CBF) And Volume Research Articles

Deep Learning for Perfusion Cerebral Blood Flow (CBF) and Volume (CBV) Predictions and Diagnostics

Dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) is a non-invasive imaging technique for hemodynamic measurements. Various perfusion parameters, such as cerebral blood volume (CBV) and cerebral blood flow (CBF), can be derived from DSC-MRP, hence this non-invasive imaging protocol is widely used clinically for the diagnosis and assessment of intracranial pathologies. Currently, most institutions use commercially available software to compute the perfusion parametric maps. However, these conventional methods often have limitations, such as being time-consuming and sensitive to user input, which can lead to inconsistent results; this highlights the need for a more robust and efficient approach like deep learning. Using the relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) perfusion maps generated by FDA-approved software, we trained a multistage deep learning model. The model, featuring a combination of a 1D convolutional neural network (CNN) and a 2D U-Net encoder-decoder network, processes each 4D MRP dataset by integrating temporal and spatial features of the brain for voxel-wise perfusion parameters prediction. An auxiliary model, with similar architecture, but trained with truncated datasets that had fewer time-points, was designed to explore the contribution of temporal features. Both qualitatively and quantitatively evaluated, deep learning-generated rCBV and rCBF maps showcased effective integration of temporal and spatial data, producing comprehensive predictions for the entire brain volume. Our deep learning model provides a robust and efficient approach for calculating perfusion parameters, demonstrating comparable performance to FDA-approved commercial software, and potentially mitigating the challenges inherent to traditional techniques.

Quantitative Hemodynamic Measurements in Cortical Vessels Using Functional Ultrasound Imaging.

Red blood cell velocity (RBCv), cerebral blood flow (CBF), and volume (CBV) are three key parameters when describing brain hemodynamics. Functional ultrasound imaging is a Doppler-based method allowing for real-time measurement of relative CBV at high spatiotemporal resolution (100 × 110 × 300 μm3, up to 10 Hz) and large scale. Nevertheless, the measure of RBCv and CBF in small cortical vessels with functional ultrasound imaging remains challenging because of their orientation and size, which impairs the ability to perform precise measurements. We designed a directional flow filter to overpass these limitations allowing us to measure RBCv in single vessels using a standard functional ultrasound imaging system without contrast agents (e.g., microbubbles). This method allows to quickly extract the number of vessels in the cortex that was estimated to be approximately 650/cm3 in adult rats, with a 55–45% ratio for penetrating arterioles versus ascending venules. Then, we analyzed the changes in RBCv in these vessels during forepaw stimulation. We observed that ∼40 vessels located in the primary somatosensory forelimb cortex display a significant increase of the RBCv (median ΔRBCv ∼15%, maximal ΔRBCv ∼60%). As expected, we show that RBCv was higher for penetrating arterioles located in the center than in the periphery of the activated area. The proposed approach extends the capabilities of functional ultrasound imaging, which may contribute to a better understanding of the neurovascular coupling at the brain-wide scale.

Abstract WMP17: Computerized Tomography Perfusion to Characterize Lack of Clinical Improvement After Recanalization in Acute Ischemic Stroke

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

BackgroundThis study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD).Material/MethodsWhole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system.ResultsFifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00–9.98 mL/100 g/min and CBV 0.00–0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity.In the non-brain-dead group, CTP results revealed CBF 2.37–37.59 mL/100 g/min and CBV 0.73–2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31–1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31–1.00) for CTA in diagnosis of BD.ConclusionsWhole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Computed Tomography Perfusion is a\xa0Useful Adjunct to Computed Tomography Angiography in the Diagnosis of Brain Death

