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Introduction - According to the 2017 Portuguese Program for Cardio-Cerebrovascular Diseases, the OECD reports that cardiovascular diseases are the leading cause of death in member states of the European Union, representing about 36% of deaths in the region in 2010. This figure includes brain vascular diseases. It was intended to evaluate the value of cerebral blood flow (CBF) that best predicts the outcomes from the Via Verde procedure in stroke, with patients undergoing thrombectomy. It was also purpose of this study to increase the reliability of prognosis, optimizing the technique and radiological procedures for determining volumes of 'core' and 'penumbra'. Methods - This was a retrospective study whose clinical cases were collected from the database of Hospital de Beatriz Ângelo (Loures, PT) based on predefined inclusion criteria. After the acquisition of perfusion computed tomography (PCT), a sample of 17 patients, admitted through the Via Verde stroke program, was post-processed using the syngo.via software (NEURO Perfusion application). The data resulting from the perfusion maps were analyzed statistically using the SPSS® [IBM v. 23.0], allowing an analysis that reflected the CBF values related to the volumes of 'core' and 'penumbra'. Results - It was found that there is no statistically significant correlation between age, stroke time extends, and pre-therapeutic ASPECTS with the other variables under study. Relating the post-therapeutic ASPECTS to the core levels 10, 20, and 30 of CBF, it was found that the higher value of ASPECTS corresponds lower volume of the core. A statistically significant reduction (p=0.003) of the ASPECTS values was detected from pre- to post-therapy. The 'core' 10CBF value presents a lower volume of brain tissue infarcted in relation to the 'core' 30CBF, pointing to an inverse trend with the value of 'penumbra' volume. Conclusion - This study proves that it is possible, with a CBF of 10mL / 100g / min, to restore the flow needed to repair the neurological function of affected tissue, and with this CBF the largest volume of brain tissue is obtained for the 'penumbra' and a lower volume of 'core'. The processing and interpretation of the perfusion maps induce variation in the volume of the score of 'core' and 'penumbra'. [ABSTRACT FROM AUTHOR]

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale. [ABSTRACT FROM AUTHOR]

Intravenous dipyridamole (DP) can induce transient perfusion abnormalities in the heart but also the brain indicated by brain SPECT. L-arginine can regulate the vascular tone via nitric oxide (NO). Therefore, we examined cerebral blood volume (CBV) by perfusion MRI and L-arginine level before and after DP stress in patients, who developed transient neurological signs, and compared these to unaffected patients. A total of nine patients with ischemic coronary disease after myocardial perfusion scintigraphy were selected for this prospective pilot study. Four had DP-induced transient mild neurologic signs during myocardial perfusion scintigraphy, while five had no neurological signs. By using perfusion MRI in both groups in a second stage, we examined CBV in identical areas of the two hemispheres before and during DP stress. Besides, pre-and post-stress L-arginine serum levels were also analyzed by high-performance liquid chromatography. Trial registration: NCT03688815. CBV in the sensory-motor area at baseline was significantly higher in patients with DP-induced transient neurological signs compared to patients without signs (p = 0.028). Intravenous DP normalized the higher perfusion by decreasing CBV, and also increased serum L-arginine level (p = 0.001). Intravenous DP changed the CBV accompanied by a systemic elevation of L-arginine: this indicates a direct vasorelaxing effect on brain vessels, and an indirect vasodilator effect through L-arginine release presumably via NO. In areas with decreased CBV before DP, such double effects caused transient neurological symptoms presumably due to steal phenomenon. Therefore, intravenous DP may have a potential to identify patients with high risk for cerebral ischemia. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast takes advantage of the coupling between neuronal activity and the hemodynamics to allow a non-invasive localisation of the neuronal activity. In general, fMRI experiments assume a linear relationship between neuronal activation and the observed hemodynamics. However, the relationship between BOLD responses, neuronal activity, and behaviour are often nonlinear. In addition, the nonlinearity between BOLD responses and behaviour may be related to neuronal process rather than a neurovascular uncoupling. Further, part of the nonlinearity may be driven by vascular nonlinearity effects in particular from large vessel contributions. fMRI based on cerebral blood volume (CBV), promises a higher microvascular specificity, potentially without vascular nonlinearity effects and reduced contamination of the large draining vessels compared to BOLD. In this study, we aimed to investigate differences in BOLD and VASO-CBV signal changes during a hand movement task over a broad range of movement rates. We used a double readout 3D-EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the sensorimotor cortex. The measured BOLD and VASO-CBV responses increased very similarly in a nonlinear fashion, plateauing for movement rates larger than 1 Hz. Our findings show a tight relationship between BOLD and VASO-CBV responses, indicating that the overall interplay of CBV and BOLD responses are similar for the assessed range of movement rates. These results suggest that the observed nonlinearity of neuronal origin is already present in VASO-CBV measurements, and consequently shows relatively unchanged BOLD responses.

