Trevor Carpenter

Lacunar stroke is associated with diffuse blood–brain barrier dysfunction†

Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood–brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke.

Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Background and Purpose— Increased blood–brain barrier (BBB) permeability occurs in cerebral small vessel disease. It is not known if BBB changes predate progression of small vessel disease. Methods— We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3–6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging. Results— Among 70 patients with mean age of 68 (SD±11) years, median time to clinical follow-up was 39 months (interquartile range, 30–45) and median Oxford Handicap Score was 2 (interquartile range, 1–3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, WMH progression at follow-up was associated with baseline WMH (ANCOVA P<0.0001) and age (ANCOVA P=0.032). Conclusions— Further long-term studies to evaluate the role of BBB dysfunction in progression of small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.

Computed tomography perfusion imaging denoising using gaussian process regression.

Brain perfusion weighted images acquired using dynamic contrast studies have an important clinical role in acute stroke diagnosis and treatment decisions. However, computed tomography (CT) images suffer from low contrast-to-noise ratios (CNR) as a consequence of the limitation of the exposure to radiation of the patient. As a consequence, the developments of methods for improving the CNR are valuable. The majority of existing approaches for denoising CT images are optimized for 3D (spatial) information, including spatial decimation (spatially weighted mean filters) and techniques based on wavelet and curvelet transforms. However, perfusion imaging data is 4D as it also contains temporal information. Our approach using gaussian process regression (GPR), which takes advantage of the temporal information, to reduce the noise level. Over the entire image, GPR gains a 99% CNR improvement over the raw images and also improves the quality of haemodynamic maps allowing a better identification of edges and detailed information. At the level of individual voxel, GPR provides a stable baseline, helps us to identify key parameters from tissue time-concentration curves and reduces the oscillations in the curve. GPR is superior to the comparable techniques used in this study.

An open source toolkit for medical imaging de-identification

ObjectiveMedical imaging acquired for clinical purposes can have several legitimate secondary uses in research projects and teaching libraries. No commonly accepted solution for anonymising these images exists because the amount of personal data that should be preserved varies case by case. Our objective is to provide a flexible mechanism for anonymising Digital Imaging and Communications in Medicine (DICOM) data that meets the requirements for deployment in multicentre trials.MethodsWe reviewed our current de-identification practices and defined the relevant use cases to extract the requirements for the de-identification process. We then used these requirements in the design and implementation of the toolkit. Finally, we tested the toolkit taking as a reference those requirements, including a multicentre deployment.ResultsThe toolkit successfully anonymised DICOM data from various sources. Furthermore, it was shown that it could forward anonymous data to remote destinations, remove burned-in annotations, and add tracking information to the header. The toolkit also implements the DICOM standard confidentiality mechanism.ConclusionA DICOM de-identification toolkit that facilitates the enforcement of privacy policies was developed. It is highly extensible, provides the necessary flexibility to account for different de-identification requirements and has a low adoption barrier for new users.

Protocol for the perfusion and angiography imaging sub-study of the Third International Stroke Trial (IST-3) of alteplase treatment within six-hours of acute ischemic stroke.

Rationale Intravenous thrombolysis with recombinant tissue Plasminogen Activator improves outcomes in patients treated early after stroke but at the risk of causing intracranial hemorrhage. Restricting recombinant tissue Plasminogen Activator use to patients with evidence of still salvageable tissue, or with definite arterial occlusion, might help reduce risk, increase benefit and identify patients for treatment at late time windows. Aims To determine if perfusion or angiographic imaging with computed tomography or magnetic resonance help identify patients who are more likely to benefit from recombinant tissue Plasminogen Activator in the context of a large multicenter randomized trial of recombinant tissue Plasminogen Activator given within six-hours of onset of acute ischemic stroke, the Third International Stroke Trial. Design Third International Stroke Trial is a prospective multicenter randomized controlled trial testing recombinant tissue Plasminogen Activator (0·9 mg/kg, maximum dose 90 mg) started up to six-hours after onset of acute ischemic stroke, in patients with no clear indication for or contraindication to recombinant tissue Plasminogen Activator. Brain imaging (computed tomography or magnetic resonance) was mandatory pre-randomization to exclude hemorrhage. Scans were read centrally, blinded to treatment and clinical information. In centers where perfusion and/or angiography imaging were used routinely in stroke, these images were also collected centrally, processed and assessed using validated visual scores and computational measures. Study outcomes The primary outcome in Third International Stroke Trial is alive and independent (Oxford Handicap Score 0–2) at 6 months; secondary outcomes are symptomatic and fatal intracranial hemorrhage, early and late death. The perfusion and angiography study additionally will examine interactions between recombinant tissue Plasminogen Activator and clinical outcomes, infarct growth and recanalization in the presence or absence of perfusion lesions and/or arterial occlusion at presentation. The study is registered ISRCTN25765518.

Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study

Background In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators. Objective To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres. Methods We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography. Results Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1–30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively). Conclusion Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial

BACKGROUND Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear. METHODS We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters. We examined associations between SVD features (individually and summed) and presence of hypoperfusion using logistic regression adjusted for age, sex, baseline National Institutes of Health Stroke Scale, hypertension, and diabetes. RESULTS A total of 115 patients with median (interquartile range) age of 81 (72-86) years, 78 (52%) of which were male, had complete perfusion data. Hypoperfusion was most frequent on mean transit time (MTT; 63 patients, 55%) and least frequent on time to maximum flow (19 patients, 17%). The SVD score showed stronger independent associations with hypoperfusion (e.g., MTT, odds ratio [OR] = 2.80; 95% confidence interval [CI] = 1.56-5.03) than individual SVD markers (e.g., white matter hypoattenuation score, MTT, OR = 1.49, 95% CI = 1.09-2.04). Baseline blood pressure did not differ by presence or absence of hypoperfusion or across strata of SVD score. Presence of white matter hypoperfusion increased with SVD summed score. CONCLUSIONS The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.

Lesion Area Detection Using Source Image Correlation Coefficient for CT Perfusion Imaging

Computer tomography (CT) perfusion imaging is widely used to calculate brain hemodynamic quantities such as cerebral blood flow, cerebral blood volume, and mean transit time that aid the diagnosis of acute stroke. Since perfusion source images contain more information than hemodynamic maps, good utilization of the source images can lead to better understanding than the hemodynamic maps alone. Correlation-coefficient tests are used in our approach to measure the similarity between healthy tissue time-concentration curves and unknown curves. This information is then used to differentiate penumbra and dead tissues from healthy tissues. The goal of the segmentation is to fully utilize information in the perfusion source images. Our method directly identifies suspected abnormal areas from perfusion source images and then delivers a suggested segmentation of healthy, penumbra, and dead tissue. This approach is designed to handle CT perfusion images, but it can also be used to detect lesion areas in magnetic resonance perfusion images.

Spatiotemporal Dynamic Simulation of Acute Perfusion/Diffusion Ischemic Stroke Lesions Evolution: A Pilot Study Derived from Longitudinal MR Patient Data

The spatiotemporal evolution of stroke lesions, from acute injury to final tissue damage, is complex. Diffusion-weighted (DWI) and perfusion-weighted (PWI) imaging is commonly used to detect early ischemic changes and attempts to distinguish between permanently damaged and salvageable tissues. To date, 2D and 3D measures of diffusion/perfusion regions at individual timepoints have been widely used but may underestimate the true lesion spatio-temporal dynamics. Currently there is no spatio-temporal 4D dynamic model that simulates the continuous evolution of ischemic stroke from MR images. We determined whether a 4D current-based diffeomorphic model, developed in the field of statistical modeling for measuring the variability of anatomical surfaces, could estimate patient-specific spatio-temporal continuous evolution for MR PWI (measured as mean transit time, (MTT)) and DWI lesions. In our representative pilot sample, the model fitted the data well. Our dynamic analysis of lesion evolution showed different patterns; for example, some DWI/PWI dynamic changes corresponded with DWI lesion expansion into PWI lesions, but other patterns were much more complex and diverse. There was wide variation in the time when the final tissue damage was reached after stroke for DWI and MTT.

Parallel perfusion imaging processing using GPGPU

Background and purpose The objective of brain perfusion quantification is to generate parametric maps of relevant hemodynamic quantities such as cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) that can be used in diagnosis of acute stroke. These calculations involve deconvolution operations that can be very computationally expensive when using local Arterial Input Functions (AIF). As time is vitally important in the case of acute stroke, reducing the analysis time will reduce the number of brain cells damaged and increase the potential for recovery. Methods GPUs originated as graphics generation dedicated co-processors, but modern GPUs have evolved to become a more general processor capable of executing scientific computations. It provides a highly parallel computing environment due to its large number of computing cores and constitutes an affordable high performance computing method. In this paper, we will present the implementation of a deconvolution algorithm for brain perfusion quantification on GPGPU (General Purpose Graphics Processor Units) using the CUDA programming model. We present the serial and parallel implementations of such algorithms and the evaluation of the performance gains using GPUs. Results Our method has gained a 5.56 and 3.75 speedup for CT and MR images respectively. Conclusions It seems that using GPGPU is a desirable approach in perfusion imaging analysis, which does not harm the quality of cerebral hemodynamic maps but delivers results faster than the traditional computation.