Increase In Cerebral Blood Volume Research Articles

Peculiarities of cerebral blood flow and vascular reactivity in patients with large and giant tumors of the cerebello-pontine angle

Background. Vestibular schwannomas and posterior fossa meningiomas are one of the most difficult tumors for surgical treatment. The mortality rate after their removal reaches 13,5 %. The main causes of death are hemorrhagic and ischemic complications. There are no studies in the literature on tissue perfusion of brainstem structures and cerebellum and reactivity of vertebral and basilar arteries in patients with extraaxial tumors of the posterior cranial fossa. Therefore, the study of the blood supply of the brainstem structures and cerebellum, as well as the functional characteristics of the vertebral and basilar arteries in these patients is of considerable interest.Aim. To evaluate tissue perfusion of the pons and cerebellum, as well asthe reactivity of the vertebral and basilar arteries in patients with large and giant vestibular schwannomas and posterior fossa meningiomas.Materials and methods. Eighty-two patients with large and giant extraaxial tumors of the base of the posterior cranial fossa were examined. The median age was 54 [44; 61] years. Vestibular schwannomas were diagnosed in 52.4 % of patients, and meningiomas of the posterior cranial fossa were diagnosed in 47.6 %. All patients underwent duplex scanning of the basilar and vertebral arteries. We evaluated linear blood flow and coefficients of reactivity and index of vasomotor reactivity. We investigated the metabolic reactivity of cerebral blood flow by conducting hyper- and hypocapnic tests. Computed tomography perfusion imaging was performed in 18 patients. We detected cerebral blood volume, cerebral blood flow, mean transit time of contrast agent and time to peak of contrast agent. Measurements were carried out in six regions of interest located symmetrically on the pons and in the white matter of the cerebellar hemispheres on the side of the tumor and on the opposite side.Results. Linear blood flow rates in the intracranial segments of the vertebral and the basilar arteries in patients with tumors were higher than in the comparison group (p<0.05). These patients are characterized by a decrease of reactivity coefficients in the vertebral and basilar arteries, especially when performing hypercapnic tests (p <0.05). Paradoxical reactivity and areactivity were diagnosed in 34.9 % of patients with vestibularschwannomas and 25.6 % with meningiomas. In the pons on the side of the tumor in patients with vestibularschwannomas, a decrease in cerebral blood flow by 19.3 %, an increase in cerebral blood volume by 33.3 % and an increase in mean transit time of contrast agent and in time to peak of contrast agent by 48.1 % and 71.1 % (p <0.05) were found. In patients with meningiomas in the pons on the side of the tumor, all perfusion parameters were higher (p<0.05). In the deep regions of the cerebellar hemisphere on the side of the tumor in patients with tumors, all perfusion parameters were higher compared to the opposite side.Conclusion. The results of the study made it possible to quantify cerebral blood flow in patients with large and giant vestibular schwannomas and meningiomas of the posterior cranial fossa base. The revealed changes indicate the risk of developing pathological vascular reactions and disorders of cerebral blood flow in the postoperative period.

Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Perioperative Craniotomy Excision of Dextra Subtemporal Tumor with Thiopental, Sufentanyl and Invasive Monitor

Intracranial masses can arise from a variety of aetiologies, including congenital, neoplastic, infectious, or vascular processes, each requiring distinct diagnostic and management considerations. Establishing the presence or absence of intracranial hypertension is a critical component of the preoperative evaluation for patients undergoing craniotomy for mass lesions. Hemodynamic is an examination of the physical aspects of blood circulation, cardiac function and physiological characteristics of peripheral vasculature. A 74 year old man was admitted to the hospital because of cephalgia, and left limb weakness. Previously, the patient often felt headaches that came and went since six months ago. Three days before being admitted, the patient felt weak in his left limb and experienced decreasing in consciousness. The patient was given thiopental because the onset of action of thiopental was very short. Administration of intravenous doses of thiopental can cause cerebral vasoconstriction. Sufentanil was administered as an analgesic, because sufentanil is an opioid that has a rapid onset and analgesic potential, compared to fentanyl, intravenous and sufentanil is 5–10 times stronger. This efficacy to maintain adequate cerebral perfusion pressure (CPP), reduce cerebral blood flow (CBF), maintain normal autoregulation, reduce cerebral metabolic rate for oxygen (CMRO2). Arterial cannulation with continuous transduction is considered the gold standard for blood pressure monitoring during anaesthetic procedures. Rapid fluctuations in blood pressure can occur due to patient positioning, surgical manipulation, and the effects of anaesthetics drugs, and close monitoring of these changes is crucial for maintaining hemodynamic stability. The impact of anaesthetic management on CBF is also an integral component of neuroanesthesia, as increases in CBF are associated with increases in cerebral blood volume (CBV). An effective neuro-anesthesia management program that incorporates both invasive blood pressure monitoring and optimization of cerebral perfusion that can help preserving hemodynamic stability and improving outcomes for patients undergoing craniotomy surgery

