Spatial Correlation of Pathology and Perfusion Changes within the Cortex and White Matter in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The spatial correlation between WM and cortical GM disease in multiple sclerosis is controversial and has not been previously assessed with perfusion MR imaging. We sought to determine the nature of association between lobar WM, cortical GM, volume and perfusion. MATERIALS AND METHODS: Nineteen individuals with secondary-progressive multiple sclerosis, 19 with relapsing-remitting multiple sclerosis, and 19 age-matched healthy controls were recruited. Quantitative MR perfusion imaging was used to derive CBF, CBV, and MTT within cortical GM, WM, and T2-hyperintense lesions. A 2-step multivariate linear regression (corrected for age, disease duration, and Expanded Disability Status Scale) was used to assess correlations between perfusion and volume measures in global and lobar normal-appearing WM, cortical GM, and T2-hyperintense lesions. The Bonferroni adjustment was applied as appropriate. RESULTS: Global cortical GM and WM volume was significantly reduced for each group comparison, except cortical GM volume of those with relapsing-remitting multiple sclerosis versus controls. Global and lobar cortical GM CBF and CBV were reduced in secondary-progressive multiple sclerosis compared with other groups but not for relapsing-remitting multiple sclerosis versus controls. Global and lobar WM CBF and CBV were not significantly different across groups. The distribution of lobar cortical GM and WM volume reduction was disparate, except for the occipital lobes in patients with secondary-progressive multiple sclerosis versus those with relapsing-remitting multiple sclerosis. Moderate associations were identified between lobar cortical GM and lobar normal-appearing WM volume in controls and in the left temporal lobe in relapsing-remitting multiple sclerosis. No significant associations occurred between cortical GM and WM perfusion or volume. Strong correlations were observed between cortical-GM perfusion, normal appearing WM and lesional perfusion, with respect to each global and lobar region within HC, and RRMS and SPMS patients (R2 ≤ 0.96, P < .006 and R2 ≤ 0.738, P < .006). CONCLUSIONS: The weak correlation between lobar WM and cortical GM volume loss and perfusion reduction suggests the independent pathophysiology of WM and cortical GM disease.

Detection of Volume-Changing Metastatic Brain Tumors on Longitudinal MRI Using a Semiautomated Algorithm Based on the Jacobian Operator Field.

BACKGROUND AND PURPOSE: Accurate follow-up of metastatic brain tumors has important implications for patient prognosis and management. The aim of this study was to develop and evaluate the accuracy of a semiautomated algorithm in detecting growing or shrinking metastatic brain tumors on longitudinal brain MRIs. MATERIALS AND METHODS: We used 50 pairs of successive MR imaging datasets, 30 on 1.5T and 20 on 3T, containing contrast-enhanced 3D T1-weighted sequences. These yielded 150 growing or shrinking metastatic brain tumors. To detect them, we completed 2 major steps: 1) spatial normalization and calculation of the Jacobian operator field to quantify changes between scans, and 2) metastatic brain tumor candidate segmentation and detection of volume-changing metastatic brain tumors with the Jacobian operator field. Receiver operating characteristic analysis was used to assess the detection accuracy of the algorithm, and it was verified with jackknife resampling. The reference standard was based on detections by a neuroradiologist. RESULTS: The areas under the receiver operating characteristic curves were 0.925 for 1.5T and 0.965 for 3T. Furthermore, at its optimal performance, the algorithm achieved a sensitivity of 85.1% and 92.1% and specificity of 86.7% and 91.3% for 1.5T and 3T, respectively. Vessels were responsible for most false-positives. Newly developed or resolved metastatic brain tumors were a major source of false-negatives. CONCLUSIONS: The proposed algorithm could detect volume-changing metastatic brain tumors on longitudinal brain MRIs with statistically high accuracy, demonstrating its potential as a computer-aided change-detection tool for complementing the performance of radiologists, decreasing inter- and intraobserver variability, and improving efficacy.

Comparison of Quantitative Cerebral Blood Flow Measurements Performed by Bookend Dynamic Susceptibility Contrast and Arterial Spin-Labeling MRI in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative CBF usage as a biomarker for cognitive impairment and disease progression in MS is potentially a powerful tool for longitudinal patient monitoring. Dynamic susceptibility contrast perfusion with bookend T1-calibration (bookend technique) and pseudocontinuous arterial spin-labeling have recently been used for CBF quantification in relapsing-remitting MS. The noninvasive nature of pseudocontinuous arterial spin-labeling is advantageous over gadolinium-based techniques, but correlation between the techniques is not well-established in the context of MS. MATERIALS AND METHODS: We compared pseudocontinuous arterial spin-labeling CBF with the bookend technique in a prospective cohort of 19 healthy controls, 19 subjects with relapsing-remitting MS without cognitive impairment, and 20 subjects with relapsing-remitting MS with cognitive impairment on a voxelwise and Brodmann region basis. The linear Pearson correlation, SNR, and coefficient of variation were quantified. RESULTS: Voxelwise paired t tests revealed no significant CBF differences between techniques after normalization of global mean intensities. The highest Pearson correlations were observed in deep GM structures (average r = 0.71 for the basal ganglia and r = 0.65 for the thalamus) but remained robust for cortical GM, WM, and white matter lesions (average r = 0.51, 0.53, 0.54, respectively). Lower Pearson correlations were observed for cortical lesions (average r = 0.23). Brodmann region correlations were significant for all groups. All correlations were maintained in healthy controls and in patients with relapsing-remitting multiple sclerosis. The highest SNR was present in bookend perfusion, while the highest coefficient of variation was present in white matter lesions. CONCLUSIONS: Agreement between pseudocontinuous arterial spin-labeling and bookend technique CBF measurements is demonstrated in healthy controls and patients with relapsing-remitting MS.

Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline.

BACKGROUND AND PURPOSE: Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in patients with MS, contributing to cognitive impairment. We sought to localize perfusion distribution differences in patients with relapsing-remitting MS with and without cognitive impairment and healthy controls. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS (20 cognitively impaired, 19 nonimpaired) and 19 age- and sex-matched healthy controls underwent a neurocognitive battery and MR imaging. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. RESULTS: After we adjusted for localized volumetric differences in the right frontal, temporal, and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for patients with cognitive impairment compared with patients without impairment and controls. Compared with healthy controls, reduced CBF was present in the limbic regions of patients with cognitive impairment, and reduced CBV was present in the right middle frontal gyrus in patients with cognitive impairment and in the temporal gyrus of relapsing-remitting MS patients without cognitive impairment. CONCLUSIONS: Consistent regional frontal cortical perfusion deficits are present in patients with relapsing-remitting MS, with more widespread hypoperfusion in those with cognitive impairment, independent of structural differences, indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS.

Cortical Perfusion Alteration in Normal-Appearing Gray Matter Is Most Sensitive to Disease Progression in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND PURPOSE: The role of gray matter in multiple sclerosis is increasingly evident; however, conventional images demonstrate limitations in cortical lesion identification. Perfusion imaging appears sensitive to changes in tissue type and disease severity in MS. We sought to use bookend perfusion to quantify parameters in healthy controls and normal-appearing and lesional tissue at different relapsing-remitting MS stages. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS and 19 age-matched healthy controls were prospectively recruited. The Minimal Assessment of Cognitive Function in MS battery was used to assess cognitive performance. Perfusion parameters, including cerebral blood flow and volume and mean transit time, were compared for healthy controls and normal-appearing and lesional tissue for all study groups. Dispersion of perfusion measures for white matter lesions and cortical lesions was assessed. RESULTS: Twenty of the 39 patients with relapsing-remitting MS were cognitively impaired. Significant differences were displayed between all relapsing-remitting MS subgroups and healthy controls in all comparisons except for normal-appearing gray matter CBV between healthy controls and unimpaired patients with relapsing-remitting MS and for all normal-appearing white matter perfusion parameters between healthy controls and unimpaired patients with relapsing-remitting MS. White matter lesion but not cortical lesion perfusion was significantly reduced in cognitively impaired patients with relapsing-remitting MS versus unimpaired patients with relapsing-remitting MS. Perfusion reduction with disease progression was greater in normal-appearing gray matter and normal-appearing white matter compared with cortical lesions and white matter lesions. Smaller dispersion was observed for cortical lesions compared with white matter lesions for each perfusion parameter. CONCLUSIONS: Quantitative GM and WM analysis demonstrated significant but disproportionate white matter lesion, cortical lesion, normal-appearing white matter, and normal-appearing gray matter changes present between healthy controls and patients with relapsing-remitting MS with and without cognitive impairment, necessitating absolute rather than relative lesion perfusion measurement.

Effect of Collaterals on Clinical Presentation, Baseline Imaging, Complications, and Outcome in Acute Stroke.

BACKGROUND AND PURPOSE: Good CTA collaterals independently predict good outcome in acute ischemic stroke. Our aim was to evaluate the role of collateral circulation and its added benefit over CTP-derived total ischemic volume as a predictor of baseline NIHSS score, total ischemic volume, hemorrhagic transformation, final infarct size, and a modified Rankin Scale score >2. MATERIALS AND METHODS: This was a retrospective study of 395 patients with stroke dichotomized by recanalization (recanalization positive/recanalization negative) and collateral status. Clot burden score was quantified on baseline CTA. Total ischemic volumes were derived from thresholded CTP maps. Final infarct size was assessed on follow-up CT/MRI. We performed uni-/multivariate analyses for each outcome, adjusting for rtPA status, using general linear (continuous variables) and logistic (binary variables) regression. Model comparison with collateral score and total ischemic volume was performed using the F or likelihood ratio test. RESULTS: Collateral presence independently and inversely predicted all outcomes except hemorrhagic transformation in patients who were recanalization negative and mRS >2 in patients who were recanalization positive. The greatest collateral benefit occurred in patients who were recanalization negative, contributing 16.5% and 19.2% of the variability for final infarct size and mRS >2. The collateral score model is superior to the total ischemic volume for mRS >2 prediction, but a combination of total ischemic volume and collateral score is superior for mRS >2 and final infarct prediction (24% and 28% variability, respectively). In patients who were recanalization positive, a model including collateral score and total ischemic volume was superior to that of total ischemic volume for hemorrhagic transformation and final infarct prediction but was muted compared with patients who were recanalization negative (11.3% and 16.9% variability). CONCLUSIONS: Collateral circulation is an independent predictor of all outcomes, but the magnitude of significance varies, greater in patients who were recanalization negative versus recanalization positive. Total ischemic volume assessment is complementary to collateral score in many cases.