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A method to visualize surface EEG electrodes on conventional high-resolution magnetic resonance (MR) images is presented. Because conventional silver or gold electrodes generate an insignificant artifactual signal signature in MR images, a plastic capsule filled with gadolinium-doped water was designed to mold onto each electrode, thereby outlining the electrode surfaces as a negative imprint on MR images. MR images of the head with capsules affixed clearly demonstrated the location and shape of the electrodes. Selected cranial tissues were identified by using semi-automatic image segmentation to determine their three-dimensional spatial relationship to the electrodes. Such representations could be used as a starting point for more precise EEG source localization modeling applicable to individual patients.

Rationale and Objectives. We investigated the multicompartmental nature of T2 decay in a specific white matter edema model. Methods. Triethyltin (TET) intoxication was produced in six male New Zealand White rabbits. Images were obtained over the 23-day study duration using a 64-echo Carr-Purcell-Meiboom-Gill (CPMG) sequence (repetition time = 3000 msec, echo time = 20 msec). T2 decay curves were extracted from 0.7 × 0.7 × 3.0 mm 3 voxels in the corpus callosum and contiguous white matter tracts, cortex, thalamic nuclei, hypothalamic nuclei, and the masseter muscles. The curves were fit with biexponential functions. Results. Increased signal intensity in the corpus callosum was evident 2–3 days after the first TET injection. At this time, a substantial slowly relaxing component appeared in the decay curves of the corpus callosum and, to a lesser extent, in the thalamus and hypothalamus. Changes in the rabbits' body weight, general physical condition, and neurologic state paralleled the growth and regression of the second, slowly relaxing component. Conclusion. The appearance and regression of a slowly decaying second component in the T2 decay curve is consistent with the formation and shrinkage of intracellular vesicles in the intramyelin sheaths of central white matter.

OBJECTIVE A line scan spectroscopic imaging method providing variable T2-weighted spectra from many small voxels along selected tissue columns was applied to study the chemical composition of hematopoietic and fatty marrow in the knees of adults and children. MATERIALS AND METHODS Line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequences were implemented on a 1.5 T clinical scanner. Variable T2-weighted proton spectra from 128 locations along 20 cm long, 5 mm2 columns oriented superiorly to inferiorly through knees were collected from eight healthy adults and eight children. RESULTS In adult yellow marrow, olefinic protons, water, a composite lipid proton peak, and methyl/methylene protons contributed 6.4 +/- 0.4, 4.2 +/- 1.5, 7.2 +/- 0.5, and 82.2 +/- 1.9% (mean +/- SD) to the spectra, respectively. Marrow spectra were largely independent of position along the column. Marrow spectra of normal children showed distinct positional dependences. Epiphyseal marrow spectra of children (8-16 years old) resembled adult spectra but with more water (mean 15 vs. 4%). Metaphyseal marrow had higher, variable water content, reflecting the extent of marrow conversion and generally obscuring the olefinic proton peak. CONCLUSIONS Spectroscopic imaging of columns is a time-efficient method for sampling extensive regions of bone marrow with high spatial resolution. It should prove useful for proton spectroscopic studies of hematologic pathologies and conditions requiring the monitoring of lipid composition.

Objective: To define brain MRI characteristics of MS patients who experience a malignant course in comparison with disease duration (DD) or disability (EDSS) matched non-malignant patients. Background Malignant MS is defined as rapid accumulation of disability: reaching EDSS≥6 in less than five years from first symptoms. Little is known about the MRI characteristics of malignant MS. Design/Methods: Patients meeting criteria for malignant MS who had at least one brain MRI scan after reaching malignant status were selected. Patients were from both relapsing- and progressive-onset disease categories. The first available MRI closest to attainment of EDSS≥6 was assessed. Two comparison groups were matched to the malignant group by age and gender. The first group was matched based on DD ( Results: 27 malignant (16 females), 31 DD-matched and 24 EDSS-matched patients were selected. BPF in malignant MS patients (mean±SD, 0.82±0.06) was significantly lower than the DD-matched group (BPF 0.87±0.04, p 0.05). T2 lesion volume was significantly larger in the EDSS-matched compared to the malignant group (p Conclusions: Malignant MS patients demonstrate increased brain atrophy compared to DD-matched patients, with similar brain atrophy and lower T2 lesion volumes compared to EDSS-matched patients. These results suggest more rapid cerebral neurodegeneration in malignant MS patients. Supported by: Merck Serono (HLW), National MS Society-RG (TC). Disclosure: Dr. Gholipour has received research support from Merck Serono. Dr. Egorova has nothing to disclose. Dr. Sevdalinova has nothing to disclose. Dr. Healy has nothing to disclose. Dr. Bakshi has received personal compensation for activities with Biogen Idec, Novartis, Questcor, and Teva Neuroscience as a consultant. Dr. Bakshi has received personal compensation in an editorial capacity for serving as a Associate Editor for the journal Neurotherapeutics. Dr. Bakshi has received research support from Biogen Idec, EMD Serono, and Teva Neuroscience. Dr. Guttmann has nothing to disclose. Dr. Khoury has received personal compensation for activities with EpiVax, Argos, LifeCycle, TcLand, and Wyeth as a consultant. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neurosciences, GlaxoSmithKline, Nasvax, Xenoport and Genzyme Corporation as consulting and/or speaking activities. Dr. Weiner has received research support from Merck Serono. Dr. Chitnis has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Chitnis has received research support from Merck Serono.

