Flow augmentation STA-MCA bypass evaluation for patients with acute stroke and unilateral large vessel occlusion: a proposal for an urgent bypass flowchart

OBJECTIVE Endovascular recanalization trials have shown a positive impact on the preservation of ischemic penumbra in patients with acute large vessel occlusion (LVO). The concept of penumbra salvation can be extended to surgical revascularization with bypass in highly selected patients. For selecting these patients, the authors propose a flowchart based on multimodal MRI. METHODS All patients with acute stroke and persisting internal carotid artery (ICA) or M1 occlusion after intravenous lysis or mechanical thrombectomy undergo advanced neuroimaging in a time window of 72 hours after stroke onset including perfusion MRI, blood oxygenation level–dependent functional MRI to evaluate cerebrovascular reactivity (BOLD-CVR), and noninvasive optimal vessel analysis (NOVA) quantitative MRA to assess collateral circulation. RESULTS Symptomatic patients exhibiting persistent hemodynamic impairment and insufficient collateral circulation could benefit from bypass surgery. According to the flowchart, a bypass is considered for patients 1) with low or moderate neurological impairment (National Institutes of Health Stroke Scale score 1–15, modified Rankin Scale score ≤ 3), 2) without large or malignant stroke, 3) without intracranial hemorrhage, 4) with MR perfusion/diffusion mismatch > 120%, 5) with paradoxical BOLD-CVR in the occluded vascular territory, and 6) with insufficient collateral circulation. CONCLUSIONS The proposed flowchart is based on the patient’s clinical condition and multimodal MR neuroimaging and aims to select patients with acute stroke due to LVO and persistent inadequate collateral flow, who could benefit from urgent bypass.

Implementation of a Multi-Zone Numerical Blow-by Model and Its Integration with CFD Simulations for Estimating Collateral Mass and Heat Fluxes in Optical Engines

Nowadays reducing green-house gas emissions and pushing the fossil fuel savings in the field of light-duty vehicles is compulsory to slow down climate change. To this aim, the use of new combustion modes and dilution strategies to increase the stability of operations rich in diluent is an effective technique to reduce combustion temperatures and heat losses in throttled operations. Since the combustion behavior in those solutions highly differs from that of typical market systems, fundamental analyses in optical engines are mandatory in order to gain a deep understanding of those and to tune new models for improving the mutual support between experiments and simulations. However, it is known that optical accessible engines suffer from significant blow-by collateral flow due to the installation of the optical measure line. Thus, a reliable custom blow-by model capable of being integrated with both mono-dimensional and three-dimensional simulations was developed and validated against experimental data. The model can work for two different configurations: (a) stand-alone, aiming at providing macroscopic data on the ignitable mixture mass loss/recover through the piston rings; (b) combined, in which it is integrated in CFD engine simulations for the local analysis of likely collateral heat release induced by blow-by. Furthermore, once the model was validated, the effect of the engine speed and charge dilution on the blow-by phenomenon in the optical engine were simulated and discussed in the stand-alone mode.

Mechanisms of Flow-Mediated Dilation of Pial Collaterals and the Effect of Hypertension

Leptomeningeal anastomoses are small distal anastomotic vessels also known as pial collaterals in the brain. These vessels redirect blood flow during an occlusion and are important for stroke treatment and outcome. Pial collaterals have unique hemodynamic forces and experience significantly increased luminal flow and shear stress after the onset of ischemic stroke. However, there is limited knowledge of how pial collaterals respond to flow and shear stress, and whether this response is altered in chronic hypertension. Using an in vitro system, pial collaterals from normotensive and hypertensive rats (n=6–8/group) were isolated and luminal flow was induced with intravascular pressure maintained at 40 mm Hg. Collateral lumen diameter was measured following each flow rate in the absence or presence of pharmacological inhibitors and activators. Collaterals from male and female Wistar rats dilated similarly to increased flow (2 µL/minute: 58.4±18.7% versus 67.9±7.4%; P =0.275), and this response was prevented by inhibition of the transient receptor potential vanilloid type 4 channel, as well as inhibitors of nitric oxide and intermediate-conductance calcium-activated potassium channels, suggesting shear stress-induced activation of this pathway was involved. However, the vasodilation was significantly impaired in hypertensive rats (2 µL/minute: 17.7±7.7%), which was restored by inhibitors of reactive oxygen species and mimicked by angiotensin II. Thus, flow- and shear stress-induced vasodilation of pial collaterals appears to be an important stimulus for increasing collateral flow during large vessel occlusion. Impairment of this response during chronic hypertension may be related to poorly engaged pial collaterals during ischemic stroke in hypertensive subjects.

