Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes.

BACKGROUND AND PURPOSE: Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). METHOD: This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. RESULTS: A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were comparable between groups. Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On multivariable analysis, CASOD was an independent predictor of moderate/good collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). CONCLUSIONS: Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke.

Automated Cerebral Hemorrhage Detection Using RAPID.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is an important event that is diagnosed on head NCCT. Increased NCCT utilization in busy hospitals may limit timely identification of ICH. RAPID ICH is an automated hybrid 2D-3D convolutional neural network application designed to detect ICH that may allow for expedited ICH diagnosis. We determined the accuracy of RAPID ICH for ICH detection and ICH volumetric quantification on NCCT. MATERIALS AND METHODS: NCCT scans were evaluated for ICH by RAPID ICH. Consensus detection of ICH by 3 neuroradiology experts was used as the criterion standard for RAPID ICH comparison. ICH volume was also automatically determined by RAPID ICH in patients with intraparenchymal or intraventricular hemorrhage and compared with manually segmented ICH volumes by a single neuroradiology expert. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID ICH were determined. RESULTS: We included 308 studies. RAPID ICH correctly identified 151/158 ICH cases and 143/150 ICH-negative cases, which resulted in high sensitivity (0.956, CI: 0.911-0.978), specificity (0.953, CI: 0.907-0.977), positive predictive value (0.956, CI: 0.911-0.978), and negative predictive value (0.953, CI: 0.907-0.977) for ICH detection. The positive likelihood ratio (20.479, CI 9.928-42.245) and negative likelihood ratio (0.046, CI 0.023-0.096) for ICH detection were similarly favorable. RAPID ICH volumetric quantification for intraparenchymal and intraventricular hemorrhages strongly correlated with expert manual segmentation (correlation coefficient r = 0.983); the median absolute error was 3 mL. CONCLUSIONS: RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.

MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging.

The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.

Cerebral Venous Thrombosis Associated with COVID-19.

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling. MATERIALS AND METHODS: Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model. RESULTS: Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (F-statistic, P = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral (P = .007), contralateral (P = .004), and infarction core (P = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic (P ≤ .01) and ipsilateral (P = .04) brain temperatures, but not contralateral brain temperature (P = .08). CONCLUSIONS: Successful physiologic and continuous postischemic cerebral MR thermography was conducted and prescribed in a nonhuman primate infarction model to facilitate translatability. The results confirm hypothesized temperature disturbance and decoupling of physiologic brain-systemic temperature gradients. These findings inform a developing paradigm of brain thermoregulation and the applicability of brain temperature as a neuroimaging biomarker in CNS injury.

The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level-Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation.

BACKGROUND AND PURPOSE: Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level-dependent MR imaging. MATERIALS AND METHODS: A 20-minute resting-state blood oxygen level-dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level-dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent-based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion. RESULTS: Visually, temporal-shift analysis of blood oxygen level-dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) (P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration (P = .015 for default mode network, repeated-measures ANOVA). CONCLUSIONS: Temporal-shift analysis of blood oxygen level-dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

The Brain Thermal Response as a Potential Neuroimaging Biomarker of Cerebrovascular Impairment.

BACKGROUND AND PURPOSE: Brain temperature is critical for homeostasis, relating intimately to cerebral perfusion and metabolism. Cerebral thermometry is historically challenged by the cost and invasiveness of clinical and laboratory methodologies. We propose the use of noninvasive MR thermometry in patients with cerebrovascular disease, hypothesizing the presence of a measurable brain thermal response reflecting the tissue hemodynamic state. MATERIALS AND METHODS: Contemporaneous imaging and MR thermometry were performed in 10 patients (32-68 years of age) undergoing acetazolamide challenge for chronic, anterior circulation steno-occlusive disease. Cerebrovascular reactivity was calculated with blood oxygen level-dependent imaging and arterial spin-labeling methods. Brain temperature was calculated pre- and post-acetazolamide using previously established chemical shift thermometry. Mixed-effects models of the voxelwise relationships between the brain thermal response and cerebrovascular reactivity were computed, and the significance of model coefficients was determined with an F test (P < .05). RESULTS: We observed significant, voxelwise quadratic relationships between cerebrovascular reactivity from blood oxygen level-dependent imaging and the brain thermal response (x coefficient = 0.052, P < .001; x2coefficient = 0.0068, P < .001) and baseline brain temperatures (x coefficient = 0.59, P = .008; x2 coefficient = -0.13, P < .001). A significant linear relationship was observed for the brain thermal response with cerebrovascular reactivity from arterial spin-labeling (P = .001). CONCLUSIONS: The findings support the presence of a brain thermal response exhibiting complex but significant interactions with tissue hemodynamics, which we posit to reflect a relative balance of heat-producing versus heat-dissipating tissue states. The brain thermal response is a potential noninvasive biomarker for cerebrovascular impairment.