Background and Aims: Intracranial compliance refers to the relationship between a change in intracranial volume and the resultant change in intracranial pressure (ICP). Measurement of compliance is useful in managing cardiovascular and respiratory failure; however, there are no contemporary means to assess intracranial compliance. Knowledge of intracranial compliance could complement ICP and cerebral perfusion pressure (CPP) monitoring in patients with severe traumatic brain injury (TBI) and may enable a proactive approach to ICP management. In this proof-of-concept study, we aimed to capitalize on the physiologic principles of intracranial compliance and vascular reactivity to CO2, and standard-of-care neurocritical care monitoring, to develop a method to assess dynamic intracranial compliance. Methods: Continuous ICP and end-tidal CO2 (ETCO2) data from children with severe TBI were collected after obtaining informed consent in this Institutional Review Board-approved study. An intracranial pressure-PCO2 Compliance Index (PCI) was derived by calculating the moment-to-moment correlation between change in ICP and change in ETCO2. As such, "good" compliance may be reflected by a lack of correlation between time-synched changes in ICP in response to changes in ETCO2, and "poor" compliance may be reflected by a positive correlation between changes in ICP in response to changes in ETCO2. Results: A total of 978 h of ICP and ETCO2 data were collected and analyzed from eight patients with severe TBI. Demographic and clinical characteristics included patient age 7.1 ± 5.8 years (mean ± SD); 6/8 male; initial Glasgow Coma Scale score 3 [3–7] (median [IQR]); 6/8 had decompressive surgery; 7.1 ± 1.4 ICP monitor days; ICU length of stay (LOS) 16.1 ± 6.8 days; hospital LOS 25.9 ± 8.4 days; and survival 100%. The mean PCI for all patients throughout the monitoring period was 0.18 ± 0.04, where mean ICP was 13.7 ± 2.1 mmHg. In this cohort, PCI was observed to be consistently above 0.18 by 12 h after monitor placement. Percent time spent with PCI thresholds > 0.1, 0.2, and 0.3 were 62% [24], 38% [14], and 23% [15], respectively. The percentage of time spent with an ICP threshold > 20 mmHg was 5.1% [14.6]. Conclusions: Indirect assessment of dynamic intracranial compliance in TBI patients using standard-of-care monitoring appears feasible and suggests a prolonged period of derangement out to 5 days post-injury. Further study is ongoing to determine if the PCI—a new physiologic index, complements utility of ICP and/or CPP in guiding management of patients with severe TBI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objectives: To evaluate the added value of MR dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI)-derived tumour microvascular and oxygenation information with cerebral blood volume (CBV) to distinguish pseudoprogression from true progression (TP) in post-treatment glioblastoma., Methods: This retrospective single-institution study included patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and a newly developed or enlarging measurable contrast-enhancing mass within 12 weeks after concurrent chemoradiotherapy. CBV, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) were obtained from DSC-PWI. Predictors were selected using univariable logistic regression, and performance was measured with adjusted diagnostic odds with tumour volume and area under the curve (AUC) of receiver operating characteristics analysis., Results: A total of 103 patients were included (mean age, 59.6 years; 59 women), with 67 cases of TP and 36 cases of pseudoprogression. Pseudoprogression exhibited higher CTH (4.0 vs. 3.4, p = .019) and higher OEF (12.7 vs. 10.7, p = .014) than TP, but a similar CBV (1.48 vs. 1.53, p = .13) and CMRO 2 (7.7 vs. 7.3s, p = .598). Independent of tumour volume, both high CTH (adjusted odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.11-2.09, p = .009) and high OEF (adjusted OR 1.17; 95% CI:1.03-1.33, p = .016) were predictors of pseudoprogression. The combination of CTH, OEF, and CBV yielded higher diagnostic performance (AUC 0.71) than