Monitoring Of Cerebral Blood Flow Research Articles

Visualization of Blood-Brain Barrier Disruption in Septic Mice with the New Method Based on in Vivo Imaging Technology.

Dynamic monitoring of the blood-brain barrier (BBB) functional status in septic mice can help to explore the pathological mechanisms. Therefore, we proposed a new method for monitoring BBB permeability and applied it to the detection of sepsis models. The new method involves the construction of an optical cranial window and in vivo imaging. We performed dynamic monitoring of BBB permeability and cerebral blood flow (CBF) in cecal ligation puncture (CLP) and endotoxemia (lipopolysaccharide [LPS]) mice. The sensitivity and accuracy of this method were higher than those of Evans blue evaluation. The increase of BBB permeability in the group of CLP mice was relatively mild and correlated with overall survival, and the damage was irreversible. Contrarily, BBB damage in the LPS group was more acute and severe, unrelated to overall survival, but recoverable. The CBF decreased significantly in both model mouse groups 24h after modeling, but only the CBF proportion decrease in the LPS group was significantly correlated with an increase in BBB permeability. Within 24h after both models were established, the decrease in blood flow in the digestive organs occurred earlier than in the brain and kidneys, and the decrease in small intestine blood flow in the LPS group progressed faster. We have successfully demonstrated the feasibility of our novel method to detect BBB permeability in mice. Our results revealed a significant difference in the BBB permeability change trend between the CLP and LPS model mice when survival curves were consistent. Notably, the CLP-model mice demonstrated a closer resemblance to clinical patients. Our findings suggest that early-stage brain tissue hypoperfusion has a greater impact on BBB function damage in endotoxemia mice, which is related to the faster progression of blood flow redistribution.

Pathlength-selective, interferometric diffuse correlation spectroscopy (PaLS-iDCS).

Diffuse correlation spectroscopy (DCS) is an optical method that offers non-invasive assessment of blood flow in tissue through the analysis of intensity fluctuations in diffusely backscattered coherent light. The non-invasive nature of the technique has enabled several clinical applications for deep tissue blood flow measurements, including cerebral blood flow monitoring as well as tumor blood flow mapping. While a promising technique, in measurement configurations targeting deep tissue hemodynamics, the standard DCS implementations suffer from insufficient signal-to-noise ratio (SNR), depth sensitivity, and sampling rate, limiting their utility. In this work, we present an enhanced DCS method called pathlength-selective, interferometric DCS (PaLS-iDCS), which improves upon both the sensitivity of the measurement to deep tissue hemodynamics and the SNR of the measurement using pathlength-specific coherent gain. Through interferometric detection, PaLS-iDCS can provide time-of-flight (ToF) specific blood flow information without the use of expensive time-tagging electronics and low-jitter detectors. The new technique is compared to time-domain DCS (TD-DCS), another enhanced DCS method able to resolve photon ToF in tissue, through Monte Carlo simulation, phantom experiments, and human subject measurements. PaLS-iDCS consistently demonstrates improvements in SNR (>2x) for similar measurement conditions (same photon ToF), and the SNR improvements allow for measurements at extended photon ToFs, which have increased sensitivity to deep tissue hemodynamics (~50% increase). Further, like TD-DCS, PaLS-iDCS allows direct estimation of tissue optical properties from the sampled ToF distribution without the need for a separate spectroscopic measurement. This method offers a relatively straightforward way to allow DCS systems to make robust measurements of blood flow with greatly enhanced sensitivity to deep tissue hemodynamics, enabling further applications of this non-invasive technology.

