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As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1–2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.

BOLD fMRI is widely applied in human neuroscience but is limited in its spatial specificity due to a cortical-depth-dependent venous bias. This reduces its localization specificity with respect to neuronal responses, a disadvantage for neuroscientific research. Here, we modified a submillimeter BOLD protocol to selectively reduce venous and tissue signal and increase cerebral blood volume weighting through a pulsed saturation scheme (dubbed Arterial Blood Contrast) at 7 T. Adding Arterial Blood Contrast on top of the existing BOLD contrast modulated the intracortical contrast. Isolating the Arterial Blood Contrast showed a response free of pial-surface bias. The results suggest that Arterial Blood Contrast can modulate the typical fMRI spatial specificity, with important applications in in-vivo neuroscience. CA extern

Magnetic resonance imaging (MRI) features of meningiomas typically reveal a well-circumscribed and contrast-enhancing dural mass. Here we discuss the differences in MRI findings between typically benign and atypical meningioma, and their clinical implications. An MRI of a 67-year-old man revealed a substantial homogeneous enhancing tumor nodule. The MRI also showed two components in the tumor, and the regional cerebral blood volume (rCBV) was higher in the lateral than in the medial mass. A pathological examination also revealed features of both benign and atypical meningiomas. The Ki-67 labeling index was 1% on the medial side and 5% on the lateral side. There were clearly two components within the tumor mass, and the MRI revealed differential rCBV in the tumor. The results indicated a nontypical MRI of meningiomas, allowing for predictability of atypical meningiomas using MRI before surgical resection.

Despite providing cerebral tissue oxygen saturation (StOTo investigate if the additional monitoring of cerebral blood volume by TD-NIRS facilitates the understanding of cerebral hemodynamic conditions in patients with congenital heart disease.Preoperative TD-NIRS values were retrospectively reviewed in patients who underwent a cardiac surgery or catheter examination. We compared the values between patients with single and two ventricles. Moreover, we investigated the association of these values with the demographic and clinical variables.There was no significant difference in StO2 between single ventricle and two ventricles groups (median: 59.9 vs. 54.4, median difference [95% CI]: -4.06 [-9.90 to 2.90], p = .37). However, cerebral blood volume was significantly higher in the single ventricle group (median: 4.68 vs. 2.84, median difference [95% CI]: -2.01 [-2.88 to -1.06], p .001). Spearman's rank correlation analysis demonstrated an association between StO2 and postmenstrual age (r = 0.35, p = .03). In contrast, cerebral blood volume was correlated with single ventricle physiology (r = 0.62, p .001), postmenstrual age (r = 0.74, p .001), central venous pressure (r = 0.38, p = .02), and SaO2 (r = -0.38, p = .02). The multivariable regression analysis identified the postmenstrual age, single ventricle physiology, and SaO2 as independent factors associated with cerebral blood volume. In the logistic analysis, cerebral blood volume was identified as a significant predictor of unfavorable conditions.Cerebral blood volume monitoring detected differences in cerebral hemodynamic conditions, related to the age and the type of ventricle physiologies. However, the differences were not apparent in StO

PURPOSE Dynamic susceptibility contrast (DSC)-MRI is a perfusion imaging technique from which useful quantitative imaging biomarkers can be derived. Relative cerebral blood volume (rCBV) is such a biomarker commonly used for evaluating brain tumors. To account for the extravasation of contrast agents in tumors, post-processing leakage correction is often applied to improve rCBV accuracy. Digital reference objects (DRO) are ideal for testing the post-processing software, because the biophysical model used to generate the DRO can be matched to the one that the software uses. This study aims to develop DROs to validate the leakage correction of software using Weisskoff model and to examine the effect of background signal time curves that are required by the model. METHODS Three DROs were generated using the Weisskoff model, each composed of nine foreground lesion objects with combinations of different levels of rCBV and contrast leakage parameter (K2). Three types of background were implemented for these DROs: (1) a multi-compartment brain-like background, (2) a sphere background with a constant signal time curve, and (3) a sphere background with signal time curve identical to that of the brain-like DRO's white matter (WM). The DROs were then analyzed with an FDA-cleared software with and without leakage correction. Leakage correction was tested with and without brain segmentation. RESULTS Accuracy of leakage correction was able to be verified using the brain-like phantom and the sphere phantom with WM background. The sphere with constant background did not perform well with leakage correction with or without brain segmentation. The DROs were able to verify that for the particular software tested, leakage correction with brain segmentation achieved the lowest error. CONCLUSIONS DSC-MRI DROs with biophysical model matched to that of the post-processing software can be well used for the software's validation, provided that the background signals are also properly simulated for generating the reference time curve required by the model. Care needs to be taken to consider the interaction of the design of the DRO with the software's implementation of brain segmentation to extract the reference time curve.

Background and Purpose: Basilar artery occlusion is associated with high morbidity and mortality. Optimal imaging and treatment strategy are still controversial and prognosis estimation challenging. We, therefore, aimed to determine the predictive value of computed tomography perfusion (CTP) parameters for functional outcome in patients with basilar artery occlusion in the context of endovascular treatment. Methods: Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score on noncontrast computed tomography, computed tomography angiography (CTA) source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps. Good functional outcome was defined as modified Rankin Scale score ≤3 at 90 days. Statistical analysis included binary logistic regressions and receiver operating characteristics analyses. Results: Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, National Institutes of Health Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome ( P Conclusions: CTP imaging parameters contain prognostic information for functional outcome in patients with stroke due to basilar artery occlusion and may identify patients with higher risk of disability at an early stage of hospitalization.

The benefit of endovascular treatment (EVT) for patients with low Alberta Stroke Program early computed tomography score (ASPECTS) is still ambiguous and is currently being investigated in randomized trials. Computed tomography (CT) perfusion, used to estimate infarct extent and progression, might predict early neurological improvement (ENI) after EVT. We hypothesized that the degree of relative cerebral blood volume (rCBV) reduction is directly associated with ENI in low ASPECTS patients undergoing EVT.Ischemic stroke patients with ASPECTS ≤ 5 who received multimodal CT and underwent thrombectomy were analyzed. rCBV reduction was defined as the ratio of cerebral blood volume (CBV), measured in the ischemic lesion to contralateral CBV. Complete reperfusion was defined as an expanded Thrombolysis in Cerebral Infarction score 2c-3. The clinical endpoint was ENI at 24 h, defined continuously (National Institutes of Health Stroke Scale [NIHSS] score change from baseline to 24 h) and binarized (NIHSS score at 24 h ≤ 8).A total of 102 patients were included. Lower rCBV reduction and complete EVT were independently associated with ENI (-11.4 NIHSS points, p = 0.04; -7.3 points, p lt; 0.0001, respectively). The effect of complete EVT on ENI was directly linked to the degree of rCBV reduction: the probability for binary ENI was +34.6% (p = 0.004) in patients with low rCBV reduction versus +8.2% (p = 0.28) in patients with high rCBV reduction).In patients with ischemic stroke with low ASPECTS, ENI was directly linked to the degree of rCBV reduction, a potential indicator of ischemia depth in extensive baseline infarction. Lower rCBV reduction was associated with higher probability of ENI after complete reperfusion, suggesting less pronounced lesion progression despite its large extent and hence, a higher susceptibility to EVT.

