Decreased Quantitative Cerebral Blood Volume Is Associated With Poor Outcomes in Large Core Patients.

BACKGROUND: Recent large core trials have highlighted the effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke with large vessel occlusion. Variable perfusion-imaging thresholds and poor Alberta Stroke Program Early Computed Tomography Score reliability underline the need for more standardized, quantitative ischemia measures for MT patient selection. We aimed to identify the computed tomography perfusion parameter most strongly associated with poor outcomes in patients with acute ischemic stroke-large vessel occlusion with significant ischemic cores. METHODS: In this study from 2 comprehensive stroke centers from 2 comprehensive stroke centers within the Johns Hopkins Medical Enterprise (Johns Hopkins Hospita-East Baltimore and Bayview Medical Campus) from July 29, 2019 to January 29, 2023 in a continuously maintained database, we included patients with acute ischemic stroke-large vessel occlusion with ischemic core volumes defined as relative cerebral blood flow <30% and ≥50 mL on computed tomography perfusion or Alberta Stroke Program Early Computed Tomography Score <6. We used receiver operating characteristics to find the optimal cutoff for parameters like cerebral blood volume (CBV) <34%, 38%, 42%, and relative cerebral blood flow >20%, 30%, 34%, 38%, and time-to-maximum >4, 6, 8, and 10 seconds. The primary outcome was unfavorable outcomes (90-day modified Rankin Scale score 4-6). Multivariable models were adjusted for age, sex, diabetes, baseline National Institutes of Health Stroke Scale, intravenous thrombolysis, and MT. RESULTS: We identified 59 patients with large ischemic cores. A receiver operating characteristic curve analysis showed that CBV<42% ≥68 mL is associated with unfavorable outcomes (90-day modified Rankin Scale score 4-6) with an area under the curve of 0.90 (95% CI, 0.82-0.99) in the total and MT-only cohorts. Dichotomizing at this CBV threshold, patients in the ≥68 mL group exhibited significantly higher relative cerebral blood flow, time-to-maximum >8 and 10 seconds volumes, higher CBV volumes, higher HIR, and lower CBV index. The multivariable model incorporating CBV<42% ≥68 mL predicted poor outcomes robustly in both cohorts (area under the curve for MT-only subgroup was 0.87 [95% CI, 0.75-1.00]). CONCLUSIONS: CBV<42% ≥68 mL most effectively forecasts poor outcomes in patients with large-core stroke, confirming its value alongside other parameters like time-to-maximum in managing acute ischemic stroke-large vessel occlusion.

Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data.

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

Refining hemodynamic correction in in vivo wide-field fluorescent imaging through linear regression analysis.

Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

PURPOSE: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. METHODS: Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single-slice iVASO, and the reproducibility of whole-brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall-superparamagnetic-iron-oxides-enhanced MRI to validate its arterial origin. RESULTS: 3D iVASO scans showed signal-to-noise ratio (SNR) and CBVa measures consistent with single-slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole-brain 3D iVASO scan with a motion-sensitized-driven-equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well-suppressed signals in venous vessels. CONCLUSION: A whole-brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion-sensitized-driven-equilibrium-based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO.

Enhanced parameter estimation in multiparametric arterial spin labeling using artificial neural networks.

PURPOSE: Multiparametric arterial spin labeling (MP-ASL) can quantify cerebral blood flow (CBF) and arterial cerebral blood volume (CBVa). However, its accuracy is compromised owing to its intrinsically low SNR, necessitating complex and time-consuming parameter estimation. Deep neural networks (DNNs) offer a solution to these limitations. Therefore, we aimed to develop simulation-based DNNs for MP-ASL and compared the performance of a supervised DNN (DNNSup), physics-informed unsupervised DNN (DNNUns), and the conventional lookup table method (LUT) using simulation and in vivo data. METHODS: MP-ASL was performed twice during resting state and once during the breath-holding task. First, the accuracy and noise immunity were evaluated in the first resting state. Second, CBF and CBVa values were statistically compared between the first resting state and the breath-holding task using the Wilcoxon signed-rank test and Cliff's delta. Finally, reproducibility of the two resting states was assessed. RESULTS: Simulation and first resting-state analyses demonstrated that DNNSup had higher accuracy, noise immunity, and a six-fold faster computation time than LUT. Furthermore, all methods detected task-induced CBF and CBVa elevations, with the effect size being larger with the DNNSup (CBF, p = 0.055, Δ = 0.286; CBVa, p = 0.008, Δ = 0.964) and DNNUns (CBF, p = 0.039, Δ = 0.286; CBVa, p = 0.008, Δ = 1.000) than that with LUT (CBF, p = 0.109, Δ = 0.214; CBVa, p = 0.008, Δ = 0.929). Moreover, all the methods exhibited comparable and satisfactory reproducibility. CONCLUSION: DNNSup outperforms DNNUns and LUT with respect to estimation performance and computation time.