We have used MR monitoring to guide and evaluate the effects of the Nd:YAG interstitial laser on a well-characterized rat brain tumor model (C6). MRI was used to determine the tumor size, verify the location of the interstitial probe, and evaluate the size and location of the laser–induced lesion during and after treatment. During laser irradiation, an irreversible loss of signal intensity at the fiber tip and a reversible decrease in signal intensity around it were observed with MRI. None of the treatment protocols affected mean rat survival significantly. Although MRI-guided interstitial laser therapy appears to be safe and easy, it does not provide a curative treatment for spatially disseminated gliomas where a “target volume” cannot be adequately defined. Better results can be expected, especially in well-defined tumors, with improvements of both the imaging techniques and the laser treatment protocol. © 1993 Wiley-Liss, Inc. © 1993 Wiley-Liss, Inc.

Background Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS). We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD) influence brain volume and cognition in MS patients. Methods/Principal Findings MS subjects were genotyped for five single nucleotide polymorphisms (SNPs) associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF) measurements obtained from Magnetic Resonance Imaging (MRI) data and cognitive function using the Symbol Digit Modalities Test (SDMT). Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD) age at enrollment of 41 (±10) years were followed for 44 (±28) months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G) is associated with a smaller average brain volume (P = 0.0047) at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P = 0.0088). Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P = 0.0089) at the last MRI visit. Conclusion/Significance Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

Objective To assess whole and regional spinal cord atrophy in patients with multiple sclerosis (MS) using 3T MRI. Background Spinal cord damage is common in MS and provides a unique and clinically relevant means to monitor disease progression and therapeutic effects. Whereas regional spinal cord atrophy has been studied extensively in MS, whole spinal cord atrophy has not been previously assessed. Design/Methods Whole spinal cord 3 mm thick T2-weighted axial fast spin-echo MRI images were obtained at 3T on 34 patients with MS [26 women and 8 men; 26 relapsing–remitting, 2 clinically isolated syndrome, 4 secondary progressive, 2 primary progressive; Expanded Disability Status Scale (EDSS) (mean ± SD) 1.95 ± 1.72, range 0–6.5] and 15 age-matched normal controls [11 women and 4 men]. The global and regional (cervical, C2–3, and thoracic) cord volumes were determined using a semi-automated tool and were normalized by the segment length and intracranial volume. Spinal cord lesions were also determined using a semi-automated edge finding tool. Results Whole cord, C2–3, cervical, and thoracic volumes were lower in progressive vs. relapsing patients or normal controls (all p Conclusions The established method of estimating spinal cord atrophy, C2–3 cross-sectional volume, provides a useful surrogate of overall global or regional spinal cord atrophy. Spinal cord atrophy is most common in progressive forms of MS and is related to neurologic disability. Support This study was supported by grants from the National Institutes of Health ( 1R01NS055083-01 ) and the National Multiple Sclerosis Society ( RG3705A1 ; RG3798A2 ).

A computerized system for processing spin-echo magnetic resonance (MR) imaging data was implemented to estimate whole brain (gray and white matter) and cerebrospinal fluid volumes and to display three-dimensional surface reconstructions of specified tissue classes. The techniques were evaluated by assessing the radiometric variability of MR volume data and by comparing automated and manual procedures for measuring tissue volumes. Results showed (a) the homogeneity of the MR data and (b) that automated techniques were consistently superior to manual techniques. Both techniques, however, were affected by the complexity of the structure, with simpler structures (eg, the intracranial cavity) showing less variability and better spatial correlation of segmentation results between raters. Moreover, the automated techniques were completed for whole brain in a fraction of the time required to complete the equivalent segmentation manually. Additional evaluations included interrater reliability and an evaluation that included longitudinal measurement, in which one subject was imaged sequentially 24 times, with reliability computed from data collected by three raters over 1 year. Results showed good reliability for the automated segmentation procedures.

We have developed a 4D connected component labeling algorithm to identify automatically individual lesions on MRI brain images of multiple sclerosis patients, and to follow the changes in each lesion over time. We were also able to use this algorithm as a noise reduction filter to remove misclassified components from the binarized segmentations of the images.