Differentiation Between High-Grade Glioma and Brain Metastasis Using Cerebral Perfusion-Related Parameters (Cerebral Blood Volume and Cerebral Blood Flow): A Systematic Review and Meta-Analysis of Perfusion-weighted MRI Techniques.

Distinguishing high-grade gliomas (HGGs) from brain metastases (BMs) using perfusion-weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear. To compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation. Systematic review and meta-analysis. Twenty-four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488). Arterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast-enhanced (DSCE) sequences at 1.5 T and 3.0 T. Following the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs. Standardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I2 statistic was used to assess statistical heterogeneity. A P-value<0.05 was considered significant. HGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05-0.69) and CBV (SMD = 0.26, 95% CI: 0.01-0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08). ASL-derived CBF may be more useful than DSC-derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible. Stage 2.

Altitude illnesses.

Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.

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

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

Prediction of Intracranial Atherosclerotic Disease-Related Large-Vessel Occlusion Stroke on the Basis of Novel Cerebral Blood Volume Parameters.

Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P<0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD. An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.

Abstract TMP78: Using Interventional CT Perfusion Imaging To Evaluate Cerebral Blood Volume Surrounding Intracerebral Hemorrhage Site Following Minimally Invasive Evacuation

Introduction: Computed tomography perfusion (CTP) characterizes hemodynamic changes within brain tissue, particularly after stroke. This study aims to quantify cerebral blood volume (CBV) changes and identify predictors of CBV increase in the pericavity parenchyma after minimally invasive intracerebral hemorrhage evacuation (MIS for ICH). Methods: Thirty-two patients underwent MIS for ICH with pre/postoperative native CT imaging and intraoperative perfusion imaging (DynaCT PBV Neuro, Artis Q, Siemens). Scans were segmented using ITK-SNAP software to calculate hematoma volumes pre/post-evacuation and to delineate the pericavity tissue. Helical CT segmentations were registered to cone beam CT data using elastix software. Mean CBVs were computed inside subvolumes by dilating the segmentations with spheres with varying diameters. Results: In 27 patients with complete imaging, CTP analysis demonstrated significant increases in CBV from the 6 mm to 20 mm pericavity regions. CBV increased on average 32.7% from 2.27 mL/100mg (IQR 1.87-3.02) to 2.80 mL/100mg (2.41-3.61) in the 10 mm pericavity region (P=0.003). Factors associated with increased CBV in the univariate analysis (P≤0.10) included age (P=0.082) and percentage of hematoma evacuation (P=0.078). Upon multivariate linear regression, age (OR 4.49, [95% CI, 1.01-1.98], P=0.048) and percentage of hematoma evacuation (OR 4.09, [95% CI, 1.70-9.84], P=0.046) remained significantly predictive of increased CBV. Conclusions: CTP analysis demonstrated a significant increase in pericavity cerebral blood volume after MIS for ICH. Patient age and hematoma evacuation percentage may be predictive of CBV increase after MIS for ICH. Figure 1: Topographic map showing blood flow improvement at different distances from the lesion.

Cerebral hemodynamic response during the resuscitation period after hypoxic-ischemic insult predicts brain injury on day 5 after insult in newborn piglets

Perinatal hypoxic-ischemic brain injury of neonates remains a significant problem worldwide. During the resuscitation period, changes in cerebral hemoglobin oxygen saturation (ScO2) have been identified by near-infrared spectroscopy (NIRS). However, in asphyxiated neonates, the relationship between these changes and brain injury is not known. Three-wavelength near-infrared time-resolved spectroscopy, an advanced technology for NIRS, allows for the estimation of ScO2 and cerebral blood volume (CBV). Here, we studied changes in ScO2 and CBV during the resuscitation period after hypoxic-ischemic insult and the relationship between these changes after insult and histopathological brain injuries on day 5 after insult using an asphyxiated piglet model. Of 36 newborn piglets subjected to hypoxic-ischemic insult, 29 were analyzed. ScO2 and CBV were measured 0, 5, 10, 15, and 30 min after the insult. Brain tissue was histologically evaluated on day 5. ScO2 and CBV increased immediately after the insult, reached a peak, and then maintained a consistent value. The increase in CBV 5 to 30 min after the insult was significantly correlated with histopathological injury scores. However, there was no correlation with ScO2. In conclusion, an increase in CBV within 30 min after hypoxic-ischemic insult reflects the histopathological brain injury on day 5 after insult in a piglet model.