Electroacupuncture enhances cerebral blood perfusion by inhibiting HIF-1α in rat subarachnoid hemorrhage

ObjectiveCerebral blood perfusion (CBP) reduction is a prevalent complication following subarachnoid hemorrhage (SAH) in clinical practice, often associated with long-term cognitive impairment and prognosis. Electroacupuncture (EA), a widely utilized traditional Chinese therapy for central nervous system disorders, has demonstrated promising therapeutic effects. This study aims to investigate the therapeutic potential of EA in restoring CBP in SAH rats and to explore the mechanisms involving HIF-1α in this process. MethodsRats were randomly assigned to one of five groups, including Sham, SAH, EA, EA + Saline, and EA + dimethyloxallyl glycine (DMOG) groups. EA treatment was administered for 10 min daily, while DMOG were intraperitoneally injected. Behavioral tests, cerebral blood flow monitoring, vascular thickness measurement, western blotting, and immunofluorescence staining were conducted to assess the therapeutic effects of EA on cerebral blood flow. ResultsSAH resulted in elevated levels of HIF-1α, endothelin (ET), ICAM-1, P-SELECTIN, E-SELECTIN, and decreased level of eNOS in the brain. This led to cerebral vasospasm, decreased CBF, and cognitive deficits in the rat SAH model. EA intervention downregulated the expression of HIF-1α, ET, ICAM-1, P-SELECTIN, and E-SELECTIN, while increasing eNOS expression. This alleviated cerebral vasospasm, restored CBF, and improved cognitive function. However, the administration of the HIF-1α stabilizer (DMOG) counteracted the therapeutic effects of EA. ConclusionEA promotes the recovery of cerebral blood flow after SAH injury, attenuates cerebral vasospasm, and accelerates the recovery of cognitive dysfunction, and its mechanism of action may be related to the inhibition of the HIF-1α signaling pathway.

Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke

BackgroundEarly detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we...

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants. DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver.

Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), ; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 ). Beat-to-beat rBV and CBFv were also strongly correlated, , but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Finite difference-embedded UNet for solving transcranial ultrasound frequency-domain wavefield.

Transcranial ultrasound imaging assumes a growing significance in the detection and monitoring of intracranial lesions and cerebral blood flow. Accurate solution of partial differential equation (PDE) is one of the prerequisites for obtaining transcranial ultrasound wavefields. Grid-based numerical solvers such as finite difference (FD) and finite element methods have limitations including high computational costs and discretization errors. Purely data-driven methods have relatively high demands on training datasets. The fact that physics-informed neural network can only target the same model limits its application. In addition, compared to time-domain approaches, frequency-domain solutions offer advantages of reducing computational complexity and enabling stable and accurate inversions. Therefore, we introduce a framework called FD-embedded UNet (FEUNet) for solving frequency-domain transcranial ultrasound wavefields. The PDE error is calculated using the optimal 9-point FD operator, and it is integrated with the data-driven error to jointly guide the network iterations. We showcase the effectiveness of this approach through experiments involving idealized skull and brain models. FEUNet demonstrates versatility in handling various input scenarios and excels in enhancing prediction accuracy, especially with limited datasets and noisy information. Finally, we provide an overview of the advantages, limitations, and potential avenues for future research in this study.

Dynamic cerebral blood flow assessment based on electromagnetic coupling sensing and image feature analysis.

