Can the ischemic penumbra be identified on noncontrast CT of acute stroke?

<p><b>Background and Purpose:</b> Early ischemic changes on noncontrast CT in acute stroke include both hypoattenuation and brain swelling, which may have different pathophysiological significance.</p> <p><b>Methods:</b> Noncontrast CT and CT perfusion brain scans from patients with suspected acute stroke <6 hours after onset were reviewed. Five raters independently scored noncontrast CTs blind to clinical data using the Alberta Stroke Program Early CT Score (ASPECTS). Each ASPECTS region was scored as hypodense or swollen. A separate reviewer measured time to peak and cerebral blood volume in each ASPECTS region on CT perfusion. Time to peak and cerebral blood volume were compared for each region categorized as normal, hypodense, or isodense and swollen.</p> <p><b>Results:</b> Scans of 32 subjects a median 155 minutes after onset yielded 228 regions with both CT perfusion and noncontrast CT data. Isodense swelling was associated with significantly higher cerebral blood volume (P=0.016) and with penumbral perfusion (posttest:pretest likelihood ratio 1.44 [95% CI: 0.68 to 2.90]), whereas hypodensity was associated with more severe time to peak delay and with core perfusion (likelihood ratio 3.47 [95% CI: 1.87 to 6.34]). Neither isodense swelling nor hypodensity was sensitive for prediction of perfusion pattern, but appearances were highly specific (87.2% and 91.0% for penumbra and core, respectively). Intrarater agreement was good or excellent, but interrater agreement for both hypodensity and swelling was poor.</p> <p><b>Conclusions:</b> Regions exhibiting hypoattenuation are likely to represent the infarct core, whereas regions that are isodense and swollen have increased cerebral blood volume and are more likely to signify penumbral perfusion. Although noncontrast CT is not sensitive for detection of core and penumbra, appearances are specific. Some information on tissue viability can therefore be obtained from noncontrast CT.</p&gt

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside. (c) 2006 Elsevier Inc. All rights reserved

Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice

The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (ΔCBV) as one correlate of neuronal and neurovascular activities. In this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-typemice. Cocaine acts to block the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional ΔCBV in brain structures involved inmediating reward in both DAT genotypes. The largest effects (−20% to −30% ΔCBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated ΔCBV amplitudes, shortened times to peak response, and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice

Optoelectronic Neural Implant Sensors for Cerebral Blood Volume Monitoring

Nearly 50 million people are afflicted with epilepsy, worldwide. These patients suffer from unprovoked seizures, where neurons in the cerebral cortex under go uncontrolled, hypersynchronous firing of neurons. 30\% of patients with epilepsy do not respond to drug treatments. For these patients, surgical treatment involving the removal or disconnection of brain matter is one of the only alternatives. Such surgical treatments often rely on long-term monitoring of neuronal activity in the brain using subdurally implanted surface electrodes to locate the epileptic focus, but these clinical methods for mapping neuronal activity suffer from low spatial resolutions and poor noise, which can limit the success of surgical treatments where an error of even 1 mm can be critical. The work described here involves the development of an implantable system for performing optical recordings of intrinsic signal (ORIS) on the surface of the brain. By taking advantage of the unique absorption spectrum of hemoglobin, cerebral blood volume (CBV) can be measured via reflectivity changes in the brain at at specific wavelengths of light. Due to the metabolic demands of the brain, the exaggerated neuronal activity and spiking associated with epileptic seizures can be detected indirectly through changes in CBV. While high resolution ORIS measurements have been recorded using externally mounted CCD sensors, this work presents some of the first developments in producing a fully implantable ORIS sensor. Progress in the development of an implantable ORIS sensor described here includes: an implantable organic light emitting diode (OLED) and organic photodetector (OPD) integrated on a highly flexible parylene-c substrate, an implantable sensor using a microLED array embedded on a flexible polyimide substrate, and the application of quantum dots to microLEDs for optical down-conversion. Successful in vivo detection of seizures is achieved with high signal-to-noise using these methods. Additionally, spatial localization of seizure activity is performed using the microLED array. These developments represent crucial first steps in the development of a full 2D neuronal mapping system using implantable ORIS devices

Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours

INTRODUCTION: The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the −1p/−19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy. METHODS: Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12–15, and 10q22–26 and p53 mutation (exons 5–8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33). RESULTS: 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student’s t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The −1p/−19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss. CONCLUSION: rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the −1p/−19q genotype