CBV alone (AUC 0.65)., Conclusion: High intratumoural capillary transit heterogeneity and high oxygen extraction fraction derived from DSC-PWI have enhanced the diagnostic value of CBV in pseudoprogression of post-treatment IDH-wild type glioblastoma., Clinical Relevance Statement: In the early post-treatment stage of glioblastoma, pseudoprogression exhibited both high oxygen extraction fraction and high capillary transit heterogeneity and these dynamic susceptibility contrast-perfusion weighted imaging derived parameters have added value in cerebral blood volume-based noninvasive differentiation of pseudoprogression from true progression., Key Points: • Capillary transit time heterogeneity and oxygen extraction fraction can be measured noninvasively through processing of dynamic susceptibility contrast imaging. • Pseudoprogression exhibited higher capillary transit time heterogeneity and higher oxygen extraction fraction than true progression. • A combination of cerebral blood volume, capillary transit time heterogeneity, and oxygen extraction fraction yielded the highest diagnostic performance (area under the curve 0.71)., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: Functional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, the latter of which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging using standard gradient‐echo EPI sequences. Gradient and spin‐echo (GRASE) BOLD imaging has also shown greater specificity when compared with standard gradient‐echo EPI BOLD. Here we directly compare CBV and BOLD contrasts in high‐resolution imaging of the primary motor cortex for laminar functional MRI in four combinations of signal labeling, CBV using slice‐selective slab‐inversion vascular space occupancy (VASO) and BOLD, each with 3D gradient‐echo EPI and zoomed 3D‐GRASE image readouts. Methods: Activations were measured using each sequence and contrast combination during a motor task. Activation profiles across cortical depth were measured to assess the sensitivity and specificity (pial bias) of each method. Results: Both CBV imaging using gradient‐echo 3D‐EPI and BOLD imaging using 3D‐GRASE show similar specificity and sensitivity and are therefore useful tools for mesoscopic functional MRI in the human cortex. The combination of GRASE and VASO did not demonstrate high levels of sensitivity, nor show increased specificity. Conclusion: Three‐dimensional EPI with VASO contrast and 3D‐GRASE with BOLD contrast both demonstrate sufficient sensitivity and specificity for laminar functional MRI to be used by neuroscientists in a wide range of investigations of depth‐dependent neural circuitry in the human brain. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) lymphoma presents as the dense infiltration of tumor cells in the perivascular space and blood-brain barrier disruption, on histopathological examination. The Ki-67 expression has been significantly correlated with tumor proliferation and is considered to be a prognostic factor. Objectives: This study aimed at analyzing the correlations among the apparent diffusion coefficient (ADC), the relative cerebral blood volume (rCBV), and the Ki-67 proliferation index in CNS lymphoma. Methods: From August 2019 to March 2020,26 patients (14 men and 12 women) who underwent biopsy or surgery and were histologically confirmed as CNS lymphoma were included in this retrospective study. Diffusion and perfusion acquisitions were performed in 26 and 10 examinations, respectively. The Ki-67 proliferation index was available for all cases. Results: The mean tADC, rADC, and rCBV values were 0.61 ± 0.12 x 10-3 mm²/s, 0.73 ± 0.14, and 1.1 ± 0.32, respectively. Negative correlations were identified between both tADC and rADC and the Ki-67 proliferation index (r = -0.656, P < 0.01 and r = -0.540, P < 0.01, respectively). No significant correlations were found between rCBV values and the Ki-67 proliferation index, between rCBV and rADC, or between rCBV and tADC. Conclusions: tADC and rADC values can be used as noninvasive indicators to predict cell proliferation in CNS lymphoma. [ABSTRACT FROM AUTHOR]