Automatic removal of large blood vasculature for objective assessment of brain tumors using quantitative dynamic contrast-enhanced magnetic resonance imaging.

The presence of a normal large blood vessel (LBV) in a tumor region can impact the evaluation of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and tumor classification. Hence, there is a need for automatic removal of LBVs from brain tissues including intratumoral regions for achieving an objective assessment of tumors. This retrospective study included 103 histopathologically confirmed brain tumor patients who underwent MRI, including DCE-MRI data acquisition. Quantitative DCE-MRI analysis was performed for computing various parameters such as wash-out slope (Slope-2), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), blood plasma volume fraction (Vp), and volume transfer constant (Ktrans). An approach based on data-clustering algorithm, morphological operations, and quantitative DCE-MRI maps was proposed for the segmentation of normal LBVs in brain tissues, including the tumor region. Here, three widely used data-clustering algorithms were evaluated on two types of quantitative maps: (a) Slope-2, and (b) a new proposed combination of rCBV and Slope-2 maps. Fluid-attenuated inversion recovery-MRI hyperintense lesions were also automatically segmented using deep learning-based architecture. The accuracy of LBV segmentation was qualitatively assessed blindly by two experienced observers, and Likert scoring was also obtained from each individual and compared using Cohen's Kappa test, and multiple statistical features from quantitative DCE-MRI parameters were obtained in the segmented tumor. t-test and receiver operating characteristic (ROC) curve analysis were performed for comparing the effect of removal of LBVs on parameters as well as on tumor grading. k-means clustering exhibited better accuracy and computational efficiency. Tumors, in particular high-grade gliomas (HGGs), showed a high contrast compared with normal tissues (relative % difference = 18.5%) on quantitative maps after the removal of LBVs. Statistical features (95th percentile values) of all parameters in the tumor region showed a statistically significant difference (p < 0.05) between with and without LBV maps. Similar results were obtained for the ROC curve analysis for differentiation between low-grade gliomas and HGGs. Moreover, after the removal of LBVs, the rCBV, rCBF, and Vp maps show better visualization of tumor regions.

Differentiating IDH-mutant astrocytomas and 1p19q-codeleted oligodendrogliomas using DSC-PWI: high performance through cerebral blood volume and percentage of signal recovery percentiles.

OBJECTIVE: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. METHODS: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010-2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. RESULTS: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. CONCLUSIONS: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. CLINICAL RELEVANCE STATEMENT: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. KEY POINTS: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification.

High relative cerebral blood volume is associated with good long term clinical outcomes in acute ischemic stroke: a retrospective cohort study.

