Faculty Bibliography

Magnetic resonance (MR) techniques have had a major impact in the last 10-15 years in understanding and managing multiple sclerosis. This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: (i) technical issues; (ii) role in diagnosis; (iii) natural history studies in understanding the disease; (iv) application in clinical trials. The theory and methodology of relevant technical issues is outlined, in order to provide a framework with which to understand the potential and limitations of MR in addressing biological and clinical questions in multiple sclerosis. The principles underlying signal-to-noise and contrast-to-noise ratio are discussed, along with the techniques and clinical results for conventional and fast spin echo T2-weighted imaging, fluid-attenuated inversion recovery, detection of blood-brain barrier break down and hypointense lesions on T1-weighted images, magnetization transfer, T2 decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and quantification of lesion load and atrophy. MRI has an extremely valuable role in confirming the clinical diagnosis of multiple sclerosis. T2-weighted brain imaging remains the standard diagnostic tool, but in some instances it is usefully complemented with gadolinium enhancement and spinal imaging. The caveat that the diagnosis of multiple sclerosis remains primarily a clinical one cannot be over-emphasized. Serial MRI studies have added much to our understanding of the natural history and pathophysiology of the disease. Blood-brain barrier breakdown is a consistent early feature of new lesion development in relapsing-remitting and secondary progressive multiple, sclerosis, and this usually correlates with active inflammation and myelin breakdown. A number of the acute MR changes are reversible, but chronic persistent abnormalities in a number of MR parameters, such as reduced N-acetyl aspartate, low magnetization transfer ratios, atrophy and T1-hypointensity, suggest the presence of demyelination and/or axonal degeneration in many chronic lesions. The presence and extent of T2-weighted MRI abnormalities at first presentation with a clinically isolated syndrome suggestive of demyelination strongly predicts the risk of developing clinically definite multiple sclerosis in the next few years. In established multiple sclerosis, however, the correlations between T2 abnormalities and disability are modest. This poor relationship partly relates to the discrepancy between lesion site and function in attempting to correlate locomotor disability with brain MRI findings. However, the correlations between brain lesion load and cognitive dysfunction in multiple sclerosis, whilst more evident, are still modest. A more important limitation is the low pathological specificity of abnormalities seen on T2-weighted images. Stronger correlations have been found between disability and new putative MR markers for demyelination and/or axonal degeneration. Serial studies using multiple MR techniques are now needed to further clarify pathophysiological mechanisms in multiple sclerosis. Serial MR has become an important tool in monitoring treatment efficacy. It provides data which can be readily analysed in a blinded fashion and which directly inspects the pathological evolution; it also enables a rapid and sensitive measure of treatment outcome in early relapsing-remitting and secondary progressive disease. Because of the modest clinical correlations it is, however, still appropriate that the definitive determinant of treatment efficacy remains a clinical one. Further work is needed to address issues of quality control in serial studies, statistical calculation of appropriate sample sizes, and optimization of the nature and frequency of MR outcomes measured

A 32 year old man with symptoms of an upper respiratory infection one week prior presented with mental status changes, diffuse hyperreflexia, and bilateral extensor plantar responses. An MRI scan showed multifocal areas of high signal intensity predominantly in the parietal and occipital white matter, unassociated with mass affect. Despite aggressive treatment, the patient's symptoms rapidly progressed and he was declared brain dead. Post-mortem examination revealed acute hemorrhagic leukoencephalopathy. The clinical and pathologic features of this disorder are reviewed

