS AND METHODS: We analyzed 915 examinations from weekly to monthly MR imaging in 40 patients with MS using a time-series model, emulating 2 opposing processes of T2 prolongation and shortening, respectively. Patterns of activity, duration, and residual hyperintensity within new T2 lesions were measured and evaluated for relationships to disability, atrophy, and clinical phenotype in long-term follow-up.

    RESULTS: Significant T2 activity was observed for 8 to 10 weeks beyond contrast enhancement, which suggests that T2 MR imaging is sensitive to noninflammatory processes such as degeneration and repair. Larger lesions showed longer subacute phases but disproportionally more recovery. Patients with smaller average peak lesion size showed trends toward greater disability and proportional residual damage. Higher rates of disability or atrophy were associated with subjects whose lesions showed greater residual hyperintensity.

    CONCLUSION: Smaller lesions appeared disproportionally more damaging than larger lesions, with lesions in progressive MS smaller and of shorter activity than in relapsing-remitting MS. Associations of lesion dynamics with rates of atrophy and disability and clinical subtype suggest that changes in lesion dynamics may represent a shift from inflammatory toward degenerative disease activity and greater proximity to a progressive stage, possibly allowing staging of the progression of MS earlier, before atrophy or disability develops.

    D.S. Meiera, H.L. Weinerb and C.R.G. Guttmanna

    a Department of Radiology, Center for Neurological Imaging, Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston Mass b Department of Neurology, Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston Mass

    Source: American Journal of Neuroradiology 28:1956-1963, November-December 2007 © 2007 American Society of Neuroradiology (13/11/07)

    Improved Identification of Intracortical Lesions in Multiple Sclerosis with Phase-Sensitive Inversion Recovery in Combination with Fast Double Inversion Recovery MR Imaging
    BACKGROUND AND PURPOSE: Accurate detection and classification of purely intracortical lesions in multiple sclerosis (MS) are important in understanding their role in disease progression and impact on the clinical manifestations of the disease. However, detection of these lesions with conventional MR imaging remains a challenge. Although double inversion recovery (DIR) has been shown to improve the sensitivity of the detection of cortical lesions, this sequence has low signal-to-noise ratio (SNR), poor delineation of lesion borders, and is prone to image artifacts. We demonstrate that intracortical lesions can be identified and classified with greater confidence by the combination of DIR with phase-sensitive inversion recovery (PSIR) images.

    MATERIALS AND METHODS: A total of 16 subjects with MS were included in this study. DIR, PSIR, and fluid-attenuated inversion recovery (FLAIR) images were acquired and inspected by 3 experts, with identification of lesions by consensus. PSIR and DIR images were jointly used to classify lesions as purely intracortical, mixed gray-white matter, and juxtacortical. The difference in the number of lesions detected in each category was compared between combined PSIR and DIR and conventional FLAIR.

    RESULTS: PSIR consistently allowed a clearer classification and delineation of lesions. Combined PSIR and DIR images showed a 337% improvement in the total number of lesions detected compared with FLAIR alone. Detection of intracortical lesions was improved by 417% compared with FLAIR. Detection of mixed gray-white matter and juxtacortical lesions was improved by 396% and 130%, respectively, compared with FLAIR.

    CONCLUSION: Reliable detection and classification of intracortical lesions in MS are greatly improved by combined use of PSIR and DIR.

    F. Nelsona, A.H. Poonawallab, P. Houb, F. Huanga, J.S. Wolinskya and P.A. Narayanab

    a Department of Neurology, University of Texas Health Science Center at Houston, Houston, Tex b Departments of Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, Tex.

    Source: American Journal of Neuroradiology 28:1645-1649, October 2007 © 2007 American Society of Neuroradiology (09/10/07)

    Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage

    MRI is routinely used for in vivo detection of multiple sclerosis (MS) lesions. Histopathological correlates of MRI signal alterations are still poorly defined.

    In the present study, we describe a mouse model of MS presenting with inflammatory brain lesions. During the acute disease phase, two independent lesion patterns were identified by T1- and T2-weighted high-resolution 3D MRI: lesions with reduced signal intensity on both T1- and T2-weighted images (type A) and lesions with slightly reduced signal intensity on T1-weighted images and increased signal intensity on T2-weighted images (type B). Type A lesions were characterised by significantly denser inflammatory cell infiltrates and more myelin loss than type B lesions.