Dynamic assessment of cerebral blood flow (CBF) is crucial for guiding personalized management and treatment strategies, and improving the prognosis of stroke. However, a safe, reliable, and effective method for dynamic CBF evaluation is currently lacking in clinical practice. In this study, we developed a CBF monitoring system utilizing electromagnetic coupling sensing (ECS). This system detects variations in brain conductivity and dielectric constant by identifying the resonant frequency (RF) in an equivalent circuit containing both magnetic induction and electrical coupling. We evaluated the performance of the system using a self-made physical model of blood vessel pulsation to test pulsatile CBF. Additionally, we recruited 29 healthy volunteers to monitor cerebral oxygen (CO), cerebral blood flow velocity (CBFV) data and RF data before and after caffeine consumption. We analyzed RF and CBFV trends during immediate responses to abnormal intracranial blood supply, induced by changes in vascular stiffness, and compared them with CO data. Furthermore, we explored a method of dynamically assessing the overall level of CBF by leveraging image feature analysis. Experimental testing substantiates that this system provides a detection range and depth enhanced by three to four times compared to conventional electromagnetic detection techniques, thereby comprehensively covering the principal intracranial blood supply areas. And the system effectively captures CBF responses under different intravascular pressure stimulations. In healthy volunteers, as cerebral vascular stiffness increases and CO decreases due to caffeine intake, the RF pulsation amplitude diminishes progressively. Upon extraction and selection of image features, widely used machine learning algorithms exhibit commendable performance in classifying overall CBF levels. These results highlight that our proposed methodology, predicated on ECS and image feature analysis, enables the capture of immediate responses of abnormal intracranial blood supply triggered by alterations in vascular stiffness. Moreover, it provides an accurate diagnosis of the overall CBF level under varying physiological conditions.

Comparing the performance potential of speckle contrast optical spectroscopy and diffuse correlation spectroscopy for cerebral blood flow monitoring using Monte Carlo simulations in realistic head geometries.

The non-invasive measurement of cerebral blood flow based on diffuse optical techniques has seen increased interest as a research tool for cerebral perfusion monitoring in critical care and functional brain imaging. Diffuse correlation spectroscopy (DCS) and speckle contrast optical spectroscopy (SCOS) are two such techniques that measure complementary aspects of the fluctuating intensity signal, with DCS quantifying the temporal fluctuations of the signal and SCOS quantifying the spatial blurring of a speckle pattern. With the increasing interest in the use of these techniques, a thorough comparison would inform new adopters of the benefits of each technique. We systematically evaluate the performance of DCS and SCOS for the measurement of cerebral blood flow. Monte Carlo simulations of dynamic light scattering in an MRI-derived head model were performed. For both DCS and SCOS, estimates of sensitivity to cerebral blood flow changes, coefficient of variation of the measured blood flow, and the contrast-to-noise ratio of the measurement to the cerebral perfusion signal were calculated. By varying complementary aspects of data collection between the two methods, we investigated the performance benefits of different measurement strategies, including altering the number of modes per optical detector, the integration time/fitting time of the speckle measurement, and the laser source delivery strategy. Through comparison across these metrics with simulated detectors having realistic noise properties, we determine several guiding principles for the optimization of these techniques and report the performance comparison between the two over a range of measurement properties and tissue geometries. We find that SCOS outperforms DCS in terms of contrast-to-noise ratio for the cerebral blood flow signal in the ideal case simulated here but note that SCOS requires careful experimental calibrations to ensure accurate measurements of cerebral blood flow. We provide design principles by which to evaluate the development of DCS and SCOS systems for their use in the measurement of cerebral blood flow.

Automatic Max-Likelihood Envelope Detection Algorithm for Quantitative High-Frame-Rate Ultrasound for Neonatal Brain Monitoring

Background and AimPostoperative brain injury in neonates may result from disturbed cerebral perfusion, but accurate perioperative monitoring is lacking. High frame rate (HFR) cerebral ultrasound could visualize and quantify flow in all detectable vessels using spectral Doppler; however, automated quantification in small vessels is challenging due to low signal amplitude. We have developed an automatic envelope detection algorithm for HFR pulsed wave spectral Doppler signals, enabling neonatal brain quantitative parameter maps during and after surgery. MethodsHFR ultrasound data from high-risk neonatal surgeries were recorded with a custom HFR mode (framerate 1000Hz) on a Zonare ZS3 system. A pulsed wave Doppler spectrogram was calculated for each pixel containing blood flow in the image, and spectral-peak velocity was tracked using a max-likelihood estimation algorithm of signal and noise regions in the spectrogram, where the most likely cross-over point marks the blood flow velocity. The resulting peak-systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) were compared with other detection schemes, manual tracking, and RI from regular pulsed wave Doppler measurements in 10 neonates. ResultsEnvelope detection was successful in both high- and low-quality arterial and venous flow spectrograms. Our technique had the lowest root mean square error for EDV, PSV, and RI (0.46cm/s, 0.53 cm/s, and 0.15, respectively) when compared with manual tracking. There was good agreement between the clinical pulsed wave Doppler RI and HFR measurement with a mean difference of 0.07. ConclusionThe max-likelihood algorithm is a promising approach for accurate, automated cerebral blood flow monitoring with high-frame rate imaging in neonates.