BackgroundIn the diagnosis of brain death (BD), computed tomography angiography (CTA) results in some cases show intracranial filling, leading to diagnostic confusion. Because cerebral circulatory arrest commences at the capillary level, we hypothesized that computed tomography perfusion (CTP) would be a more sensitive approach than CTA; therefore, the aim of the study was to compare the sensitivities of CTP and CTA in the diagnosis of BD.Material and MethodsWhole brain CTP was performed in patients in the intensive care unit diagnosed with BD and CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. The CTP findings were interpreted as being consistent with a diagnosis of BD (positive) when CBF and CBV in all regions of interest (ROIs) were below 10 ml/100 g/min and 1.0 ml/100 g, respectively. The CTA findings were interpreted using a 4-point grading system.ResultsA total of 50 patients were included in the study. The CTP results revealed CBF from 0.00 to 9.98 ml/100 g/min (mean, 1.98 ± 1.68 ml/100 g/min) and CBV from 0.00 to 0.99 ml/100 g (mean, 0.14 ± 0.12 ml/100 g) and were thus interpreted as positive in all 50 patients. In contrast, the CTA results suggested 7 negative cases, providing a sensitivity of 86%. The difference between the CTP and CTA sensitivity results for the diagnosis of BD was statistically significant (p = 0.006).ConclusionWhole brain CTP may potentially be a feasible and highly sensitive test for diagnosing BD: therefore, performing CTP in combination with CTA in cases when CTA results are negative for BD could increase the sensitivity of CTA.

Effects of reduced oxygen availability on the vascular response and oxygen consumption of the activated human visual cortex.

To identify the impact of reduced oxygen availability on the evoked vascular response upon visual stimulation in the healthy human brain by magnetic resonance imaging (MRI). Functional MRI techniques based on arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and vascular space occupancy (VASO)-dependent contrasts were utilized to quantify the BOLD signal, cerebral blood flow (CBF), and volume (CBV) from nine subjects at 3T (7M/2F, 27.3 ± 3.6 years old) during normoxia and mild hypoxia. Changes in visual stimulus-induced oxygen consumption rates were also estimated with mathematical modeling. Significant reductions in the extension of activated areas during mild hypoxia were observed in all three imaging contrasts: by 42.7 ± 25.2% for BOLD (n = 9, P = 0.002), 33.1 ± 24.0% for ASL (n = 9, P = 0.01), and 31.9 ± 15.6% for VASO images (n = 7, P = 0.02). Activated areas during mild hypoxia showed responses with similar amplitude for CBF (58.4 ± 18.7% hypoxia vs. 61.7 ± 16.1% normoxia, P = 0.61) and CBV (33.5 ± 17.5% vs. 25.2 ± 13.0%, P = 0.27), but not for BOLD (2.5 ± 0.8% vs. 4.1 ± 0.6%, P = 0.009). The estimated stimulus-induced increases of oxygen consumption were smaller during mild hypoxia as compared to normoxia (3.1 ± 5.0% vs. 15.5 ± 15.1%, P = 0.04). Our results demonstrate an altered vascular and metabolic response during mild hypoxia upon visual stimulation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:142-149.

FMRI and electrophysiology of cortical layer-dependent processes in primary sensory cortex

To understand cortical function, it is important to better understand the cortical functional units, i.e., its columns and layers. High-resolution fMRI can offer tremendous advantages for the study of cortical circuits in vivo, evidenced by the increasing interest in high-resolution fMRI. However, many questions remain about the size of the cortical features that can be resolved, and how neural activity gives rise to the blood oxygenation dependent (BOLD) signal measured with fMRI. We use high-resolution fMRI combined with electrophysiology to study laminar processing, with the aim of gaining insight into the layer-dependent neural processing and the mechanisms of neurovascular coupling in the primary visual cortex (V1) and temporal lobe of awake and anesthetized macaques. We investigated whether laminar differences in the BOLD, cerebral blood flow (CBF), and volume (CBV) responses can be detected for excitatory and inhibitory stimuli, and found that the mechanisms for positive and negative BOLD responses differ, but also that neurovascular coupling differs in the cortical layers. Furthermore, neuromodulators such as dopamine can alter neurovascular coupling. Our results suggest that neurovascular coupling depends on multiple factors, and that the combination of high-resolution fMRI with electrophysiology can be used to resolve neurovascular coupling in functional microcircuits.

Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes

Understanding how changes in the cardiovascular system contribute to cerebral blood flow (CBF) and volume (CBV) increases is critical for interpreting hemodynamic signals. Here we investigated how systemic cardiovascular changes affect the cortical hemodynamic response during voluntary locomotion. In the mouse, voluntary locomotion drives an increase in cortical CBF and arterial CBV that is localized to the forelimb/hindlimb representation in the somatosensory cortex, as well as a diffuse venous CBV increase. To determine if the heart rate increases that accompany locomotion contribute to locomotion-induced CBV and CBF increases, we occluded heart rate increases with the muscarinic cholinergic receptor antagonist glycopyrrolate, and reduced heart rate with the β1-adrenergic receptor antagonist atenolol. We quantified the effects of these cardiovascular manipulations on CBV and CBF dynamics by comparing the hemodynamic response functions (HRF) to locomotion across these conditions. Neither the CBF HRF nor the arterial component of the CBV HRF was significantly affected by pharmacological disruption of the heart rate. In contrast, the amplitude and spatial extent of the venous component of the CBV HRF were decreased by atenolol. These results suggest that the increase in venous CBV during locomotion was partially driven by peripheral cardiovascular changes, whereas CBF and arterial CBV increases associated with locomotion reflect central processes.

Comparing perfusion CT evaluation algorithms for predicting outcome after endovascular treatment in anterior circulation ischaemic stroke

To analyse perfusion CT (PCT) evaluation algorithms for their predictive value for outcome after endovascular therapy (ET) in acute ischaemic stroke. Twenty-six patients were prospectively enrolled to undergo endovascular therapy for moderate to severe [National Institute of Health Stroke Scale (NIHSS) score of ≥5] anterior circulation stroke ≤6 h of onset. PCT datasets were evaluated according to three algorithms: visual mismatch estimate (VME), Alberta Stroke Programme Early CT Score (ASPECTS) perfusion, and quantitative perfusion ratios (QPRs: RCBF, RCBV) of cerebral blood flow (CBF) and volume (CBV). Results were correlated with outcome measures [NIHSS score at discharge, NIHSS score change until discharge (ΔNIHSSA/D), mRS at 90 days (mRS90d)] and compared with a matched control group. Recanalization was achieved in 73%, median NIHSS score decreased from 14 to 5 at discharge. The treatment and control group did not differ by VME and ASPECTS perfusion, nor did VME correlate with any of the three outcome measures. ASPECTS perfusion was not predictive of any outcome measure in the ET group. RCBF and RCBV were associated with ΔNIHSSA/D in controls and, inversely, the ET group, but not with mRS90d. Receiver operating characteristic (ROC) analysis of RCBF (and RCBV) showed a positive predictive and negative predictive value of 87% (78%) and 74% (73%), respectively, for discriminating major neurological improvement (ΔNIHSSA/D <7 versus ≥7). Implementation of QPRs for CBF and CBV are superior to clinically used VME and ASPECTS perfusion evaluation methods for predicting early outcome after ET for anterior circulation stroke.

Maximizing negative correlations in resting-state functional connectivity MRI by time-lag.

This paper aims to better understand the physiological meaning of negative correlations in resting state functional connectivity MRI (r-fcMRI). The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. Consequently, neuronal regulation of brain circulation may be deduced from the valence of r-fcMRI connectivity.

Cerebral small-resistance artery structure and cerebral blood flow in normotensive subjects and hypertensive patients.

