Cerebrovascular super-resolution 4D Flow MRI – using deep learning to non-invasively quantify velocity, flow, and relative pressure

ABSTRACTThe development of cerebrovascular disease is tightly coupled to changes in cerebrovascular hemodynamics, with altered flow and relative pressure indicative of the onset, development, and acute manifestation of pathology. Image-based monitoring of cerebrovascular hemodynamics is, however, complicated by the narrow and tortuous vasculature, where accurate output directly depends on sufficient spatial resolution. To address this, we present a method combining dedicated deep learning and state-of-the-art 4D Flow MRI to generate super-resolution full-field images with coupled quantification of relative pressure using a physics-driven image processing approach. The method is trained and validated in a patient-specific in-silico cohort, showing good accuracy in estimating velocity (relative error: 12.0 ± 0.1%, mean absolute error (MAE): 0.07 ± 0.06 m/s at peak velocity), flow (relative error: 6.6 ± 4.7%, root mean square error (RMSE): 0.5 ± 0.1 mL/s at peak flow), and with maintained recovery of relative pressure through the circle of Willis (relative error: 11.0 ± 7.3%, RMSE: 0.3 ± 0.2 mmHg). Furthermore, the method is applied to an in-vivo volunteer cohort, effectively generating data at <0.5mm resolution and showing potential in reducing low-resolution bias in relative pressure estimation. Our approach presents a promising method to non-invasively quantify cerebrovascular hemodynamics, applicable to dedicated clinical cohorts in the future.

Cerebral Hemodynamics and Intracranial Compliance Impairment in Critically Ill COVID-19 Patients: A Pilot Study

Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC) due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcomes. Methods: Fifty consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and non-invasive monitoring of ICC. Subjects were included upon ICU admission; CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI), and estimated cerebral perfusion pressure (eCPP), while ICC was assessed by using the P2/P1 ratio of the non-invasive ICP curve. A CVH/ICC score was computed using all these variables. The primary composite outcome was unsuccessful in weaning from respiratory support or death on day 7 (defined as UO). Results: At the first assessment (n = 50), only the P2/P1 ratio (median 1.20 [IQRs 1.00–1.28] vs. 1.00 [0.88–1.16]; p = 0.03) and eICP (14 [11–25] vs. 11 [7–15] mmHg; p = 0.01) were significantly higher among patients with an unfavorable outcome (UO) than others. Patients with UO had a significantly higher CVH/ICC score (9 [8–12] vs. 6 [5–7]; p < 0.001) than those with a favorable outcome; the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75–0.97); a score > 8.5 had 63 (46–77)% sensitivity and 87 (62–97)% specificity to predict UO. For those patients undergoing a second assessment (n = 29), after a median of 11 (5–31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n = 30) and survivors were observed. Conclusions: ICC impairment and CVH disturbances are often present in COVID-19 severe illness and could accurately predict an early poor outcome.

Impairment of Cerebrovascular Hemodynamics in Patients With Severe and Milder Forms of Sickle Cell Disease

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ0-thal), 20 patients with mild SCD (HbSC and HbSβ+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p &lt; 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p &lt; 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis

Background: Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined. Methods: Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task. Results: Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes (P &lt; .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions (P &lt; .05). There were no condition × time interactions for cognitive performance. Conclusions: Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS.

Cerebral Hemodynamics and Intracranial Compliance Impairment in Critically Ill Covid-19 Patients: A Pilot Study

Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC) due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcome.Methods: 50 consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and a non-invasive monitoring of ICC. Subjects were included upon ICU admission; CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI) and estimated cerebral perfusion pressure (eCPP) while ICC was assessed by using the P2/P1 ratio of estimated ICP curve (B4C device). The primary composite outcome was unsuccessful weaning from respiratory support or death on day 7.Results: At the first assessment (n= 50) only P2/P1 (1.20 [1.00-1.28] vs. 1.00 [0.88-1.16]; p=0.03) and eICP (14 [11-25] vs. 11 [7-15] mmHg; p=0.01) were significantly higher among patients with unfavorable outcome (UO) than others. Patients with UO had a significantly higher CVH/ICC score (9 [8-12] vs. 6 [5-7]; p<0.001) than those with favorable outcome; the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75-0.97); a score > 8.5 had 63 (46-77)% sensitivity and 87 (62-97)% specificity to predict UO. For those patients undergoing a second assessment (n=29) after a median of 11 (5-31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n=30) and survivors were observed.Conclusions: ICCI and CVH disturbances are often present in COVID-19 severe illness and could accurately predict early poor outcome.

Cerebral Hemodynamics and Intracranial Compliance Impairment In Critically Ill COVID-19 Patients: A Pilot Study

Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC), due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcome. Methods: 50 consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and a non-invasive monitoring of ICC. Subjects were included on ICU admission; CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI) and estimated cerebral perfusion pressure (eCPP), while ICC using the P2/P1 ratio of estimated ICP curve (B4C device). The primary composite outcome was unsuccessful weaning from respiratory support or death at day 7.Results: On the first assessment (n= 50), only P2/P1 (1.20 [1.00-1.28] vs. 1.00 [0.88-1.16]; p=0.03) and eICP (14 [11-25] vs. 11 [7-15] mmHg; p=0.01) were significantly higher among patients with UO than others. Patients with UO had a significantly higher CVH/ICC score (9 [8-12] vs. 6 [5-7]; p<0.001) than those with favorable outcome; the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75-0.97); a score > 8.5 had 63 (46-77)% sensitivity and 87 (62-97)% specificity to predict UO. For those patients undergoing a second assessment (n=29) after a median of 11 (5-31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n=30) and survivors were observed.Conclusions: ICCI and CVH disturbances are often present in COVID-19 severe illness and could accurately predict early poor outcome.

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.

SART 3.5D - Recovering cerebrovascular hemodynamics from standard 3D digital subtraction angiography cone-beam CT data-sets

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