Body Temperature Modulates Infarction Growth following Endovascular Reperfusion.

BACKGROUND AND PURPOSE: The neuronal substrate is highly sensitive to temperature elevation; however, its impact on the fate of the ischemic penumbra has not been established. We analyzed interactions between temperature and penumbral expansion among successfully reperfused patients with acute ischemic stroke, hypothesizing infarction growth and worse outcomes among patients with fever who achieve full reperfusion. MATERIALS AND METHODS: Data from 129 successfully reperfused (modified TICI 2b/3) patients (mean age, 65 ± 15 years) presenting within 12 hours of onset were examined from a prospectively collected acute ischemic stroke registry. CT perfusion was analyzed to produce infarct core, hypoperfusion, and penumbral mismatch volumes. Final DWI infarction volumes were measured, and relative infarction growth was computed. Systemic temperatures were recorded throughout hospitalization. Correlational and logistic regression analyses assessed the associations between fever (>37.5°C) and both relative infarction growth and favorable clinical outcome (90-day mRS of ≤2), corrected for NIHSS score, reperfusion times, and age. An optimized model for outcome prediction was computed by using the Akaike Information Criterion. RESULTS: The median presentation NIHSS score was 18 (interquartile range, 14-22). Median (interquartile range) CTP-derived volumes were: core = 9.6 mL (1.5-25.3 mL); hypoperfusion = 133 mL (84.2-204 mL); and final infarct volume = 9.6 mL (8.3-45.2 mL). Highly significant correlations were observed between temperature of >37.5°C and relative infarction growth (Kendall τ correlation coefficient = 0.24, P = .002). Odds ratios for favorable clinical outcome suggested a trend toward significance for fever in predicting a 90-day mRS of ≤2 (OR = 0.31, P = .05). The optimized predictive model for favorable outcomes included age, NIHSS score, procedure time to reperfusion, and fever. Likelihood ratios confirmed the superiority of fever inclusion (P < .05). Baseline temperature, range, and maximum temperature did not meet statistical significance. CONCLUSIONS: These findings suggest that imaging and clinical outcomes may be affected by systemic temperature elevations, promoting infarction growth despite reperfusion.

Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

BACKGROUND AND PURPOSE: Endovascular trials suggest that revascularization benefits a subset of acute ischemic stroke patients with large-artery occlusion and small-core infarct volumes. The objective of our study was to identify thresholds of noncontrast CT-ASPECTS and collateral scores on CT angiography that best predict ischemic core volume thresholds quantified by CT perfusion among patients with acute ischemic stroke. MATERIALS AND METHODS: Fifty-four patients with acute ischemic stroke (<12 hours) and MCA/intracranial ICA occlusion underwent NCCT/CTP during their initial evaluation. CTP analysis was performed on a user-independent platform (RApid processing of PerfusIon and Diffusion), computing core infarct (defined as CBF of <30% normal). A target mismatch profile consisting of infarction core of ≤50 mL was selected to define candidates with acute ischemic stroke likely to benefit from revascularization. RESULTS: NCCT-ASPECTS of ≥9 with a CTA collateral score of 3 had 100% specificity for identifying patients with a CBF core volume of ≤50 mL. NCCT-ASPECTS of ≤6 had 100% specificity for identifying patients with a CBF core volume of >50 mL. In our cohort, 44 (81%) patients had an NCCT-ASPECTS of ≥9, a CTA collateral score of 3, or an NCCT-ASPECTS of ≤6. CONCLUSIONS: Using an NCCT-ASPECTS of ≥9 or a CTA collateral score of 3 best predicts CBF core volume infarct of ≤50 mL, while an NCCT-ASPECTS of ≤6 best predicts a CBF core volume infarct of >50 mL. Together these thresholds suggest that a specific population of patients with acute ischemic stroke not meeting such profiles may benefit most from CTP imaging to determine candidacy for revascularization.