PurposeTo compare "standardization," "Gaussian normalization," and "Z-score normalization" intensity transformation techniques in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) estimates of cerebral blood volume (CBV) in human gliomas. DSC-MRI is a well-established biomarker for CBV in brain tumors; however, DSC-MRI estimates of CBV are semiquantitative. The use of image intensity transformation algorithms provides a mechanism for obtaining quantitatively similar CBV maps with the same intensity scaling.Materials and methodsThe coefficient of variance (CV) in normal-appearing white matter and relative contrast between tumor regions and normal tissue was compared between the three CBV transformations across five different MR scanners in 96 patients with gliomas.ResultsThe results suggest all normalization techniques improved variability and relative tumor contrast of CBV measurements compared with nonnormalized CBV maps. The results suggest Gaussian normalization of CBV maps provided slightly lower CV in normal white matter and provided slightly higher tumor contrast for glioblastomas (WHO grade IV) compared with other techniques.ConclusionThe results suggest Gaussian normalization of leakage-corrected CBV maps may be the best choice for image intensity correction for use in large-scale, multicenter clinical trials where MR scanners and protocols vary widely due to ease of implementation, lowest variability, and highest tumor to normal tissue contrast.

Tongue pressure measurement (TPM) is an indicator of oral function. However, the association between tongue pressure and cerebral activation remains unclear. We used near-infrared spectroscopy (NIRS) to examine the correlation between cerebral cortex activation and tongue pressure stimulation against the anterior palatal mucosa. We measured voluntary maximum tongue pressure (MTP) using a TPM device; a pressure value of approximately 60% of the MTP was used for the experimental tongue pressure (MTP60%). We examined the effect of oral functional tongue pressure stimulation against the anterior palatal mucosa on cerebral activation using NIRS in 13 adults. Tongue pressure stimulation caused significant changes in cerebral blood flow in some areas compared with controls (p < 0.05). We performed a correlation analysis (p < 0.05) between MTP60% and changes in oxygenated hemoglobin in all 47 NIRS channels. MTP60% triggered activation of the right somatosensory motor area and right dorsolateral prefrontal cortex and deactivation of the anterior prefrontal cortex (APFC). TPM balloon-probe insertion in the oral cavity activated the bilateral somatosensory motor area and deactivated the wide area of the APFC. Moreover, MTP60% via the TPM balloon probe activated the bilateral somatosensory and motor cortex areas. Tongue pressure stimulation changes cerebral blood flow, and NIRS is useful in investigating the relationship between oral stimulation and brain function.

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 <<.01). Conclusion: Upon further validation of the quantification model, the method is expected to have merit for 3D CBVv measurements across the entire brain. [ABSTRACT FROM AUTHOR]

Mouse functional MRI (fMRI) has been of great interest due to the abundance of transgenic models. Due to a mouse's small size, spontaneous breathing has often been used. Because the vascular physiology affecting fMRI might not be controlled normally, its effects on functional responses were investigated with optical intrinsic signal (OIS) imaging and 9.4 T BOLD fMRI. Three conditions were tested in C57BL/6 mice: spontaneous breathing under ketamine and xylazine anesthesia (KX), mechanical ventilation under KX, and mechanical ventilation under isoflurane. Spontaneous breathing under KX induced an average pCO2 of 83 mmHg, whereas a mechanical ventilation condition achieved a pCO2 of 37‐41 mmHg within a physiological range. The baseline diameter of arterial and venous vessels was only 7%‐9% larger with spontaneous breathing than with mechanical ventilation under KX, but it was much smaller than that in normocapnic isoflurane‐anesthetized mice. Three major functional studies were performed. First, CBV‐weighted OIS and arterial dilations to 4‐second forepaw stimulation were rapid and larger at normocapnia than hypercapnia under KX, but very small under isoflurane. Second, CBV‐weighted OIS and arterial dilations by vasodilator acetazolamide were measured for investigating vascular reactivity and were larger in the normocapnic condition than in the hypercapnic condition under KX. Third, evoked OIS and BOLD fMRI responses in the contralateral mouse somatosensory cortex to 20‐second forepaw stimulation were faster and larger in the mechanical ventilation than spontaneous breathing. BOLD fMRI peaked at the end of the 20‐second stimulation under hypercapnic spontaneous breathing, and at ~9 seconds under mechanical ventilation. The peak amplitude of BOLD fMRI was 2.2% at hypercapnia and ~3.4% at normocapnia. Overall, spontaneous breathing induces sluggish reduced hemodynamic and fMRI responses, but it is still viable for KX anesthesia due to its simplicity, noninvasiveness, and well‐localized BOLD activity in the somatosensory cortex. [ABSTRACT FROM AUTHOR]

