Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.

Introduction: Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.

Methods: We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo MRI, to investigate early capillary dysfunction in Tg-SwDI mice without memory impairment.

Diffusional kurtosis imaging as a possible prognostic marker of cervical incomplete spinal cord injury outcome: a prospective pilot study.

Background: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue.

Theophylline as an Add-On to Thrombolytic Therapy in Acute Ischemic Stroke: A Randomized Placebo-Controlled Trial.

Background And Purpose: Delayed recanalization increases the risk of infarct growth and poor clinical outcome in acute ischemic stroke. The vasoactive agent theophylline has shown neuroprotective effects in animal stroke models but inconclusive results in case series and randomized clinical trials. The primary objective of this study was to evaluate whether theophylline, as an add-on to thrombolytic therapy, is safe and effective in acute ischemic stroke patients.

Comparison of classification methods for tissue outcome after ischaemic stroke.

In acute ischaemic stroke, identifying brain tissue at high risk of infarction is important for clinical decision-making. This tissue may be identified with suitable classification methods from magnetic resonance imaging data. The aim of the present study was to assess and compare the performance of five popular classification methods (adaptive boosting, logistic regression, artificial neural networks, random forest and support vector machine) in identifying tissue at high risk of infarction on human voxel-based brain imaging data.

Bayesian modeling of Dynamic Contrast Enhanced MRI data in cerebral glioma patients improves the diagnostic quality of hemodynamic parameter maps.

Purpose: The purpose of this work is to investigate if the curve-fitting algorithm in Dynamic Contrast Enhanced (DCE) MRI experiments influences the diagnostic quality of calculated parameter maps.

Material And Methods: We compared the Levenberg-Marquardt (LM) and a Bayesian method (BM) in DCE data of 42 glioma patients, using two compartmental models (extended Toft's and 2-compartment-exchange model). Logistic regression and an ordinal linear mixed model were used to investigate if the image quality differed between the curve-fitting algorithms and to quantify if image quality was affected for different parameters and algorithms.

Transit time homogenization in ischemic stroke - A novel biomarker of penumbral microvascular failure?

Cerebral ischemia causes widespread capillary no-flow in animal studies. The extent of microvascular impairment in human stroke, however, is unclear. We examined how acute intra-voxel transit time characteristics and subsequent recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126 acute ischemic stroke patients.

The effects of hypercapnia on cortical capillary transit time heterogeneity (CTH) in anesthetized mice.

Capillary flow patterns are highly heterogeneous in the resting brain. During hyperemia, capillary transit-time heterogeneity (CTH) decreases, in proportion to blood's mean transit time (MTT) in passive, compliant microvascular networks. Previously, we found that functional activation reduces the CTH:MTT ratio, suggesting that additional homogenization takes place through active neurocapillary coupling mechanisms.

MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter.

Background: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI.

Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.

Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH).

Functional hyperemia reduces oxygen extraction efficacy unless counteracted by a reduction of capillary transit-time heterogeneity of blood. We adapted a bolus tracking approach to capillary transit-time heterogeneity estimation for two-photon microscopy and then quantified changes in plasma mean transit time and capillary transit-time heterogeneity during forepaw stimulation in anesthetized mice (C57BL/6NTac). In addition, we analyzed transit time coefficient of variance = capillary transit-time heterogeneity/mean transit time, which we expect to remain constant in passive, compliant microvascular networks.

Does b1000-b0 Mismatch Challenge Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery Mismatch in Stroke?

Background And Purpose: Our aim was to explore whether the mismatch in lesion visibility between b1000 and b0 images is an alternative to mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery imaging as a surrogate marker of stroke age.

Methods: We analyzed patients from the European multicenter I-KNOW database. Independent readers assessed the visibility of ischemic lesions of the anterior circulation on b0 and fluid-attenuated inversion recovery imaging images.

Sequential MR Assessment of the Susceptibility Vessel Sign and Arterial Occlusion in Acute Stroke.

Purpose: Susceptibility vessel sign (SVS) may likely influence recanalization after thrombolysis. We assessed, through the European sequential MRI database "I-KNOW," the relationship between the presence of SVS on T2-weighted gradient echo imaging, its angiographic counterpart on magnetic resonance angiography and its subsequent impact on recanalization after thrombolysis.

Materials And Methods: Initial clinical and MRI characteristics and early follow up were analyzed in acute ischemic stroke patients treated with rt-Pa within 4.

Evaluation of Early Reperfusion Criteria in Acute Ischemic Stroke.

Background And Purpose: Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion criteria that predicts clinical outcome in ischemic stroke.

Reperfusion within 6 hours outperforms recanalization in predicting penumbra salvage, lesion growth, final infarct, and clinical outcome.

Background And Purpose: The relative merits of reperfusion versus recanalization to predict tissue and clinical outcomes in anterior circulation stroke have been previously assessed using data acquired >12 hours postonset. To avoid late-occurring confounders such as non-nutritional reperfusion, futile recanalization and no-reflow phenomenon, we performed ultraearly assessment of reperfusion and recanalization.

Methods: From a multicenter prospective database, 46 patients with acute magnetic resonance angiography-visible occlusion and in whom both reperfusion and recanalization were assessed on follow-up magnetic resonance imaging ≤6 hours of symptom onset were identified.

Biased visualization of hypoperfused tissue by computed tomography due to short imaging duration: improved classification by image down-sampling and vascular models.

Objectives: Lesion detection in acute stroke by computed-tomography perfusion (CTP) can be affected by incomplete bolus coverage in veins and hypoperfused tissue, so-called bolus truncation (BT), and low contrast-to-noise ratio (CNR). We examined the BT-frequency and hypothesized that image down-sampling and a vascular model (VM) for perfusion calculation would improve normo- and hypoperfused tissue classification.

Methods: CTP datasets from 40 acute stroke patients were retrospectively analysed for BT.

The impact of reliable prebolus T 1 measurements or a fixed T 1 value in the assessment of glioma patients with dynamic contrast enhancing MRI.

Introduction: Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T 1 prior to contrast injection (T 1). We evaluate (i) T 1 estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T 1 value when differentiating high- from low-grade gliomas.

Methods: The accuracy and precision of T 1 measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.

Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI.

Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST.

The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage.

The mortality after aneurysmal subarachnoid hemorrhage (SAH) is 50%, and most survivors suffer severe functional and cognitive deficits. Half of SAH patients deteriorate 5 to 14 days after the initial bleeding, so-called delayed cerebral ischemia (DCI). Although often attributed to vasospasms, DCI may develop in the absence of angiographic vasospasms, and therapeutic reversal of angiographic vasospasms fails to improve patient outcome.

Very low cerebral blood volume predicts parenchymal hematoma in acute ischemic stroke.

Background And Purpose: Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization.

The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia.

Infarction of 'non-core-non-penumbral' tissue after stroke: multivariate modelling of clinical impact.

There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e.

Predicting infarction within the diffusion-weighted imaging lesion: does the mean transit time have added value?

Background And Purpose: There is ample evidence that in anterior circulation stroke, the diffusion-weighted imaging (DWI) lesion may escape infarction and thus is not a reliable infarct predictor. In this study, we assessed the predictive value of the mean transit time (MTT) for final infarction within the DWI lesion, first in patients scanned back-to-back with 15O-positron emission tomography and MR (DWI and perfusion-weighted imaging; "Cambridge sample") within 7 to 21 hours of clinical onset, then in a large sample of patients with anterior circulation stroke receiving DWI and perfusion-weighted imaging within 12 hours (85% within 6 hours; "I-KNOW sample").

Methods: Both samples underwent structural MRI at approximately 1 month to map final infarcts.