Changes In Cerebral Blood Volume Research Articles

Functional ultrasound neuroimaging reveals mesoscopic organization of saccades in the lateral intraparietal area of posterior parietal cortex.

The lateral intraparietal cortex (LIP) located within the posterior parietal cortex (PPC) is an important area for the transformation of spatial information into accurate saccadic eye movements. Despite extensive research, we do not fully understand the functional anatomy of intended movement directions within LIP. This is in part due to technical challenges. Electrophysiology recordings can only record from small regions of the PPC, while fMRI and other whole-brain techniques lack sufficient spatiotemporal resolution. Here, we use functional ultrasound imaging (fUSI), an emerging technique with high sensitivity, large spatial coverage, and good spatial resolution, to determine how movement direction is encoded across PPC. We used fUSI to record local changes in cerebral blood volume in PPC as two monkeys performed memory-guided saccades to targets throughout their visual field. We then analyzed the distribution of preferred directional response fields within each coronal plane of PPC. Many subregions within LIP demonstrated strong directional tuning that was consistent across several months to years. These mesoscopic maps revealed a highly heterogenous organization within LIP with many small patches of neighboring cortex encoding different directions. LIP had a rough topography where anterior LIP represented more contralateral upward movements and posterior LIP represented more contralateral downward movements. These results address two fundamental gaps in our understanding of LIP's functional organization: the neighborhood organization of patches and the broader organization across LIP. These findings were achieved by tracking the same LIP populations across many months to years and developing mesoscopic maps of direction specificity previously unattainable with fMRI or electrophysiology methods.

#658 Analysis of cerebral blood volume and flow changes in ESRD patients undergoing hemodialysis using functional near-infrared spectroscopy

Abstract Background and Aims End stage renal disease (ESRD) patients undergoing hemodialysis experience diverse neurological complications. However, studies regarding how hemodialysis is related to these neurological problems are limited. This study investigated cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. Method ESRD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 – HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. Results Thirty hemodialysis patients were analyzed. Between the Pre-HD and Post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p=0.046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p=0.029). Additionally, between Pre-HD and Post-HD periods, HbD tended to increase; however, this was not statistically significant (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p=0.094). Conclusion We demonstrated that during one hemodialysis session, the relative change in CBV increased post-HD compared with pre-HD. These results are expected to help understand the mechanisms underlying the effects of hemodialysis on brain function.

CO2 as an engine for neurofluid flow: Exploring the coupling between vascular reactivity, brain clearance, and changes in tissue properties.

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO2 ) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level-dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO2 -induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO2 ) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes.

Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations.

Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain's response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain's electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.

Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice

Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field potentials (LFP) during bicuculline-induced interictal events in both isoflurane-anesthetized and awake mice. Isoflurane significantly affected LFP amplitude but had little impact on the amplitude and area of the calcium signal. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread. Cerebral blood volume change provided the best spatial estimation of excitatory neuronal activity in both states. Targeted silencing of the thalamus in awake mice failed to recapitulate the impact of anesthesia on hemodynamic responses suggesting that isoflurane’s interruption of the thalamocortical loop did not contribute either to the dissociation between the LFP and the calcium signal nor to the alterations in interictal neurovascular coupling. The blood volume increase associated with interictal spikes represents a promising mapping signal in both the awake and anesthetized states.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

Time course of cerebral oxygenation and cerebrovascular reactivity in Kyrgyz highlanders. A five-year prospective cohort study.

