Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow.

Background: Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature can be detrimental to the host. Recent work has demonstrated that Toxoplasma gondii infects and lyses central nervous system (CNS) endothelial cells that form the blood-brain barrier (BBB).

Semi-automated protocol to quantify and characterize fluorescent three-dimensional vascular images.

The microvasculature facilitates gas exchange, provides nutrients to cells, and regulates blood flow in response to stimuli. Vascular abnormalities are an indicator of pathology for various conditions, such as compromised vessel integrity in small vessel disease and angiogenesis in tumors. Traditional immunohistochemistry enables the visualization of tissue cross-sections containing exogenously labeled vasculature.

Quantifying tissue properties and absolute hemodynamics using coherent spatial imaging.

Significance: Measuring hemodynamic function is crucial for health assessment. Optical signals provide relative hemoglobin concentration changes, but absolute measurements require costly, bulky technology. Speckleplethysmography (SPG) uses coherent light to detect speckle fluctuations.

Quantitative hemodynamic imaging: a method to correct the effects of optical properties on laser speckle imaging.

Significance: Studying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement.

Intrinsic, widefield optical imaging of hemodynamics in rodent models of Alzheimer's disease and neurological injury.

The complex cerebrovascular network is critical to controlling local cerebral blood flow (CBF) and maintaining brain homeostasis. Alzheimer's disease (AD) and neurological injury can result in impaired CBF regulation, blood-brain barrier breakdown, neurovascular dysregulation, and ultimately impaired brain homeostasis. Measuring cortical hemodynamic changes in rodents can help elucidate the complex physiological dynamics that occur in AD and neurological injury.

Identification of Responders to Balneotherapy among Adults over 60 Years of Age with Chronic Low Back Pain: A Pilot Study with Trajectory Model Analysis.

Balneotherapy may be a relevant treatment for chronic low back pain (LBP) in individuals > 60 years old. This pilot study aimed to determine the effectiveness of balneotherapy for chronic LBP in people > 60 years old and to determine profiles of responders with trajectory model analysis. This was a pilot prospective open cohort study, with repeated measurements using validated questionnaires; participants were their own controls.

Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome.

Background: Spreading depolarizations (SDs) are self-propagating waves of neuronal and glial depolarizations often seen in neurological conditions in both humans and animal models. Because SD is thought to worsen neurological injury, the role of SD in a variety of cerebral insults has garnered significant investigation. Anoxic SD is a type of SD that occurs because of anoxia or asphyxia.

Spectroscopic and deep learning-based approaches to identify and quantify cerebral microhemorrhages.

Cerebral microhemorrhages (CMHs) are associated with cerebrovascular disease, cognitive impairment, and normal aging. One method to study CMHs is to analyze histological sections (5-40 μm) stained with Prussian blue. Currently, users manually and subjectively identify and quantify Prussian blue-stained regions of interest, which is prone to inter-individual variability and can lead to significant delays in data analysis.

Simple methodology to visualize whole-brain microvasculature in three dimensions.

To explore brain architecture and pathology, a consistent and reliable methodology to visualize the three-dimensional cerebral microvasculature is beneficial. Perfusion-based vascular labeling is quick and easily deliverable. However, the quality of vascular labeling can vary with perfusion-based labels due to aggregate formation, leakage, rapid photobleaching, and incomplete perfusion.

High-speed quantitative optical imaging of absolute metabolism in the rat cortex.

Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury. We demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen ( ) in the rodent brain on an absolute scale ( ). We use laser speckle imaging at 809 nm and spatial frequency domain imaging at 655, 730, and 850 nm to obtain spatiotemporal maps of cerebral blood flow, tissue absorption ( ), and tissue scattering ( ).

Cerebral Blood Flow in Chronic Kidney Disease.

The prevalence of mild cognitive impairment increases with age and is further exacerbated by chronic kidney disease (CKD). CKD is associated with (1) mild cognitive impairment, (2) impaired endothelial function, (3) impaired blood-brain barrier, (4) increased cerebral microhemorrhage burden, (5) increased cerebral blood flow (CBF), (6) impaired cerebral autoregulation, (7) impaired cerebrovascular reactivity, and (8) increased arterial stiffness. We report preliminary findings from our group that demonstrate altered cerebrovascular reactivity in a mouse model of CKD-associated vascular calcification.

Transcranial chronic optical access to longitudinally measure cerebral blood flow.