Background: Perfusion imaging, one of MRI's techniques, is widely used to test damaged tissues of the body. The parameters used in this technique include cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The MRI scanner contains a device called a "phantom", which controls the accuracy of various imaging models. Objective: Our goal is to design and produce a microphantom to control the perfusion-imaging model in MRI scanners. Material and Methods: Firstly, in an analytical study type, we designed the phantom based on Murray's minimum work rule using AutoCAD software. Next, the phantom was fabricated using lithography and then imaged using a Siemens Magnetom 3T Prisma MRI scanner at the National Brain Laboratory. Finally, the velocity and pressure in the capillary network was simulated using COMSOL software. Results: CBF, CBV, and MTT curves for the capillary network were obtained at different times. In addition, the simulations showed that the velocity and pressure in the capillary network were between 0.0001 and 0.0005 m/s and between 5 and 25 mm/Hg, respectively. Conclusion: The fabricated microphantom was used to simulate the movement of blood within tissues of the body. Different parameters of perfusion imaging were measured inside the phantom, and they in the phantom were similar to in the body. [ABSTRACT FROM AUTHOR]

The Monro-Kellie hypothesis (MKH) states that volume changes in any intracranial component (blood, brain tissue, cerebrospinal fluid) should be counterbalanced by a co-occurring opposite change to maintain intracranial pressure within the fixed volume of the cranium. In this feasibility study, we investigate the MKH application to structural magnetic resonance imaging (MRI) in observing compensating intracranial volume changes during hypercapnia, which causes an increase in cerebral blood volume. Seven healthy subjects aged from 24 to 64 years (median 32), 4 males and 3 females, underwent a 3-T three-dimensional T1-weighted MRI under normocapnia and under hypercapnia. Intracranial tissue volumes were computed. According to the MKH, the significant increase in measured brain parenchymal volume (median 6.0 mL; interquartile range 4.5, 8.5; p = 0.016) during hypercapnia co-occurred with a decrease in intracranial cerebrospinal fluid (median -10.0 mL; interquartile range -13.5, -6.5; p = 0.034). These results convey several implications: (i) blood volume changes either caused by disorders, anaesthesia, or medication can affect outcome of brain volumetric studies; (ii) besides probing tissue displacement, this approach may assess the brain cerebrovascular reactivity. Future studies should explore the use of alternative sequences, such as three-dimensional T2-weighted imaging, for improved quantification of hypercapnia-induced volume changes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cerebral vasospasm in the setting of subarachnoid hemorrhage causes morbidity and mortality due to delayed cerebral ischemia and permanent neurological deficits. Vasospasm treatment includes intra-arterial injection of a spasmolytic during cerebral angiography. To evaluate effectiveness, neurointerventionalists subjectively examine a posttreatment cerebral angiogram to determine change in vessel diameter or increase in microvascular perfusion. Flat-detector computed tomography (FDCT) scanner has the ability to quantitatively measure cerebral blood volume (CBV) within the parenchyma and detect a quantitative change following treatment.Methods: This is a prospective study at a single institution between October 5, 2017 and June 3, 2019 that examines CBV studies from the Artis Q biplane (Siemens). Regions of interest were made in various territories to measure the CBV within the parenchyma before and after treatment with the spasmolytic verapamil. All instances of vasospasm involved vasculature within the left middle cerebral artery or internal carotid artery. The Wilcoxon signed-rank test was used to determine significance before and after treatment.Results: Our cohort consists of 6 patients who underwent Digital Subtraction Angiography (DSA) and FDCT scans for cerebral vasospasm within the left hemisphere. After intra-arterial injection of 20 mg of verapamil, average increases in blood volume were 59%, 22%, and 24% for the temporal, frontal, and parietal lobes, respectively. P-values associated were .03. We also observed decrease in the mean arterial blood pressure and transcranial Doppler values after treatment.Conclusion: In conclusion, FDCT could measure the effectiveness of a change in CBV from infusion of verapamil in the setting of cerebral vasospasm. The authors believe quantifying the change allows for reassurance of improvement of cerebral vasospasm. [ABSTRACT FROM AUTHOR]