Introduction: This prospective cohort study assessed the effects of chronic hypoxaemia due to high-altitude residency on the cerebral tissue oxygenation (CTO) and cerebrovascular reactivity. Methods: Highlanders, born, raised, and currently living above 2,500m, without cardiopulmonary disease, participated in a prospective cohort study from 2012 until 2017. The measurements were performed at 3,250m. After 20min of rest in supine position while breathing ambient air (FiO2 0.21) or oxygen (FiO2 1.0) in random order, guided hyperventilation followed under the corresponding gas mixture. Finger pulse oximetry (SpO2) and cerebral near-infrared spectroscopy assessing CTO and change in cerebral haemoglobin concentration (cHb), a surrogate of cerebral blood volume changes and cerebrovascular reactivity, were applied. Arterial blood gases were obtained during ambient air breathing. Results: Fifty three highlanders, aged 50 ± 2years, participated in 2017 and 2012. While breathing air in 2017 vs. 2012, PaO2 was reduced, mean ± SE, 7.40 ± 0.13 vs. 7.84 ± 0.13kPa; heart rate was increased 77 ± 1 vs. 70 ± 1bpm (p < 0.05) but CTO remained unchanged, 67.2% ± 0.7% vs. 67.4% ± 0.7%. With oxygen, SpO2 and CTO increased similarly in 2017 and 2012, by a mean (95% CI) of 8.3% (7.5-9.1) vs. 8.5% (7.7-9.3) in SpO2, and 5.5% (4.1-7.0) vs. 4.5% (3.0-6.0) in CTO, respectively. Hyperventilation resulted in less reduction of cHb in 2017 vs. 2012, mean difference (95% CI) in change with air 2.0 U/L (0.3-3.6); with oxygen, 2.1 U/L (0.5-3.7). Conclusion: Within 5years, CTO in highlanders was preserved despite a decreased PaO2. As this was associated with a reduced response of cerebral blood volume to hypocapnia, adaptation of cerebrovascular reactivity might have occurred.

Enhancing diffuse correlation spectroscopy pulsatile cerebral blood flow signal with near-infrared spectroscopy photoplethysmography.

Combining near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) allows for quantifying cerebral blood volume, flow, and oxygenation changes continuously and non-invasively. As recently shown, the DCS pulsatile cerebral blood flow index () can be used to quantify critical closing pressure (CrCP) and cerebrovascular resistance (). Although current DCS technology allows for reliable monitoring of the slow hemodynamic changes, resolving pulsatile blood flow at large source-detector separations, which is needed to ensure cerebral sensitivity, is challenging because of its low signal-to-noise ratio (SNR). Cardiac-gated averaging of several arterial pulse cycles is required to obtain a meaningful waveform. Taking advantage of the high SNR of NIRS, we demonstrate a method that uses the NIRS photoplethysmography (NIRS-PPG) pulsatile signal to model DCS , reducing the coefficient of variation of the recovered pulsatile waveform () and allowing for an unprecedented temporal resolution (266Hz) at a large source-detector separation (). In 10 healthy subjects, we verified the quality of the NIRS-PPG during common tasks, showing high fidelity against ( ). We recovered CrCP and at 0.25Hz, times faster than previously achieved with DCS. NIRS-PPG improves DCS SNR, reducing the number of gate-averaged heartbeats required to recover CrCP and .

Functional magnetic particle imaging (fMPI) of cerebrovascular changes in the rat brain during hypercapnia

Objective. Non-invasive functional brain imaging modalities are limited in number, each with its own complex trade-offs between sensitivity, spatial and temporal resolution, and the directness with which the measured signals reflect neuronal activation. Magnetic particle imaging (MPI) directly maps the cerebral blood volume (CBV), and its high sensitivity derives from the nonlinear magnetization of the superparamagnetic iron oxide nanoparticle (SPION) tracer confined to the blood pool. Our work evaluates functional MPI (fMPI) as a new hemodynamic functional imaging modality by mapping the CBV response in a rodent model where CBV is modulated by hypercapnic breathing manipulation. Approach. The rodent fMPI time-series data were acquired with a mechanically rotating field-free line MPI scanner capable of 5 s temporal resolution and 3 mm spatial resolution. The rat’s CBV was modulated for 30 min with alternating 5 min hyper-/hypocapnic states, and processed using conventional fMRI tools. We compare our results to fMRI responses undergoing similar hypercapnia protocols found in the literature, and reinforce this comparison in a study of one rat with 9.4T BOLD fMRI using the identical protocol. Main results. The initial image in the time-series showed mean resting brain voxel SNR values, averaged across rats, of 99.9 following the first 10 mg kg−1 SPION injection and 134 following the second. The time-series fit a conventional General Linear Model with a 15%–40% CBV change and a peak pixel CNR between 12 and 29, 2–6× higher than found in fMRI. Significance. This work introduces a functional modality with high sensitivity, although currently limited spatial and temporal resolution. With future clinical-scale development, a large increase in sensitivity could supplement other modalities and help transition functional brain imaging from a neuroscience tool focusing on population averages to a clinically relevant modality capable of detecting differences in individual patients.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