Background Individual magnetic resonance imaging (MRI) disease severity measures, such as atrophy or lesions, show weak relationships to clinical status in patients with multiple sclerosis (MS). Objective To combine MS-MRI measures of disease severity into a composite score. Design Retrospective analysis of prospectively collected data. Setting Community-based and referral subspecialty clinic in an academic hospital. Patients A total of 103 patients with MS, with a mean (SD) Expanded Disability Status Scale (EDSS) score of 3.3 (2.2), of whom 62 (60.2%) had the relapsing-remitting, 33 (32.0%) the secondary progressive, and 8 (7.8%) the primary progressive form. Main Outcome Measures Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV (T1:T2) assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1:T2. Results The MRDSS score averaged 5.1 (SD, 2.6). Baseline MRI and EDSS correlations were moderate for BPF, T1:T2, and MRDSS and weak for T2LV. The MRDSS showed a larger effect size than the individual MRI components in distinguishing patients with the relapsing-remitting form from those with the secondary progressive form. Models containing either T2LV or MRDSS were significantly associated with disability progression during the mean (SD) 3.2 (0.3)–year observation period, when adjusting for baseline EDSS score. Conclusion Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity.

Objective Combine MRI measures of disease severity into a composite score in patients with multiple sclerosis (MS). Background Brain MRI lesion and atrophy measures assessed individually have fairly weak ability to predict clinical progression in MS. Methods In the Comprehensive Longitudinal Investigation of MS at Brigham, we studied 103 patients [age (mean ± SD) 42.7 ± 9.1 years, disease duration 14.1 ± 9.2 years, Expanded Disability Status Scale (EDSS) score 3.3 ± 2.2, 60% (n = 62) relapsing–remitting (RR), 32% (n = 33) secondary progressive (SP), and 8% (n = 8) primary progressive]. Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume, and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1/T2 ratio. Results MRDSS score averaged 5.1 ± 2.6. Baseline MRI and EDSS correlations were moderate for BPF, T1/T2, and MRDSS and weak for T2LV. MRDSS showed a larger effect size than any of the individual MRI components in distinguishing RR from SP patients. Models containing either T2LV or MRDSS were significantly associated with EDSS disability progression during the 3.2 ± 0.3 year observation period, when adjusting for baseline EDSS score. Conclusions These results show that combining brain MRI lesion and atrophy measures can predict clinical progression in patients with MS and provide the basis to develop an MRI-based continuous scale as a marker of MS disease severity.

The applications of laser in both adults and pediatric neurosurgery are being steadily refined today. For many routine tumor removals, contemporary lasers do not add to ultrasonic aspiration or suction resection. However, there are some tumors in which one CO2 laser is invaluable; brain stem astrocytomas, skull base tumors, and intraspinal tumors are examples. Similarly, in resections of spinal lipomas they are useful to vaporize lipomas from the roots. Laser welding of vessels is technically possible but has generally not been useful. Perhaps the most exciting application is a combination of laser energy transfer with stereotactic technology. The MRI can be used to visualize structural changes in cerebral tissue. We have used this technology in 40 rats with gliomas and have been able to demonstrate destruction.

Objective: To determine whether changes in activation markers on peripheral blood T cells correlate with disease activity in patients with multiple sclerosis. Design: In a prospective longitudinal study during 1 year, we analyzed the change in percentage of activated T lymphocytes in the peripheral blood of 40 patients with multiple sclerosis in relation to clinical findings and changes on brain magnetic resonance imaging (MRI) scans. The patients underwent repeated imaging of the brain (mean number of MRIs for each patient, 22) at the time blood samples were obtained as well as at monthly neurological examinations, and at the time of scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and ambulation index scale. Results: A change in the percentage of cells expressing the activation markers interleukin 2 receptor (CD25), class II major histocompatibility complex (MHC) (I3) or surface dipeptidyl peptidase (CD26) correlated significantly with a change in lesion volume or a change in number of gadolinium-enhancing lesions as detected on MRI. Changes in CD25 + cells and in CD4 + cells expressing class II MHC also correlated with changes in disability as measured by EDSS in patients with relapsing-remitting disease, and changes in CD4 + CD25 + cells correlated with the occurrence of attacks in patients with relapsingremitting disease. These correlations are dependent on measurement of changes between time points sampled at 1- or 2-week intervals. Conclusion: There is a linkage between peripheral Tlymphocyte activation as measured by cell surface markers and disease activity in patients with multiple sclerosis. Arch Neurol. 2000;57:1183-1189

We followed 18 multiple sclerosis patients clinically and with repeated brain MRIs with and without gadolinium for over 1 year. Clinical evaluations included scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI) scale. There was a significant correlation between the change in EDSS or AI and the change in number of lesions on MRI and between cumulative number of lesions on MRI and cumulative change in EDSS or AI. Our findings support the validity of MRI as a measure of clinical activity and potentially as an objective quantitative outcome measure for assessing response to therapy.