Background: The main objective of this study was to generate a hemodynamically stable swine model to detect spreading depolarizations (SDs) using electrocorticography (ECoG) and intrinsic optical signal (IOS) imaging and laser speckle flowmetry (LSF) after a 30-h middle cerebral artery (MCA) occlusion (MCAo) in German Landrace Swine. Methods: A total of 21 swine were used. The study comprised a training group (group 1, n = 7), a group that underwent bilateral craniectomy and MCAo (group 2, n = 10) and a group used for 2,3,5-triphenyltetrazolium (TTC) staining (group 3, n = 5). Results: In group 2, nine animals that underwent MCAo survived for 30 h, and one animal survived for 12 h. We detected MCA variants with 2 to 4 vessels. In all cases, all of the MCAs were occluded. The intensity changes exhibited by IOS and LSF after clipping were closely correlated and indicated a lower blood volume and reduced blood flow in the middle cerebral artery territory. Using IOS, we detected a mean of 2.37 ± (STD) 2.35 SDs/h. Using ECoG, we detected a mean of 0.29 ± (STD) 0.53 SDs/h. Infarctions were diagnosed using histological analysis. TTC staining in group 3 confirmed that the MCA territory was compromised and that the anterior and posterior cerebral arteries were preserved. Conclusions: We confirm the reliability of performing live monitoring of cerebral infarctions using our MCAo protocol to detect SDs. [ABSTRACT FROM AUTHOR]

Magnetic particle imaging (MPI) is a fast and sensitive technique for imaging of magnetic nanoparticle (MNP) concentrations. MPI directly measures and maps the particle concentration over a measured spatial position. Functional MPI (fMPI) is a specific application of MPI that aims to detect the change of cerebral blood volume (CBV) through imaging. Assuming that the concentration of MNPs in the CBV is uniform, the resultant concentration of MNPs can indicate the CBV changes. Magnetic particle spectroscopy (MPS) is basically a zero-dimensional MPI scanner which can be used to conduct spectroscopic studies and fMPI. In this letter, we suggest an MPS for fMPI with a bore size of 50 mm compatible with rat head dimensions. The system utilizes 0.015 T magnetic field at a frequency of 29.5 kHz and uses an integrated method to measure the small iron component of magnetic particles. Based on the integrated output signal, the MPS consisting of an excitation coil and a gradiometer coil with three parts—a receive coil, a cancellation coil, and a calibration coil—can detect down to 25 ng of Fe. The suggested MPS has demonstrated the achievement of sensitivity that is feasible for fMPI. [ABSTRACT FROM AUTHOR]

Background: Inflow‐based vascular‐space‐occupancy (iVASO) MRI is a noninvasive perfusion technique that does not require administration of exogenous contrast agents. Arteriolar cerebral blood volume (CBVa) obtained from iVASO MRI is hypothesized to be an indicator of tumor microvasculature. Purpose: To assess the diagnostic performance of iVASO MRI implemented at 3T in predicting histologic grades of cerebral gliomas. Study Type: Retrospective. Subjects: Forty‐five patients (31 males) consisting of 14 WHO grade IV glioblastoma multiformes, 14 grade III, and 17 grade II gliomas. Field Strength/Sequence: At 3T we acquired CBVa data using an iVASO sequence. Assessment: The maximum and mean CBVa (CBVa_max and CBVa_mean) values were calculated in the tumor and normalized to the contralateral thalamus (nCBVa_max and nCBVa_mean). Statistical Tests: Kruskal–Wallis test, Mann–Whitney test, and receiver operating characteristics (ROC) curve were used for statistical analysis. Results: Both CBVa_max and nCBVa_max increased with tumor grade (P < 0.001). Grade II gliomas showed CBVa_max <0.78 ml / 100 ml in 10/17 cases and nCBVa_max <1.20 in 11/17 cases. Grade III gliomas showed both CBVa_max >0.78 ml / 100 ml and nCBVa_max >1.20 in 13/14 cases, and CBVa_max <2.06 ml / 100 ml in 13/14 cases and nCBVa_max <2.33 in 11/14 cases. Grade IV gliomas showed CBVa_max >2.06 ml / 100 ml in 9/14 cases and nCBVa_max >2.33 in 13/14 cases. The areas under the ROC curve, sensitivity, and specificity were 0.839 (P < 0.001), 92.9% (26/28), and 64.7% (11/17) for CBVa_max, and 0.883 (P < 0.001), 92.9% (26/28), and 70.6% (12/17) for nCBVa_max in the discrimination between grade II and high‐grade (grade III and grade IV) tumors, respectively. Data Conclusion: iVASO MRI might be used to help determine and predict glioma grade. Level of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1817–1823. [ABSTRACT FROM AUTHOR]