Association between cerebral blood flow changes and blood–brain barrier compromise in spontaneous intracerebral haemorrhage

To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the association between the alterations in cerebral blood flow and BBB permeability around the haematoma. Spontaneous ICH patients underwent unenhanced computed tomography (CT) and CT perfusion (CTP) simultaneously. Haematoma volume was measured on CT. The values of cerebral haemodynamic parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and permeability-surface area product (PS) were measured in the perihaematomal region and the contralateral mirror region, and then relative values were calculated for statistical analysis. Linear regression was used to evaluate associations between BBB permeability and variables. A total of 87 ICH patients were included in this study. The focally elevated BBB permeability was observed in the perihaematomal region in ICH patients. Linear regression showed that reduced rCBF (β=-0.379, p=0.001) and increased rCBV (β=0.412, p=0.000) correlated independently with increased relative PS (rPS) value in deep ICH, while only increased rCBV (β=0.423, p=0.071) correlated to increased rPS value in patients with lobar ICH. BBB permeability is focally elevated in the region around the haematoma. Cerebral haemodynamic alterations are associated with increased BBB permeability. Cerebral hypoperfusion may aggravate BBB compromise, and a compensatory increase in CBV may lead to reperfusion injury on BBB.

Differences in cerebral blood flow measurement using arterial spin labeling MRI between patients with moyamoya disease and patients with arteriosclerotic cerebrovascular disease.

It is unclear whether the accuracy of arterial spin labeling (ASL) magnetic resonance imaging (MRI) is the same between moyamoya disease (MMD), which is known to have markedly elevated cerebral blood volume (CBV), and atherosclerotic intracranial arterial stenosis (AS), which has relatively less elevated CBV. To investigate how the differences in hemodynamics affect measurement of ASL-cerebral blood flow (CBF) using ASL for patients with MMD and AS. Fourteen MMD and ten AS patients were evaluated with ASL-MRI, magnetic resonance angiography (MRA), and 15O-gas positron emission computed tomography (PET). The regional CBF values of ASL using two post-labeling delays (PLDs; 1525 ms and 2525 ms) were compared with the PET-derived CBF, CBV, and mean transit time (MTT). Corresponding anterior circulation results were evaluated by flow territory map-based analysis. The correlation between the ASL-CBF values (2525 ms) and PET-CBF declined in the MMD group (r = 0.28; P < 0.01), while the AS group showed good correlation (r = 0.77; P < 0.01). In the MMD group, the ASL-CBF values (2525 ms) overestimated the PET-CBF values as the regional CBV values increased (r = 0.35; P < 0.01). When the regions of interest were divided into two subgroups according to the degree of arterial stenosis by MRA, the correlation coefficient between the ASL-CBF (2525 ms) and PET-CBF values improved (mild stenosis: r = 0.36; P = 0.06; severe stenosis: r = 0.51; P < 0.01). The accuracy of CBF measurements using ASL-MRI differed between patients with MMD and AS. The prominent increase of CBV and the degree of arterial stenosis may have affected the accuracy of ASL-CBF in patients with MMD.

Cerebral Blood Perfusion is Improved Regionally After Shunt Surgery in the High-Pressure Hydrocephalic Brain.

To show the abnormal cerebral hemodynamics, in high-pressure hydrocephalic patients, could be restored by shunt surgery, and the tympanic membrane temperature (TMT) could be used to non-invasively monitor this recovery process. One-hundred-and-four patients, with high-pressure hydrocephalus (spinal tap opening pressure > 180 mmH2O), were prospectively enrolled in our study. The computed tomography perfusion (CTP) was scheduled for 7-10 days preand post-shunt surgery. The TMT and Glasgow Coma Scale (GCS) scores were collected during the same session. The CTP after the shunt surgery revealed a significant increase in cerebral blood volume (CBV) in both hemispheres (p < 0.05). More specifically, this CBV increase was observed in the midbrain, cerebellum, basal ganglion, temporal lobe, and frontal lobe regions (all p < 0.05). Simultaneously, patients' post-surgical TMT and GCS scores also increased compared to their pre-surgical scores since the first post-shunt follow-up (p < 0.01). Notably, while the GCS scores continued to increase during the post-shunt follow-up, the TMT exhibited a fluctuation period after the shunt and required seven days to reach a steady state. Our study revealed that a shunt could significantly increase cerebral perfusion in high-pressure hydrocephalic patients in a region-specific manner. During the perioperative period of hydrocephalus, TMT can be used to monitor cerebral hemodynamic changes.