A Wearable Device for Dynamic Monitoring of Cerebral Blood Flow Based on Electromagnetic Coupling Sensing

A Wearable Device for Dynamic Monitoring of Cerebral Blood Flow Based on Electromagnetic Coupling Sensing

Acupuncture with specific mode electro-stimulation effectively and transiently opens the BBB through Shh signaling pathway.

To explore a new method that patients with brain diseases such as stroke sequelae are hindered by blood-brain barrier (BBB) in clinical treatment. Research preliminarily found that acupuncture with specific mode electro-stimulation (EA) to open BBB-assisted drug delivery may be is an effective means to improve the clinical efficacy of brain disease patients. So here we further explore the features and mechanism. Middle cerebral artery occlusion/R recovery rats were employed as the animal model. Laser Doppler monitoring cerebral blood flow decreased to 45 ± 10% of the baseline value as modeling criteria and TTC staining observed infarcted areas of brain tissue. The permeability of FITC-Dextran and EB in the frontal lobe of rats was observed by microscope. After that, Western blot and Immunofluorescence staining for the detection of the shh and Gli1 signal molecule, Claudin-5 Occludin ZO-1 tight junction (TJ) proteins. EA can open the BBB stably and effectively, and has the characteristics of starting to close soon after the end of EA; EA inhibits the Shh-Gli1 signaling pathway, and downregulates Occludin ZO-1 TJ proteins. These results suggest that EA is safe and reversible in opening the BBB, and its mechanism is related to the inhibition of Shh signaling pathway to down-regulate the expression of TJ proteins.

Abstract 001: Microvascular reperfusion during endovascular therapy: the balance of supply and demand

Introduction Endovascular therapy (EVT) has revolutionized acute stroke treatment, but large vessel recanalization does not always result in tissue‐level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. Here we aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post‐EVT outcomes. Methods Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre‐EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS‐derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit ‐ microvascular reperfusion. Good functional outcome was defined as 90‐day modified Rankin Scale ≤2. Results 36 (of 40) patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median: 1%; IQR: ‐11%–16%) than patients with poor outcomes (median: 28%; IQR: 2%–50%), p=0.02. Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. Conclusion CBF augmentation alone does not predict post‐EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post‐EVT care aimed at CBF optimization.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand

BackgroundEndovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during...

Non-Invasive Continuous Optical Monitoring of Cerebral Blood Flow after Traumatic Brain Injury in Mice Using Fiber Camera-Based Speckle Contrast Optical Spectroscopy.

Neurocritical care focuses on monitoring cerebral blood flow (CBF) to prevent secondary brain injuries before damage becomes irreversible. Thus, there is a critical unmet need for continuous neuromonitoring methods to quantify CBF within the vulnerable cortex continuously and non-invasively. Animal models and imaging biomarkers can provide valuable insights into the mechanisms and kinetics of head injury, as well as insights for potential treatment strategies. For this purpose, we implemented an optical technique for continuous monitoring of blood flow changes after a closed head injury in a mouse model, which is based on laser speckle contrast imaging and a fiber camera-based approach. Our results indicate a significant decrease (~10%, p-value < 0.05) in blood flow within 30 min of a closed head injury. Furthermore, the low-frequency oscillation analysis also indicated much lower power in the trauma group compared to the control group. Overall, blood flow has the potential to be a biomarker for head injuries in the early phase of a trauma, and the system is useful for continuous monitoring with the potential for clinical translation.

