Richard H. Swartz

Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI

Background: Conventional arterial imaging focuses on the vessel lumen but lacks specificity because different pathologies produce similar luminal defects. Wall imaging can characterize extracranial arterial pathology, but imaging intracranial walls has been limited by resolution and signal constraints. Higher-field scanners may improve visualization of these smaller vessels. Methods: Three-tesla contrast-enhanced MRI was used to study the intracranial arteries from a consecutive series of patients at a tertiary stroke center. Results: Multiplanar T2-weighted fast spin echo and multiplanar T1 fluid-attenuated inversion recovery precontrast and postcontrast images were acquired in 37 patients with focal neurologic deficits. Clinical diagnoses included atherosclerotic disease (13), CNS inflammatory disease (3), dissections (3), aneurysms (3), moyamoya syndrome (2), cavernous angioma (1), extracranial source of stroke (5), and no definitive clinical diagnosis (7). Twelve of 13 with atherosclerotic disease had focal, eccentric vessel wall enhancement, 10 of whom had enhancement only in the vessel supplying the area of ischemic injury. Two of 3 with inflammatory diseases had diffuse, concentric vessel wall enhancement. Three of 3 with dissection showed bright signal on T1, and 2 had irregular wall enhancement with a flap and dual lumen. Conclusions: Three-tesla contrast-enhanced MRI can be used to study the wall of intracranial blood vessels. T2 and precontrast and postcontrast T1 fluid-attenuated inversion recovery images at 3 tesla may be able to differentiate enhancement patterns of intracranial atherosclerotic plaques (eccentric), inflammation (concentric), and other wall pathologies. Prospective studies are required to determine the sensitivity and specificity of arterial wall imaging for distinguishing the range of pathologic conditions affecting cerebral vasculature.

Vessel Wall MRI to Differentiate Between Reversible Cerebral Vasoconstriction Syndrome and Central Nervous System Vasculitis Preliminary Results

Background and Purpose— Prospective differentiation between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis can be challenging. We hypothesized that high-resolution vessel wall MRI would demonstrate arterial wall enhancement in central nervous system vasculitis but not in reversible cerebral vasoconstriction syndrome. Methods— We identified all patients with multifocal segmental narrowing of large intracranial arteries who had high-resolution vessel wall MRI and follow-up angiography at our institute over a 4-year period and performed a detailed chart review. Results— Three patients lacked arterial wall enhancement, and these all had reversal of arterial narrowing within 3 months. Four patients demonstrated arterial wall enhancement, and these had persistent or progressive arterial narrowing at a median follow-up of 17 months (range, 6–36 months) with final diagnoses of central nervous system vasculitis (3) and cocaine vasculopathy (1). Conclusions— Preliminary results suggest that high-resolution contrast-enhanced vessel wall MRI may enable differentiation between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis.

A New Visual Rating Scale to Assess Strategic White Matter Hyperintensities Within Cholinergic Pathways in Dementia

Background and Purpose— One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease. Methods— Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing. Results— The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (r=0.40; P=0.02) and accounted for 12% of the variance (corrected r2). A similar model was not significant for general WMH scores. Conclusions— The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.

Independent Cognitive Effects of Atrophy and Diffuse Subcortical and Thalamico-Cortical Cerebrovascular Disease in Dementia

Background and Purpose— Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD. Methods— Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility. Results— A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures. Conclusions— These data support the hypothesis that the thalamico-cortical network subserves both short-term and working memory. The findings also suggest that each type of pathology (atrophy, small vessel disease, and strategic infarcts) contribute independently to the pattern of cognitive disabilities associated with dementia. Particular attention to cerebrovascular disease in deep white or gray matter structures of the thalamico-cortical system is certainly warranted.

High-Resolution Magnetic Resonance Imaging An Emerging Tool for Evaluating Intracranial Arterial Disease

Atherosclerosis occurs in diverse vascular beds and may result in tissue ischemia. Current understanding of atherosclerotic disease has been advanced by imaging techniques such as high-resolution magnetic resonance imaging (HRMRI) studies of the coronary and carotid arteries. In these vessels, atherosclerotic plaque components can be visualized to risk-stratify patients, select treatments and advance our understanding of atherosclerosis pathophysiology in vivo. These imaging techniques are now being applied to evaluate intracranial arterial disease, both atherosclerotic and non-atherosclerotic. This review highlights the mechanisms by which intracranial atherosclerotic disease (ICAD) causes ischemia, the potential of HRMRI for identifying intracranial arterial pathology, the limitations of HRMRI in the intracranial circulation, and future applications of HRMRI for ICAD.