The aim of this study was to prospectively investigate whether the structure of cerebral small-resistance arteries is related to cerebral perfusion parameters as measured with dynamic susceptibility-weighted contrast magnetic resonance imaging (DSC-MRI) in a selected cohort of hypertensive and normotensive patients. Ten hypertensive and 10 normotensive patients were included in the study. All patients underwent neurosurgical intervention for an intracranial tumor and were investigated with DSC-MRI at 1.5 T. Cerebral small-resistance arteries were dissected from a small portion of morphologically normal cerebral tissue and mounted on an isometric myograph for the measurement of the media-to-lumen (M/L) ratio. A quantitative assessment of cerebral blood flow (CBF) and volume (CBV) was performed with a region-of-interest approach. Correlation coefficients were calculated for normally distributed variables. The institutional review board approved the study, and informed consent was obtained from all patients. Compared with normotensive subjects, hypertensive patients had significantly lower regional CBF (mL/100 g/min) in the cortical grey matter (55.63 ± 1.90 vs 58.37 ± 2.19, p < 0.05), basal ganglia (53.34 ± 4.39 vs 58.22. ± 4.33, p < 0.05), thalami (50.65 ± 3.23 vs 57.56 ± 4.45, p < 0.01), subcortical white matter (19.32 ± 2.54 vs 22.24 ± 1.9, p < 0.05), greater M/L ratio (0.099 ± 0.013 vs 0.085 ± 0.012, p < 0.05), and lower microvessel density (1.66 ± 0.67 vs 2.52 ± 1.28, p < 0.05). A statistically significant negative correlation was observed between M/L ratio of cerebral arteries and CBF in the cortical grey matter (r = -0.516, p < 0.05), basal ganglia (r = -0.521, p < 0.05), thalami (r = -0.527 p < 0.05), and subcortical white matter (r = -0.612, p < 0.01). Our results indicate that microvascular structure might play a role in controlling CBF, with possible clinical consequences.

Three-dimensional acquisition of cerebral blood volume and flow responses during functional stimulation in a single scan

In addition to the BOLD scan, quantitative functional MRI studies require measurement of both cerebral blood volume (CBV) and flow (CBF) dynamics. The ability to detect CBV and CBF responses in a single additional scan would shorten the total scan time and reduce temporal variations. Several approaches for simultaneous CBV and CBF measurement during functional MRI experiments have been proposed in two-dimensional (2D) mode covering one to three slices in one repetition time (TR). Here, we extended the principles from previous work and present a three-dimensional (3D) whole-brain MRI approach that combines the vascular-space-occupancy (VASO) and flow-sensitive alternating inversion recovery (FAIR) arterial spin labeling (ASL) techniques, allowing the measurement of CBV and CBF dynamics, respectively, in a single scan. 3D acquisitions are complicated for such a scan combination as the time to null blood signal during a steady state needs to be known. We estimated this using Bloch simulations and demonstrate that the resulting 3D acquisition can detect activation patterns and relative signal changes of quality comparable to that of the original separate scans. The same was found for temporal signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). This approach provides improved acquisition efficiency when both CBV and CBF responses need to be monitored during a functional task.

