Faculty Bibliography

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS

This study was designed to evaluate with magnetization transfer imaging (MTI) and conventional magnetic resonance (MR) imaging the manifestation of diffuse axonal injury (DAI) in an animal model of injury via nonimpact coronal plane rotational acceleration. A second objective was to investigate the diagnostic use of quantitative MTR imaging based on statistical parameters in a single subject, as opposed to grouped analysis. Seven mini-swine were subjected to brain trauma known to produce isolated DAI and to MR imaging at two time points. Following sacrifice, the brains were harvested for histopathologic examination. Magnetization transfer ratio (MTR) maps were generated for double-blinded comparison of regions with abnormal MTR values and regions with documented DAI. Positive and negative predictive values for MTR detection of DAI were 67 and 56%, respectively, and in acute studies alone, 89 and 61%. Gains in sensitivity over conventional imaging for detection of DAI were demonstrated

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS

PURPOSE: To investigate the cross-sectional relationships among multiple quantitative brain magnetic resonance (MR) imaging measurements in patients with relapsing-remitting versus chronic progressive multiple sclerosis (MS). MATERIALS AND METHODS: Thirty-eight patients with MS (relapsing-remitting, 26, chronic progressive, 12) were examined. Lesion volume on T2-weighted MR images, contrast material-enhancing lesion volume, percentage of brain parenchymal volume (brain volume/[brain volume + cerebrospinal fluid volume), and magnetization transfer ratio histogram peak height for the whole brain were calculated. RESULTS: Significant negative correlation was noted between volume on T2-weighted images and magnetization transfer ratio histogram peak height for both the relapsing-remitting and chronic progressive groups (P < .001 for both). A positive correlation was demonstrated for lesion volume on T2-weighted images and enhancing lesion volume in the relapsing-remitting group (P < .01) but not in the chronic progressive group. Negative correlations were demonstrated for enhancing lesion volume and magnetization transfer ratio histogram peak height (P = .02), for Expanded Disability Status Scale score and magnetization transfer histogram peak height (P = .02), and for Expanded Disability Status Scale score and percentage of brain parenchymal volume in the relapsing-remitting group (P = .004) but not in the chronic progressive group. CONCLUSION: The cross-sectional relationships among multiple quantitative brain MR imaging measurements are different between relapsing-remitting and chronic progressive MS

OBJECTIVE: To review studies on the assessment of correlations between magnetization transfer ratio (MTR) histogram analysis and measures of clinical and neuropsychological function. BACKGROUND: Since its recent introduction, MTR histogram analysis has attracted attention in the field of multiple sclerosis (MS). METHODS: In this paper, studies are discussed that deal with MTR histogram analysis. The principles of MTR, application of MTR methodology as regional and volumetric MTR analysis, clinical and neuropsychological correlates, and potential use of MTR histogram analysis as an estimate of cerebral lesion load in MS are discussed respectively. RESULTS: In several preliminary studies, it has been shown that in MS patients, measures derived from MTR histograms correlate with measures of clinical and particularly neuropsychological function. CONCLUSION: MTR histogram analysis is a promising method to estimate cerebral lesion load in MS patients. Before it can be routinely used as an outcome measure in clinical trials, a number of questions about this technique have to be addressed

Magnetic resonance (MR) imaging is the pre-eminent modality for the detection and characterization of central nervous system pathology. However, in a variety of disease processes, histopathologic studies have often shown more extensive abnormalities in the brain and spinal cord than could be detected on conventional MR images. Magnetization transfer contrast (MTC) can be used qualitatively to augment differences between tissues and to accentuate gadolinium enhancement. Additionally, MTC may be used quantitatively to characterize tissues and potentially to detect otherwise microscopic disease

The evolution of our understanding of multiple sclerosis (MS) has been facilitated by the technique of magnetization transfer, which has the ability to detect and categorize lesions that are both visible and occult by conventional magnetic resonance (MR) imaging. The methodology can be applied to individual MS lesions as well as to the global brain disease. The results of studies performed in centers throughout the world reveal multiple correlations with clinical parameters as well as greater specificity and sensitivity to lesion than other presently available MR measures

The intra-individual and inter-individual variations of the global N-acetylaspartate (NAA) concentration were measured in a cohort of five 42+/-5 year-old normal females. The total NAA signal from the whole head was obtained with non-localized non-echo proton spectroscopy (1H-MRS) and converted into absolute mole amounts using phantom replacement. Since NAA is assumed to be present only in neurons, its concentration was obtained by dividing these mole amounts with the brains' volume, calculated from high resolution MRI. The key feature of the procedure is its near-complete suppression of the intense subcutaneous and bone marrow lipids' signals, whose chemical shifts neighbor and underlay the NAA. This was achieved by exploiting the lipids' much shorter T1s, compared to that of NAA, for destructive interference of their signals in co-addition following alternating, nonselective 180 degrees inversions. The average global, inter-individual NAA concentration in that group was found to be 10.63 mM with a 95% confidence interval of 10.43-10.82 mM