While the cerebellum plays a critical role in motor coordination and control no studies have investigated its involvement in idiopathic mobility impairment in community-dwelling elderly. In this study we tested the hypothesis that structural changes in the cerebellar peduncles not detected by conventional magnetic resonance imaging are associated with reduced mobility performance. The analysis involved eighty-five subjects (age range: 75–90 years) who had no clinical signs of cerebellar dysfunction. Based on the short physical performance battery (SPPB) score, we defined mobility status of the subjects in the study as normal (score 11–12, n = 26), intermediate (score 9–10, n = 27) or impaired (score, Highlights • DTI study of the cerebellar peduncles and mobility in elderly. • Fractional anisotropy and axial diffusivity of inferior peduncle predict mobility. • Decreased anisotropy in the peduncles in the absence of T2 lesions. • Findings likely reflect axonal degeneration of proprioceptive afferent fibers. • Abnormalities in infratentorial white matter are novel findings in the field.

Background The disease course in multiple sclerosis (MS) is influenced by many factors, including age, sex, and sex hormones. Little is known about sex-specific changes in disease course around age 50, which may represent a key biological transition period for reproductive aging. Methods Male and female subjects with no prior chemotherapy exposure were selected from a prospective MS cohort to form groups representing the years before (38–46 years, N=351) and after (54–62 years, N=200)age 50. Primary analysis assessed for interaction between effects of sex and age on clinical (Expanded Disability Status Scale, EDSS; relapse rate) and radiologic (T2 lesion volume, T2LV; brain parenchymal fraction, BPF) outcomes. Secondarily, we explored patient-reported outcomes (PROs). Results As expected, there were age- and sex- related changes with male and older cohorts showing worse disease severity (EDSS), brain atrophy (BPF), and more progressive course. There was no interaction between age and sex on cross-sectional adjusted clinical (EDSS, relapse rate) or radiologic (BPF, T2LV) measures, or on 2-year trajectories of decline. There was a significant interaction between age and sex for a physical functioning PRO (SF-36): the older female cohort reported lower physical functioning than men (p=0.002). There were no differences in depression (Center for Epidemiological Study – Depression, CES-D) or fatigue (Modified Fatigue Impact Scale, MFIS) scores. Conclusions There was no interaction between age and sex suggestive of an effect of reproductive aging on clinical or radiologic progression. Prospective analyses across the menopausal transition are needed.

Introduction Le developpement peri-veinulaires des lesions de SEP est un phenomene bien connu [1] , [2] , [3] . Cependant, meme si certains auteurs ont rapporte une stenose des veinules [4] intra-lesionnelles, aucune etude n’a caracterise de maniere dynamique ce phenomene. Dans cette etude, nous proposons d’analyser la cinetique ainsi que la localisation de la stenose des veinules dans les lesions actives de SEP. Materiel et methodes Un suivi hebdomadaire a ete mene pendant 8 semaines sur cinq patients non traites atteints d’une forme remittente de SEP en IRM cerebrale 3 T [5] , [6] avec une exploration par imagerie de susceptibilite magnetique (SWI) et 3DT1 apres injection de gadolinium. La selection des lesions impliquait leur localisation sur une veine de diametre superieur a deux voxels et une prise de contraste comprise entre les premiere et derniere acquisitions exclues. Au total 3 lesions repondaient a ces criteres. L’analyse des dynamiques d’interactions veine/lesion a ete faite sur des regions d’interet (ROI) grâce a un algorithme7 regroupant automatiquement les voxels dont le signal evolue de maniere similaire. Resultats Parmi les 3 lesions, un hypersignal transitoire a ete mis en evidence en SWI au sein de la veinule centrale concomitant avec la prise de contraste, objective par une evolution commune du signal des voxels situes au cœur de la lesion ( Fig. 1 ) Ces evolutions particulieres du signal aux interfaces veine/lesion apparaissent au meme moment ( Fig. 2 , Fig. 3 ) ou anterieurement ( Fig. 4 ) a la prise de contraste. Conclusion Nous avons mis en evidence une modification transitoire du signal a l’interface veine/lesion compatible avec une stenose des veinules synchronisee a la rupture de la barriere hemato-encephalique, probablement en relation avec le manchon inflammatoire decrit histologiquement. L’ideal serait de pouvoir generaliser ces resultats sur un effectif plus grand meme si cela pose des problemes de faisabilite (de moins en moins de patients non traites, injections repetees de gadolinium).