Cerebral Perfusion Changes in Chronic Subdural Hematoma

To the Editor: With interest we have read the recent article of Slotty and colleagues. They performed computed tomography (CT) perfusion imaging in patients with chronic subdural hemorrhage to investigate global and local (hematoma-related) cortical perfusion and volume parameters and their association with neurological deficits. Mildly affected patients (median National Institutes of Health Stroke Scale of 3) before surgical decompression were included, unfortunately without reporting clinical or radiological follow-up.1 In our opinion, their interpretation and statement that intact local brain perfusion autoregulation is present in these patients seems preliminary for several reasons. First, dimensionless “relative” values of cerebral blood flow (CBF) and volume (CBV) in presumed vascular territories were used. It is not clear what served as the reference region of interest for this calculation. Using (mirrored parts of) the compressed contralateral hemisphere is not ideal. Therefore, conclusions regarding hyperaemia, oligaemia, or autoregulation status as explanations for their group-averaged findings (and individual associations with neurological deficits) is, in our opinion, not possible.2 Second, the researchers state that the brain maintains normal perfusion despite the overlying hematoma, which is contrary to their findings of a significant difference between the CBF and CBV values below the hematoma and the contralateral hemisphere. A simultaneous increase in CBF and CBV does not imply intact autoregulation, which is a mechanism of maintaining stability of CBF, and has not been previously reported to lead overshoot and hyperemia. Conversely, with hypertension (blood-pressure values were not measured in this cohort), the observed increases in CBF and CBV could represent local vasoparalysis and pressure passivity (i.e., impaired autoregulation).3 On the other hand, these findings could be a consequence of factors such as the release of vasoactive substances from the hematoma or venous congestion resulting from outflow obstruction caused by the hematoma, which were not discussed.4 Third, CBF and CBV were increased in the cortex below the hematoma, but global perfusion was comparable between the hemispheres. To accomplish the latter, cortical areas with reduced or elevated CBF and CBV have to be present elsewhere in the brain or the cortical hyperemia is just small and, overall, did not significantly contribute to the whole-hemisphere values.4 Fourth, the interpretation of mean transit time as abnormal in both hemispheres is dangerous because, in the referred study, no patient data could be found.5 And finally, the exclusion of more-severe patients limits the generalizability of their observation, in particular, because deteriorating patients are expected to show more-severe autoregulation disturbances. Performing a perfusion CT in combination with the obligatory unenhanced CT brain is not expected to cause major delay before surgical decompression.2 The comparison of perfusion parameters of compressed cortical tissue between mildly and severely affected patients would provide at least some support of the assumptions in the discussion and conclusion (increased local intracranial pressure, intact autoregulation, or symptomatic borderline perfusion).

Erythropoietin prevents delayed hemodynamic dysfunction after subarachnoid hemorrhage in a randomized controlled experimental setting

IntroductionErythropoietin (EPO) was proven as a promising approach for experimental subarachnoid hemorrhage (SAH). Clinical data are, however, inconclusive so far. A detailed characterization of specific EPO effects could facilitate the design of trials. The aim of the present investigation was, therefore, to characterize these effects on prevention of delayed proximal cerebral vasospasm (CVS), impaired microcirculation and cerebral blood flow (CBF) after experimental SAH. Methods27 male Sprague–Dawley rats were randomized in 3 groups: Sham, SAH control, and SAH EPO. SAH was induced by injection of 0.2ml autologous blood into the cisterna magna on days 1 and 2. Animals of the SAH EPO group received 5000iU rh EPO α 6h after the 2nd SAH intravenously. Surviving animals were examined on day 5 by MR perfusion weighted imaging (PWI). Cerebral blood flow (CBF) and volume (CBV) were determined by PWI, proximal CVS by basilar artery (BA) diameter, and neuroprotection by hippocampal cell count (CA1–CA4). ResultsBA diameter was significantly reduced in both SAH groups, but improved significantly after EPO (Sham: 144±3μm, SAH control: 79±6μm, SAH EPO 109±4μm). The rrCBV ratio was 8.78±0.72 Sham, 5.14±1.73 SAH control, and 6.80±0.44 SAH EPO. The improvement by EPO did not reach statistical significance. RrCBF ratio was also significantly reduced in both SAH groups, but was significantly improved by EPO (Sham: 8.78±0.34, SAH control: 4.26±1.05, SAH EPO 5.85±0.46). Surviving neuronal cells were significantly reduced in SAH controls in all areas, but in SAH EPO only in CA1. ConclusionThe present data suggest that an EPO application in a timely distance to the SAH is sufficient to prevent delayed proximal CVS, but that the doses were insufficient to improve microcirculation or to be directly neuroprotective.