PURPOSE: To develop 3D MRI methods for cerebral blood volume (CBV) and venous cerebral blood volume (vCBV) estimation with whole-brain coverage using Fourier-transform based velocity-selective (FT-VS) pulse trains. METHODS: For CBV measurement, FT-VS saturation (FT-VSS) pulse trains were employed to suppress static tissue while CSF contamination was corrected voxel-by-voxel using a multi-readout acquisition and a fast CSF T(2) scan. The vCBV mapping was achieved by inserting an arterial-nulling module which included a FT-VS inversion (FT-VSI) pulse train. Using these methods, CBV and vCBV maps were obtained on six healthy volunteers at 3T. RESULTS: The mean CBV and vCBV values in gray matter and white matter in different areas of the brain showed high correlation (r = 0.95 and p < 0.0001). The averaged CBV and vCBV values of the whole-brain were 5.4±0.6 and 2.5±0.3 mL/100g in gray matter, and 2.6±0.5 and 1.5±0.2 mL/100g in white matter, respectively, comparable to the literature. CONCLUSION: The feasibility of FT-VS based CBV and vCBV estimation was demonstrated for 3D acquisition with large spatial coverage.

Background and purpose Meningiomas and schwannomas are common extra-axial brain tumors. Discrimination is challenging in some locations when characteristic imaging features are absent. This study investigated the accuracy of percentage signal recoveries obtained from dynamic susceptibility contrast perfusion imaging (DSC-PI) in discriminating meningiomas and schwannomas. Material and methods Retrospective database research was conducted. Sixty nine meningioma and 15 schwannoma having DSC-PI between January 2016 and February 2020 were included. Time to signal intensity curves (TSIC) were analyzed and grouped as T1-dominant leakage, T2*-dominant leakage and return to baseline. Relative cerebral blood volume (rCBV), relative mean transit time (rMTT), percentage signal recovery 1 (PSR 1) and PSR 2 values were calculated. The differences between the groups were investigated. Receiver operating characteristic curves were operated. Results rCBV, rMTT, PSR 1 and PSR 2 values were statistically different between meningiomas and schwannomas. PSR 2 provided the best discrimination. With the cut off value of 1.08 for PSR 2, meningiomas and schwannomas were differentiated with 95.7% sensitivity and 93.3% specificity. TSICs were also different between two groups. Most of meningiomas showed T2*-dominant leakage (78.2%), whereas most of shwannomas showed T1-dominant leakage (93.3%). Conclusion DSC-PI is a useful imaging tool for non-invasive discrimination of meningiomas and schwannomas. Particularly, percentage signal recoveries discriminates meningiomas and schwannomas with high sensitivity and specificity.

Tissue conductivity measurements made with electrical properties tomography (EPT) can be used to define temporal changes in tissue habitats on longitudinal multiparametric MRI. We aimed to demonstrate the added insights for identifying tumor habitats obtained by including EPT with diffusion- and perfusion-weighted MRI, and to evaluate the use of these tumor habitats for determining tumor treatment response in post-treatment glioblastoma. Tumor habitats were developed from EPT, diffusion-weighted, and perfusion-weighted MRI in 60 patients with glioblastoma who underwent concurrent chemoradiotherapy. Voxels from EPT, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps were clustered into habitats, and each habitat was serially examined to assess its temporal change. The usefulness of temporal changes in tumor habitats for diagnosing tumor progression and treatment-related change was investigated using logistic regression. The performance of significant predictors was measured using the area under the curve (AUC) from receiver-operating-characteristics analysis with 1000-fold bootstrapping. Five tumor habitats were identified, and of these, the hypervascular cellular habitat (odds ratio [OR] 5.45; 95% CI, 1.75–31.42; p = .02), hypovascular low conductivity habitat (OR 2.00; 95% CI, 1.45–3.05; p < .001), and hypovascular intermediate habitat (OR 1.57; 95% CI, 1.18–2.30; p = .006) were predictive of tumor progression. Low EPT and low CBV reflected a unique hypovascular low conductivity habitat that showed the highest diagnostic performance (AUC 0.86; 95% CI, 0.76–0.96). The combined habitats showed high performance (AUC 0.90; 95% CI, 0.82–0.98) in the differentiation of tumor progression from treatment-related change. EPT reveals low conductivity habitats that can improve the diagnosis of tumor progression in post-treatment glioblastoma. • Electrical properties tomography (EPT) demonstrated lower conductivity in tumor progression than in treatment-related change. • EPT allowed identification of a unique hypovascular low conductivity habitat when combined with cerebral blood volume mapping. • Tumor habitats with a hypovascular low conductivity habitat, hypervascular cellular habitat, and hypovascular intermediate habitat yielded high diagnostic performance for diagnosing tumor progression.

We assessed extracranial contamination of the near-infrared spectroscopy (NIRS) signal during administration of phenylephrine. The study was performed with NIRO 200NX which employs both the Modified Beer-Lambert (MBL) method to measure total hemoglobin (tHb, expressed in µM), and Spatially Resolved Spectroscopy (SRS) to measure total hemoglobin content (nTHI, expressed in arbitrary units (a.u.)). SRS tends to not be affected by extracranial blood flow. As vasoconstriction with phenylephrine mainly occurs in the extracranial area, we hypothesized that if NIRS measurements are indeed prone to extracranial contamination, tHb will be more affected by the administration of phenylephrine than nTHI. After ethical committee approval, 20 consenting cardiac surgery patients were included. Phenylephrine was administered whenever clinically indicated and its effect on nTHI and tHb was evaluated. To adjust for the difference in raw scale units, Z-scores were calculated. Data were analyzed with Wilcoxon Signed Ranks Test and the Hodges-Lehmann method. A total of 191 data sets were obtained in 20 patients (10 male, 65 ± 15 years, 77 ± 16 kg, 166 ± 11 cm). The median difference before and after administration of phenylephrine was − 0.006 a.u. [95%CI − 0.010 to − 0.002] (p

Purpose Oxygen extraction fraction (OEF) is a biomarker for the viability of brain tissue in ischemic stroke. However, acquisition of the OEF map using positron emission tomography (PET) with oxygen-15 gas is uncomfortable for patients because of the long fixation time, invasive arterial sampling, and radiation exposure. We aimed to predict the OEF map from magnetic resonance (MR) and PET images using a deep convolutional neural network (CNN) and to demonstrate which PET and MR images are optimal as inputs for the prediction of OEF maps. Methods Cerebral blood flow at rest (CBF) and during stress (sCBF), cerebral blood volume (CBV) maps acquired from oxygen-15 PET, and routine MR images (T1-, T2-, and T2*-weighted images) for 113 patients with steno-occlusive disease were learned with U-Net. MR and PET images acquired from the other 25 patients were used as test data. We compared the predicted OEF maps and intraclass correlation (ICC) with the real OEF values among combinations of MRI, CBF, CBV, and sCBF. Results Among the combinations of input images, OEF maps predicted by the model learned with MRI, CBF, CBV, and sCBF maps were the most similar to the real OEF maps (ICC: 0.597 ± 0.082). However, the contrast of predicted OEF maps was lower than that of real OEF maps. Conclusion These results suggest that the deep CNN learned useful features from CBF, sCBF, CBV, and MR images and predict qualitatively realistic OEF maps. These findings suggest that the deep CNN model can shorten the fixation time for 15O PET by skipping 15O2 scans. Further training with a larger data set is required to predict accurate OEF maps quantitatively.