The impact of central and obstructive respiratory events on cerebral oxygenation in adults with sleep disordered breathing

Obstructive sleep apnea (OSA) and central sleep apnea (CSA) are two main types of sleep disordered breathing (SDB). While the changes in cerebral hemodynamics triggered by OSA events have been well studied using near-infrared spectroscopy (NIRS), they are essentially unknown in CSA in adults. Therefore, in this study, we compared the changes in cerebral oxygenation between OSA and CSA events in adult patients using NIRS. Cerebral tissue oxygen saturation (StO2) in 13 severe SDB patients who had both CSA and OSA events was measured using frequency-domain NIRS. The changes in cerebral StO2 desaturation and blood volume (BV) in the first hour of natural sleep were compared between different types of respiratory events (i.e., 277 sleep hypopneas, 161 OSAs and 113 CSAs) with linear mixed-effect models controlling for confounders. All respiratory events occurred during non-rapid eye movement (NREM) sleep. We found that apnea events induced greater cerebral desaturations and BV fluctuations compared to hypopneas, but there was no difference between OSA and CSA. These results suggest that cerebral autoregulation in our patients are still capable to counteract the pathomechanisms of apneas, in particularly the negative intrathoracic pressure (ITP) caused by OSA events. Otherwise larger BV fluctuations in OSA compared to CSA should be observed due to the negative ITP that reduces cardiac stroke volume and leads to lower systematic blood supply. Our study suggests that OSA and CSA may have similar impact on cerebral oxygenation during NREM sleep in adult patients with SDB.

Comparison of Cerebral Blood Volume during Cold and Warm Stimulation in Elderly and Young Subjects.

Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of temperature sensation declines. Studies measuring brain blood volume using near-infrared light have reported that patients suffering from dementia have less activation than healthy elderly people. However, the majority of these studies used tests related to cognitive function and the frontal lobe, and few have examined thermal sensation. The present study aimed to investigate the effect of cold and warm stimulation on cerebral blood volume in elderly and young subjects. This observational study measured changes in oxygenated hemoglobin concentrations in the frontal cortex during cold and warm stimulation in elderly and young subjects using a near-infrared light device. The mean and standard deviation of the change in oxygenated hemoglobin concentration before and after cold and warm stimulation, as well as the center-of-gravity values, were compared between the young and the elderly. During warm stimulation, the younger subjects showed an increase in blood oxygenated hemoglobin levels; however, the difference was not significant. For the elderly, no change was observed during the task. The center of gravity values was lower in the young compared to the elderly which was similar to the reaction threshold. No significant changes were observed during cold stimulation. Thermal sensation thresholds were impaired in the elderly compared to the young; however, cerebral blood volume changes were unclear.

Brain-wide mapping of resting-state networks in mice using high-frame rate functional ultrasound

Functional ultrasound (fUS) imaging is a method for visualizing deep brain activity based on cerebral blood volume changes coupled with neural activity, while functional MRI (fMRI) relies on the blood-oxygenation-level-dependent signal coupled with neural activity. Low-frequency fluctuations (LFF) of fMRI signals during resting-state can be measured by resting-state fMRI (rsfMRI), which allows functional imaging of the whole brain, and the distributions of resting-state network (RSN) can then be estimated from these fluctuations using independent component analysis (ICA). This procedure provides an important method for studying cognitive and psychophysiological diseases affecting specific brain networks. The distributions of RSNs in the brain-wide area has been reported primarily by rsfMRI. RSNs using rsfMRI are generally computed from the time-course of fMRI signals for more than 5 min. However, a recent dynamic functional connectivity study revealed that RSNs are still not perfectly stable even after 10 min. Importantly, fUS has a higher temporal resolution and stronger correlation with neural activity compared with fMRI. Therefore, we hypothesized that fUS applied during the resting-state for a shorter than 5 min would provide similar RSNs compared to fMRI. High temporal resolution rsfUS data were acquired at 10 Hz in awake mice. The quality of the default mode network (DMN), a well-known RSN, was evaluated using signal-noise separation (SNS) applied to different measurement durations of rsfUS. The results showed that the SNS did not change when the measurement duration was increased to more than 210 s. Next, we measured short-duration rsfUS multi-slice measurements in the brain-wide area. The results showed that rsfUS with the short duration succeeded in detecting RSNs distributed in the brain-wide area consistent with RSNs detected by 11.7-T MRI under awake conditions (medial prefrontal cortex and cingulate cortex in the anterior DMN, retrosplenial cortex and visual cortex in the posterior DMN, somatosensory and motor cortexes in the lateral cortical network, thalamus, dorsal hippocampus, and medial cerebellum), confirming the reliability of the RSNs detected by rsfUS. However, bilateral RSNs located in the secondary somatosensory cortex, ventral hippocampus, auditory cortex, and lateral cerebellum extracted from rsfUS were different from the unilateral RSNs extracted from rsfMRI. These findings indicate the potential of rsfUS as a method for analyzing functional brain networks and should encourage future research to elucidate functional brain networks and their relationships with disease model mice.

