Multiparametric MRI and CT models of infarct core and favorable penumbral imaging patterns in acute ischemic stroke.

BACKGROUND AND PURPOSE: Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were (1) to develop magnetic resonance imaging (MRI) and computed tomography (CT) multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and (2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization. METHODS: An analysis of imaging and clinical data was performed on 2 cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified. RESULTS: The MRI and CT models were developed and validated from 34 and 32 patients, using 943 320 and 1 236 917 voxels, respectively. The derivation MRI and 2-branch CT models had an overall accuracy of 74% and 80%, respectively, and were independently validated with an accuracy of 71% and 79%, respectively. The imaging criteria of (1) predicted infarct core ≤90 mL and (2) ratio of predicted infarct tissue within the at-risk region ≤70% identified patients as having a favorable penumbral pattern with 78% to 100% accuracy. CONCLUSIONS: Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.

Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.

BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMP) may play a role in blood-brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke. METHODS: Patients underwent MRI on presentation and approximately 24 hours later. The MRI marker, termed hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked immunosorbent assay. Logistic regression models tested for predictors of HARM on 24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1. RESULTS: For the 41 patients enrolled, diagnoses were: acute ischemic cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001-1.019; P=0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27-19.14; P=0.021). CONCLUSIONS: Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption.

Development and validation of a simple conversion model for comparison of intracerebral hemorrhage volumes measured on CT and gradient recalled echo MRI.

BACKGROUND AND PURPOSE: Gradient recalled echo MRI (GRE) has been shown to be as accurate as CT for the detection of acute intracerebral hemorrhage (ICH). However, because of the differences in the signal parameter being detected, apparent hemorrhage size is expected to vary by imaging modality, with GRE providing larger volumes attributable to susceptibility effects. METHODS: Image data from patients participating in 3 ICH studies were retrospectively reviewed. Patients with acute ICH were included if (1) concurrent MRI and CT were performed within 72 hours of symptom onset, and (2) each modality was performed within 240 minutes of each other. ICH volumes were calculated using a semiautomated image analysis program. The least squares method was used to develop a conversion equation based on a linear regression of GRE volume on CT volume. RESULTS: Thirty-six patients met inclusion criteria. MRI was performed first in 18, CT first in 18. Mean hemorrhage volume was 25.2 cc (range 0.1 to 83.9 cc) on CT and 32.7 cc (range 0.1 to 98.7 cc) measured on GRE. A linear relationship defined by CT Volume=GRE Volume*0.8 (Spearman's correlation coefficient=0.992, P<0.001) was derived. CONCLUSIONS: Acute ICH volumes as measured on GRE pulse sequences are consistently larger than CT volumes. A simple mathematical conversion model has been developed: CT volume=0.8*GRE volume. This formula can be used in studies using both imaging modalities, across different studies, or to track ICH growth over time independent of imaging modality in an individual patient.

Image Updating for Brain Shift Compensation During Resection.

BACKGROUND: In open-cranial neurosurgery, preoperative magnetic resonance (pMR) images are typically coregistered for intraoperative guidance. Their accuracy can be significantly degraded by intraoperative brain deformation, especially when resection is involved. OBJECTIVE: To produce model updated MR (uMR) images to compensate for brain shift that occurred during resection, and evaluate the performance of the image-updating process in terms of accuracy and computational efficiency. METHODS: In 14 resection cases, intraoperative stereovision image pairs were acquired after dural opening and during resection to generate displacement maps of the surgical field. These data were assimilated by a biomechanical model to create uMR volumes of the evolving surgical field. A tracked stylus provided independent measurements of feature locations to quantify target registration errors (TREs) in the original coregistered pMR and uMR as surgery progressed. RESULTS: Updated MR TREs were 1.66 ± 0.27 and 1.92 ± 0.49 mm in the 14 cases after dural opening and after partial resection, respectively, compared to 8.48 ± 3.74 and 8.77 ± 4.61 mm for pMR, respectively. The overall computational time for generating uMRs after partial resection was less than 10 min. CONCLUSION: We have developed an image-updating system to compensate for brain deformation during resection using a computational model with data assimilation of displacements measured with intraoperative stereovision imaging that maintains TREs less than 2 mm on average.

Intraoperative image updating for brain shift following dural opening.