Background Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). Purpose To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. Material and Methods A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. Results ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score ( PConclusion Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO2 were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases. PET/MRI measurements with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C15O), oxygen (15O2), and carbon dioxide (C15O2) were performed on nine healthy men. Two kinds of attenuation correction for PET were performed using MRI with Dixon sequence (DIXON) and Dixon sequence with model-based bone segmentation (DIXONbone). A real-time motion correction of PET images was also performed using simultaneously measured MR images to detect head motion. Mean and SD values of CBF, CBV, OEF, and CMRO2 in the cerebral cortices with attenuation correction by DIXON were 31 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.5 ± 0.3 mL/100 mL/min without real-time motion correction, and 33 ± 4 mL/100 mL/min, 2.7 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.6 ± 0.3 mL/100 mL/min with real-time motion correction, respectively. Values with of CBF, CBV, OEF, and CMRO2 with attenuation correction by DIXONbone were 35 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 2.8 ± 0.3 mL/100 mL/min without real-time motion correction, and 38 ± 5 mL/100 mL/min, 2.8 ± 0.2 mL/mL, 0.40 ± 0.07, and 3.0 ± 0.4 mL/100 mL/min with real-time motion correction, respectively. Using PET/MRI with oxygen-15 labeled gases, CBF, CBV, OEF, and CMRO2 could be measured. Values of CBF, CBV, and CMRO2 measured with attenuation correction by DIXON were significantly lower than those measured with correction by DIXONbone. One of the reasons for this is that attenuation correction of DIXON does not take into consideration of the photon absorption by bone. OEF values, corresponding to ratios of CMRO2 to CBF, were not affected by attenuation correction methods. Values of CBF and CMRO2 with a real-time motion correction were significantly higher than those without correction. Using PET/MRI with adequate corrections, similar values of CBF, CBV, OEF, and CMRO2 as PET alone scanner system reported previously were obtained. The UMIN clinical trial number: UMIN000033382.

While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia.

To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) ＜6 undergoing endovascular therapy (EVT).This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS ＜6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH.A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90 days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (n = 8) was higher than mRS 4-5 group (n = 14) (P＜0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (n = 5) and non-sICH group (n = 17).AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.

To investigate the predictive value of static O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET) and cerebral blood volume (CBV) for glioma grading and determining isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status. Fifty-two patients with newly diagnosed gliomas who underwent simultaneous 18F-FET PET and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) examinations on hybrid PET/MR were retrospectively enrolled. The mean and max tumor-to-brain ratio (TBR) and normalized CBV (nCBV) were calculated based on whole tumor volume segmentations with reference to PET/MR images. The predictive efficacy of FET PET and CBV in glioma according to the 2016 World Health Organization (WHO) classification was evaluated by receiver operating characteristic curve analyses with the area under the curve (AUC). TBRmean, TBRmax, nCBVmean, and nCBVmax differed between low- and high-grade gliomas, with the highest AUC of nCBVmean (0.920). TBRmax and nCBVmean showed significant differences between gliomas with and without IDH mutation (p = 0.032 and 0.010, respectively). Furthermore, TBRmean, TBRmax, and nCBVmean discriminated between IDH-wildtype glioblastomas and IDH-mutated astrocytomas (p = 0.049, 0.034 and 0.029, respectively). The combination of TBRmax and nCBVmean showed the best predictive performance (AUC, 0.903). Only nCBVmean differentiated IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas (p < 0.001) (AUC, 0.829), but none of the parameters discriminated between oligodendrogliomas and astrocytomas. Both FET PET and DSC-PWI might be non-invasive predictors for glioma grades and IDH mutation status. FET PET combined with CBV could improve the differentiation of IDH-mutated astrocytomas and IDH-wildtype glioblastomas. However, FET PET and CBV might be limited for identifying oligodendrogliomas. • Static 18F-FET PET and DSC-PWI parameters differed between low- and high-grade gliomas, with the highest AUC of the mean value of normalized CBV. • Static 18F-FET PET and DSC-PWI parameters based on hybrid PET/MR showed predictive value in identifying glioma IDH mutation subtypes, which have gained importance for both determining the diagnosis and prognosis of gliomas according to the 2016 WHO classification. • Static 18F-FET PET and DSC-PWI parameters have limited potential in differentiating IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas or IDH-mutated astrocytomas.

Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO2 responses were observed in premanifest and early manifest HD patients compared to controls ( P 2 = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

Purpose The vascular space occupancy (VASO) is a functional MRI technique for probing cerebral blood volume changes noninvasively, including during neuronal activation in humans. An important consideration when implementing VASO is the BOLD effect in the signal. Assessing the physical origin of this BOLD contamination and the capabilities of correction methods could improve the quantification of cerebral blood volume changes with VASO. Methods Given the heterogeneity of cerebral microvascular architecture, the vascular geometry within an MRI voxel can influence both BOLD and VASO signals. To investigate this effect, 3D high-resolution images of mouse cerebral vasculature measured with two-photon microscopy were used to model BOLD and VASO signals from first principles using Monte Carlo diffusion of water protons. Quantitative plots of VASO together with intravascular and extravascular BOLD signals as a function of TE at B0 fields 1.5 T to 14 T were obtained. Results The BOLD contamination of the VASO response was on the order of 50% for gradient echo and 5% for spin echo at 7 T and TE = 6 ms and significantly increased with TE and B0 . Two currently used correction schemes were shown to account for most of this contamination and recover accurate relative signal changes, with optimal correction obtained using TEs as short as possible. Conclusion These results may provide useful information for optimizing sequence parameters in VASO and BOLD functional MRI, leading the way to a wider application of these techniques in healthy and diseased brain.

Background and Purpose— Despite recanalization, almost 50% of patients undergoing endovascular treatment (EVT) experience poor outcome. We aim to evaluate the value of computed tomography perfusion as immediate outcome predictor postendovascular treatment. Methods— Consecutive patients receiving endovascular treatment who achieved recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] 2a-3) underwent computed tomography perfusion within 30 minutes from recanalization (CTPpost). Hypoperfusion was defined as the Tmax>6 second volume; hyperperfusion as visually increased cerebral blood flow/cerebral blood volume with reduced Tmax compared with unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. Delayed recovery was defined as no-DCR with favorable outcome (modified Rankin Scale score 0–2) at 3 months. Results— We included 151 patients: median National Institutes of Health Stroke Scale score 16 (interquartile range, 10–21), median admission ASPECTS 9 (interquartile range, 8–10). Final recanalization was the following: mTICI2a 11 (7.3%), mTICI2b 46 (30.5%), and mTICI3 94 (62.3%). On CTPpost, 80 (52.9%) patients showed hypoperfusion (median Tmax>6 seconds: 4 cc [0–25]) and 32 (21.2%) hyperperfusion. There was an association between final TICI and CTPpost hypoperfusion(median Tmax>6: 91 [56–117], 15 [0–37.5], and 0 [0–7] cc, for mTICI 2a, 2b, and 3, respectively, P P P P P Conclusions— Hypoperfusion on CTPpost constitutes an immediate accurate surrogate marker of success after endovascular treatment and identifies those patients with delayed recovery and favorable outcome.