    Lesion cellularity, myelin loss and immunoglobulin deposition correlated with MRI signal intensities in both lesion types. Gd-DTPA enhancement correlated with Ig deposition and spacially matched to areas with abundant activated microglia cells at the lesion border. Using serial MRI, type A lesions revealed a persistent hypointense pattern reflecting axon and myelin loss. Signal intensity increases on T2-weighted images of type B lesions decreased during lesion evolution, and no significant T1 signal alterations developed. Taken together, MRI of mouse EAE models with brain lesions provide new insights into lesion pathology and evolution and may prove useful for the in vivo assessment of new therapeutic strategies in MS.

    Stefan Nessler1,*, Susann Boretius2,*, Christine Stadelmann3,*, Alwina Bittner4, Doron Merkler3, Hans-Peter Hartung1, Thomas Michaelis2, Wolfgang Brück3, Jens Frahm2, Norbert Sommer4, and Bernhard Hemmer1,

    1Clinical Neuroimmunology Group, Department of Neurology, Klinikum rechts der Isar, Technische Universität, Ismaninger Str. 21, Munich, Germany, 2Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37070 Göttingen, Germany, 3Institute of Neuropathology, Georg-August-University, 37099 Göttingen, Germany and 4Clinical Neuroimmunology Group, Department of Neurology, Philipps-University, Rudolf-Bultmann-Strasse 8, 35039 Marburg, Germany

    Source: Brain Copyright © 2007 Guarantors of Brain (08/07/07

    Pyramidal tract mapping by diffusion tensor magnetic

    BACKGROUND: Current magnetic resonance imaging (MRI) outcome measures such as T2 lesion load correlate poorly with disability in multiple sclerosis. Diffusion tensor imaging (DTI) of the brain can provide unique information regarding the orientation and integrity of white matter tracts in vivo.

    OBJECTIVE: To use this information to map the pyramidal tracts of patients with multiple sclerosis, investigate the relation between burden of disease in the tracts and disability, and compare this with more global magnetic resonance estimates of disease burden.

    METHODS: 25 patients with relapsing-remitting multiple sclerosis and 17 healthy volunteers were studied with DTI. An algorithm was used that automatically produced anatomically plausible maps of white matter tracts. The integrity of the pyramidal tracts was assessed using relative anisotropy and a novel measure (L(t)) derived from the compounded relative anisotropy along the tracts. The methods were compared with both traditional and more recent techniques for measuring disease burden in multiple sclerosis (T2 lesion load and "whole brain" diffusion histograms).

    RESULTS: Relative anisotropy and L(t) were significantly lower in patients than controls (p < 0.05). Pyramidal tract L(t) in the patients correlated significantly with both expanded disability status scale (r = -0.48, p < 0.05), and to a greater degree, the pyramidal Kurtzke functional system score (KFS-p) (r = -0.75, p < 0.0001). T2 lesion load and diffusion histogram parameters did not correlate with disability.

    CONCLUSIONS: Tract mapping using DTI is feasible and may increase the specificity of MRI in multiple sclerosis by matching appropriate tracts with specific clinical scoring systems. These techniques may be applicable to a wide range of neurological conditions.

    Wilson M, Tench CR, Morgan PS, Blumhardt LD.

    Division of Clinical Neurology, Queens Medical Centre, Nottingham University, Nottingham, UK.

    Source: Pubmed (28/06/07)

    New Imaging Technique Could Promote Early Detection of Multiple Sclerosis

    New imaging techniques graphic

    Researchers from Purdue University have studied and recorded how myelin degrades real-time in live mice using a new imaging technique. Myelin is the fatty sheath coating the axons, or nerve cells, that insulate and aid in efficient nerve fibre conduction. In diseases such as multiple sclerosis, the myelin sheath has been found to degrade.

    This unprecedented feat of looking real-time at the actual progress of demyelination will advance understanding of and perhaps promote early detection of conditions such as multiple sclerosis.