BACKGROUND: Endovascular therapy for acute ischemic stroke has been shown to be highly effective in selected patients. However, the ideal criteria for patient selection are still debated. It is well known that collateral flow is an important factor, but the assessment is often subjective and time-consuming. Relative cerebral blood volume (rCBV) is a putative indicator of collateral capacity and can be quickly and easily determined by automated quantitative analysis. We investigated the relationship between rCBV of the affected region and clinical outcome in patients with acute ischemic stroke after endovascular therapy. METHODS: We conducted a retrospective study on consecutive patients between January 2017 and May 2019. Patients with acute ischemic stroke of the anterior circulation who underwent imaging including computed tomography perfusion and were treated with mechanical thrombectomy (MT) were eligible for inclusion. rCBV was calculated automatically with RAPID software by dividing the average cerebral blood volume (CBV) of the affected region (time-to-maximum (Tmax) > 6 s) by the CBV of the unaffected contralateral side. The primary outcome was determined by the modified Rankin Scale (mRS) after 90 days. Good clinical outcome was defined as mRS ≤ 2. We compared means, performed mono- and multivariate logistical regression and calculated a receiver operating characteristic (ROC)-analysis to determine the ideal cutoff value to predict clinical outcomes. RESULTS: 155 patients were enrolled in this study. 66 patients (42.58%) had good clinical outcomes. Higher rCBV was associated with good clinical outcome (p < 0.001), even after adjustment for the patients' status according to mRS and National Institute of Health Stroke Scale (NIHSS) age and Alberta stroke program early computed tomography score (ASPECTS) at baseline (p = 0.006). ROC-analysis revealed 0.650 (confidence interval: 0.616-0.778) as the optimal cutoff value. CONCLUSION: Higher rCBV at baseline is associated with good clinical long-term outcomes in patients with acute ischemic stroke treated by MT. In this study we provide the biggest collective so far that gives evidence that rCBV can be a valuable tool to identify patients who might benefit from MT and are able give a threshold to help to offer patients MT in borderline cases.

DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions.

PURPOSE: The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. METHODS: This retrospective study, spanning 2016-2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. RESULTS: The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. CONCLUSION: Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma's pure edema.

Precision and normal values of cerebral blood volume in preterm neonates using time-resolved near-infrared spectroscopy.

AIM: To investigate cerebral blood volume (CBV) in preterm neonates using time-resolved near-infrared spectroscopy. METHODS: In this prospective observational study, time-resolved near-infrared spectroscopy measurements of CBV using tNIRS-1 were performed in 70 preterm neonates. For measurements, a sensor was placed for a duration of 1 min, followed by four further reapplications of the sensor, overall five measurements. RESULTS: In this study, 70 preterm neonates with a mean ± SD gestational age of 33.4 ± 1.7 weeks and a birthweight of 1931 ± 398 g were included with a postnatal age of 4.7 ± 2.0 days. Altogether, 2383 CBV values were obtained with an overall mean of 1.85 ± 0.30 mL/100 g brain. A total of 95% of the measured CBV values varied in a range from -0.31 to 0.33 from the overall individual mean. Taking the deviation of the mean of each single application for each patient, this range reduced from -0.07 to 0.07. The precision of the measurement defined as within-variation in CBV was 0.24 mL/100 g brain. CONCLUSION: The overall mean CBV in stable preterm neonates was 1.85 ± 0.30 mL/100 g brain. The within-variation in CBV was 0.24 mL/100 g brain. Based on the precision obtained by our data, CBV of 1.85 ± 0.30 mL/100 g brain may be assumed as normal value for this cohort.

Analysis of prefrontal cerebral blood volume and flow changes in ESKD patients undergoing hemodialysis using functional near-infrared spectroscopy.

BACKGROUND: End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. METHODS: ESKD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 - HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. RESULTS: Thirty hemodialysis patients were analyzed. The change in HbO2, HbT, and HbD levels showed significant differences according to the hemodialysis period. Between the pre-HD and post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p = .046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p = .029). Additionally, between pre-HD and post-HD periods, HbD tended to increase (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p = .094). CONCLUSIONS: We demonstrated that during one hemodialysis session, the relative change in prefrontal CBV increased post-HD compared with pre-HD. These results are expected to help understanding the mechanisms underlying the effects of hemodialysis on brain function.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

Quantitative Cerebral Blood Volume Image Synthesis from Standard MRI Using Image-to-Image Translation for Brain Tumors.