PURPOSE Venous cerebral blood volume (CBVv ) is a major contributor to BOLD contrast, and therefore is an important parameter for understanding the underlying mechanism. Here, we propose a velocity-selective venous spin labeling (VS-VSL)-prepared 3D turbo spin echo pulse sequence for whole-brain baseline CBVv mapping. METHODS Unlike previous CBVv measurement techniques that exploit the interrelationship between BOLD signals and CBVv , in the proposed VS-VSL technique both arterial blood and cerebrospinal fluid (CSF) signals were suppressed before the VS pulse train for exclusive labeling of venous blood, while a single-slab 3D turbo spin echo readout was used because of its relative immunity to magnetic field variations. Furthermore, two approximations were made to the VS-VSL signal model for simplified derivation of CBVv . In vivo studies were performed at 3T field strength in 8 healthy subjects. The performance of the proposed VS-VSL method in baseline CBVv estimation was first evaluated in comparison to the existing, hyperoxia-based method. Then, data were also acquired using VS-VSL under hypercapnic and hyperoxic gas breathing challenges for further validation of the technique. RESULTS The proposed technique yielded physiologically plausible baseline CBVv values, and when compared with the hyperoxia-based method, showed no statistical difference. Furthermore, data acquired using VS-VSL yielded average CBVv of 2.89%/1.78%, 3.71%/2.29%, and 2.88%/1.76% for baseline, hypercapnia, and hyperoxia, respectively, in gray/white matter regions. As expected, hyperoxia had negligible effect (P > .8), whereas hypercapnia demonstrated vasodilation (P <

The current study aimed to evaluate the clinical practice for hemodynamic tissue signature (HTS) method in IDH genotype prediction in three groups derived from high-grade gliomas. Preoperative MRI examinations of 44 patients with known grade and IDH genotype were assigned into three study groups: glioblastoma multiforme, grade III, and high-grade gliomas. Perfusion parameters were analyzed and were used to automatically draw the four reproducible habitats (high-angiogenic enhancing tumor habitats, low-angiogenic enhancing tumor habitats, infiltrated peripheral edema habitats, vasogenic peripheral edema habitats) related to vascular heterogeneity. These four habitats were then compared between inter-patient with IDH mutation and their wild-type counterparts at these three groups, respectively. The discriminating potential for HTS in assessing IDH mutation status prediction was assessed by ROC curves. Compared with IDH wild type, IDH mutation had significantly decreased relative cerebral blood volume (rCBV) at the high-angiogenic enhancing tumor habitats and low-angiogenic enhancing tumor habitats. ROC analysis revealed that the rCBVs in habitats had great ability to discriminate IDH mutation from their wild type in all groups. In addition, the Kaplan-Meier survival analysis yielded significant differences for the survival times observed from the populations dichotomized by low ( 4.31) rCBV in the low-angiogenic enhancing tumor habitat. The HTS method has been proven to have high prediction capabilities for IDH mutation status in high-grade glioma patients, providing a set of quantifiable habitats associated with tumor vascular heterogeneity. • The HTS method has a high accuracy for molecular stratification prediction for all subsets of HGG. • The HTS method can give IDH mutation–related hemodynamic information of tumor-infiltrated and vasogenic edema. • IDH-relevant rCBV difference in habitats will be a great prognosis factor in HGG.

BACKGROUND AND PURPOSE: Our aim was to investigate the effects of intratumoral hemorrhage, calcification, and postoperative changes on the sensitivity of arterial spin-labeling and DSC perfusion MR imaging in patients with primary brain tumors. MATERIALS AND METHODS: Eighty-six brain tumor lesions were examined with single-phase and multiphase arterial spin-labeling and DSC perfusion MR imaging. The lesions that had no intratumoral bleeding/calcifications and history of surgery were assigned to group 1 (n = 38), and the lesions that had these were assigned to group 2 (n = 48). The relative regional cerebral blood flow was calculated in both perfusion methods, and relative regional cerebral blood volume was calculated in DSC. Imaging results were correlated with histopathology or follow-up. RESULTS: In the quantitative evaluation, the sensitivity and specificity of relative regional cerebral blood flow in multiphase arterial spin-labeling perfusion were 94.4% and 80% in group 1 and 78.3% and 88% in group 2, respectively. The sensitivity and specificity of relative regional cerebral blood flow in DSC perfusion were 88.9% and 75% in group 1 and 78.3% and 84% in group 2, respectively. The sensitivity and specificity of relative regional cerebral blood volume in DSC perfusion were 66.7% and 100% in group 1 and 69.6% and 96% in group 2, respectively. In the qualitative evaluation, the sensitivities for single-phase and multiphase arterial spin-labeling were 48.2% and 79.3%, respectively, with 100% specificity for both. CONCLUSIONS: The sensitivity and specificity of multiphase arterial spin-labeling were similar to those of DSC perfusion irrespective of bleeding and calcification in primary brain tumors. Thus, we suggest that noncontrast multiphase arterial spin-labeling can be used instead of DSC perfusion MR imaging in the diagnosis and follow-up of intracranial tumors.

The Brain Tumor Reporting and Data System (BT-RADS) category 3 is suitable for identifying cases with intermediate probability of tumor recurrence that do not meet the Response Assessment in Neuro-Oncology (RANO) criteria for progression. The aim of this study was to evaluate the added value of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC PWI) and diffusion-weighted imaging (DWI) to BT-RADS for differentiating tumor recurrence from non-recurrence in postoperative high-grade glioma (HGG) patients with category 3 lesions. Patients with BT-RADS category 3 lesions were included. The maximal relative cerebral blood volume (rCBVmax) and the mean apparent diffusion coefficient (ADCmean) values were measured. The added value of DSC PWI and DWI to BT-RADS was evaluated by receiver operating characteristic (ROC) curve analysis. Fifty-one of 91 patients had tumor recurrence, and 40 patients did not. There were significant differences in rCBVmax and ADCmean between the tumor recurrence group and non-recurrence group. Compared to BT-RADS alone, the addition of DSC PWI to BT-RADS increased the area under curve (AUC) from 0.76 (95% confidence interval [CI] 0.66–0.84) to 0.90 (95% CI 0.81–0.95) for differentiating tumor recurrence from non-recurrence. The addition of DWI to BT-RADS increased the AUC from 0.76 (95% CI 0.66–0.84) to 0.88 (95% CI 0.80–0.94). The combination of BT-RADS, DSC PWI, and DWI exhibited the best diagnostic performance (AUC = 0.95; 95% CI 0.88–0.98) for differentiating tumor recurrence from non-recurrence. Adding DSC PWI and DWI to BT-RADS can significantly improve the diagnostic performance for differentiating tumor recurrence from non-recurrence in BT-RADS category 3 lesions.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease and the most common movement disorder characterized by motor impairments resulting from midbrain dopamine neuron loss. Abnormalities in small pial arteries and arterioles, which are the primary pathways of local delivery of nutrients and oxygen in brain tissue, have been reported in many neurodegenerative diseases including PD. Mutations in LRRK2 cause genetic PD and contribute to sporadic PD. The most common PD-linked mutation LRRK2 G2019S contributes 20–47% of genetic forms of PD in Caucasian populations. The human LRRK2 G2019S transgenic mouse model displays PD-like movement impairment and was used to identify novel LRRK2 inhibitors, which provides a useful model for studying microvascular abnormalities in PD. Objectives: To investigate abnormalities in arteriolar cerebral blood volume (CBVa) in various brain regions using the inflow-based vascular-space occupancy (iVASO) MRI technique in LRRK2 mouse models of PD. Methods: Anatomical and iVASO MRI scans were performed in 5 female and 7 male nontransgenic (nTg), 3 female and 4 male wild-type (WT) LRRK2, and 5 female and 7 male G2019S-LRRK2 mice of 9 months of age. CBVa was calculated and compared in the substantia nigra (SN), olfactory cortex, and prefrontal cortex. Results: Compared to nTg mice, G2019S-LRRK2 mice showed decreased CBVa in the SN, but increased CBVa in the olfactory and prefrontal cortex in both male and female groups, whereas WT-LRRK2 mice showed no change in CBVa in the SN (male and female), the olfactory (female), and prefrontal (female) cortex, but a slight increase in CBVa in the olfactory and prefrontal cortex in the male group only. Conclusions: Alterations in the blood volume of small arteries and arterioles (CBVa) were detected in the G2019S-LRRK2 mouse model of PD. The opposite changes in CBVa in the SN and the cortex indicate that PD pathology may have differential effects in different brain regions. Our results suggest the potential value of CBVa as a marker for clinical PD studies.