    Using a technique called coherent anti-Stokes Raman scattering microscopy, or CARS, scientists injected a compound called lysophosphatidylcholine (LPC) into the myelin of a mouse. Then, using CARS, they observed an influx of calcium ions into the myelin. This influx is now believed to start the process of myelin degradation.

    The research was supported by the National Science Foundation.

    Source: The National Science Foundation (27/06/07)

    Ultra-high-field MRI allows for earlier diagnosis of multiple sclerosis
    Ultra-high-field (7T) MRI can detect multiple sclerosis lesions better than MRI which can lead to possible earlier diagnosis and treatment, according to a new study by researchers from Ohio State University in Columbus, and Columbia University in New York.

    For the study, the researchers analysed post-mortem brain slices from a multiple sclerosis patient using both 3T and 7T MRI. 7T MRI made it possible to detect numerous multiple sclerosis lesions that were not detectable at 3T MRI, said Steffen Sammet, MD, PhD, lead author of the study.

    "Multiple sclerosis is difficult to diagnose in its early stages," said Dr. Sammet. "The greater sensitivity of 7T MRI for multiple sclerosis can delay disease conversion, and may lead to improved monitoring of neurological deficits in multiple sclerosis. MRI at 7T can give additional information about the lesion microstructure to help us better understand the disease," said Dr. Sammet.

    "Ultra-high field strength has been an experimental methodology evolving over the last decade. In recent years, and especially as part of the OSU-based effort of the Wright Center of Innovation, we have been pushing, to evolve ultra-high field into a clinically capable imaging method. The significant advantage of higher field strength is the gain in signal that can be used in many different ways to increase sensitivity and increase the speed of acquisition or to increase resolution," said Dr. Sammet.

    The full results of this study will be presented as an electronic exhibit Monday, May 7 through Thursday May 10 during the American Roentgen Ray Society's annual meeting in Orlando, FL.

    Source: American Roentgen Ray Society (05/05/07)

    New imaging approach promises insights into multiple sclerosis

    This picture was taken with two microscopic imaging techniques combined in the same platform, enabling researchers to conduct more specific and precise molecular analyses for research regarding multiple sclerosis.

    Researchers have developed a way to use three types of microscopic imaging techniques simultaneously to analyse living tissue and learn more about the molecular mechanisms of multiple sclerosis, information that could help lead to earlier detection and new treatments.

    The combined imaging method is enabling the researchers to study how multiple sclerosis causes an overproduction of "astroglial filaments," which form bundles between critical nerve fibres and interfere with proper spinal cord functioning. The technique also promises to yield new information about how the disease degrades the myelin sheath, which insulates nerve fibres and enables them to properly conduct impulses in the spinal cord, brain and in the "peripheral nervous system" throughout the body, said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.

    The three imaging techniques - called sum frequency generation, two-photon-excitation fluorescence and coherent anti-Stokes Raman scattering - ordinarily are used alone. Purdue researchers have developed a way to combine all three methods in the same platform, promising to reveal new details about the spinal cord and myelin sheath, Cheng said.

    "Combining these three methods allows us to conduct more specific and precise molecular analyses," he said. "Ultimately, this work paves the way toward studying the degradation of the myelin sheath as a result of multiple sclerosis and analysing living tissue to study the mechanisms of disease."

    Multiple sclerosis affects more than 350,000 people in the United States and 2 million worldwide.

    Findings will be detailed in a paper appearing in May in the Biophysical Journal and is currently online. The paper was authoured by biomedical engineering doctoral student Yan Fu and postdoctoral research associate Haifeng Wang; Riyi Shi, an associate professor of basic medical science in Purdue's School of Veterinary Medicine and also an associate professor of biomedical engineering; and Cheng.

    Shi, a member of Purdue's Center for Paralysis Research, specialises in spinal cord and brain trauma and chronic neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple sclerosis.

    "We are using a unique and powerful combination of technologies to uncover the mechanisms of multiple sclerosis," Shi said. "We hope to one day establish an effective intervention to not only slow down, but even possibly reverse the development of this disease, which will potentially have profound economic and social impacts on this nation and the world."

    Because the imaging techniques work without using dyes to "label" cells and structures, they can be used to study living tissues, representing a major advantage over conventional microscopic imaging technologies.