Cortical neurons with similar properties are grouped in columnar structures and supplied by matching vascular networks. The hemodynamic response to neuronal activation, however, is not well described on a fine spatial scale. We investigated the spatiotemporal characteristics of microvascular responses to neuronal activation in rat barrel cortex using optical intrinsic signal imaging and spectroscopy. Imaging was performed at 570 nm to provide functional maps of cerebral blood volume (CBV) changes and at 610 nm to estimate oxygenation changes. To emphasize parenchymal rather than large vessel contributions to the functional hemodynamic responses, we developed an ANOVA-based statistical analysis technique. Perfusion-based maps were compared with underlying neuroanatomy with cytochrome oxidase staining. Statistically determined CBV responses localized accurately to individually stimulated barrel columns and could resolve neighboring columns with a resolution better than 400 mum. Both CBV and early oxygenation responses extended beyond anatomical boundaries of single columns, but this vascular point spread did not preclude spatial specificity. These results indicate that microvascular flow control structures providing targeted flow increases to metabolically active neuronal columns also produce finely localized changes in CBV. This spatial specificity, along with the high contrast/noise ratio, makes the CBV response an attractive mapping signal. We also found that functional oxygenation changes can achieve submillimeter specificity not only during the transient deoxygenation ("initial dip") but also during the early part of the hyperoxygenation. We, therefore, suggest that to optimize hemodynamic spatial specificity, appropriate response timing ( using less than or equal to2-3 sec changes) is more important than etiology (oxygenation or volume).

Objective: To determine the usefulness of the dynamic contrast-enhanced MRI (DCE-MRI) technique for differentiating between low-grade glioma and high-grade glioma and compare with dynamic susceptibility contrast (DSC) MRI. Methods: Conventional MRI, DCE-MRI, and DSC-MRI were performed preoperatively in 17 patients with gliomas. Permeability indices (Ktrans, rKtrans, Ve, and Kep) from DCE-MRI and cerebral blood volume (CBV), rCBV from DSCMRI were quantified. The differences in Ktrans, rKtrans, Ve, Kep, CBV and rCBV between low-grade glioma and high-grade glioma were analyzed and compared. Receiver operating characteristic (ROC) curve analyses were conducted. Results: Ktrans, rKtrans, Ve, CBV and rCBV were significantly different between low grade glioma and high grade glioma (p = 0.001, 0.014, 0.02, 0.025, and 0.034, respectively). The areas under the ROC curve for Ktrans, rKtrans, Ve, rCBV and CBV were 0.986, 0.896, 0.829, 0.852, and 0.833, respectively. Ktrans was the best parameter for differentiating low grade glioma from high grade glioma with cutoff value of 0.0091 min-1 (sensitivity 100%, specificity 80%, PPV 87.5%, NPV 100%, accuracy 94.1%). Conclusion: DCE-MRI could be used to estimate neovascular permeability and for pre-operative grading of glioma. Among the perfusion parameters, Ktrans was the best parameter for differentiating low grade glioma from high grade glioma . DCE-MRI may be promising for better diagnostic performance than DSC-MRI.

Functional magnetic resonance imaging (fMRI) techniques can be used to assess cerebrovascular dysfunction in Alzheimer’s disease, an important and early contributor to pathology. We hypothesized that bradykinin receptor inhibition alleviates the vascular dysfunction in a transgenic arcAβ mouse model of cerebral amyloidosis and that fMRI techniques can be used to monitor the treatment response. Transgenic arcAβ mice, and non-transgenic littermates of 14 months-of-age were either treated with the bradykinin receptors 1 and 2 blocker noscapine or received normal drinking water as control over 3 months (n = 8–11/group) and all mice were assessed using fMRI at the end of the treatment period. Perfusion MRI using an arterial spin labeling technique showed regional hypoperfusion in arcAβ compared to non-transgenic controls, which was alleviated by noscapine treatment. Similarly, measuring cerebral blood volume changes upon pharmacological stimulation using vessel dilator acetazolamide revealed recovery of regional impairment of cerebral vascular reactivity in arcAβ mice upon noscapine treatment. In addition, we assessed with immunohistochemistry beta-amyloid (Aβ) and inflammation levels in brain sections. Immunohistological stainings for Aβ deposition (6E10) and related microgliosis (Iba1) in the cortex and hippocampus were found comparable between noscapine-treated and untreated arcAβ mice. In addition, levels of soluble and insoluble Aβ38, Aβ40, Aβ42 were found to be similar in brain tissue homogenates of noscapine-treated and untreated arcAβ mice using electro-chemiluminescent based immunoassay. In summary, bradykinin receptors blockade recovered cerebral vascular dysfunction in a mouse model of cerebral amyloidosis. fMRI methods revealed the functional deficit in disease condition and were useful tools to monitor the treatment response.