FUNCTIONAL MR OF BRAIN ACTIVITY AND PERFUSION IN PATIENTS WITH CHRONIC CORTICAL STROKE

PURPOSE: (1) To determine whether functional MR can reliably map functional deficits in patients with stroke in the primary visual cortex; (2) to determine whether functional MR can reliably map perfusion deficits; and (3) to determine whether functional MR can give any additional diagnostic information beyond conventional MR. METHODS: Seven patients who had had a stroke in their primary visual system were examined using two functional MR techniques: (1) dynamic susceptibility contrast imaging, and (2) cortical activation mapping during full-field visual stimulation. Maps of relative cerebral blood volume and activation were created and compared with visual field examinations and conventional T2-weighted images on a quadrant-by-quadrant basis in five of these patients. RESULTS: Visual field mapping matched with both T2-weighted conventional images and activation mapping of 16 of 18 quadrants. In two quadrants, the activation maps detected abnormalities that were present on the visual field examination but not present on the T2-weighted images nor on the relative cerebral blood volume maps, which may indicate abnormal function without frank infarction. In addition, the activation maps demonstrated decreased activation in extrastriate cortex and had normal T2 signal and relative cerebral blood volume but was adjacent to infarcted primary cortex, mapping in vivo how stroke in one location can affect the function of distant tissue. CONCLUSION: Functional MR techniques can accurately map functional and perfusion deficits and thereby provide additional clinically useful information. Additional studies will be needed to determine the prognostic utility of functional MR in stroke patients

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL.

Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF

Magnetic resonance imaging of local and remote vascular remodelling after experimental stroke.

The pattern of vascular remodelling in relation to recovery after stroke remains largely unclear. We used steady-state contrast-enhanced magnetic resonance imaging to assess the development of cerebral blood volume and microvascular density in perilesional and exofocal areas from (sub)acutely to chronically after transient stroke in rats. Microvascular density was verified histologically after infusion with Evans Blue dye. At day 1, microvascular cerebral blood volume and microvascular density were reduced in and around the ischemic lesion (intralesional borderzone: microvascular cerebral blood volume = 72 ± 8%; microvascular density = 76 ± 8%) (P < 0.05), while total cerebral blood volume remained relatively unchanged. Perilesional microvascular cerebral blood volume and microvascular density subsequently normalized (day 7) and remained relatively stable (day 70). In remote ipsilateral areas in the thalamus and substantia nigra - not part of the ischemic lesion - microvascular density gradually increased between days 1 and 70 (thalamic ventral posterior nucleus: microvascular density = 119 ± 9%; substantia nigra: microvascular density = 122 ± 8% (P < 0.05)), which was confirmed histologically. Our data indicate that initial microvascular collapse, with maintained collateral flow in larger vessels, is followed by dynamic revascularization in perilesional tissue. Furthermore, progressive neovascularization in non-ischemic connected areas may offset secondary neuronal degeneration and/or contribute to non-neuronal tissue remodelling. The complex spatiotemporal pattern of vascular remodelling, involving regions outside the lesion territory, may be a critical endogenous process to promote post-stroke brain reorganization.FSW – Publicaties zonder aanstelling Universiteit Leide

Perfusion CT to evaluate the effect of transluminal angioplasty on cerebral perfusion in the treatment of vasospasm after subarachnoid hemorrhage

INTRODUCTION: Delayed ischemic neurologic deficits secondary to vasospasm are a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Treatment of vasospasm after SAH is associated with complications, and reliable techniques for evaluating effects of treatment of vasospasm in such patients are warranted. We present the use of perfusion computed tomography (PTC) to evaluate the effect of transluminal percutaneous angioplasty in a with SAH and vasospasm-induced ischemia. METHODS: Dynamic PCT with deconvolution produced maps of time-to-peak, mean transit time, regional cerebral blood flow, and regional cerebral blood volume, with a computerized automated map of the infarct and penumbra. CT scanners with quadruple detector array were used before and after angioplasty. RESULTS: Before angioplasty and intraarterial papaverine, PCT showed normal to decreased cerebral blood flow and increased cerebral blood volume and mean transit time in the middle cerebral artery territory of the left hemisphere. After angioplasty and intraarterial papaverine, PCT showed normalization of perfusion parameters. CONCLUSION: PCT can be a useful technique in monitoring angioplasty treatment effects in patients with vasospasm after SA