    Raman microscopy, an imaging technique invented more than three decades ago, cannot be used effectively to study living tissue because the extremely weak "Raman scattering" signals require hours to yield an image, whereas coherent anti-Stokes Raman scattering, or CARS, overcomes this limitation, Cheng said.

    "CARS microscopy permits label-free imaging of specific molecules with a speed of one frame per second or even faster," he said.

    CARS imaging takes advantage of the fact that molecules vibrate at specific frequencies. In a CARS microscope, two laser beams are overlapped to produce a single beam having a new frequency representing the difference between the original two beams. This new frequency then drives specific molecules to vibrate together "in phase," amplifying the Raman signals from those molecules.

    "It's like pushing someone on a swing," Cheng said. "If you push in synch with the upswing, the swing will go higher. That's the same as being in phase."

    Sum frequency generation imaging does just the opposite, adding the frequencies of the two original beams, producing a new signal with a frequency that is the sum of the original beams.

    The third imaging technique, two-photon excitation fluorescence, provides higher contrast and brighter images than conventional fluorescent imaging methods. Photons are the individual particles that make up light. In two-photon excitation fluorescence, two photons are used to illuminate a target.

    The researchers have used the imaging methods to observe living spinal tissue extracted from guinea pigs. The technique of extracting the tissue and then keeping it alive long enough to analyse was developed in Shi's lab.

    Conventional microscopic imaging techniques require samples to be labeled with dyes, killing the tissues in the process. Being able to analyse living tissue could allow researchers to determine the molecular mechanisms responsible for multiple sclerosis and other conditions, Cheng said.

    The myelin sheath is made of molecules called lipids, which consist of a head and tail segment. The new findings show that images can reveal whether the orientation of the chemical bonds in these lipid molecules is "scrambled," when the myelin sheath is unhealthy and degraded from disease, Cheng said.

    "We can see the myelin sheath with CARS, and that's great, but it's not enough," Cheng said. "We also want to study other molecules and see the interactions between cells."

    Researchers simultaneously took images of astroglial filaments, critical components of structures called astrocyte processes, which provide structural support for the nerve fibres in a spinal column. The sum frequency generation imaging reveals details about the astroglial filaments.

    Two-photon excitation fluorescence reveals information about the influx of calcium into cells, which causes damage to nerve fibres.

    "So, having all three of these imaging methods in the same platform enables us to study many elements of the disease process simultaneously in the same tissue samples," Cheng said.

    Researchers hope one day to use the combined approach to design a "minimally invasive" system for diagnosing patients in the hospital or doctor's office, he said.

    "There are two directions of this research," Cheng said. "One is to study the mechanisms of disease, and that should form the foundation for designing new treatments. The other is to keep pushing the technology to make it less and less invasive, which will help in the early detection of multiple sclerosis."

    The astroglial filaments also are involved in producing scar tissues following trauma injuries to the central nervous system, so a better understanding of their workings could lead to new treatments for repairing damage caused in accidents.

    Source: Purdue University (18/04/07)

    MRI developer Paul Lauterbur dies
    Physicist Paul C. Lauterbur, who received the 2003 Nobel Prize in Physiology or Medicine for giving physicians the ability to look inside the human body without using harmful radiation, died Tuesday at his home in Urbana, Ill.

    He was 77 and had kidney disease.

    Lauterbur played a key role in the development of magnetic resonance imaging, or MRI, which produces highly detailed images of soft tissues and organs without using X-rays.

    The first MRI instruments became available in the early 1980s, and their use has exploded to the point that more than 60 million MRI examinations are performed each year.

    The technique is particularly valuable for imaging the brain and spinal cord, monitoring the progress of diseases such as multiple sclerosis and assessing damage to knees and other joints.

    MRI relies on the magnetic properties of the hydrogen in water, which accounts for about two-thirds of the human body. When the hydrogen atoms are placed in a powerful magnetic field and bombarded with radio waves, they emit radio signals that provide information about their local environment.

    Before Lauterbur's work at State University of New York at Stony Brook, chemists used this technique, called nuclear magnetic resonance, to help determine the structure of organic molecules.