Background and Objective: 200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans., Methods: Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (V p ), volume of extravascular extracellular space (EES) per volume of tissue (V e ), blood-brain barrier (BBB) permeability (K trans ), and time constant for gadolinium reflux from EES back into the vascular system (K ep ). Between-group comparisons were performed using rank-sum analysis, and bootstrapping evaluated likely reproducibility of the results., Results: Among 13 pMRI datasets (11 nGBM, 2 recurrent GBM), therapies included temozolomide-only ( n = 9) and temozolomide + TTFields ( n = 4). No significant differences were found in patient or tumor characteristics. Compared to temozolomide-only, temozolomide + TTFields did not significantly affect the percent-change in pMRI metrics from baseline to 2 months. But during the 2- to 6-month period, temozolomide + TTFields significantly increased the percent-change in nRCBV (+26.9% [interquartile range 55.1%] vs -39.1% [37.0%], p = 0.049), sRCBV (+9.5% [39.7%] vs -30.5% [39.4%], p = 0.049), K trans (+54.6% [1768.4%] vs -26.9% [61.2%], p = 0.024), V e (+111.0% [518.1%] vs -13.0% [22.5%], p = 0.048), and V p (+98.8% [2172.4%] vs -24.6% [53.3%], p = 0.024) compared to temozolomide-only., Conclusion: Using pMRI, we provide initial in-human validation of pre-clinical studies regarding the effects of TTFields on tumor blood volume and BBB permeability in GBM., Competing Interests: Declaration of conflicting interestshe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CBP is a co-inventor on patents with Novocure, Ltd. related to TTFields and has served as a consultant and on advisory boards with Novocure, Ltd. CBP declares research support from the AACR-Novocure Career Development Award for TTFields Research (22-20-62-PATE).

Perfusion measures of the total vasculature are commonly derived with gradient-echo (GE) dynamic susceptibility contrast (DSC) MR images, which are acquired during the early passes of a contrast agent. Alternatively, spin-echo (SE) DSC can be used to achieve specific sensitivity to the capillary signal. For an improved contrast-to-noise ratio, ultra-high-field MRI makes this technique more appealing to study cerebral microvascular physiology. Therefore, this study assessed the applicability of SE-DSC MRI at 7 T. Forty-one elderly adults underwent 7 T MRI using a multi-slice SE-EPI DSC sequence. The cerebral blood volume (CBV) and cerebral blood flow (CBF) were determined in the cortical grey matter (CGM) and white matter (WM) and compared to values from the literature. The relation of CBV and CBF with age and sex was investigated. Higher CBV and CBF values were found in CGM compared to WM, whereby the CGM-to-WM ratios depended on the amount of largest vessels excluded from the analysis. CBF was negatively associated with age in the CGM, while no significant association was found with CBV. Both CBV and CBF were higher in women compared to men in both CGM and WM. The current study verifies the possibility of quantifying cerebral microvascular perfusion with SE-DSC MRI at 7 T.

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 (CBV dHb ) rather than CVR. With this in mind, a new method was implemented to map a marker of CBV dHb , 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emma Biondetti reports financial support was provided by European Union, Italian Ministry of Education, University and Research. Richard G. Wise reports financial support was provided by European Union, Wellcome Trust. Michael Germuska reports financial support was provided by Wellcome Trust, UK Engineering and Physical Sciences Research Council. Kevin Murphy reports financial support was provided by Wellcome Trust. Valentina Tomassini reports financial support was provided by Multiple Sclerosis Society UK. Valentina Tomassini reports a relationship with Biogen, Almirall, Lundbeck, Roche, Novartis, Viatris, Alexion that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)