Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage

Christian Fung, Dieter Henrik Heiland, Raluca Reitmeir, Wolf-Dirk Niesen, Andreas Raabe, Jens Eyding, Oliver Schnell, Roland Rölz, Werner J Z Graggen, Jürgen Beck, Christian Fung, Dieter Henrik Heiland, Raluca Reitmeir, Wolf-Dirk Niesen, Andreas Raabe, Jens Eyding, Oliver Schnell, Roland Rölz, Werner J Z Graggen, Jürgen Beck

Abstract

Background: Delayed cerebral ischemia increases mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Various techniques are applied to detect cerebral vasospasm and hypoperfusion. Contrast-enhanced ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion in acute ischemic stroke. This prospective study aimed to evaluate the use of UPI to enable detection of cerebral hypoperfusion after aSAH.

Methods: We prospectively enrolled patients with aSAH and performed UPI examinations every second day after aneurysm closure. Perfusion of the basal ganglia was outlined to normalize the perfusion records of the anterior and posterior middle cerebral artery territory. We applied various models to characterize longitudinal perfusion alterations in patients with delayed ischemic neurologic deficit (DIND) across the cohort and predict DIND by using a multilayer classification model.

Results: Between August 2013 and December 2015, we included 30 patients into this prospective study. The left-right difference of time to peak (TTP) values showed a significant increase at day 10-12. Patients with DIND demonstrated a significant, 4.86 times increase of the left-right TTP ratio compared with a mean fold change in patients without DIND of 0.9 times (p = 0.032).

Conclusions: UPI is feasible to enable detection of cerebral tissue hypoperfusion after aSAH, and the left-right difference of TTP values is the most indicative result of this finding.

Trial registration: ClinicalTrials.gov NCT02907879.

Keywords: Perfusion; Subarachnoid hemorrhage; Ultrasonography; Vasospasm (intracranial).

Conflict of interest statement

The authors report no conflict of interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Illustration of the workflow of examined patients (a) and region of interests that were evaluated by postprocessing offline analysis (b). The graphs represent ultrasound perfusion measurements after normalization with the corresponding midline region for TTP (c) and MTT (d). MCA, middle cerebral artery, Mid, midline region, MTT, mean transit time, SAH, subarachnoid hemorrhage, TTP, time to peak
Fig. 2
Fig. 2
The interpatient variance of TTP (a) and MTT (b) values for the middle cerebral artery territories. In addition, intrapatient variance of TTP (c) and MTT (d) values are displayed. The variance of the MTT values is increased compared with TTP values. MCA, middle cerebral artery, MTT, mean transit time, TTP, time to peak
Fig. 3
Fig. 3
Analysis of TTP values in patients before (red) and after (green) spasmolysis (a). TTP values show a significant decline after spasmolysis. b Comparison between normalized (red) and nonnormalized (gray) TTP values in one patient (patient #1) before and after spasmolysis. Normalized values show a clear decrease in TTP values at day 10 after spasmolysis, which was indicated because of a new neurologic deficit. In contrast, nonnormalized values don’t reflect the effect of spasmolysis on TTP values. TTP, time to peak, UPI, ultrasound perfusion imaging
Fig. 4
Fig. 4
Comparison between left-to-right ratios of TTP values between patients who present a delayed ischemic neurologic deficit and those who do not (a). b Longitudinal analysis of TTP values between these two groups. Patients with a delayed ischemic neurologic deficit (red) show a significant increase of left-to-right ratios, especially between days 10 and 12. TTP, time to peak
Fig. 5
Fig. 5
Illustration of left-to-right TTP ratios of all evaluated ultrasound perfusion examinations. Patients who present a delayed ischemic neurologic deficit are marked in red and those who presented without a delayed ischemic neurologic deficit are marked in green. Patients with delayed ischemic neurology deficit show an increase in TTP ratios, especially during the critical time period (8–12 days). TTP, time to peak
Fig. 6
Fig. 6
TTP CT imaging (left vs. right) measurements (red, with vasospasm; green, without vasospasm), correlation, and p values are determined by Pearson correlation coefficient (a). b Comparison between TTP longitudinal UPI (in black) and CT imaging (orange). c Barplot of differences between the left-to-right ratio within UPI (left) and CT (right) with vasospasm and without vasospasm. CT, computed tomography, TTP, time to peak, UPI, ultrasound perfusion imaging
Fig. 7
Fig. 7
Decision tree model to sort out patients at risk for DIND. One layer must be positive to be graded as high-risk. A/P-Ratio, anterior/posterior ratio, L/R-Ratio, left-to-right ratio, Min, minimum, TTP, time to peak
Fig. 8
Fig. 8
Example of two patients being graded according to our decision tree model. min, xxx, max, xxx, nP, xxx, TTP, time to peak, UPI, ultrasound perfusion imaging

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