Detection of Collaterals from Cone-Beam CT Images in Stroke

Collateral vessels play an important role in the restoration of blood flow to the ischemic tissues of stroke patients, and the quality of collateral flow has major impact on reducing treatment delay and increasing the success rate of reperfusion. Due to high spatial resolution and rapid scan time, advance imaging using the cone-beam computed tomography (CBCT) is gaining more attention over the conventional angiography in acute stroke diagnosis. Detecting collateral vessels from CBCT images is a challenging task due to the presence of noises and artifacts, small-size and non-uniform structure of vessels. This paper presents a technique to objectively identify collateral vessels from non-collateral vessels. In our technique, several filters are used on the CBCT images of stroke patients to remove noises and artifacts, then multiscale top-hat transformation method is implemented on the pre-processed images to further enhance the vessels. Next, we applied three types of feature extraction methods which are gray level co-occurrence matrix (GLCM), moment invariant, and shape to explore which feature is best to classify the collateral vessels. These features are then used by the support vector machine (SVM), random forest, decision tree, and K-nearest neighbors (KNN) classifiers to classify vessels. Finally, the performance of these classifiers is evaluated in terms of accuracy, sensitivity, precision, recall, F-Measure, and area under the receiver operating characteristics curve. Our results show that all classifiers achieve promising classification accuracy above 90% and able to detect the collateral and non-collateral vessels from images.

Hyperintense posterior cerebral artery sign in patients with reversible cerebral vasoconstriction syndrome

Background: This study investigated hyperintense vessel signs (HVS) on fluid-attenuated inversion recovery imaging in the P1–2 portions of posterior cerebral arteries (PCAs) as a “hyperintense PCA sign” and HVS of cortical arteries. We retrospectively examined whether these signs would be useful in diagnosing reversible cerebral vasoconstriction syndrome (RCVS) in the acute phase. Methods: Eighty patients with RCVS who underwent initial magnetic resonance imaging (MRI) within 7 days of onset were included in this study. HVS and related clinical factors were examined. Results: On initial MRI of RCVS patients, hyperintense PCA sign and HVS of cortical arteries were seen in 21 cases (26%) and 38 cases (48%), respectively. In patients showing hyperintense PCA sign, vasoconstriction of the A2–3 portion was a significant clinical factor. Conversely, vasoconstriction of the M1 and P1 portions and the presence of white matter hyperintensity on initial and chronic-stage MRI were significantly associated with the presence of HVS in cortical arteries. Conclusion: Because rich collateral flow exists around PCAs, the frequency of hyperintense PCA sign is not high. However, hyperintense PCA sign findings in patients with suspected RCVS offer credible evidence of extreme flow decreases due to vasoconstriction in peripheral PCAs and other arteries associated with the collateral circulation of PCAs. Conversely, HVS in cortical arteries tend to reflect slow antegrade circulation due to vasoconstriction of peripheral vessel and major trunks. Both signs appear useful for auxiliary diagnosis of acute-phase RCVS.

Adverse fibrosis remodeling and aortopulmonary collateral flow are associated with poor Fontan outcomes

Background The extent and significance in of cardiac remodeling in Fontan patients are unclear and were the subject of this study. Methods This retrospective cohort study compared cardiovascular magnetic resonance (CMR) imaging markers of cardiac function, myocardial fibrosis, and hemodynamics in young Fontan patients to controls. Results Fifty-five Fontan patients and 44 healthy controls were included (median age 14 years (range 7–17 years) vs 13 years (range 4–14 years), p = 0.057). Fontan patients had a higher indexed end-diastolic ventricular volume (EDVI 129 ml/m2 vs 93 ml/m2, p < 0.001), and lower ejection fraction (EF 45% vs 58%, p < 0.001), circumferential (CS − 23.5% vs − 30.8%, p < 0.001), radial (6.4% vs 8.2%, p < 0.001), and longitudinal strain (− 13.3% vs − 24.8%, p < 0.001). Compared to healthy controls, Fontan patients had higher extracellular volume fraction (ECV) (26.3% vs 20.6%, p < 0.001) and native T1 (1041 ms vs 986 ms, p < 0.001). Patients with a dominant right ventricle demonstrated larger ventricles (EDVI 146 ml/m2 vs 120 ml/m2, p = 0.03), lower EF (41% vs 47%, p = 0.008), worse CS (− 20.1% vs − 25.6%, p = 0.003), and a trend towards higher ECV (28.3% versus 24.1%, p = 0.09). Worse EF and CS correlated with longer cumulative bypass (R = − 0.36, p = 0.003 and R = 0.46, p < 0.001), cross-clamp (R = − 0.41, p = 0.001 and R = 0.40, p = 0.003) and circulatory arrest times (R = − 0.42, p < 0.001 and R = 0.27, p = 0.03). T1 correlated with aortopulmonary collateral (APC) flow (R = 0.36, p = 0.009) which, in the linear regression model, was independent of ventricular morphology (p = 0.9) and EDVI (p = 0.2). The composite outcome (cardiac readmission, cardiac reintervention, Fontan failure or any clinically significant arrhythmia) was associated with increased native T1 (1063 ms vs 1026 ms, p = 0.029) and EDVI (146 ml/m2 vs 118 ml/m2, p = 0.013), as well as decreased EF (42% vs 46%, p = 0.045) and worse CS (− 22% vs − 25%, p = 0.029). APC flow (HR 5.5 CI 1.9–16.2, p = 0.002) was independently associated with the composite outcome, independent of ventricular morphology (HR 0.71 CI 0.30–1.69 p = 0.44) and T1 (HR1.006 CI 1.0–1.13, p = 0.07). Conclusions Pediatric Fontan patients have ventricular dysfunction, altered myocardial mechanics and increased fibrotic remodeling. Cumulative exposure to cardiopulmonary bypass and increased aortopulmonary collateral flow are associated with myocardial dysfunction and fibrosis. Cardiac dysfunction, fibrosis, and collateral flow are associated with adverse outcomes.