Background Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced (DSC) MRI are useful but not commonly available in clinical scenarios. Purpose To test image-to-image translation techniques for generating CBV maps from standard MRI sequences of brain tumors using the bookend technique DSC MRI as ground-truth references. Materials and Methods A total of 756 MRI examinations, including quantitative CBV maps produced from bookend DSC MRI, were included in this retrospective study. Two algorithms, the feature-consistency generative adversarial network (GAN) and three-dimensional encoder-decoder network with only mean absolute error loss, were trained to synthesize CBV maps. The performance of the two algorithms was evaluated quantitatively using the structural similarity index (SSIM) and qualitatively by two neuroradiologists using a four-point Likert scale. The clinical value of combining synthetic CBV maps and standard MRI scans of brain tumors was assessed in several clinical scenarios (tumor grading, prognosis prediction, differential diagnosis) using multicenter data sets (four external and one internal). Differences in diagnostic and predictive accuracy were tested using the z test. Results The three-dimensional encoder-decoder network with T1-weighted images, contrast-enhanced T1-weighted images, and apparent diffusion coefficient maps as the input achieved the highest synthetic performance (SSIM, 86.29% ± 4.30). The mean qualitative score of the synthesized CBV maps by neuroradiologists was 2.63. Combining synthetic CBV with standard MRI improved the accuracy of grading gliomas (standard MRI scans area under the receiver operating characteristic curve [AUC], 0.707; standard MRI scans with CBV maps AUC, 0.857; z = 15.17; P < .001), prediction of prognosis in gliomas (standard MRI scans AUC, 0.654; standard MRI scans with CBV maps AUC, 0.793; z = 9.62; P < .001), and differential diagnosis between tumor recurrence and treatment response in gliomas (standard MRI scans AUC, 0.778; standard MRI scans with CBV maps AUC, 0.853; z = 4.86; P < .001) and brain metastases (standard MRI scans AUC, 0.749; standard MRI scans with CBV maps AUC, 0.857; z = 6.13; P < .001). Conclusion GAN image-to-image translation techniques produced accurate synthetic CBV maps from standard MRI scans, which could be used for improving the clinical evaluation of brain tumors. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Branstetter in this issue.

Relationship of cerebral blood volume with arterial and venous flow velocities in extremely low-birth-weight infants.

Unstable cerebral blood flow is theorised to contribute to the occurrence of intraventricular haemorrhage (IVH) in extremely low-birth-weight infants (ELBWIs), which can be caused by increased arterial flow, increased venous pressure, and impaired autoregulation of brain vasculature. As a preliminary step to investigate such instability, we aimed to check for correlations of cerebral blood volume (CBV), as measured using near-infrared spectroscopy, with the flow velocities of the anterior cerebral artery (ACA) and internal cerebral vein (ICV), as measured using Doppler ultrasonography. Data were retrospectively analysed from 30 ELBWIs uncomplicated by symptomatic patent ductus arteriosus, which can influence ACA velocity, and severe IVH (grade ≥ 3), which can influence ICV velocity and CBV. The correlation between tissue oxygen saturation (StO2) and mean blood pressure was also analysed as an index of autoregulation. CBV was not associated with ACA velocity; however, it was significantly correlated with ICV velocity (Pearson R = 0.59 [95% confidence interval: 0.29-0.78], P = 0.00061). No correlation between StO2 and mean blood pressure was observed, implying that autoregulation was not impaired.    Conclusion: Although our findings are based on the premise that cerebral autoregulation was unimpaired in the ELBWIs without complications, the same result cannot be directly applied to severe IVH cases. However, our results may aid future research on IVH prediction by investigating the changes in CBV when severe IVH occurs during ICV velocity fluctuation. What is Known: • The pathogenesis of IVH includes unstable cerebral blood flow affected by increased arterial flow, increased venous pressure, and impaired cerebral autoregulation. • The approaches that can predict IVH are under discussion. What is New: • ACA velocity is not associated with CBV, but ICV velocity is significantly correlated with CBV. • CBV measured using NIRS may be useful in future research on IVH prediction.

Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI.

Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.