    Lauterbur's inspiration -- conceived at a restaurant table and sketched out on a napkin -- was to establish a gradient in the field, varying its intensity at different points in the sample. That made it possible to determine where each atom was in relation to the others.

    His thought processes were unique, said chemist John D. Baldeschwieler, of California Institute of Technology.

    ''For years, everyone in the field was trying to get the most homogeneous field in order to get the highest possible resolution,'' he said. ''Lauterbur thought about the problem in a completely inverse way. If you didn't have a homogeneous field, but a gradient, then the frequency would indicate position in space.''

    Assembling his apparatus, Lauterbur placed a test tube inside and startled his colleagues with a faint picture. His first living subject was a clam taken from nearby Long Island Sound.

    In his original publication in the journal Nature, he called the new technique zeugmatography -- from the Greek zeugma, or yoke -- because it yoked together two different types of radiation, magnetic and radiofrequency.

    That name did not last. Marketers also removed the ''nuclear'' from the name for fear it would invoke images of lethal radiation.

    British physicist Sir Peter Mansfield of the University of Nottingham, who shared the 2003 Nobel Prize with Lauterbur, devised techniques for sequentially altering the magnetic gradient so the device could produce an image of a two-dimensional slice of the human body. He also perfected techniques to speed up the process, cutting the required time for producing an image from hours to seconds.

    Lauterbur's university decided not to file patent applications based on his work. ''The company that was in charge of such applications decided that it would not repay the expense of getting a patent,'' Lauterbur said in 2003. ''That turned out not to be a spectacularly good decision.''

    The University of Nottingham did file patents, however, and Mansfield became wealthy enough to donate a new MRI center to the university.

    Lauterbur tried for years to get the federal government, particularly the National Institutes of Health, to fund a prototype of the instrument to image people, according to Baldeschwieler. ''It was an extraordinarily bold step. Nobody thought such a thing would be possible,'' he said.

    It took Lauterbur nearly a decade to get the funds and complete the instrument.

    Once the technique was perfected, Lauterbur traveled around the world tirelessly promoting its advantages, said medical physicist Paul Bottomley of Johns Hopkins University. ''It was an orphan technology, not in the mainstream of physics or chemistry, and not in mainstream radiology either,'' he said. ''Radiologists thought MRI could never replace computed tomography'' until Lauterbur convinced them otherwise.

    Meanwhile, he kept at work in his laboratory, inventing a variety of refinements, including MRI contrast agents and techniques to obtain chemical information from specific sites in the body.

    ''He was really the father of MRI,'' Bottomley said.

    MRI has been so successful that the original technique has spawned numerous offspring. Functional MRI, for example, measures brain activity by detecting oxygen levels in specific areas. Diffusion MRI can detect strokes by measuring the movement of water across microscopic distances in the brain. MRI angiography helps in the diagnosis of heart disorder by taking pictures of blood vessels.

    Paul Christian Lauterbur was born May 6, 1929, in Sidney, Ohio. His earliest inspirations, he said, were his aunt Anna Lauterbur, who gave him a subscription to Natural History magazine and fed his interest in the world around him, and a high school chemistry teacher who allowed him and other advanced students to conduct experiments while the rest of the class received a lecture.

    He enrolled at Case Institute of Technology, now part of Case Western Reserve University in Cleveland, on the recommendation of his father, who said that he didn't know what scientists did for a living but that engineers could always get a job.

    Despite that recommendation, he chose chemistry as a major.

    After graduation, he went to work at the Dow Corning Corp.'s Mellon Institute laboratories in Pittsburgh, which allowed him to take graduate courses for free at the University of Pittsburgh. At Mellon, he began working on the new technology of nuclear magnetic resonance, but that work was interrupted when he was drafted into the Army.

    He initially served at the Army Chemical Center in Edgewood, Md., studying chemical-warfare technology. Another unit at the center purchased an NMR machine, and he wangled a transfer to help set it up and use it. That work led to four published papers, unusual for a draftee.

    After he was mustered out of the Army, he returned to Mellon but soon began looking for brighter horizons. When he was refused an academic position because he didn't have a doctorate, he took more classes at the University of Pittsburgh. His work at Mellon provided the basis for his dissertation, and he received the degree in 1969.