Multiple sclerosis (MS) is a disease of the white matter. Magnetic resonance imaging (MRI) is proven to be a sensitive method of monitoring the progression of this disease and of its changes due to treatment protocols. Quantification of the severity of the disease through estimation of MS lesion volume via MR imaging is vital for understanding and monitoring the disease and its treatment. This paper presents a novel methodology and a system that can be routinely used for segmenting and estimating the volume of MS lesions via dual-echo fast spin-echo MR imagery. A recently developed concept of fuzzy objects forms the basis of this methodology. An operator indicates a few points in the images by pointing to the white matter, the grey matter, and the cerebro-spinal fluid (CSF). Each of these objects is then detected as a fuzzy connected set. The holes in the union of these objects correspond to potential lesion sites which are utilized to detect each potential lesion as a three-dimensional (3-D) fuzzy connected object. These objects are presented to the operator who indicates acceptance/rejection through the click of a mouse button. The number and volume of accepted lesions is then computed and output. Based on several evaluation studies, we conclude that the methodology is highly reliable and consistent, with a coefficient of variation (due to subjective operator actions) of 0.9% (based on 20 patient studies, three operators, and two trials) for volume and a mean false-negative volume fraction of 1.3%, with a 95% confidence interval of 0%-2.8% (based on ten patient studies)

We report a semiautomated postprocessing method based on magnetization transfer MR imaging that can quantify the extent of global disease in patients with multiple sclerosis. The technique combines segmentation and quantitative analysis of imaging data reflecting the structural integrity of white matter. Applications of this technique may include assessment of disease progress and of the efficacy of experimental therapeutic intervention. The height of the histogram peak corresponding to white matter was found to be lowered in patients with multiple sclerosis and the overall distribution of magnetization transfer ratios was shifted to lower values

OBJECTIVE: To determine the extent and significance of serum angiotensin-converting enzyme (ACE) elevation in multiple sclerosis (MS) and the correlation between serum ACE activity and clinical and magnetic resonance imaging (MRI) indicators of disease activity. DESIGN: A retrospective cross-sectional study of 45 consecutive patients with clinically definite MS and a longitudinal study of 30 additional patients with clinically definite MS involved in a long-term study of neurologic function and MRI in MS. SETTING: Comprehensive MS center of a tertiary care university hospital. SUBJECTS: A total of 75 patients with clinically definite MS and 31 healthy controls. METHODS: Serum ACE activity was measured using a spectrophotometric assay and correlated with clinical indicators of disease activity and with total cerebral MS lesion volume measured by MRI. RESULTS: An elevated ACE activity was found in 17 (23%) of 75 patients with MS as compared with 2 (6%) of 31 healthy controls. Changes in serum ACE activity correlated with changes in total plaque volume on MRI. CONCLUSIONS: Serum ACE activity may be an indicator of disease activity in longitudinal analysis. Also, elevated ACE activity in a patient with otherwise typical MS need not raise suspicions of alternative diagnoses

PURPOSE: To confirm the expected superiority of fluid-attenuated inversion-recovery (FLAIR) over conventional fast spin-echo MR imaging in the detection of multiple sclerosis (MS) of the spinal cord. METHODS: Fifteen subjects with known MS involving the spinal cord and brain were studied prospectively. The entire cord was imaged with a phased-array coil on a 1.5-T MR system. Sagittal T1-weighted and fast spin-echo proton density- and T2-weighted images were followed by fast FLAIR images. FLAIR parameters were varied to optimize lesion conspicuity with optimal inversion times (TIs) ranging from 2400 to 2600. Lesion conspicuity and detection were compared between the fast spin-echo and FLAIR images by three radiologists who reached agreement by consensus. RESULTS: The FLAIR technique effectively suppressed cerebrospinal fluid (CSF) signal and reduced CSF pulsation and truncation artifacts in all cases. Shorter imaging parameters (repetition time of 4000 to 6000, TI of 1500 to 2000) uniformly decreased lesion conspicuity in all subjects. Of 11 cord lesions in five subjects imaged with the longer parameters (repetition time of 8000 to 11,000, TI of 2400 to 2600), three were not seen on FLAIR images, four were less conspicuous on FLAIR images, and four were seen equally or better on FLAIR images. CONCLUSION: Although successful in suppressing CSF signal and reducing imaging artifacts, fast FLAIR imaging appears unreliable in the detection of MS lesions in the spinal cord

