Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model

Purpose: To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO2 challenge in mechanically ventilated juvenile pigs. Materials and Methods: Precise end-tidal partial pressure CO2 (PETCO2) control was achieved via a computer-controlled model-driven prospective end-tidal targeting (MPET) system integrated with mechanical ventilation using a custom-built secondary breathing circuit. Test-retest blood-oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso-oxic square-wave PETCO2 changes. For comparison, test-retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra-class correlation coefficient (ICC) and coefficient of variation (CV). Results: The repeatability of the PETCO2 (CV \u3c 2%) step changes resulted in BOLD CVR ICC \u3e 0.94 and CV \u3c 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC \u3e 0.96 and CV \u3c 4%). Conclusion: This study demonstrates the feasibility and precision of CVR imaging with an MPET CO2 challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia. © 2010 Wiley-Liss, Inc

High posterior cerebral artery flow predicts ischemia recurrence in patients with internal carotid artery occlusion

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p = <0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia

Single-antiplatelet regimen in ruptured cerebral blood blister and dissecting aneurysms treated with flow-diverter stent reconstruction

BackgroundFlow diversion treatment of ruptured cerebral aneurysms remains challenging due to the need for double-antiplatelet therapy. We report our experience with flow-diverter stent (FDS) reconstruction with single-antiplatelet therapy of ruptured cerebral blood blister and dissecting aneurysms.MethodsIn this case series we performed a retrospective analysis of all patients with ruptured cerebral aneurysms who were treated with a phosphoryl-bonded FDS between 2019 and 2022 in a single center. Periprocedurally, all patients received weight-adapted eptifibatide IV and heparin IV. After 6–24 hours, eptifibatide was switched to oral prasugrel as monotherapy. We analyzed the rate of bleeding complications, thromboembolic events, occlusion rate and clinical outcome.ResultsNine patients with subarachnoid hemorrhage were treated, eight within 24 hours of symptom onset. Seven patients were treated with one FDS and two patients received two FDS in a telescopic fashion. Two aneurysms were additionally coil embolized. Fatal re-rupture occurred in one case; eight patients survived and had no adverse events associated with the FDS. Six patients showed complete occlusion of the aneurysm after 3 months (n=2) and 1 year (n=4), respectively. Two patients showed subtotal occlusion of the aneurysm at the last follow-up after 3 months and 6 months, respectively. Favorable clinical outcome was achieved in five patients.ConclusionsPeri-interventional single-antiplatelet therapy with eptifibatide followed by prasugrel was sufficient to prevent thromboembolic events and reduce re-bleeding using an anti-thrombogenic FDS. FDS with single-antiplatelet therapy might be a viable option for ruptured blood blister and dissecting cerebral aneurysms

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH

High posterior cerebral artery flow predicts ischemia recurrence in patients with internal carotid artery occlusion

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p = &lt;0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system

The voxel-wise analysis of false negative fMRI activation in regions of provoked impaired cerebrovascular reactivity

Task-evoked Blood-oxygenation-level-dependent (BOLD-fMRI) signal activation is widely used to interrogate eloquence of brain areas. However, data interpretation can be improved, especially in regions with absent BOLD-fMRI signal activation. Absent BOLD-fMRI signal activation may actually represent false-negative activation due to impaired cerebrovascular reactivity (BOLD-CVR) of the vascular bed. The relationship between impaired BOLD-CVR and BOLD-fMRI signal activation may be better studied in healthy subjects where neurovascular coupling is known to be intact. Using a model-based prospective end-tidal carbon dioxide (CO2) targeting algorithm, we performed two controlled 3 tesla BOLD-CVR studies on 17 healthy subjects: 1: at the subjects' individual resting end-tidal CO2 baseline. 2: Around +6.0 mmHg CO2 above the subjects' individual resting baseline. Two BOLD-fMRI finger-tapping experiments were performed at similar normo- and hypercapnic levels. Relative BOLD fMRI signal activation and t-values were calculated for BOLD-CVR and BOLD-fMRI data. For each component of the cerebral motor-network (precentral gyrus, postcentral gyrus, supplementary motor area, cerebellum und fronto-operculum), the correlation between BOLD-CVR and BOLD-fMRI signal changes and t-values was investigated. Finally, a voxel-wise quantitative analysis of the impact of BOLD-CVR on BOLD-fMRI was performed. For the motor-network, the linear correlation coefficient between BOLD-CVR and BOLD-fMRI t-values were significant (p<0.01) and in the range 0.33-0.55, similar to the correlations between the CVR and fMRI Δ%signal (p<0.05; range 0.34-0.60). The linear relationship between CVR and fMRI is challenged by our voxel-wise analysis of Δ%signal and t-value change between normo- and hypercapnia. Our main finding is that BOLD fMRI signal activation maps are markedly dampened in the presence of impaired BOLD-CVR and highlights the importance of a complementary BOLD-CVR assessment in addition to a task-evoked BOLD fMRI to identify brain areas at risk for false-negative BOLD-fMRI signal activation