Dissociated coupling between cerebral oxygen metabolism and perfusion in the prefrontal cortex during exercise: a NIRS study.

Purpose: The present study used near-infrared spectroscopy to investigate the relationships between cerebral oxygen metabolism and perfusion in the prefrontal cortex (PFC) during exercises of different intensities. Methods: A total of 12 recreationally active men (age 24 ± 6years) were enrolled. They performed 17min of low-intensity exercise (ExL), followed by 3min of moderate-intensity exercise (ExM) at constant loads. Exercise intensities for ExL and ExM corresponded to 30% and 45% of the participants' heart rate reserve, respectively. Cardiovascular and respiratory parameters were measured. We used near-infrared time-resolved spectroscopy (TRS) to measure the cerebral hemoglobin oxygen saturation (ScO2) and total hemoglobin concentration ([HbT]), which can indicate the cerebral blood volume (CBV). As the cerebral metabolic rate for oxygen (CMRO2) is calculated using cerebral blood flow (CBF) and ScO2, we assumed a constant power law relationship between CBF and CBV based on investigations by positron emission tomography (PET). We estimated the relative changes in CMRO2 (rCMRO2) and CBV (rCBV) from the baseline. During ExL and ExM, the rate of perceived exertion was monitored, and alterations in the subjects' mood induced by exercise were evaluated using the Profile of Moods Scale-Brief. Results: Three minutes after exercise initiation, ScO2 decreased and rCMRO2 surpassed rCBV in the left PFC. When ExL changed to ExM, cardiovascular variables and the sense of effort increased concomitantly with an increase in [HbT] but not in ScO2, and the relationship between rCMRO2 and rCBV was dissociated in both sides of the PFC. Immediately after ExM, [HbT], and ScO2 increased, and the disassociation between rCMRO2 and rCBV was prominent in both sides of the PFC. While blood pressure decreased and a negative mood state was less prominent following ExM compared with that at rest, ScO2 decreased 15min after exercise and rCMRO2 surpassed rCBV in the left PFC. Conclusion: Dissociated coupling between cerebral oxidative metabolism and perfusion in the PFC was consistent with the effort required for increased exercise intensity and associated with post-exercise hypotension and altered mood status after exercise. Our result demonstrates the first preliminary results dealing with the coupling between cerebral oxidative metabolism and perfusion in the PFC using TRS.

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

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

Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.

We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.

Evaluation of Non-invasive Optogenetic Stimulation with Transcranial Functional Ultrasound Imaging.

Optogenetics employs engineered viruses to genetically modify cells to express specific light-sensitive ion channels. The standard method for gene delivery in the brain involves invasive craniotomies that expose the brain and direct injections of viruses that invariably damage neural tissue along the syringe tract. A recently proposed alternative in which non-invasive optogenetics is performed with focused ultrasound (FUS)-mediated blood-brain barrier (BBB) openings has been found to non-invasively facilitate gene delivery for optogenetics in mice. Although gene delivery can be performed non-invasively, validating successful viral transduction and expression of encoded ion channels in target tissue typically involves similar invasive techniques, such as craniotomies in longitudinal studies and/or postmortem histology. Functional ultrasound imaging (fUSi) is an emerging neuroimaging technique that can be used to transcranially detect changes in cerebral blood volume following introduction of a stimulus. In this study, we implemented a fully non-invasive combined FUS-fUSi technique for performing optogenetics in mice. FUS successfully delivered viruses encoding the red-shifted channelrhodopsin variant ChrimsonR in all treated subjects. fUSi successfully identified stimulus-evoked cerebral blood volume changes preferentially in brain regions expressing the light-sensitive ion channels. Improvements in cell-specific targeting of viral vectors and transcranial ultrasound imaging will make the combined technique a useful tool for neuroscience research in small animals.