PURPOSE: To study the utility of a computer-assisted method of quantitating enhancing multiple sclerosis (MS) lesions and to correlate this quantitation with the type and duration of disease. METHODS: Forty untreated patients with MS were studied. The patients had been classified clinically as having either relapsing-remitting (n = 27) or chronic-progressive (n = 13) disease. Postcontrast contiguous 3-mm-thick MR images of the brain were obtained for up to 3 years. The computer program selected potential lesion sites automatically on the basis of the theory of 'fuzzy connectedness,' which was incorporated into 3DVIEWNIX software. True lesions were selected from these previously detected potential lesions by means of yes/no responses to the program query. The number of enhancing lesions and the enhancing lesions volume were subsequently computed. RESULTS: The enhancing lesion volume in patients with relapsing-remitting disease was statistically significantly higher than that of patients with chronic-progressive disease. There was a strong positive correlation between the number of enhancing lesions and the enhancing lesion volume. No significant correlation was noted between the change in score on the expanded disability status scale (EDSS) and the change in the number of enhancing lesions, or between the change in EDSS score and the change in enhancing lesion volume. A negative correlation was found between enhancing lesion volume and duration of disease, and between the number of enhancing lesions and duration of disease in the patients who had enhancing lesions. CONCLUSIONS: Our data suggest that enhancing lesion volume reflects differences in the classification of clinical MS and in the disease activity over time. Computer-assisted quantitation of enhancing lesion volume is a robust, practical, and objective measure of MS activity

We report a patient with biopsy-proven progressive multifocal leukoencephalopathy (PML) who was serially imaged with MRI and magnetization transfer imaging. The magnetization transfer ratio (MTR) was profoundly and significantly diminished when compared with normal control subjects. The pattern of MTR was distinct from that of MS and periventricular ischemic white matter disease. Magnetization transfer imaging techniques may aid in the differential diagnosis of PML

PURPOSE: To determine whether magnetic susceptibility artifact on magnetic resonance (MR) images can be used to grade gliomas. MATERIALS AND METHODS: Twenty-nine patients with gliomas were prospectively examined with spin-echo T1-weighted MR imaging without and with contrast material enhancement, spin-echo or fast spin-echo T2- and proton-density-weighted MR imaging, and gradient-echo T2*-weighted MR imaging. Images were reviewed by two neuroradiologists, and susceptibility artifacts in the tumor region were graded. Heterogeneity, mass effect, contrast enhancement, and necrosis were also graded. Tumors were graded according to the World Health Organization classification. RESULTS: Increased susceptibility artifact was detected by at least one observer on gradient-echo MR images of 19 tumors. This feature was seen on only 10 of the spin-echo or fast spin-echo T2-weighted MR images of lesions. Fifteen neoplasms with increased susceptibility artifact detected on MR images by at least one observer were high-grade lesions (anaplastic astrocytoma or glioblastoma multiforme). Lesion susceptibility artifact detected on T2*-weighted MR images was associated with tumor grade (P < .05). CONCLUSION: Susceptibility artifacts on T2*-weighted gradient-echo MR images appear to be valuable in the preoperative evaluation of gliomas

PURPOSE: Our goal is to describe a new computerized method for the detection and quantification of enhanced multiple sclerosis (MS) lesions. METHOD: Gd-DTPA-enhanced, thin section, T1-weighted images of seven patients (involving 336 slice images) with definite MS were analyzed using a new method based on the theory of 'fuzzy connected components,' developed and implemented on the 3DVIEWNIX software system. Four neuroradiologists selected 'true' lesions from the computer-detected potential lesions with a yes/no response to the program query on 2 different days. The enhanced lesion volume and number of enhancing lesions for each image and each observer were subsequently computed. Additional studies involving 720 slices were conducted to determine lesions that were missed by the system. RESULTS: The intra- and interobserver variability in the system was 0%. It took approximately 1 min of operator time per 3D study. The system output has no false positives and a mean false-negative volume of 1.3%. CONCLUSION: The novel system calculates enhancing lesion volume and the number of enhancing lesions with very little operator time, inter- and intraoperator variability, or false-positive and false-negative volumes. Computer-based quantification of enhancing lesion volume is an important objective measure of the activity of MS. The system is now in routine use in clinical investigations that study the role of enhancing lesions in the MS disease