Performance and Predictive Value of a User-Independent Platform for CT Perfusion Analysis: Threshold-Derived Automated Systems Outperform Examiner-Driven Approaches in Outcome Prediction of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Treatment strategies in acute ischemic stroke aim to curtail ischemic progression. Emerging paradigms propose patient subselection using imaging biomarkers derived from CT, CTA, and CT perfusion. We evaluated the performance of a fully-automated computational tool, hypothesizing enhancements compared with qualitative approaches. The correlation between imaging variables and clinical outcomes in a cohort of patients with acute ischemic stroke is reported. MATERIALS AND METHODS: Sixty-two patients with acute ischemic stroke and MCA or ICA occlusion undergoing multidetector CT, CTA, and CTP were retrospectively evaluated. CTP was processed on a fully operator-independent platform (RApid processing of PerfusIon and Diffusion [RAPID]) computing automated core estimates based on relative cerebral blood flow and relative cerebral blood volume and hypoperfused tissue volumes at varying thresholds of time-to-maximum. Qualitative analysis was assigned by 2 independent reviewers for each variable, including CT-ASPECTS, CBV-ASPECTS, CBF-ASPECTS, CTA collateral score, and CTA clot burden score. Performance as predictors of favorable clinical outcome and final infarct volume was established for each variable. RESULTS: Both RAPID core estimates, CT-ASPECTS, CBV-ASPECTS, and clot burden score correlated with favorable clinical outcome (P < .05); CBF-ASPECTS and collateral score were not significantly associated with favorable outcome, while hypoperfusion estimates were variably associated, depending on the selected time-to-maximum thresholds. Receiver operating characteristic analysis demonstrated disparities among tested variables, with RAPID core and hypoperfusion estimates outperforming all qualitative approaches (area under the curve, relative CBV = 0.86, relative CBF = 0.81; P < .001). CONCLUSIONS: Qualitative approaches to acute ischemic stroke imaging are subject to limitations due to their subjective nature and lack of physiologic information. These findings support the benefits of high-speed automated analysis, outperforming conventional methodologies while limiting delays in clinical management.

Proton resonance frequency chemical shift thermometry: experimental design and validation toward high-resolution noninvasive temperature monitoring and in vivo experience in a nonhuman primate model of acute ischemic stroke.

BACKGROUND AND PURPOSE: Applications for noninvasive biologic temperature monitoring are widespread in biomedicine and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation, therefore, remains controversial, motivating the development of noninvasive approaches such as temperature-sensitive nuclear MR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry by using proton resonance frequency chemical shift. We tested 3 methodologies, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3T. MATERIALS AND METHODS: A conventional, paired approach (difference [DIFF]-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MR thermometry derived simultaneously from temperature-sensitive changes in the water proton chemical shift (∼0.01 ppm/°C). MR thermometry was subsequently performed in a series of in vivo nonhuman primate experiments under physiologic and ischemic conditions, testing its reproducibility and overall performance. RESULTS: Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all 3 approaches (DIFF-1: linear regression R(2) = 0.994; P < .001; acquisition time = 4 minutes 40 seconds; DIFF-2: R(2) = 0.996; P < .001; acquisition time = 4 minutes; DIFF-3: R(2) = 0.998; P < .001; acquisition time = 40 seconds). CONCLUSIONS: These findings confirm the comparability in performance of 3 competing approaches to MR thermometry and present in vivo applications under physiologic and ischemic conditions in a primate stroke model.

Improved quality and diagnostic confidence achieved by use of dose-reduced gadolinium blood-pool agents for time-resolved intracranial MR angiography.