Carmustine was one of the first systemic chemotherapies to gain FDA approval for the treatment of brain tumors. More recently, carmustine-infused polymer wafers have been used to deliver locally higher doses of chemotherapy directly to the surgical tumor bed while obviating systemic side effects, such as myelosuppression and pulmonary toxicity.

Background: MRI is the standard technique for diagnosis of brain tumors, but the challenge is determination of brain tumor grade.Aim of Study: To assess the role of Apparent Diffusion Coefficient (ADC) and relative Cerebral Blood Volume (rCBV) in brain tumors grading.Patients and Methods: Our prospective comparative analytic study involved 26 patients that were diagnosed to have brain tumors. All patients were subjected to revision of their medical history, full neurological and cognitive functions assessment, anatomical brain assessment by conventional MRI examination of the brain, diffusion and perfusion MRI with measurement of mADC & rCBV values respectively. Correlation of results with the histopathological findings of the resected tumors as a gold standard were performed.Results: The diagnostic capability of mADC by using cut off value of 3.22 & >2.33) with significant difference in between (p=0.001 & 0.002). The diagnostic capability of rCBV by using cut off value of >3.22 & >2.33, had a sensitivity of 68.4%, 90.9 respectively and a specificity of 100% at p-value of

In this study we evaluated the benefit on survival of the combination of MGMT methylation and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included at the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of temozolomide for MGMT methylated patients with high vascular glioblastomas. Preliminary results suggest that patients with moderate vascularity and methylated MGMT would benefit more from prolonged adjuvant chemotherapy.Simple SummaryDespite the complete treatment with surgery, chemotherapy and radiotherapy, patients with glioblastoma have a devasting prognosis. Although the role of extending temozolomide treatment has been explored, the results are inconclusive. Recent evidence suggested that tumor vascularity may be a modulating factor in combination with MGMT methylation on the effect of temozolomide-based therapies, opening new possibilities for personalized treatments. Before proposing a prospective interventional clinical study, it is necessary to confirm the beneficial effect of the combined effect of MGMT methylation and moderate tumor vascularity. As well as the lack of benefit of temozolomide in patients with a highly vascular tumor.

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 TThe DANTE and TWhile TMicrovascular compartment signals were eliminated from the total ASL signals by DANTE. CBV

BACKGROUND AND PURPOSE The role of CT perfusion (CTP)in the evaluation of acute basilar artery occlusion (aBAO) patients undergoing endovascular thrombectomy (EVT) is unclear. We investigated the association of individual CTP parameters with functional outcomes in aBAO patients undergoing EVT. METHODS A health system's prospectively collected code stroke registry was used in this retrospective analysis of aBAO patients treated with EVT presenting between January 2017 and February 2021 with pre-EVT CTP. The primary outcome measure was modified Rankin Scale (mRS) score 0-2 at 90 days. Factors with a univariate association (p < .05) with mRS 0-2 were combined in a multivariable regression model to determine independent predictors of 90-day favorable functional outcome. RESULTS Forty-six subjects, with median age 67 years and median National Institutes of Health Stroke Scale 16, were included, of whom 17 (37%) achieved mRS 0-2 at 90 days. In the multivariable logistic regression model, CTP cerebral blood volume (CBV) index (per 0.1-point increase, odds ratio = 1.843; 95% confidence interval: 1.039, 3.268; p-value .0365) was independently associated with a favorable 90-day outcome. CONCLUSIONS CBV index was independently associated with a favorable 90-day outcome in aBAO patients treated with EVT, a novel finding in this patient population. CBV index may assist in treatment and prognosis discussions and inform future studies investigating the role of CTP in aBAO.

Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have important implications during states of critical neurological illness. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of PE in traumatic brain injury (TBI), evaluating both animal models and human studies. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to January 2020. We identified 12 studies with various animal models and 4 studies in humans with varying TBI pathology. There was a trend toward a consistent increase in mean arterial pressure (MAP) by the injection of PE systemically, and by proxy, an increase of the cerebral perfusion pressure (CPP). There was a consistent constriction of cerebral vessels by PE reported in the small number of studies documenting such a response. However, the heterogeneity of the literature on the CBF/cerebral blood volume (CBV) response makes the strength of the conclusions on PE limited. Studies were heterogeneous in design and had significant limitations, with most failing to adjust for confounding factors in cerebrovascular/CBF response. This review highlights the significant knowledge gap on the cerebrovascular/CBF effects of PE administration in TBI, calling for further study on the impact of PE on the cerebrovasculature both in vivo and in experimental settings.

Cerebral blood flow (CBF) / cerebral blood volume (CBV) ratio derived by [15O] H2O/ CO2 and CO positron emission tomography (PET) examination has been used empirically as an index for cerebral perfusion pressure (CPP). However, this equation lacks a theoretical basis and furthermore, has not been confirmed to be proportionate to CPP, as direct measurement of local CPP is not practical.We have developed a new index for CPP using the Poiseuille equation based on a simple model. Our model suggests that CBF/CBV2 is proportionate to CPP and that it is mathematically a more accurate index than CBF/CBV.