Assessing depth sensitivity in laser interferometry speckle visibility spectroscopy (iSVS) through source-to-detector distance variation and cerebral blood flow monitoring in humans and rabbits.

Recently, speckle visibility spectroscopy (SVS) was non-invasively applied on the head to monitor cerebral blood flow. The technique, using a multi-pixel detecting device (e.g., camera), allows the detection of a larger number of speckles, increasing the proportion of light that is detected. Due to this increase, it is possible to collect light that has propagated deeper through the brain. As a direct consequence, cerebral blood flow can be monitored. However, isolating the cerebral blood flow from the other layers, such as the scalp or skull components, remains challenging. In this paper, we report our investigations on the depth-sensitivity of laser interferometry speckle visibility spectroscopy (iSVS). Specifically, we varied the depth of penetration of the laser light into the head by tuning the source-to-detector distance, and identified the transition point at which cerebral blood flow in humans and rabbits starts to be detected.

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Perivascular Macrophages Mediate Microvasospasms After Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is characterized by acute and delayed reductions of cerebral blood flow (CBF) caused, among others, by spasms of cerebral arteries and arterioles. Recently, the inactivation of perivascular macrophages (PVM) has been demonstrated to improve neurological outcomes after experimental SAH, but the underlying mechanisms of protection remain unclear. The aim of our exploratory study was, therefore, to investigate the role of PVM in the formation of acute microvasospasms after experimental SAH. PVMs were depleted in 8- to 10-week-old male C57BL/6 mice (n=8/group) by intracerebroventricular application of clodronate-loaded liposomes and compared with mice with vehicle liposome injections. Seven days later, SAH was induced by filament perforation under continuous monitoring of CBF and intracranial pressure. Results were compared with sham-operated animals and animals who underwent SAH induction but no liposome injection (n=4/group each). Six hours after SAH induction or sham surgery, numbers of microvasospasms per volume of interest and % of affected pial and penetrating arterioles were examined in 9 standardized regions of interest per animal by in vivo 2-photon microscopy. Depletion of PVMs was proven by quantification of PVMs/mm3 identified by immunohistochemical staining for CD206 and Collagen IV. Statistical significance was tested with t tests for parametric data and Mann-Whitney U test for nonparametric data. PVMs were located around pial and intraparenchymal arterioles and were effectively depleted by clodronate from 671±28 to 46±14 PVMs/mm3 (P<0.001). After SAH, microvasospasms was observed in pial arteries and penetrating and precapillary arterioles and were accompanied by an increase to 1405±142 PVMs/mm3. PVM depletion significantly reduced the number of microvasospasms from 9 IQR 5 to 3 IQR 3 (P<0.001). Our results suggest that PVMs contribute to the formation of microvasospasms after experimental SAH.

A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Freely Behaving Mice.

Wearable technologies for functional brain monitoring in freely behaving subjects can advance our understanding of cognitive processing and adaptive behavior. Existing technologies are lacking in this capability or need procedures that are invasive and/or otherwise impede brain assessments during social behavioral conditions, exercise, and sleep. In response a complete system was developed to combine relative cerebral blood flow (rCBF) measurement, O2 and CO2 supplies, and behavior recording for use on conscious, freely behaving mice. An innovative diffuse speckle contrast flowmetry (DSCF) device and associated hardware were miniaturized and optimized for rCBF measurements in small subject applications. The use of this wearable, fiber-free, near-infrared DSCF head-stage/probe allowed no craniotomy, minimally invasive probe implantation, and minimal restraint of the awake animal. Significant correlations were found between measurements with the new DSCF design and an optical standard. The system successfully detected rCBF responses to CO2-induced hypercapnia in both anesthetized and freely behaving mice. Collecting rCBF and activity information together during natural behaviors provides realistic physiological results and opens the path to exploring their correlations with pathophysiological conditions.