    He spent more than a decade at SUNY Stony Brook before his marriage to the former Rose Mary Caputo began to disintegrate. After divorcing, he met an American physiologist named Joan Dawson, who was working at University College, London. To be together, they both took positions at the University of Illinois in 1984.

    Lauterbur is survived by Joan; a son and daughter from his first marriage, Daniel Lauterbur of Perry, Mich., and Sharyn Lauterbur-DiGeronimo of Selden, N.Y.; and a daughter from his second marriage, Elise Lauterbur, a student at Oberlin College. His first wife lives in East Setauket, N.Y.

    Source: The Monterey County Herald Copyright 2007 The Monterey County Herald All Rights Reserved (29/03/07)

    Scots' MRI scanning breakthrough 'has potential to save thousands'
    A major breakthrough in scanning technology, which could save thousands of lives by allowing doctors to spot developing diseases such as cancer and multiple sclerosis at a much earlier stage, was announced by Scottish researchers yesterday (22/03/07).

    The new scanning device can provide up to 100 different images from inside the body - compared to one from a conventional scanner - and reveal views which are hidden from current equipment.

    The scientists behind the technology say it should allow clinicians to make diagnoses and gain important information about diseases at a much earlier stage, developments cancer experts said last night would make a "dramatic" difference to saving lives. It could also be used for detecting other illnesses including Parkinson's disease and Alzheimer's.

    The technology has been developed at Aberdeen University where, 25 years ago, scientists were the first in the world to successfully use new magnetic resonance imaging (MRI) to scan the entire body of patient, heralding the dawn of a new area in medical diagnostics.

    MRI technology is based on the use of a large magnet to create a magnetic field inside the human body and a scanner which sends out bursts of radio waves to obtain return signals from various tissues to produce images of internal organs.

    Current MRI scanners operate on a set magnetic field, but the new equipment will allow patients to be quickly scanned with a range of magnetic fields, allowing clinicians to obtain new information about what is happening in the body.

    Two prototypes of the revolutionary new scanner have already been built and the research team has been awarded £2.5 million in funding from the Engineering and Physical Sciences Research Council to perfect the new "fast field-cycling" technology.

    David Lurie, professor of biomedical physics at Aberdeen University, said he and his team were "tremendously excited" about the new system.

    He explained: "It is a bit like having at our disposal 100 or more MRI scanners, each one operating at a different magnetic field - but all in the one scanner. The advantage is the new scanner will produce images of the body that will tell clinicians important information about disease processes at a much earlier stage."

    He added: "We are going to develop a new technique called 'fast field-cycling MRI' and the main difference is we will be able to switch the magnetic field in about one-twentieth of a second while the patient is in the scanner. We can obtain information about tissues at a whole range of magnetic fields. That will unlock information hidden to the standard MRI.

    "The new method will be particularly sensitive to changes in proteins in the tissues in the body and especially changes that arise from disease.

    "It will be of use in research and diagnosis into conditions such as Parkinson's disease, Alzheimer's, multiple sclerosis and, potentially, cancer. It will be used in research into what brings about all those conditions and it will, we hope, allow earlier diagnosis of these conditions which will mean better treatment.

    "We know it works in principle and we want to perfect the technology to produce a working human-sized scanner."

    Prof Lurie said the equipment, the development of which should be completed within four years, had the potential to save "thousands of lives".

    Dr Mark Matfield, scientific consultant to the Association for International Cancer Research, said: "This could be an important technological development that could tell us more about how advanced a cancer is, thus helping doctors choose the most appropriate treatments. In general, the earlier a tumour is diagnosed - particularly before it has spread - the easier it is to treat successfully.

    "In some cancers, the difference is dramatic. If breast cancer is diagnosed at an early stage - before it has spread - six out of seven patients survive for at least five years. However, if the cancer is only diagnosed when it is advanced, only one in seven patients is alive five years later."

    Kate Fearnley, policy director of Alzheimer Scotland, said:

    "Initiatives like this are vital if researchers are to understand what goes wrong in the brain and how we might be able to stop it."