The goal of this study was to investigate whether alterations in cerebral microvasculature, as measured by cerebral blood volume (CBV), contribute to age- and hypertension-related impairments in cognitive function with a focus on executive function and memory. Data were collected on 19 male rhesus monkeys ranging from 6.4 to 21.6 years of age. Hypertension was induced through surgical coarctation of the thoracic aorta. We assessed whether performance on tasks of memory and executive function corresponded to CBV in either the hippocampus or prefrontal cortex. We found a relationship between duration of hypertension and CBV in the gray matter of the prefrontal cortex, but not the hippocampus. No relationships were found with the degree of hypertension or age. Increased prefrontal CBV was related to greater impairment in executive function while hippocampal CBV was not related to memory performance. These findings suggest that duration, but not severity, of hypertension or age are important factors underlying alterations in brain microvasculature and that executive function is more vulnerable than memory function. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction: We investigated the correlation between amide proton transfer-weighted magnetic resonance imaging (APTw) MRI and dynamic susceptibility contrast (DSC) perfusion in order to assess the potential of APTw MRI as an alternative to DSC in adult brain tumor (glioma) imaging. Methods: After Ethical Committee approval, forty adult patients, treated for histopathologically confirmed glioma (World Health Organization (WHO) grade II-IV), were prospectively imaged at 3 Tesla (3T) with DSC perfusion and a commercially available three-dimensional (3D) APTw sequence. Two consultant neuroradiologists independently performed region of interest (ROI) measurements on relative cerebral blood volume (rCBV) and APTw maps, co-registered with anatomical images. The correlation APTw MRI-DSC perfusion was evaluated using Spearman’s rank-order test. Inter-observer agreement was evaluated by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) plots.Results: A statistically significant moderately strong positive correlation was observed between maximum rCBV (rCBVmax) and maximum APTw values (APTwmax) (observer 1: r=0.73; pConclusion: APTwmax values correlate positively with rCBVmax in patients treated for brain glioma. APTw imaging is a reproducible technique, with some observer dependence. Results need to be confirmed by a larger population analysis.Implications for practice: APTw MRI can be a useful addition to glioma follow-up imaging and a potential alternative to DSC perfusion, especially in patients where contrast agent is contraindicated. Introduction: We investigated the correlation between amide proton transfer-weighted magnetic resonance imaging (APTw MRI) and dynamic susceptibility contrast (DSC) perfusion in order to assess the potential of APTw MRI as an alternative to DSC in adult brain tumor (glioma) imaging. Methods: After Ethical Committee approval, forty adult patients, treated for histopathologically confirmed glioma (World Health Organization (WHO) grade II-IV), were prospectively imaged at 3 Tesla (3 T) with DSC perfusion and a commercially available three-dimensional (3D) APTw sequence. Two consultant neuroradiologists independently performed region of interest (ROI) measurements on relative cerebral blood volume (rCBV) and APTw maps, co-registered with anatomical images. The correlation APTw MRI-DSC perfusion was assessed using Spearman's rank-order test. Inter-observer agreement was evaluated by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) plots. Results: A statistically significant moderately strong positive correlation was observed between maximum rCBV (rCBV max) and maximum APTw (APTw max) values (observer 1: r = 0.73; p < 0.01; observer 2: r = 0.62; p < 0.01). We found good inter-observer agreement for APTw max (ICC = 0.82; 95% confidence interval (CI) 0.66–0.90), with somewhat broad outer 95% CI for the BA Limits of Agreement (LoA) (−1.6 to 1.9). ICC for APTw max was higher than ICC for rCBV max (ICC = 0.74; 95%; CI 0.50–0.86), but the difference was not statistically significant. Conclusion: APTw max values correlate positively with rCBV max in patients treated for brain glioma. APTw imaging is a reproducible technique, with some observer dependence. Results need to be confirmed by a larger population analysis. Implications for practice: APTw MRI can be a useful addition to glioma follow-up imaging and a potential alternative to DSC perfusion, especially in patients where contrast agent is contraindicated.

Neonatal hypoxic–ischemic encephalopathy is a notable cause of neonatal death and developmental disabilities. To achieve better outcomes, it is important in treatment strategy selection to categorize the degree of hypoxia ischemia and evaluate dose response. In an asphyxia piglet model with histopathological brain injuries that we previously developed, animals survived 5 days after insult and showed changes in cerebral blood volume (CBV) that reflected the severity of injuries. However, little is known about the relationship between changes in CBV during and after insult. In this study, an HI event was induced by varying the amount and timing of inspired oxygen in 20 anesthetized piglets. CBV was measured using near-infrared time-resolved spectroscopy before, during, and 6 h after insult. Change in CBV was calculated as the difference between the peak CBV value during insult and the value at the end of insult. The decrease in CBV during insult was found to correlate with the increase in CBV within 6 h after insult. Heart rate exhibited a similar tendency to CBV, but blood pressure did not. Because the decrement in CBV was larger in severe HI, the CBV increment immediately after insult is considered useful for assessing degree of HI insult.

Background: Differentiation between glioblastoma and brain metastasis may be challenging in conventional contrast-enhanced MRI. Purpose: To investigate if perfusion-weighted MRI is able to differentiate glioblastoma from metastasis and, as a second aim was to see if it was possible in the latter group, to predict the primary site of neoplasm. Material and methods: Hundred and fourteen patients with newly discovered tumor lesion (76 metastases and 38 glioblastomas) underwent conventional contrast-enhanced MRI including dynamic susceptibility contrast perfusion sequence. The calculated relative cerebral blood volumes were analyzed in the solid tumor area, peritumoral area, area adjacent to peritumoral area, and normal appearing white matter in contralateral semioval center. The Student t-test was used to detect statistically significant differences in relative cerebral blood volume between glioblastomas and metastases in the aforementioned areas. Furthermore, the metastasis group was divided in four sub groups (lung-, breast-, melanoma-, and gastrointestinal origin) and using one-way ANOVA test. P-values < 0.05 were considered significant. Results: Relative cerebral blood volume (rCBV) in the peritumoral edema was significantly higher in glioblastomas than in metastases (mean 3.2 ± 1.4 and mean 0.9 ± 0.7), respectively, (P < 0.0001). No significant differences in the solid tumor area or the area adjacent to edema were found, (P = 0.28 and 0.21 respectively). There were no significant differences among metastases in the four groups. Conclusion: It is possible to differentiate glioblastomas from metastases by measuring the CBV in the peritumoral edema. It is not possible to differentiate between brain metastases from different primaries (lung-, breast-, melanoma or gastrointestinal) using CBV-measurements in the solid tumor area, peritumoral edema or area adjacent to edema.

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.

PURPOSE: The development and clinical employment of a computed tomography (CT) imaging system benefit from a thorough understanding of the statistical properties of the output images; cerebral CT perfusion (CTP) imaging system is no exception. A series of articles will present statistical properties of CTP systems and the dependence of these properties on system parameters. This Part I paper focuses on the signal and noise properties of cerebral blood volume (CBV) maps calculated using a nondeconvolution-based method. METHODS: The CBV imaging chain was decomposed into a cascade of subimaging stages, which facilitated the derivation of analytical models for the probability density function, mean value, and noise variance of CBV. These models directly take CTP source image acquisition, reconstruction, and postprocessing parameters as inputs. Both numerical simulations and in vivo canine experiments were performed to validate these models. RESULTS: The noise variance of CBV is linearly related to the noise variance of source images and is strongly influenced by the noise variance of the baseline images. Uniformly partitioning the total radiation dose budget across all time frames was found to be suboptimal, and an optimal dose partition method was derived to minimize CBV noise. Results of the numerical simulation and animal studies validated the derived statistical properties of CBV. CONCLUSIONS: The statistical properties of CBV imaging systems can be accurately modeled by extending the linear CT systems theory. Based on the statistical model, several key signal and noise characteristics of CBV were identified and an optimal dose partition method was developed to improve the image quality of CBV.