Reperfusion Is a Stronger Predictor of Good Clinical Outcome than Recanalization in Ischemic Stroke

PURPOSE To assess the predictive value of reperfusion indices, recanalization, and important baseline clinical and radiologic scores for good clinical outcome prediction. MATERIALS AND METHODS The study was approved by the local research ethics board. Written consent was obtained from all participants or their caregivers. Baseline computed tomography (CT) perfusion less than 4.5 hours after stroke symptoms, follow-up CT perfusion at 24 hours or less, and 5-7-day magnetic resonance images were obtained for 114 patients. Baseline imaging was assessed blinded to outcome. Recanalization status was determined at follow-up CT angiography. Reperfusion index was calculated on baseline and on follow-up at-risk tissue volume. Kruskal-Wallis, Mann-Whitney rank sum, and Spearman correlation were used for group comparisons and correlation studies. Univariate and multivariate logistic regression tested the association of clinical and imaging parameters with good outcome. Models with and without recanalization and reperfusion were compared by using Akaike information criterion. RESULTS Reperfusion indices were significantly higher in patients with recanalization than in those without (P < .001). Despite significance of recanalization at univariate analysis, only reperfusion, age, and National Institutes of Health Stroke Scale score were significant after multivariate analysis (P < .01). Time to maximum reperfusion index had the highest accuracy (area under the receiver operating characteristic curve, 0.70) for good outcome, and reperfusion was defined as time to maximum volume of 59% or greater. Patients with reperfusion but no recanalization had significantly lower total infarct volume (P = .001) and infarct growth (P = .004) and had higher salvaged penumbra (P = .009) volumes than patients without reperfusion and recanalization. A final model with reperfusion but not recanalization was the most prognostic model of good clinical outcome. CONCLUSION Reperfusion showed stronger association with good clinical outcome than did recanalization.

Clasmatodendrosis correlating with periventricular hyperintensity in mixed dementia

We report a 79‐year‐old woman with possible Alzheimers disease and confluent periventricular white matter hyperintensities on magnetic resonance imaging in whom postmortem analysis unexpectedly demonstrated no periventricular demyelination or cerebral arteriosclerosis. However, astrocytes in the periventricular white matter exhibited clasmatodendrosis, defined as cytoplasmic swelling and vacuolation of astroglia, with beading of their dendrites. This finding represents a previously unrecognized correlate of periventricular white matter hyperintensities. Ann Neurol 2002;52:378–381

Eccentric Narrowing and Enhancement of Symptomatic Middle Cerebral Artery Stenoses in Patients With Recent Ischemic Stroke

OBJECTIVE To characterize the vessel wall imaging findings and enhancement patterns in the middle cerebral artery of patients with presumed atherosclerotic disease and recent infarction in the territory of the affected artery. DESIGN Case series. SETTING University hospital. PATIENTS We included patients with (1) 2 or more risk factors for atherosclerotic disease; (2) middle cerebral artery stenosis shown on computed tomography, magnetic resonance, or conventional angiography; and (3) recent infarction in the territory of the affected artery. INTERVENTION 3-T contrast-enhanced high-resolution magnetic resonance imaging. RESULTS Eight patients were identified: 6 had an eccentric M1 stenosis, 1 had an eccentric proximal M2 stenosis, and 1 had a distal M2 stenosis with inconclusive eccentricity. Enhancement of the lesion was observed in all patients who underwent scanning within 5 months of the index event. Four intracranial atherosclerotic plaques were found in asymptomatic vessels (1 contralateral middle cerebral artery and 3 other intracranial arteries), and none of these had enhancement. CONCLUSION Patients with presumed intracranial atherosclerosis of the middle cerebral arteries have eccentric plaques that enhance after the administration of contrast medium when imaging is performed within weeks to months of a cerebral infarct within the arterial territory.

Subtherapeutic Warfarin Is Not Associated With Increased Hemorrhage Rates in Ischemic Strokes Treated With Tissue Plasminogen Activator

Background and Purpose— Concern exists that preadmission warfarin use may be associated with an increased risk of intracerebral hemorrhage in patients with ischemic stroke receiving intravenous tissue plasminogen activator, even in those with an international normalized ratio <1.7. However, evidence to date has been derived from a small single-center cohort of patients. Methods— We used data from Phase 3 of the Registry of the Canadian Stroke Network. We compared the rates of post-tissue plasminogen activator hemorrhage, including any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and gastrointestinal hemorrhage in patients with and without preadmission warfarin use. For those receiving warfarin, we restricted the analysis to patients with an international normalized ratio <1.7 on presentation. Secondary outcomes included functional status and mortality. Multivariate analyses were performed to adjust for other prognostic factors. Results— Our cohort included 1739 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator of whom 125 (7.2%) were receiving warfarin before admission and had an international normalized ratio <1.7. Preadmission warfarin use was not associated with any secondary intracerebral hemorrhage (OR, 1.2; 95% CI, 0.7 to 2.2), symptomatic intracerebral hemorrhage (OR, 1.1; 95% CI, 0.5 to 2.3), or gastrointestinal hemorrhage (OR, 1.1; 95% CI, 0.2 to 5.6). Multivariate analysis showed that preadmission warfarin use was independently associated with a reduced risk of poor functional outcome (OR, 0.6; 95 CI, 0.3 to 0.9), but not with in-hospital mortality (OR, 0.6; 95% CI, 0.3 to 1.0). Conclusions— The results from the present study suggest that tissue plasminogen activator treatment appears to be safe in patients with acute ischemic stroke taking warfarin with an international normalized ratio <1.7 and may reduce the risk of poor functional outcome.

Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan–rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.