Flat-panel volumetric computed tomography in cerebral perfusion: Evaluation of three rat stroke models

Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to three-dimensional small animal imaging. The capability of volumetric scanning and a high resolution in time and space enables whole organ perfusion studies. We aimed to assess feasibility and validity of fpVCT in cerebral perfusion measurement with impaired hemodynamics by evaluation of three well-established rat stroke models for temporary and permanent middle cerebral artery occlusion (MCAO).Male Wistar rats were randomly assigned to temporary (group I: suture model) and permanent (group II: suture model; III: macrosphere model) MCAO and to a control group. Perfusion scans with respect to cerebral blood flow (CBF) and volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry rotation time of 1s and a total scanning time of 30s. Postmortem analysis included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC) staining.Infarct volumes did not differ significantly throughout intervention groups. After permanent MCAO, CBF significantly decreased in subcortical regions to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was less impaired with temporary vessel occlusion. CBV measurement revealed no significant differences.Results demonstrate feasibility of cerebral perfusion quantification in rats with the fpVCT, which can be a useful tool for non-invasive dynamic imaging of cerebral perfusion in rodent stroke models. In addition to methodological advantages, CBF data confirm the macrosphere model as a useful alternative to the suture model for permanent experimental MCAO.

Improvements in the Quantitative Assessment of Cerebral Blood Volume and Flow with the Removal of Vessel Voxels from MR Perfusion Images

Objective. To improve the quantitative assessment of cerebral blood volume (CBV) and flow (CBF) in the brain voxels from MR perfusion images. Materials and Methods. Normal brain parenchyma was automatically segmented with the time-to-peak criteria after cerebrospinal fluid removal and preliminary vessel voxel removal. Two scaling factors were calculated by comparing the relative CBV and CBF of the segmented normal brain parenchyma with the absolute values in the literature. Using the scaling factors, the relative values were converted to the absolute CBV and CBF. Voxels with either CBV > 8 mL/100 g or CBF > 100 mL/100 g/min were characterized as vessel voxels and were excluded from the quantitative measurements. Results. The segmented brain parenchyma with normal perfusion was consistent with the angiographic findings for each patient. We confirmed the necessity of dual thresholds including CBF and CBV for proper removal of vessel voxels. The scaling factors were 0.208 ± 0.041 for CBV, and 0.168 ± 0.037, 0.172 ± 0.037 for CBF calculated using standard and circulant singular value decomposition techniques, respectively. Conclusion. The automatic scaling and vessel removal techniques provide an alternative method for obtaining improved quantitative assessment of CBV and CBF in patients with thromboembolic cerebral arterial disease.

Evaluating quantitative approaches to dynamic susceptibility contrast MRI among carotid endarterectomy patients

To evaluate two dynamic susceptibility contrast (DSC) quantification methods in symptomatic carotid artery disease patients undergoing carotid endarterectomy (CEA) surgery by comparing methods directly and assessing the reliability of each method in the hemisphere contralateral to surgery. Absolute cerebral blood flow (CBF) and volume (CBV) was calculated in putamen and sensorimotor gray matter of 17 patients using two methods: 1) The Bookend method that scales relative DSC images to CBV values calculated from the ratio of pre- and postcontrast T1-weighted images, and 2) the Tail-scaling method that uses the ratio of area under the tails of the venous and arterial concentration time-courses to scale the DSC images. There was a positive correlation between the methods with significant correlation post-CEA (P < 0.035). Intersession correlation was greater when using the Tail-scaling method contralateral to surgery (P < 0.004). We have demonstrated correlation between methods that is significant after surgery and have found that the Tail-scaling method produces better test-retest reliability than our implementation of the Bookend method. Results from this study suggest that DSC has the potential to measure hemodynamic changes after endarterectomy and future work is required to establish clinical value.