Functional magnetic resonance imaging (fMRI) using the blood oxygenation level-dependent (BOLD) contrast indirectly probes neuronal activity changes via evoked cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2) changes. The gradient-echo BOLD signal is mostly sensitive to ascending veins in the tissue and to pial veins. Thereby, the achievable spatial specificity to neuronal activation is limited. Furthermore, the non-linear interaction of CBF, CBV and CMRO2 can hamper quantitative interpretations of the BOLD signal across cortical depths with different baseline physiology. Measuring CBF, CBV or CMRO2 directly on a depth-dependent level has the potential to overcome these limitations. Here, we review these candidates of physiologically well-defined contrasts with the particular focus on arterial spin labeling (ASL), vascular space occupancy (VASO) and calibrated fMRI. These methods are reviewed with respect to their fMRI sequence parameter space and the applicability for neuroscientific studies in humans. We show representative results of depth-dependent 'non-BOLD-fMRI' in humans and their spatiotemporal characteristics. We conclude that non-BOLD methods are promising alternatives compared to conventional fMRI as they can provide improved spatial specificity, quantifiability and, hence, physiological interpretability as a function of cortical depth. At submillimeter resolution with inherently low signal-to-noise ratio (SNR), however, their use is still challenging. Nevertheless, we believe that 'non-BOLD-fMRI' is a useful alternative for depth-dependent investigations, by providing valuable insights into neurovascular coupling models that facilitate the interpretability of fMRI for neuroscientific applications.

The ring-finger protein 213 ( RNF213) gene is a major susceptibility gene for moyamoya disease. The homozygote of the p.R4810K variant on RNF213 exhibits an early onset age and severe form of moyamoya disease. We report 4 unrelated pediatric moyamoya disease cases with the homozygous p.R4810K variant and the long-term surgical outcomes. Published reports on surgical outcome of moyamoya disease case with the homozygous p.R4810K variant were reviewed. Cerebral angiography revealed classic angiographic findings of moyamoya disease in 7 hemispheres of the 4 children. All patients underwent successful indirect revascularization. Abundant collateral blood flow from the external carotid arteries to the internal carotid arteries was observed in all bypass procedures by angiography. Improvements in symptoms and cerebral blood volume were observed in all patients at long-term follow-up. This report is the first case series in the literature on the surgical management of these patients. These cases highlight the effectiveness of indirect revascularization for moyamoya disease patients with the homozygous p.R4810K variant. Early diagnosis and treatment are crucial to avoid irreversible neurologic deficits in these patients.

To test if adding permeability measurement to perfusion obtained from dynamic susceptibility contrast MRI (DSC-MRI) improves diagnostic performance in the differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma. DSC-MRI was acquired in 145 patients with pathologically proven glioblastoma (n = 89) or PCNSL (n = 56). The permeability metrics of contrast agent extraction fraction (Ex), apparent permeability (Ka), and leakage-corrected perfusion of normalized cerebral blood volume (nCBVres) and cerebral blood flow (nCBFres) were derived from a tissue residue function. For comparison purposes, the leakage-corrected normalized CBV (nCBV) and relative permeability constant (K2) were also obtained using the established Weisskoff-Boxerman leakage correction method. The area under the receiver operating characteristics curve (AUC) and cross-validation were used to compare the diagnostic performance of the single DSC-MRI parameters with the performance obtained with the addition of permeability metrics. PCNSL demonstrated significantly higher permeability (Ex, p

PURPOSE Velocity-selective saturation (VSS) pulse trains provide a viable alternative to the spatially selective methods for measuring cerebral blood volume (CBV) by reducing the sensitivity to arterial transit time. This study is to compare the Fourier-transform-based velocity-selective saturation (FT-VSS) pulse trains with the conventional flow-dephasing VSS techniques for CBV quantification. METHODS The proposed FT-VSS label and control modules were compared with VSS pulse trains utilizing double refocused hyperbolic tangent (DRHT) and 8-segment B1-insensitive rotation (BIR-8). This was done using both numerical simulations and phantom studies to evaluate their sensitivities to gradient imperfections such as eddy currents. DRHT, BIR-8, and FT-VSS prepared CBV mapping was further compared for velocity-encoding gradients along 3 orthogonal directions in healthy subjects at 3T. RESULTS The phantom studies exhibited more consistent immunity to gradient imperfections for the utilized FT-VSS pulse trains. Compared to DRHT and BIR-8, FT-VSS delivered more robust CBV results across the 3 VS encoding directions with significantly reduced artifacts along the superior-inferior direction and improved temporal signal-to-noise ratio (SNR) values. Average CBV values obtained from FT-VSS based sequences were 5.3 mL/100 g for gray matter and 2.3 mL/100 g for white matter, comparable to literature expectations. CONCLUSION Absolute CBV quantification utilizing advanced FT-VSS pulse trains had several advantages over the existing approaches using flow-dephasing VSS modules. A greater immunity to gradient imperfections and the concurrent tissue background suppression of FT-VSS pulse trains enabled more robust CBV measurements and higher SNR than the conventional VSS pulse trains.

Background and purpose Several leakage correction algorithms for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI)-based cerebral blood volume (CBV) measurement have been proposed, and combination with a preload of contrast agent is generally recommended. A single bolus application scheme would largely simplify and facilitate standardized clinical applications, while reducing contrast agent (CA) dose. The aim of this study was, therefore, to investigate whether appropriate leakage correction redundantizes prebolus application by comparing normalized DSC-based CBV (nCBV) measures of two consecutive CA boli. Materials and methods Twenty-seven patients with suspected glioblastoma (WHO-grade-IV) underwent DSC-MRI during two consecutive boli of Gd-based CA. Four variants of two post-processing leakage correction techniques were compared with respect to nCBV in contrast enhancing tumor tissue. First, a reference curve approach with first pass and full integration of corrected Δ R 2*( t ), and second, a deconvolution-based approach using singular value decomposition (SVD) with a standard noise-dependent cutoff or Tikhonov regularization. Results Compared to respective uncorrected values, all leakage correction techniques increased nCBV for data acquired without prebolus, while there was no consistent trend for data acquired with prebolus. The best agreement between corrected nCBV values in contrast enhancing tumor, obtained in the same patients without and with prebolus, respectively, was obtained for the reference curve-based correction approach with either first pass or full integration. Conclusion The reference curve-based leakage correction approach with integration-based nCBV calculation yielded a high accordance between nCBV values without and with prebolus, respectively. Thus, it appears possible to obtain valid nCBV in glioblastoma with a single CA injection.

Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular reserve and provides important information about vascular health in a range of brain conditions and diseases. Unlike steady-state vascular parameters, such as cerebral blood flow (CBF) and cerebral blood volume (CBV), CVR measures the ability of cerebral vessels to dilate or constrict in response to challenges or maneuvers. Therefore, CVR mapping requires a physiological challenge while monitoring the corresponding hemodynamic changes in the brain. The present review primarily focuses on methods that use CO2 inhalation as a physiological challenge while monitoring changes in hemodynamic MRI signals. CO2 inhalation has been increasingly used in CVR mapping in recent literature due to its potency in causing vasodilation, rapid onset and cessation of the effect, as well as advances in MRI-compatible gas delivery apparatus. In this review, we first discuss the physiological basis of CVR mapping using CO2 inhalation. We then review the methodological aspects of CVR mapping, including gas delivery apparatus, the timing paradigm of the breathing challenge, the MRI imaging sequence, and data analysis. In addition, we review alternative approaches for CVR mapping that do not require CO2 inhalation.