BACKGROUND AND PURPOSE: Time-resolved MRA with the use of bolus injection of paramagnetic agents has proved valuable in neurovascular imaging. Standard contrast agents have limited blood-pool residence times, motivating the development of highly protein-bound blood-pool agents with greater relaxivity and longer intravascular residence, affording improved image quality at lesser doses. This study represents the first comparison of blood-pool agents to standard agents in time-resolved cerebral MRA. MATERIALS AND METHODS: One hundred datasets were acquired at 1.5 T by use of a standardized, time-resolved MRA protocol. Patients received either unit dosing of a standard extracellular agent at 0.1 mmol/kg or a blood-pool agent at 0.03 mmol/kg. Peak arterial and venous enhancement phases were identified and subsequently scored qualitatively by use of a 4-point Likert scale, with attention to 6 vascular segments: 1) intracranial ICA; 2) MCA M1; 3) MCA M2; 4) MCA M3; 5) deep cerebral veins; and 6) dural venous sinuses. RESULTS: Fifty MR angiographies were acquired with each agent. No significant differences were found between agents in generation of uncontaminated arteriograms. Blood-pool agents, at 67% dose reduction, were of significantly greater quality across most vascular segments, including ICA (P = .019), M2 (P = .003), and M3 (P < .01). Superiority in the M1 segment approached significance (P = .059). Significantly better venographic quality was noted for deep venous structures (P = .016) with the use of blood-pool agents. CONCLUSIONS: Blood-pool agents provide superior demonstration of most intracranial vessels in time-resolved MRA compared with standard agents, at reduced doses. The greater relaxation enhancement and more favorable dosing profile make blood-pool agents superior to standard agents for use in cerebral time-resolved MRA.

Contrast-enhanced time-resolved MRA for follow-up of intracranial aneurysms treated with the pipeline embolization device.

BACKGROUND AND PURPOSE: Endovascular reconstruction and flow diversion by using the Pipeline Embolization Device is an effective treatment for complex cerebral aneurysms. Accurate noninvasive alternatives to DSA for follow-up after Pipeline Embolization Device treatment are desirable. This study evaluated the accuracy of contrast-enhanced time-resolved MRA for this purpose, hypothesizing that contrast-enhanced time-resolved MRA will be comparable with DSA and superior to 3D-TOF MRA. MATERIALS AND METHODS: During a 24-month period, 37 Pipeline Embolization Device-treated intracranial aneurysms in 26 patients underwent initial follow-up by using 3D-TOF MRA, contrast-enhanced time-resolved MRA, and DSA. MRA was performed on a 1.5T unit by using 3D-TOF and time-resolved imaging of contrast kinetics. All patients underwent DSA a median of 0 days (range, 0-68) after MRA. Studies were evaluated for aneurysm occlusion, quality of visualization of the reconstructed artery, and measurable luminal diameter of the Pipeline Embolization Device, with DSA used as the reference standard. RESULTS: The sensitivity, specificity, and positive and negative predictive values of contrast-enhanced time-resolved MRA relative to DSA for posttreatment aneurysm occlusion were 96%, 85%, 92%, and 92%. Contrast-enhanced time-resolved MRA demonstrated superior quality of visualization (P = .0001) and a higher measurable luminal diameter (P = .0001) of the reconstructed artery compared with 3D-TOF MRA but no significant difference compared with DSA. Contrast-enhanced time-resolved MRA underestimated the luminal diameter of the reconstructed artery by 0.965 ± 0.497 mm (27% ± 13%) relative to DSA. CONCLUSIONS: Contrast-enhanced time-resolved MRA is a reliable noninvasive method for monitoring intracranial aneurysms following flow diversion and vessel reconstruction by using the Pipeline Embolization Device.

Unilateral calcification of the caudate and putamen: association with underlying developmental venous anomaly.

Stenosis of a DVA may result in chronic venous ischemia. We present 6 patients (3 men, 3 women; age range, 30-79 years; mean age, 53 years) with unilateral calcification of the caudate and putamen on noncontrast CT. This calcification typically spared the anterior limb of the internal capsule. No patient presented with symptoms referable to the basal ganglia or had an underlying metabolic disorder or other process associated with calcium deposition. All patients subsequently underwent gadolinium-enhanced MR imaging and/or CTA or conventional angiography demonstrating the presence of an adjacent DVA. We hypothesize that chronic venous ischemia in the drainage territory of the DVA causes the abnormal mineralization. Greater recognition of this entity will prevent misinterpretation of this finding as acute hemorrhage and will prevent unnecessary and sometimes invasive evaluation in such patients. Furthermore, this entity should be considered in the differential diagnosis of unilateral basal ganglia hyperattenuation.