Visualization of Altered Neurovascular Coupling in Chronic Stroke Patients using Multimodal Functional MRI

Evaluation of cortical reorganization in chronic stroke patients requires methods to accurately localize regions of neuronal activity. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is frequently employed; however, BOLD contrast depends on specific coupling relationships between the cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and volume (CBV), which may not exist following stroke. The aim of this study was to understand whether CBF-weighted (CBFw) and CBV-weighted (CBVw) fMRI could be used in sequence with BOLD to characterize neurovascular coupling mechanisms poststroke. Chronic stroke patients (n=11) with motor impairment and age-matched controls (n=11) performed four sets of unilateral motor tasks (60 seconds/30 seconds off/on) during CBFw, CBVw, and BOLD fMRI acquisition. While control participants elicited mean BOLD, CBFw, and CBVw responses in motor cortex (P<0.01), patients showed only mean changes in CBF (P<0.01) and CBV (P<0.01), but absent mean BOLD responses (P=0.20). BOLD intersubject variability was consistent with differing coupling indices between CBF, CBV, and CMRO(2). Thus, CBFw and/or CBVw fMRI may provide crucial information not apparent from BOLD in these patients. A table is provided outlining distinct vascular and metabolic uncoupling possibilities that elicit different BOLD responses, and the strengths and limitations of the multimodal protocol are summarized.

Changes in Cerebral Perfusion around the Time of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage Patients

Background: Because the pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear, we studied cerebral perfusion at different time points around the occurrence of DCI. Methods: We prospectively enrolled 53 patients admitted to the University Medical Center Utrecht who underwent CT perfusion (CTP) scans on admission, and within 2 weeks after hemorrhage on 2 scheduled time points or during clinical deterioration. The occurrence of DCI was assessed according to predefined criteria by 2 neurological observers blinded to perfusion results. Clinically stable patients (no-DCI) served as reference, and patients with other causes of deterioration (n = 11) were excluded. In DCI patients, the day of DCI onset and in no-DCI patients the median day of DCI onset was taken as t = 0. Scans made before and after DCI were clustered into 5 additional time points. At each time point, cerebral blood volume (CBV) and flow (CBF), and mean transit time (MTT) were measured, and absolute and relative (interhemispheric asymmetry) values were compared between DCI and no-DCI patients. Results: Absolute CBF was lower and MTT was higher in the 18 DCI patients than in the 24 no-DCI patients before, during and after DCI. MTT asymmetry increased during DCI and partially recovered afterwards in DCI patients while it remained constant in no-DCI patients. Absolute and relative CBV remained constant in both groups. Conclusions: Our findings suggest that DCI patients already have diffusely worse perfusion (absolute values) than no-DCI patients before focal worsening (increased asymmetry) occurs and becomes symptomatic. The partial recovery in the measured areas suggests that DCI can be partly reversible.

MRI measurement of the BOLD-specific flow–volume relationship during hypercapnia and hypocapnia in humans

It is widely assumed in fMRI that the relationship between cerebral blood flow (CBF) and volume (CBV) changes observed during end-tidal CO 2 (PETCO 2) perturbations is equivalent to that elicited by neuronal activation. This assumption has been validated in PET studies insofar as relating total flow to total CBV changes, but remains unconfirmed for venous CBV changes, which pertains to the primary vascular compartment modulating the BOLD signal. In this study, we measured CBF and venous CBV changes in healthy subjects in response to graded hypercapnia and hypocapnia, induced using computerized end-tidal CO 2 targeting, with a ΔPETCO 2 range of between − 6 and + 9 mm Hg. Hypercapnia was found to elicit robust increases in CBF and venous CBV, while hypocapnia produced decreases in both. We used steady-state flow and volume changes to estimate the power–law relationship for cortical and subcortical brain regions, and did not observe significant difference between the two. The combined fit resulted in a power coefficient of 0.18 ± 0.02, substantially lower than Grubb's coefficient of 0.38, but comparable to previous observations during neuronal activation. These results confirm that the BOLD-specific flow–volume relationship during CO 2 challenges is similar to that characterizing neuronal activation.