Predictive Value of CT Perfusion Imaging on the Basis of Automatic Segmentation Algorithm to Evaluate the Collateral Blood Flow Status on the Outcome of Reperfusion Therapy for Ischemic Stroke

Our objective was to study the predictive value of CT perfusion imaging based on automatic segmentation algorithm for evaluating collateral blood flow status in the outcome of reperfusion therapy for ischemic stroke. All data of 30 patients with ischemic stroke reperfusion in our hospital were collected and examined by CT perfusion imaging. Convolutional neural network (CNN) algorithm was used to segment perfusion imaging map and evaluate the results. The patients were grouped by regional leptomeningeal collateral score (rLMCs). Binary logistic regression was used to analyze the independent influencing factors of collateral blood flow on brain CT perfusion. The modified Scandinavian Stroke Scale was used to evaluate the prognosis of patients, and the effects of different collateral flow conditions on prognosis were obtained. The accuracy of CNN segmentation image is 62.61%, the sensitivity is 87.42%, the similarity coefficient is 93.76%, and the segmentation result quality is higher. Blood glucose (95% CI = 0.943, P = 0.028 ) and ischemic stroke history (95% CI = 0.855, P = 0.003 ) were independent factors affecting the collateral blood flow status of stroke patients. CBF (95% CI = 0.818, P = 0.008 ) and CBV (95% CI = 0.796, P = 0.016 ) were independent influencing factors of CT perfusion parameters. After 3 weeks of onset, the prognostic function defect score of the good collateral flow group (11.11%) was lower than that of the poor group (41.67%) ( P < 0.05 ). The automatic segmentation algorithm has more accurate segmentation ability for stroke CT perfusion imaging and plays a good auxiliary role in the diagnosis of clinical stroke reperfusion therapy. The collateral blood flow state based on CT perfusion imaging is helpful to predict the treatment outcome of patients with ischemic stroke and further predict the prognosis of patients.

Radiographic Characteristics of Mild Ischemic Stroke Patients With Visible Intracranial Occlusion: The INTERRSeCT Study

Background and Purpose: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. Methods: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. Results: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63–79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2–4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6–9] versus 6 [4–9]), similar favorable thrombus permeability (residual flow grades I–II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11–13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26–60.13]) were associated with successful recanalization among mild patients. Conclusions: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.

Collateral Circulation in Thrombectomy for Stroke After 6 to 24 Hours in the DAWN Trial

Background and Purpose: Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized. We evaluated the nature and impact of collaterals on outcomes in the late time window DAWN trial (Diffusion-Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). Methods: The DAWN Imaging Core Lab prospectively scored collateral grade on baseline computed tomography angiography (CTA; endovascular and control arms) and digital subtraction angiography (DSA; endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade (American Society of Interventional and Therapeutic Neuroradiology collateral score). Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes were separately analyzed for each treatment arm. Results: Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0–3) and DSA (n=57; median 2, 1–4) before thrombectomy in 161 DAWN subjects (mean age 69.8±13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (Tan grade 3, n=64 [44%]; 2, n=45 [31%]; 1, n=31 [22%]; 0, n=4 [3%]). DSA also showed a diverse range of collateral grades (ASITN grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except atrial fibrillation (41.6% endovascular versus 25.0% controls, P =0.04), and CTA collateral grades were balanced. Differences were seen across the 3 levels of collateral flow (good, fair, poor) for baseline National Institutes of Health Stroke Scale, blood glucose <150, diabetes, previous ischemic stroke, baseline and 24-hour core infarct volume, baseline and 24-hour Alberta Stroke Program Early CT Score, dramatic infarct progression, final Thrombolysis in Cerebral Infarction 2b+, and death. Collateral flow was a significant predictor of 90-day modified Rankin Scale score of 0 to 2 in the endovascular arm, with 43.7% (31/71) of subjects with good collaterals, 30.8% (16/52) of subjects with fair collaterals, and 17.7% (6/34) of subjects with poor collaterals reaching modified Rankin Scale score of 0 to 2 at 90 days ( P =0.026). Conclusions: DAWN subjects enrolled at 6 to 24 hours after onset with limited infarct cores had a wide range of collateral grades on both CTA and DSA. Even in this late time window, better collaterals lead to slower stroke progression and better functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02142283.