OBJECTIVE Preoperative magnetic resonance images (pMR) are typically coregistered to provide intraoperative navigation, the accuracy of which can be significantly compromised by brain deformation. In this study, the authors generated updated MR images (uMR) in the operating room (OR) to compensate for brain shift due to dural opening, and evaluated the accuracy and computational efficiency of the process. METHODS In 20 open cranial neurosurgical cases, a pair of intraoperative stereovision (iSV) images was acquired after dural opening to reconstruct a 3D profile of the exposed cortical surface. The iSV surface was registered with pMR to detect cortical displacements that were assimilated by a biomechanical model to estimate whole-brain nonrigid deformation and produce uMR in the OR. The uMR views were displayed on a commercial navigation system and compared side by side with the corresponding coregistered pMR. A tracked stylus was used to acquire coordinate locations of features on the cortical surface that served as independent positions for calculating target registration errors (TREs) for the coregistered uMR and pMR image volumes. RESULTS The uMR views were visually more accurate and well aligned with the iSV surface in terms of both geometry and texture compared with pMR where misalignment was evident. The average misfit between model estimates and measured displacements was 1.80 ± 0.35 mm, compared with the average initial misfit of 7.10 ± 2.78 mm between iSV and pMR, and the average TRE was 1.60 ± 0.43 mm across the 20 patients in the uMR image volume, compared with 7.31 ± 2.82 mm on average in the pMR cases. The iSV also proved to be accurate with an average error of 1.20 ± 0.37 mm. The overall computational time required to generate the uMR views was 7-8 minutes. CONCLUSIONS This study compensated for brain deformation caused by intraoperative dural opening using computational model-based assimilation of iSV cortical surface displacements. The uMR proved to be more accurate in terms of model-data misfit and TRE in the 20 patient cases evaluated relative to pMR. The computational time was acceptable (7-8 minutes) and the process caused minimal interruption of surgical workflow.

Design and rationale of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial.

RATIONALE: Multimodal imaging has the potential to identify acute ischaemic stroke patients most likely to benefit from late recanalization therapies. AIMS: The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy Trial is to investigate whether multimodal imaging can identify patients who will benefit substantially from mechanical embolectomy for the treatment of acute ischaemic stroke up to eight-hours from symptom onset. DESIGN: Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a randomized, controlled, blinded-outcome clinical trial. POPULATION STUDIED: Acute ischaemic stroke patients with large vessel intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of symptom onset are eligible. The study sample size is 120 patients. STUDY INTERVENTION: Patients are randomized to endovascular embolectomy employing the Merci Retriever (Concentric Medical, Mountain View, CA) or the Penumbra System (Penumbra, Alameda, CA) vs. standard medical care, with randomization stratified by penumbral pattern. OUTCOMES: The primary aim of the trial is to test the hypothesis that the presence of substantial ischaemic penumbral tissue visualized on multimodal imaging (magnetic resonance imaging or computed tomography) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischaemic stroke due to a large vessel, intracranial occlusion up to eight-hours from symptom onset. This hypothesis will be tested by analysing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome based on the distribution of scores on the modified Rankin Scale measure of global disability assessed 90 days post-stroke. Nested hypotheses test for (1) treatment efficacy in patients with a penumbral pattern pretreatment, and (2) absence of treatment benefit (equivalency) in patients without a penumbral pattern pretreatment. An additional aim will only be tested if the primary hypothesis of an interaction is negative: that patients treated with mechanical embolectomy have improved functional outcome vs. standard medical management.

Contrast agent dose effects in cerebral dynamic susceptibility contrast magnetic resonance perfusion imaging.

PURPOSE: To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC-MRI). MATERIALS AND METHODS: Sequential DSC-MRI (1.5T gradient-echo echo-planar imaging using an echo time of 61-64 msec) was performed using contrast agent doses of 0.1 and 0.2 mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12 stroke patients. RESULTS: 1) Arterial signal showed the expected doubling in relaxation response (DeltaR2*) to dose doubling. 2) The brain signal showed a less than doubled DeltaR2* response to dose doubling. 3) The 0.2 mmol/kg dose studies subtly underestimated cerebral blood volume (CBV) and cerebral blood flow (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF, the 0.2 mmol/kg studies overestimated the CBV and CBF compared with the 0.1 mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in stroke. CONCLUSION: Subtle but statistically significant dose sensitivities were found. Therefore, it is advisable to carefully control the contrast agent dose when DSC-MRI is used in clinical trials. The study also suggests that a 0.1 mmol/kg dose is adequate for hemodynamic measurements.