This article aims to provide the reader with an overview of recent developments in Arterial Spin Labeling (ASL) MRI techniques. A great deal of progress has been made in recent years in terms of the SNR and acquisition speed. New strategies have been introduced to improve labeling efficiency, reduce artefacts, and estimate other relevant physiological parameters besides perfusion. As a result, ASL techniques has become a reliable workhorse for researchers as well as clinicians. After a brief overview of the technique's fundamentals, this article will review new trends and variants in ASL including vascular territory mapping and velocity selective ASL, as well as arterial blood volume imaging techniques. This article will also review recent processing techniques to reduce partial volume effects and physiological noise. Next the article will examine how ASL techniques can be leveraged to calculate additional physiological parameters beyond perfusion and finally, it will review a few recent applications of ASL in the literature.

PURPOSE The primary goal of this study was to estimate the value of β , the exponent in the power law relating changes of the transverse relaxation rate and intra-extravascular local magnetic susceptibility differences as ΔR2∗∝(Δχ)β . The secondary objective was to evaluate any differences that might exist in the value of β obtained using a deoxyhemoglobin-weighted Δχ distribution versus a constant Δχ distribution assumed in earlier computations. The third objective was to estimate the value of β that is relevant for methods based on susceptibility contrast agents with a concentration of Δχ higher than that used for BOLD fMRI calculations. METHODS Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte-Carlo simulations to compute β from the first principles. RESULTS Our results show that β=1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of β=1 .5 using uniform Δχ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δχ , β=1 for B0≤ 9.4 T, whereas at 14 T β can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δχ is desired for experiments at high B0 . CONCLUSION These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively.

Background and purpose Our objectives were: (1) compare dynamic susceptibility-weighted (DSC) and dynamic contrast-enhanced (DCE) permeability parameters, (2) evaluate diagnostic accuracy of DSC and DCE discriminating high- and low-grade tumors, (3) analyze relationship of permeability parameters with overall (OS) and progression-free survival (PFS) and (4) assess differences in high-grade tumors classified according to molecular biomarkers. Materials and methods 49 patients with histologically proved diffuse gliomas underwent DSC and DCE imaging. Parametric maps of cerebral blood volume (CBV), CBV-leakage corrected, volume transfer coefficient (Ktrans), fractional volume of the extravascular extracellular space (EES) (Ve), fractional blood plasma volume (Vp) and rate constant between EES and blood plasma (Kep) were calculated. High-grade gliomas were also classified according to isocitrate dehydrogenase (IDH), alpha-thalassemia/mental retardation syndrome X-linked (ATRX) and O6-methylguanine-dna-methyltransferase promoter methylation (MGMT) status. Results There is correlation between parameters leakage, Ktrans and Vp. ROC curve analysis showed significance in both Ktrans and Ve for glioma grading. Threshold value of 0.075 for Ve generated the best combination of sensitivity (80%) and specificity (75%) in tumor gradation. Leakage was the only permeability parameter related to OS (P = 0.006) and PFS (0.012); with prolonged survival for leakage values lower than 1.2. IDH-mutated high-grade tumors showed lower leakage and Ktrans values. High-grade tumors with loss of ATRX presented lower leakage and Vp values. Conclusions Both DSC and DCE permeability parameters serve as non-invasive method for glioma grading. Leakage was the unique permeability parameter related to survival and the best discriminating high-grade gliomas classified according to IDH and ATRX status.

Background: Measurement of relative cerebral blood volume (rCBV) with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is used extensively for brain tumour diagnosis and follow-up. The aim of this pilot study was to assess the robustness of rCBV measurement in patients with enhancing recurrent glioma in a European multicentre trial setting.Methods: We included pre-treatment postcontrast T1 weighted (T1w) and DSC scans of 20 patients with recurrent glioma from 2 European Organisation for Research and Treatment of Cancer trials (26101 and 26091). Three reviewers independently placed a fixed circular region of interest of 70 mm 2 in the tumour area of highest rCBV (rCBV(max)). To calculate the normalised rCBVmax (nrCBV(max)), three ROIs were placed in the anterior, middle and posterior centrum semiovale normal-appearing white matter of the contralateral hemisphere. After several months, each observer repeated the assessments blinded for initial findings. Repeatability and reproducibility were estimated with a mixed model. Each measurement was also classified according to 4 clinically meaningful categories.Results: Three patients were post hoc excluded from analysis because of lack of enhancing tumour. The mean nrCBVmax repeatability was 49.5%, and reproducibility was 5.5%. In 14 of 17 patients, at least 2 reviewers classified the patient into the same category.Conclusions: Our results indicate that a well-established review process needs to be applied upfront to assess perfusion in a multicentre trial setting. While awaiting further validation, we propose as a strategy to measure rCBV in the context of recurrent glioma trials to use two central reviewers and an adjudicator in case of disagreement. (C) 2019 Elsevier Ltd. All rights reserved.

Supplemental Digital Content is available in the text., Objectives: Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PRx) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PRx is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (ΔCPP) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PRx; and 3) the determinants of greater ΔCPP. Design: Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, Paco2, and cerebral blood flow. Setting: University critical care integrative modeling and precision physiology research group. Subjects: None, in silico studies. Interventions: Simulations in blood pressure, intracranial pressure, Paco2, and impairment of cerebral autoregulation, with examination of “output” cerebral perfusion pressure versus PRx-plots, optimal cerebral perfusion pressure, and ΔCPP. Measurements and Main Results: In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PRx occurs even with intact cerebral autoregulation. In relation to ΔCPP, for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of Paco2 maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows ΔCPP greater than 10 mm Hg and less than –10 mm Hg, respectively. Conclusions: These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PRx and ΔCPP. PRx and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure.

SignificanceCerebral vascular reactivity is critical parameters of brain homeostasis in health and disease, but the investigational value of brain oxymetry is diminished by anesthesia and mechanical fixation of the mouse scull.AimWe needed to reduce the physical restrictivity of hemodynamic spectroscopy to enable Alzheimer’s disease (AD) studies in freely-moving mice.ApproachWe combined spectroscopy, spectral analysis software and a magnetic, implantable device to measure vascular reactivity in unanesthetized, freely-moving mice. We measured cerebral blood volume fraction (CBVF) and oxygen saturation (SO2).ResultsWe validated that our system could detect delayed cerebrovascular recovery from hypoxia in an orthotopic xenograft glioma model under anesthetized condition and we also found increasedCBVFand impaired vascular reactivity during hypercapnia in a freely-moving mouse model of AD compared to wild-type littermates.ConclusionsOur optomechanical approach to reproducibly getting light into and out of the brain enabled us to successfully measureCBVFandSO2during hypercapnia in unanesthetized freely-moving mice. We present hardware and software enabling oximetric analysis of metabolic activity, which provides a safe and reliable method for rapid assessment of vascular reactivity in murine disease models as well asCBVFandSO2.