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.

Quantifying Intracranial Plaque Permeability with Dynamic Contrast-Enhanced MRI: A Pilot Study.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease plaque hyperintensity and/or gadolinium contrast enhancement have been studied as imaging biomarkers of acutely symptomatic ischemic presentations using single static MR imaging measurements. However, the value in modeling the dynamics of intracranial plaque permeability has yet to be evaluated. The purpose of this study was to use dynamic contrast-enhanced MR imaging to quantify the contrast permeability of intracranial atherosclerotic disease plaques in symptomatic patients and to compare these parameters against existing markers of plaque volatility using black-blood MR imaging pulse sequences. MATERIALS AND METHODS: We performed a prospective study of contrast uptake dynamics in the major intracranial vessels proximal and immediately distal to the circle of Willis using dynamic contrast-enhanced MR imaging, specifically in patients with symptomatic intracranial atherosclerotic disease. Using the Modified Tofts model, we extracted the volume transfer constant (Ktrans) and fractional plasma volume (Vp) parameters from plaque-enhancement curves. Using regression analyses, we compared these parameters against time from symptom onset as well as intraplaque hyperintensity and postcontrast enhancement derived from T1 SPACE, a black-blood MR vessel wall imaging sequence. RESULTS: We completed analysis in 10 patients presenting with symptomatic intracranial atherosclerotic disease. Ktrans and Vp measurements were higher in plaques versus healthy white matter and similar or less than values in the choroid plexus. Only Ktrans correlated significantly with time from symptom onset (P = .02). Dynamic contrast-enhanced MR imaging parameters were not found to correlate significantly with intraplaque enhancement or intraplaque hyperintensity (P = .4 and P = .17, respectively). CONCLUSIONS: Elevated Ktrans and Vp values found in intracranial atherosclerotic disease plaques versus healthy white matter suggest that dynamic contrast-enhanced MR imaging is a feasible technique for studying vessel wall and plaque characteristics in the proximal intracranial vasculature. Significant correlations between Ktrans and symptom onset, which were not observed on T1 SPACE-derived metrics, suggest that Ktrans may be an independent imaging biomarker of acute and symptom-associated pathologic changes in intracranial atherosclerotic disease plaques.

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.

Quantifying Intracranial Aneurysm Wall Permeability for Risk Assessment Using Dynamic Contrast-Enhanced MRI: A Pilot Study.

BACKGROUND AND PURPOSE: Pathological changes in the intracranial aneurysm wall may lead to increases in its permeability; however the clinical significance of such changes has not been explored. The purpose of this pilot study was to quantify intracranial aneurysm wall permeability (K(trans), VL) to contrast agent as a measure of aneurysm rupture risk and compare these parameters against other established measures of rupture risk. We hypothesized K(trans) would be associated with intracranial aneurysm rupture risk as defined by various anatomic, imaging, and clinical risk factors. MATERIALS AND METHODS: Twenty-seven unruptured intracranial aneurysms in 23 patients were imaged with dynamic contrast-enhanced MR imaging, and wall permeability parameters (K(trans), VL) were measured in regions adjacent to the aneurysm wall and along the paired control MCA by 2 blinded observers. K(trans) and VL were evaluated as markers of rupture risk by comparing them against established clinical (symptomatic lesions) and anatomic (size, location, morphology, multiplicity) risk metrics. RESULTS: Interobserver agreement was strong as shown in regression analysis (R(2) > 0.84) and intraclass correlation (intraclass correlation coefficient >0.92), indicating that the K(trans) can be reliably assessed clinically. All intracranial aneurysms had a pronounced increase in wall permeability compared with the paired healthy MCA (P < .001). Regression analysis demonstrated a significant trend toward an increased K(trans) with increasing aneurysm size (P < .001). Logistic regression showed that K(trans) also predicted risk in anatomic (P = .02) and combined anatomic/clinical (P = .03) groups independent of size. CONCLUSIONS: We report the first evidence of dynamic contrast-enhanced MR imaging-modeled contrast permeability in intracranial aneurysms. We found that contrast agent permeability across the aneurysm wall correlated significantly with both aneurysm size and size-independent anatomic risk factors. In addition, K(trans) was a significant and size-independent predictor of morphologically and clinically defined high-risk aneurysms.