Hypoperfusion intensity ratio and CBV index as predictive parameters to identify underlying intracranial atherosclerotic stenosis in endovascular thrombectomy.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion (LVO) is difficult to diagnose before endovascular thrombectomy (EVT) in an emergency. We hypothesized that hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index reflect collateral flow and would be useful parameters to predict underlying ICAS. MATERIALS AND METHODS: Clinical and perfusion imaging parameters of patients receiving EVT for LVO were reviewed retrospectively. Patients were divided into ICAS and embolism groups with angiographical findings. The association between prespecified parameters and underlying ICAS were assessed using multivariable logistic regression analyses. Discriminative ability was assessed using receiver operating characteristic analysis. RESULTS: Among 238 consecutive patients, 47 satisfied the inclusion criteria, including 10 with ICAS-related LVO. In ROC analyses, HIR showed good discrimination with a cutoff value of 0.22 (area under the curve, 0.85; 95%CI, 0.75-0.96; sensitivity, 0.84; specificity, 0.80) for underlying ICAS. CBV index showed excellent discrimination with a cutoff value of 0.90 (area under the curve, 0.92; 95%CI, 0.81-0.98; sensitivity, 0.92; specificity, 0.79). Multivariable logistic regression analysis revealed that HIR ≤ 0.22 (OR, 22.5; 95%CI, 2.9-177.0; P = 0.003) and CBV index ≥ 0.9 (OR, 75.7; 95%CI, 5.8-994.0; P < 0.001) were significantly associated with underlying ICAS. CONCLUSION: HIR ≤ 0.22 and CBV index ≥ 0.9 were associated with underlying ICAS and may predict underlying ICAS before EVT.

Whole-brain 3D mapping of oxygen metabolism using constrained quantitative BOLD.

Quantitative BOLD (qBOLD) MRI permits noninvasive evaluation of hemodynamic and metabolic states of the brain by quantifying parametric maps of deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), and along with a measurement of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2). The method, thus should have potential to provide important information on many neurological disorders as well as normal cerebral physiology. One major challenge in qBOLD is to separate deoxyhemoglobin's contribution to R2' from other sources modulating the voxel signal, for instance, R2, R2' from non-heme iron (R'2,nh), and macroscopic magnetic field variations. Further, even with successful separation of the several confounders, it is still challenging to extract DBV and Yv from the heme-originated R2' because of limited sensitivity of the qBOLD model. These issues, which have not been fully addressed in currently practiced qBOLD methods, have so far precluded 3D whole-brain implementation of qBOLD. Thus, the purpose of this work was to develop a new 3D MRI oximetry technique that enables robust qBOLD parameter mapping across the entire brain. To achieve this goal, we employed a rapid, R2'-sensitive, steady-state 3D pulse sequence (termed 'AUSFIDE') for data acquisition, and implemented a prior-constrained qBOLD processing pipeline that exploits a plurality of preliminary parameters obtained via AUSFIDE, along with additionally measured cerebral venous blood volume. Numerical simulations and in vivo studies at 3 T were performed to evaluate the performance of the proposed, constrained qBOLD mapping in comparison to the parent qBOLD method. Measured parameters (Yv, DBV, R'2,nh, nonblood magnetic susceptibility) in ten healthy subjects demonstrate the expected contrast across brain territories, while yielding group-averages of 64.0 ± 2.3 % and 62.2 ± 3.1 % for Yv and 2.8 ± 0.5 % and 1.8 ± 0.4 % for DBV in cortical gray and white matter, respectively. Given the Yv measurements, additionally quantified CBF in seven of the ten study subjects enabled whole-brain 3D CMRO2 mapping, yielding group averages of 134.2 ± 21.1 and 79.4 ± 12.6 µmol/100 g/min for cortical gray and white matter, in good agreement with literature values. The results suggest feasibility of the proposed method as a practical and reliable means for measuring neurometabolic parameters over an extended brain coverage.

Comparing BOLD and VASO-CBV population receptive field estimates in human visual cortex.

Vascular Space Occupancy (VASO) is an alternative fMRI approach based on changes in Cerebral Blood Volume (CBV). VASO-CBV fMRI can provide higher spatial specificity than the blood oxygenation level-dependent (BOLD) method because the CBV response is thought to be limited to smaller vessels. To investigate how this technique compares to BOLD fMRI for cognitive neuroscience applications, we compared population receptive field (pRF) mapping estimates between BOLD and VASO-CBV. We hypothesized that VASO-CBV would elicit distinct pRF properties compared to BOLD. Specifically, since pRF size estimates also depend on vascular sources, we hypothesized that reduced vascular blurring might yield narrower pRFs for VASO-CBV measurements. We used a VASO sequence with a double readout 3D EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the visual cortex while participants viewed conventional pRF mapping stimuli. Both VASO-CBV and BOLD images show similar eccentricity and polar angle maps across all participants. Compared to BOLD-based measurements, VASO-CBV yielded lower tSNR and variance explained. The pRF size changed with eccentricity similarly for VASO-CBV and BOLD, and the pRF size estimates were similar for VASO-CBV and BOLD, even when we equate variance explained between VASO-CBV and BOLD. This result suggests that the vascular component of the pRF size is not dominating in either VASO-CBV or BOLD.