Whole Brain CT Perfusion Evaluation in Transient Ischaemic Attack: A Cross-sectional Study from a Tertiary Care Centre, New Delhi, India

Introduction: Few studies exist in current literature regarding imaging features in Transient Ischaemic Attack (TIA) and most of the previous studies on Computed Tomography Perfusion (CTP) have used old generation scanners with limited brain coverage. Aim: To study the spectrum of whole brain CTP parameters in patients presenting with TIA using a 256 slice CT scanner. Materials and Methods: This cross -sectional observational study was conducted at tertiary care centre in New Delhi, India over a period of 18 months from October 2017 till March 2019. All patients presenting with the first episode of TIA were evaluated with Non Contrast Computed Tomography (NCCT), Whole brain CTP, and Color doppler of carotid vessels. Quantitative assessment and statistical analysis of the alteration of CT perfusion parameters was done in areas of visualized Focal Perfusion Abnormalities (FPA) and seven predefined locations in bilateral hemispheres on perfusion maps. Results: Five out of 15 patients had FPAs in the colour maps and there was a significant elevation of Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV) in the FPA region (p-value= 0.018) suggestive of postischaemic hyperperfusion. The mean hemispheric CBF was increased in the abnormal hemisphere compared to the normal hemisphere (p-value=0.04). Conclusion: CTP parameters are significantly altered in the patients with TIA with predominant increase in CBF and CBV in the patients who have FPA on CTP. CTP shows postischaemic hyperperfusion changes in the form of increased CBF in the hemisphere corresponding to the symptoms.

Visualizing cellularity and angiogenesis in newly-diagnosed glioblastoma with diffusion and perfusion MRI and FET-PET imaging

PurposeCombining imaging modalities has become an essential tool for assessment of tumor biology in glioblastoma (GBM) patients. Aim of this study is to understand how tumor cellularity and neovascularization are reflected in O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography ([18F] FET PET) and magnetic resonance imaging (MRI) parameters, including cerebral blood volume (CBV), fractional anisotropy (FA) and mean diffusivity (MD).MethodsIn this prospective cohort, 162 targeted biopsies of 43 patients with therapy-naïve, isocitrate dehydrogenase (IDH) wildtype GBM were obtained after defining areas of interest based on imaging parameters [18F] FET PET, CBV, FA and MD. Histopathological analysis of cellularity and neovascularization was conducted and results correlated to imaging data.ResultsANOVA analysis showed a significant increase of CBV in areas with high neovascularization. For diffusion metrics, and in particular FA, a trend for inverse association with neovascularization was found. [18F] FET PET showed a significant positive correlation to cellularity, while CBV also showed a trend towards correlation with cellularity, not reaching significant levels. In contrast, MD and FA were negatively associated with cellularity.ConclusionOur study confirms that amino acid PET and MR imaging parameters are indicative of histological tumor properties in glioblastoma and highlights the ability of multimodal imaging to assess tumor biology non-invasively.

Vascular endothelial growth factor associated dissimilar cerebrovascular phenotypes in two different mouse models of Alzheimer's Disease

Vascular perturbations and cerebral hypometabolism are emerging as important components of Alzheimer's disease (AD). While various in vivo imaging modalities have been designed to detect changes of cerebral perfusion and metabolism in AD patients and animal models, study results were often heterogenous with respect to imaging techniques and animal models. We therefore evaluated cerebral perfusion and glucose metabolism of two popular transgenic AD mouse strains, TgCRND8 and 5xFAD, at 7 and 12 months-of-age under identical conditions and analyzed possible molecular mechanisms underlying heterogeneous cerebrovascular phenotypes. Results revealed disparate findings in these two strains, displaying important aspects of AD progression. TgCRND8 mice showed significantly decreased cerebral blood flow and glucose metabolism with unchanged cerebral blood volume (CBV) at 12 months-of-age whereas 5xFAD mice showed unaltered glucose metabolism with significant increase in CBV at 12 months-of-age and a biphasic pattern of early hypoperfusion followed by a rebound to normal cerebral blood flow in late disease. Finally, immunoblotting assays suggested that VEGF dependent vascular tone change may restore normoperfusion and increase CBV in 5xFAD.

Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators.

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the “epileptic dip” in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

Cerebral blood volume increment after resuscitation measured by near-infrared time-resolved spectroscopy can estimate degree of hypoxic\u2013ischemic insult in newborn piglets

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.

Advanced imaging to assess longitudinal vascular changes in brain metastases treated with checkpoint inhibition.

3059 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. Several studies demonstrate that 20-50% of BM patients respond to ICI. The reasons behind this wide variability in treatment response is not clear. Therefore, using physiologic imaging, we seek to identify the longitudinal biological changes exerted on BM as a result of ICI administration. Methods: Given the importance of aberrant tumor vasculature in cancer proliferation, we have focused on assessing changes in vascular physiology. We analyzed standard post-contrast and dynamic susceptibility contrast (DSC) MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. As per modified RECIST and RANO criteria for immunotherapy, volumetric increase of &gt; 40% was defined as progressive disease (PD), a decrease of &gt; 60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 35 patients, out of the total cohort of 60, have undergone DSC-MRI analysis. Histologies include 15 with breast cancer, 6 with non-small cell lung cancer, 4 with melanoma, and 10 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 35 evaluable patients include 4 PR, 12 SD, and 19 PD. Thus far, we found that ICI-resistant BM had a 50% increase in cerebral blood flow (CBF), 105% increase in cerebral blood volume (CBV), a 15% increase in mean transit time (MTT), and an 80% increase in vessel caliber at 6 weeks post-treatment. On the other hand, ICI-responsive BM had no change in CBF, a 33% increase in CBV, a 10% decrease in MTT, and no change in vessel caliber. Ongoing analysis to uncover additional vascular changes (e.g. tumor oxygenation, vessel size index) within BM to ICI are pending. Conclusions: Our data provides evidence that effective ICI for BM is associated with unique intra-tumoral vascular physiology. With final analysis, we will uncover other facets of vascular physiology that correlate with ICI response, and may reveal mechanisms of response/resistance within tumors to ICI.

Assessment of Cerebral Autoregulation in the Perifocal Zone of a Chronic Subdural Hematoma.

The knowledge of conservative treatment modalities for a chronic subdural hematoma (CSDH) is still based on low-grade evidence. The purpose of this study was to evaluate the condition of the microcirculation and autoregulation in the perifocal CSDH zone for understanding of the mechanism of CSDH development. Cerebral microcirculation was evaluated in patients with the aid of brain perfusion computed tomography (PCT) within the first day. Perfusion parameters were assessed quantitatively in the cortex zone adjacent to the CSDH and in a similar zone of the contralateral hemisphere. The same PCT data were assessed quantitatively without and with use of a perfusion calculation mode excluding large-vessel voxels ("remote vessels" (RVs)) in the first and second methods, respectively. The first method of analysis of a similar zone in the contralateral hemisphere revealed significant increases in cerebral blood volume and cerebral blood flow (P<0.01) in comparison with normal values. Use of the second method with RVs showed no significant changes in perfusion parameters in microcirculatory blood flow in the cortex on the side contralateral to the hematoma. The persistence of microcirculatory blood flow perfusion reflects preservation of cerebral blood flow autoregulation in patients with a CSDH.

Neurovascular coupling and bilateral connectivity during NREM and REM sleep.

To understand how arousal state impacts cerebral hemodynamics and neurovascular coupling, we monitored neural activity, behavior, and hemodynamic signals in un-anesthetized, head-fixed mice. Mice frequently fell asleep during imaging, and these sleep events were interspersed with periods of wake. During both NREM and REM sleep, mice showed large increases in cerebral blood volume ([HbT]) and arteriole diameter relative to the awake state, two to five times larger than those evoked by sensory stimulation. During NREM, the amplitude of bilateral low-frequency oscillations in [HbT] increased markedly, and coherency between neural activity and hemodynamic signals was higher than the awake resting and REM states. Bilateral correlations in neural activity and [HbT] were highest during NREM, and lowest in the awake state. Hemodynamic signals in the cortex are strongly modulated by arousal state, and changes during sleep are substantially larger than sensory-evoked responses.