    And Dr Kieran Breen, director of research and development for the Parkinson's Disease Society, added:

    "Any research that can shed more light on the causes and progression of Parkinson's, and lead to a more accurate diagnosis, will help to target new treatments and bring us closer to finding an effective cure."

    • An elderly man from the fishing town of Fraserburgh made history on 28 August, 1980, when he became the first patient in the world to receive a whole-body MRI scan.

    The scan, which picked up the tumours on his liver that would eventually claim his life, marked a massive breakthrough in magnetic resonance imaging technology. It was developed by a team of researchers at Aberdeen University, led by Professor John Mallard, who was then head of the medical physics department.

    The development of the MRI body scan was hailed at the time as the biggest improvement in medical diagnostics since the discovery of X-rays in 1895.

    Dr Francis Smith, who carried out the first scan, said: "We are fiercely proud of what was achieved all those years ago."

    Source: ©2007 (23/03/07)

    Bayer Schering To Develop Imaging Compounds To Detect Neurodegenerative Diseases
    Bayer Schering Pharma AG has signed a license and option agreement with Taisho Pharmaceutical Co., Ltd., Nihon Nohyaku Co., Ltd., and the National Institute of Radiological Sciences, Japan, to develop novel imaging compounds for the detection of neurodegenerative diseases.

    The diseases include Alzheimer's disease, Parkinson's disease and other disorders also associated with neuroinflammation such as multiple sclerosis.

    Under the terms of the agreement Bayer Schering Pharma receives worldwide exclusive rights to develop and market the respective products for use with PET scanning technology.

    Hans Maier, Head of Business Unit Diagnostic Imaging at Bayer Schering Pharma, said, "We are convinced that innovations in molecular imaging have the potential to fundamentally improve the diagnosis of neurodegenerative disorders, particularly Alzheimer's disease."

    Source: The NASDAQ Stock Market © Copyright NASDAQ (19/01/2007)

    New MRI Method Speeds MS Diagnosis
    Italian researchers say they've found a way to make faster diagnosis of the milder form of multiple sclerosis.

    The researchers say a new way of using MRI scans can catch the so-called benign form of the disease sooner than previous methods, ANSA reported.

    The findings were published in the journal Brain.

    ANSA said an estimated 2.5 million people worldwide are living with MS but the number could be much higher because of the difficulty of diagnosis.

    While there is still no cure, disease-modifying drugs can slow the progression and control symptoms of the disease, ANSA said.

    Source: Red Orbit © 2002-2007 All rights reserved (21/02/07)

    Cerebral Cortical Lesions in Multiple Sclerosis Detected by MR Imaging at 8 Tesla

    BACKGROUND AND PURPOSE: Conventional imaging of ex-vivo brain at 1.5T in multiple sclerosis (MS) detects only a small fraction of the gray matter cerebral cortical lesions that can be detected by pathology. Our purpose was to examine if imaging at 8T can detect plaques in cortical gray matter (CGM) not evident at 1.5T.

    METHODS: An ex-vivo brain obtained at autopsy from a patient with MS was formalin fixed and 1 cm coronal slices were examined using MR imaging at 8T.

    RESULTS: Numerous cerebral cortical lesions not evident at 1.5T were seen at 8T. Lesions were easily identified using gradient-echo and spin-echo (SE) as well as diffusion images. MR imaging at 8T identified many of the types of plaques previously evident only by pathology. The magnitude of the cortical involvement in this 1 patient was severe. Lesions in the gray matter readily visible by high-field MR imaging were sometimes barely visible by pathology. MR imaging at 8T often facilitated the detection of such plaques by pathology.

    CONCLUSION: This study establishes the utility of high-field imaging at 8T in the delineation of plaques in the cerebral CGM in MS.

    A. Kangarlua, E.C. Bourekasa,c, A. Ray-Chaudhuryb and K.W. Rammohanc a Department of Radiology, The Ohio State University College of Medicine, Columbus, Ohio
    b Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio
    c Department of Neurology, The Ohio State University College of Medicine, Columbus, Ohio

    Source: American Journal of Neuroradiology 28:262-266, February 2007 © 2007 American Society of Neuroradiology (13/02/07)

    © Multiple Sclerosis Resource Centre

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