Impact of cardiopulmonary bypass on cerebrovascular autoregulation assessed by ultrafast ultrasound imaging.

Newborns with congenital heart disease undergoing cardiac surgery are at risk of neurodevelopmental impairment with limited understanding of the impact of intra-operative cardiopulmonary bypass (CPB), deep hypothermia and selective cerebral perfusion on the brain. We hypothesized that a novel ultrasound technique, ultrafast power Doppler (UPD), can assess variations of cerebral blood volume (CBV) in neonates undergoing cardiac surgery requiring CPB. UPD was performed before, during and after surgery in newborns with hypoplastic left heart syndrome undergoing a Norwood operation. We found that global CBV was not significantly different between patients and controls (P=0.98) and between pre- and post-surgery (P=0.62). UPD was able to monitor changes in CBV throughout surgery, revealing regional differences in CBV during hypothermia during which CBV correlated with CPB flow rate (R2 =0.52, P=0.021). Brain injury on post-operative magnetic resonance imaging was observed in patients with higher maximum variation in CBV. Our findings suggest that UPD can quantify global and regional brain perfusion variation during neonatal cardiac surgery with this first intra-operative application demonstrating an association between CBV and CPB flow rate, suggesting loss of autoregulation. Therefore, the measurement of CBV by UPD could enable optimization of cerebral perfusion during cardiac surgery in neonates. KEY POINTS: The impact of cardiopulmonary bypass (CPB) on the neonatal brain undergoing cardiac surgery is poorly understood. Ultrafast power Doppler (UPD) quantifies cerebral blood volume (CBV), a surrogate of brain perfusion. CBV varies throughout CPB surgery and is associated with variation of the bypass pump flow rate during deep hypothermia. Association between CBV and bypass pump flow rate suggests loss of cerebrovascular autoregulatory processes. Quantitative monitoring of cerebral perfusion by UPD could provide a direct parameter to optimize CPB flow rate.

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.

Early post-bevacizumab change in rCBV from DSC-MRI identifies pseudoresponse in recurrent glioblastoma: Results from ACRIN 6677/RTOG 0625.

Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival. 37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively. Mean CBV normalized to white matter (nRCBV) and mean standardized CBV (sRCBV) were extracted from enhancing tumor. ROC curves were derived for ΔCBV using six-month PFS and one-year OS as reference standards. Kaplan-Meier survival estimates and log-rank test compared PFS and OS for both ΔCBV (increase vs. decrease) and T1 response status (stable vs. decreasing enhancement). PFS and OS were significantly worse for increasing CBV at 2 weeks (p=0.003 and p=0.002 for nRCBV, and p=0.03 and p=0.03 for sRCBV, respectively), but not for 2D-T1 patients with stable vs. decreasing enhancement (p=0.44 and p=0.86, respectively). ΔCBV at week 2 was also a good prognostic marker for OS-1 and PFS-6 using ROC analysis. By contrast, 2D-T1 response status at weeks 2, 8, and 16 was not associated with PFS-6. ΔCBV at 16 weeks (p=0.008 for sRCBV) but not 8 weeks (p=0.74 for nRCBV and p=0.56 for sRCBV) was associated with significant difference in median survival, but no difference in survival was observed for 2D-T1 patients with stable vs. decreasing enhancement at 8 weeks (p=0.69) or 16 weeks (p=0.21). At 16 weeks, OS did not differ significantly between 2D-T1 progressors and 2D-T1 non-progressors with increasing CBV (median survival 3.3 months post week 16 scan vs. 9.2 months, respectively; p=0.13), suggesting that 2D-T1 non-progressors with increasing CBV may have a prognosis like that of 2D-T1 progressors. After 2 weeks of anti-angiogenic therapy, ΔCBV in 2D-T1 non-progressors significantly prognosticated PFS and OS, whereas 2D-T1 response status did not, identifying a subpopulation that benefits from bevacizumab. Combining 2D-T1 progression and ΔCBV may yield a response assessment paradigm with 3-tiered OS stratification.