Cortical layer-specific differences in stimulus selectivity revealed with high-field fMRI and single-vessel resolution optical imaging of the primary visual cortex.

The mammalian neocortex exhibits a stereotypical laminar organization, with feedforward inputs arriving primarily into layer 4, local computations shaping response selectivity in layers 2/3, and outputs to other brain areas emanating via layers 2/3, 5 and 6. It cannot be assumed a priori that these signatures of laminar differences in neuronal circuitry are reflected in hemodynamic signals that form the basis of functional magnetic resonance imaging (fMRI). Indeed, optical imaging of single-vessel functional responses has highlighted the potential limits of using vascular signals as surrogates for mapping the selectivity of neural responses. Therefore, before fMRI can be employed as an effective tool for studying critical aspects of laminar processing, validation with single-vessel resolution is needed. The primary visual cortex (V1) in cats, with its precise neuronal functional micro-architecture, offers an ideal model system to examine laminar differences in stimulus selectivity across imaging modalities. Here we used cerebral blood volume weighted (wCBV) fMRI to examine if layer-specific orientation-selective responses could be detected in cat V1. We found orientation preference maps organized tangential to the cortical surface that typically extended across depth in a columnar fashion. We then examined arterial dilation and blood velocity responses to identical visual stimuli by using two- and three- photon optical imaging at single-vessel resolution-which provides a measure of the hemodynamic signals with the highest spatial resolution. Both fMRI and optical imaging revealed a consistent laminar response pattern in which orientation selectivity in cortical layer 4 was significantly lower compared to layer 2/3. This systematic change in selectivity across cortical layers has a clear underpinning in neural circuitry, particularly when comparing layer 4 to other cortical layers.

Separating spin compartments in arterial spin labeling using delays alternating with nutation for tailored excitation (DANTE) pulse: A validation study using T2 -relaxometry and application to arterial cerebral blood volume imaging.

PURPOSE: To clarify the type of spin compartment in arterial spin labeling (ASL) that is eliminated by delays alternating with nutation for tailored excitation (DANTE) pulse using T2 -relaxometry, and to demonstrate the feasibility of arterial cerebral blood volume (CBVa ) imaging using DANTE-ASL in combination with a simplified two-compartment model. METHOD: The DANTE and T2 -preparation modules were combined into a single ASL sequence. T2 values under the application of DANTE were determined to evaluate changes in T2 , along with the post-labeling delay (PLD) and the relationship between transit time without DANTE (TTnoVS ) and T2 . The reference tissue T2 (T2_ref ) was also obtained. Subsequently, the DANTE module was embedded into the Hadamard-encoded ASL. Cerebral blood flow (CBF) and CBVa were computed using two Hadamard-encoding datasets (with and without DANTE) in a rest and breath-holding (BH) task. RESULTS: While T2 without DANTE (T2_noVS ) decreased as the PLD increased, T2 with DANTE (T2_DANTE ) was equivalent to T2_ref and did not change with the PLD. Although there was a significant positive correlation between TTnoVS and T2_noVS with short PLD, T2_DANTE was not correlated with TTnoVS nor PLD. Baseline CBVa values obtained at rest were 0.64 ± 0.12, 0.64 ± 0.11, and 0.58 ± 0.15 mL/100 g for anterior, middle, and posterior cerebral arteries, respectively. Significant CBF and CBVa elevations were observed in the BH task. CONCLUSION: Microvascular compartment signals were eliminated from the total ASL signals by DANTE. CBVa can be measured using Hadamard-encoded DANTE-ASL in combination with a simplified two-compartment model.