MTT and Blood-Brain Barrier Disruption within Asymptomatic Vascular WM Lesions.

BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P < .046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

Manganese-Enhanced MRI of the Brain in Healthy Volunteers.

BACKGROUND AND PURPOSE: The manganese ion is used as an intracellular MR imaging contrast agent to study neuronal function in animal models, but it remains unclear whether manganese-enhanced MR imaging can be similarly useful in humans. Using mangafodipir (Teslascan, a chelated manganese-based contrast agent that is FDA-approved), we evaluated the dynamics of manganese enhancement of the brain and glandular structures in the rostral head and neck in healthy volunteers. MATERIALS AND METHODS: We administered mangafodipir intravenously at a rate of 1 mL/minute for a total dose of 5 µmol/kg body weight. Nine healthy adult volunteers (6 men/3 women; median age, 43 years) completed baseline history and physical examination, 3T MR imaging, and blood work. MR imaging also followed mangafodipir administration at various time points from immediate to 7 days, with delayed scans at 1-3 months. RESULTS: The choroid plexus and anterior pituitary gland enhanced within 10 minutes of infusion, with enhancement persisting up to 7 and 30 days, respectively. Exocrine (parotid, submandibular, sublingual, and lacrimal) glands also enhanced avidly as early as 1 hour postadministration, generally resolving by 1 month; 3 volunteers had residual exocrine gland enhancement, which resolved by 2 months in 1 and by 3 months in the other 2. Mangafodipir did not affect clinical parameters, laboratory values, or T1-weighted signal in the basal ganglia. CONCLUSIONS: Manganese ions released from mangafodipir successfully enable noninvasive visualization of intra- and extracranial structures that lie outside the blood-brain barrier without adverse clinical effects, setting the stage for future neuroradiologic investigation in disease.

Improved Visualization of Cortical Lesions in Multiple Sclerosis Using 7T MP2RAGE.

BACKGROUND AND PURPOSE: Cortical lesions are common and often extensive in multiple sclerosis but are difficult to visualize by MRI, leaving important questions about their clinical implications and response to therapy unanswered. Our aim was to determine whether cortical lesions are better visualized using magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) than T2*-weighted imaging on 7T MR imaging. MATERIALS AND METHODS: Brain MR imaging using T1-weighted MP2RAGE at 500-µm isotropic resolution, T2*-weighted gradient-echo, and T2*-weighted segmented echo-planar imaging sequences were collected for 13 patients with MS and 5 age-matched neurologically healthy controls on a 7T research system. One MS case underwent postmortem MR imaging including gradient-echo and MP2RAGE sequences, after which cortical lesions seen on MR imaging were assessed with immunohistochemistry. RESULTS: MP2RAGE detected 203 cortical lesions (median, 16 lesions/case; interquartile range, 15), compared to 92 with T2*gradient-echo (median, 7; interquartile range, 8; P < .001) and 81 with T2*EPI (median, 7; interquartile range, 5; P < .001). This increase in lesion number detected on MP2RAGE versus T2* was observed for juxtacortical, leukocortical, and intracortical lesions. Forty-three percent of all cortical lesions were identified only on MP2RAGE. White matter lesion volume correlated with total juxtacortical (r = 0.86, P < .001) and leukocortical lesion volume (r = 0.70, P < .01) but not intracortical lesion volume, suggesting that pathophysiology may differ by lesion type. Of 4 suspected lesions seen on postmortem imaging, 3 were found to be true cortical lesions while 1 represented postmortem tissue damage. CONCLUSIONS: A combination of MP2RAGE and T2*-weighted imaging at 7T improved detection of cortical lesions and should enable longitudinal studies to elucidate their spatiotemporal dynamics and clinical implications.