Faculty Bibliography

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity)

BACKGROUND AND PURPOSE: In contrast to 'normal-appearing' white matter (NAWM) in patients with multiple sclerosis (MS), there are subtle, abnormal and diffuse signal intensity changes often seen on T2-weighted MR images, which we have referred to as 'dirty-appearing' white matter (DAWM). These areas of DAWM have slightly higher signal intensity than that of NAWM, but lower than that of lesion plaques. Our study was designed to determine the volumetric and magnetization transfer ratio (MTR) features of DAWM in patients with MS. METHODS: Dual-echo fast spin-echo MR imaging and magnetization transfer imaging were performed in 22 patients with relapsing-remitting MS. Slightly hyperintense DAWM areas were manually outlined on the basis of T2-weighted imaging findings. The volume and MTR of DAWM were calculated and compared with the volume and MTR of NAWM and T2 lesion plaques. RESULTS: The average volume of DAWM (18.3 mL) was greater than the average volume of T2 lesion plaques (11.0 mL, P =.04), and the mean MTR in DAWM (38.7%) differed significantly (P <.0001) from that in NAWM (40.7%) and plaques (33.3%). There was a modest negative correlation between either mean MTR (r = -0.60; P =.003) of DAWM or peak height (r = -0.50; P =.02) of DAWM with T2 lesion load. Neither DAWM volume nor total T2 abnormality (DAWM + plaques) volume correlates with the Expanded Disability Status Scale. CONCLUSION: The results of this study indicate that MTR is able to differentiate DAWM from lesion plaques and NAWM and that DAWM might be a different pathologic process of the disease. The notion and quantification of these subtle imaging findings of DAWM areas may improve our understanding of certain stages of disease progression and disease burden in patients with relapsing-remitting MS

BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to determine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those who are asymptomatic. METHODS: We performed MR imaging and MTR studies of 15 neurologically symptomatic (seven patients) and asymptomatic (eight patients) HIV-1-seropositive patients and compared their findings with those of 10 seronegative normal control participants. MTR was computed on the basis of whole brain parenchyma segmented by using thin section dual echo MR images. RESULTS: The loss of brain tissue, indicated by fractional brain parenchyma volume, was more pronounced in neurologically symptomatic patients (P =.003) but not in asymptomatic patients (P =.23) when compared with control participants. As for whole brain MTR histogram analysis, both patient groups showed significant decrease in mean (P =.02) and median (P < or =.009) values, compared with normal control participants. There was a trend toward positive correlation (r > or = 0.56) between MTR histogram statistics and fractional brain parenchyma volume. CONCLUSION: Our results suggest that MTR histogram analysis is sensitive in detecting early involvement in neurologically asymptomatic patients with HIV and may, therefore, be used as a combined tool with volumetric measurement, which showed significant tissue loss only in symptomatic patients, to assess various stages of brain damage induced by HIV

BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and quantitative identifier of underlying structural changes in the brain. We quantitatively evaluated age- and sex-related MTR changes in global gray matter (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy volunteers (21 men, 31 women) aged 20-86 years underwent dual-echo fast spin-echo and magnetization transfer imaging performed with and then without a saturation pulse. GM and WM were distinguished by using a computer-assisted semiautomated segmentation technique. MTR histograms were generated for each segmented tissue in each subject and compared among age and sex groups. RESULTS: The mean, median, first quartile, and peak height of the MTR histogram were significantly lower in the older group (> or =50 years) than those in the younger group (<50 years) for both GM and WM. The age dependency of these values can be expressed in a quadratic fashion over the entire span of adulthood. The MTRs started to decline only after the age of approximately 40 years in both tissues. No statistically significant differences in MTR histogram measurements between the sexes were observed. CONCLUSION: The different MTR values for both GM and WM in the two age groups suggest that notable microscopic changes occur in GM and WM with advancing age, yet no significant sex-related variations in MTR measurements were found in these neurologically healthy adults. Such normative data based on the inherent contrast in MTRs are essential in studies of specific disorders of aging, and they may have implications for our understanding of the gross structural changes in both GM and WM in the aging brain

BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P =.02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process

BACKGROUND AND PURPOSE: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent. METHODS: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery). RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons

PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p </= 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p </= 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM. CONCLUSION: Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics