In Vivo Assessment of the Impact of Regional Intracranial Atherosclerotic Lesions on Brain Arterial 3D Hemodynamics.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis induces hemodynamic disturbance, which is not well-characterized, particularly in cerebral flow redistribution. We aimed to characterize the impact of regional stenotic lesions on intracranial hemodynamics by using 4D flow MR imaging. MATERIALS AND METHODS: 4D flow MR imaging was performed in 22 symptomatic patients (mean age, 68.4 ± 14.2 years) with intracranial stenosis (ICA, n = 7; MCA, n = 9; basilar artery, n = 6) and 10 age-appropriate healthy volunteers (mean age, 60.7 ± 8.1 years). 3D blood flow patterns were visualized by using time-integrated pathlines. Blood flow and peak velocity asymmetry indices were compared between patients and healthy volunteers in 4 prespecified arteries: ICAs, MCAs, and anterior/posterior cerebral arteries. RESULTS: 3D blood flow pathlines demonstrated flow redistribution across cerebral arteries in patients with unilateral intracranial stenosis. For patients with ICA stenosis compared with healthy volunteers, significantly lower flow and peak velocities were identified in the ipsilateral ICA (P = .001 and P = .001) and MCA (P < .001 and P = .001), but higher flow, in the ipsilateral PCA (P < .001). For patients with MCA stenosis, significantly lower flow and peak velocities were observed in the ipsilateral ICA (P = .009 and P = .045) and MCA (P < .001 and P = .005), but significantly higher flow was found in the ipsilateral posterior cerebral artery (P = .014) and anterior cerebral artery (P = .006). The asymmetry indices were not significantly different between patients with basilar artery stenosis and the healthy volunteers. CONCLUSIONS: Regional intracranial atherosclerotic lesions not only alter distal arterial flow but also significantly affect ipsilateral collateral arterial hemodynamics.

Impact of Pial Collaterals on Infarct Growth Rate in Experimental Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral infarction evolves at different rates depending on available blood flow suggesting that treatment time windows vary depending on the degree of pial collateral recruitment. This work sought to mathematically model infarct growth and determine whether infarct volume growth can be predicted by angiographic assessment of pial collateral recruitment in an experimental MCA occlusion animal model. MATERIALS AND METHODS: Pial collateral recruitment was quantified by using DSA, acquired 15 minutes following permanent MCA occlusion in 6 canines based on a scoring system (average pial collateral score) and arterial arrival time. MR imaging-based infarct volumes were measured 60, 90, 120, 180, 240 and 1440 minutes following MCA occlusion and were parameterized in terms of the growth rate index and final infarct volume (VFinal) as V(t) = VFinal [1 - e(-G × t)] (t = time). Correlations of the growth rate index and final infarct volume to the average pial collateral score and arterial arrival time were assessed by linear bivariate analysis. Correlations were used to generate asymptotic models of infarct growth for average pial collateral score or arterial arrival time values. Average pial collateral score- and arterial arrival time-based models were assessed by F tests and residual errors. RESULTS: Evaluation of pial collateral recruitment at 15 minutes postocclusion was strongly correlated with 24-hour infarct volumes (average pial collateral score: r2 = 0.96, P < .003; arterial arrival time: r2 = 0.86, P < .008). Infarct growth and the growth rate index had strong and moderate linear relationships to the average pial collateral score (r2 = 0.89; P < .0033) and arterial arrival time (r2 = 0.69; P < .0419), respectively. Final infarct volume and the growth rate index were algebraically replaced by angiographically based collateral assessments to model infarct growth. The F test demonstrated no statistical advantage to using the average pial collateral score- over arterial arrival time-based predictive models, despite lower residual errors in the average pial collateral score-based model (P < .03). CONCLUSIONS: In an experimental permanent MCA occlusion model, assessment of pial collaterals correlates with the infarct growth rate index and has the potential to predict asymptotic infarct volume growth.

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.

Evaluation of 4D vascular flow and tissue perfusion in cerebral arteriovenous malformations: influence of Spetzler-Martin grade, clinical presentation, and AVM risk factors.

BACKGROUND AND PURPOSE: The role of intracranial hemodynamics in the pathophysiology and risk stratification of brain AVMs remains poorly understood. The purpose of this study was to assess the influence of Spetzler-Martin grade, clinical history, and risk factors on vascular flow and tissue perfusion in cerebral AVMs. MATERIALS AND METHODS: 4D flow and perfusion MR imaging was performed in 17 patients with AVMs. Peak velocity and blood flow were quantified in AVM feeding and contralateral arteries, draining veins, and the straight sinus. Regional perfusion ratios (CBF, CBV, and MTT) were calculated between affected and nonaffected hemispheres. RESULTS: Regarding flow parameters, high-grade AVMs (Spetzler-Martin grade of >2) demonstrated significantly increased peak velocity and blood flow in the major feeding arteries (P < .001 and P = .004) and straight sinus (P = .003 and P = .012) and increased venous draining flow (P = .001). The Spetzler-Martin grade significantly correlated with cumulative feeding artery flow (r = 0.85, P < .001) and draining vein flow (r = 0.80, P < .001). Regarding perfusion parameters, perinidal CBF and CBV ratios were significantly lower (P < .001) compared with the remote ratios and correlated negatively with cumulative feeding artery flow (r = -0.60, P = .014 and r = -0.55, P = .026) and draining vein flow (r = -0.60, P = .013 and r = -0.56, P = .025). Multiple regression analysis revealed no significant association of AVM flow or perfusion parameters with clinical presentation (rupture and seizure history) and AVM risk factors. CONCLUSIONS: Macrovascular flow was significantly associated with increasing Spetzler-Martin grade and correlated with perinidal microvascular perfusion in cerebral AVMs. Future longitudinal studies are needed to evaluate the potential of comprehensive cerebral flow and perfusion MR imaging for AVM risk stratification.

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.

Intracranial 4D flow MRI: toward individualized assessment of arteriovenous malformation hemodynamics and treatment-induced changes.

BACKGROUND AND PURPOSE: Arteriovenous malformations are an important etiology of hemorrhagic stroke. However, current imaging modalities and risk do not provide insights into individual AVM hemodynamics and its role in pathophysiology. The aims of this study are to determine whether intracranial 4D flow MR imaging can provide insights into arteriovenous malformation hemodynamics independent of the Spetzler-Martin grade and to report the changes in flow observed during staged embolization. MATERIALS AND METHODS: Intracranial 3D blood flow was assessed in 20 patients with AVM (age = 39 ± 15 years, Spetzler-Martin grade ranging from 1-4) with the use of 4D flow MR imaging (temporal resolution = 45 ms, spatial resolution = [1.2-1.6mm](3)). AVM hemodynamics were visualized by means of time-integrated 3D pathlines depicting the AVM arterial feeding and venous draining patterns over the cardiac cycle. Analysis included the grading of feeding and draining velocities on a 3-point scale (0 = low <25 cm/s, 1 = medium <50 cm/s, 2 = high >50 cm/s). For 4 of 20 patients undergoing 4D flow MR imaging follow-up after staged embolization, peak velocities were quantified in arterial feeders, draining veins, the sagittal sinus, and contralateral arteries. RESULTS: In 50% of the cases with Spetzler-Martin grade >2, heterogeneous flow (velocity grade differences >1) was found across arteries and veins. Velocities in draining veins increased from Spetzler-Martin grade = 1 (grading = 0.5 ± 0.6) to Spetzler-Martin grade ≥3 (1.1 ± 0.6), whereas arterial velocities were similar (1.7 ± 0.6 versus 1.5 ± 0.6). In the postembolization subgroup of 4 patients, 4D flow MR imaging demonstrated successively more compact AVM and redistribution of velocities. Changes in arterial and venous velocities during treatment were highly different among individuals. CONCLUSIONS: Spetzler-Martin grade does not reflect differences in 3D AVM arterial and venous hemodynamics, and an individual assessment of AVM hemodynamics may be needed for improved lesion characterization. Four-dimensional flow MR imaging may have the potential to monitor and guide embolization treatment planning.

T1 gadolinium enhancement of intracranial atherosclerotic plaques associated with symptomatic ischemic presentations.

BACKGROUND AND PURPOSE: Contrast enhancement of intracranial atherosclerotic plaques has recently been investigated using high field and high resolution MR imaging as a risk factor in the development of ischemic stroke. We studied the reliability of conventional MR imaging at 1.5T in evaluating intraplaque enhancement and its relationship with acute cerebrovascular ischemic presentations in patients with severe intracranial atherosclerotic disease. MATERIALS AND METHODS: We retrospectively identified and analyzed 19 patients with 22 high-grade intracranial atherosclerotic disease plaques (>70% stenosis) in vessels cross-sectionally visualized by neuroanatomic MR imaging. Atherosclerotic plaques were classified as asymptomatic or symptomatic. Two blinded neuroradiologists independently ranked each lesion for the presence of intraplaque enhancement by use of a 5-point scale (1-5). Furthermore, plaque enhancement was quantified as the relative change in T1WI spin-echo signal intensity (postcontrast/precontrast) in the vessel wall at the site of each intracranial atherosclerotic disease lesion. RESULTS: Intraplaque enhancement was observed in 7 of 10 (70%) symptomatic plaques, in contrast to 1 of 12 (8%) asymptomatic plaques. Interobserver reliability correlated well for intraplaque enhancement (κ = 0.82). The degree of relative plaque enhancement in symptomatic versus asymptomatic lesions (63% versus 23%) was statistically significant (P = .001, t test). CONCLUSIONS: In this pilot study, we determined that intraplaque enhancement could be reliably evaluated with the use of cross-sectional imaging and analysis of vessels/plaques by use of conventional neuroanatomic MR imaging protocols. In addition, we observed a strong association between intraplaque enhancement in severe intracranial atherosclerotic disease lesions and ischemic events with the use of conventional MR imaging. Our preliminary study suggests that T1 gadolinium-enhancing plaques may be an indicator of progressing or symptomatic intracranial atherosclerotic disease.

Screening for asymptomatic bowel cancer in general practice.

General practitioners screened 4284 asymptomatic people aged over 40 to compare the incidence of large bowel cancer and polyps with a control general practice (4288 patients). Compliance was best in young women (60%), and overall it was 42%. Twenty six patients who had a positive Haemoccult test result (1.5% of those screened) were examined by colonoscopy and 10 had polyps. The incidence of cancers in the two groups was similar but in the control (unscreened patients) practice no polyps were found.