Background: The regulation of cerebral blood flow is critical for normal brain functioning, and many physiological and pathological conditions can have long-term impacts on cerebral blood flow. However, minimally invasive tools to study chronic changes in animal models are limited.

New Method: We developed a minimally invasive surgical technique (cyanoacrylate skull, CAS) allowing us to image cerebral blood flow longitudinally through the intact mouse skull using laser speckle imaging.

Neotectonics and pastoralism: How they impact flood regimes in Madagascar's highlands.

Sustainably maintaining the densely populated upland plains of Madagascar as operationally safe spaces for the food security of the nation and the urban growth of its capital city, Antananarivo, hinges critically on avoiding crop and infrastructure destruction by their through-flowing rivers. The flood regime, however, is also a function of two 'slow' variables hitherto undocumented: tectonic subsidence regime, and floodplain sedimentation rate. From a radiocarbon-dated chronostratigraphy and environmental history of the sediment sequences in three of Madagascar's semi-enclosed upland basins (Antananarivo, Ambohibary, and Alaotra), we quantify and compare how the precarious equilibrium between the two variables entails differentials in accommodation space for sediment and floodwater.

Resuscitating the Globally Ischemic Brain: TTM and Beyond.

Cardiac arrest (CA) afflicts ~ 550,000 people each year in the USA. A small fraction of CA sufferers survive with a majority of these survivors emerging in a comatose state. Many CA survivors suffer devastating global brain injury with some remaining indefinitely in a comatose state.

Dissociation of Cerebral Blood Flow and Femoral Artery Blood Pressure Pulsatility After Cardiac Arrest and Resuscitation in a Rodent Model: Implications for Neurological Recovery.

Background Impaired neurological function affects 85% to 90% of cardiac arrest (CA) survivors. Pulsatile blood flow may play an important role in neurological recovery after CA. Cerebral blood flow (CBF) pulsatility immediately, during, and after CA and resuscitation has not been investigated.

Handheld motion stabilized laser speckle imaging.

Laser speckle imaging (LSI) is a wide-field, noninvasive optical technique that allows researchers and clinicians to quantify blood flow in a variety of applications. However, traditional LSI devices are cart or tripod based mounted systems that are bulky and potentially difficult to maneuver in a clinical setting. We previously showed that the use of a handheld LSI device with the use of a fiducial marker (FM) to account for motion artifact is a viable alternative to mounted systems.

Speckleplethysmographic (SPG) Estimation of Heart Rate Variability During an Orthostatic Challenge.

Heart rate variability (HRV) provides insight into cardiovascular health and autonomic function. Electrocardiography (ECG) provides gold standard HRV measurements but is inconvenient for continuous acquisition when monitored from the extremities. Optical techniques such as photoplethysmography (PPG), often found in health and wellness trackers for heart rate measurements, have been used to estimate HRV peripherally but decline in accuracy during increased physical stress.

Multi-exposure laser speckle contrast imaging using a video-rate multi-tap charge modulation image sensor.

Multi-exposure laser speckle contrast imaging (MELSCI) systems based on high frame rate cameras are suitable for wide-field quantitative measurement of blood flow. However, high-speed camera-based MELSCI requires high power consumption, large memory, and high processing capability, which may lead to relatively large and expensive hardware. To realize a compact and cost-efficient MELSCI system, we discuss an application of the multi-tap CMOS image sensor originally designed for time-of-flight range imaging.

Optical clearing potential of immersion-based agents applied to thick mouse brain sections.

We have previously demonstrated that the use of a commercially-available immersion-based optical clearing agent (OCA) enables, within 3-6 hours, three-dimensional visualization of subsurface exogenous fluorescent and absorbing markers of vascular architecture and neurodegenerative disease in thick (0.5-1.0mm) mouse brain sections.

Comparison of speckleplethysmographic (SPG) and photoplethysmographic (PPG) imaging by Monte Carlo simulations and measurements.

Noncontact photoplethysmography (PPG) is limited by a poor signal-to-noise ratio (SNR). A solution to this limitation is the use of alternate sources of optical contrast to generate a complementary pulsatile waveform. One such source is laser speckle contrast, which is modulated in biological tissues by the flow rate of red blood cells.

Correcting for motion artifact in handheld laser speckle images.

Laser speckle imaging (LSI) is a wide-field optical technique that enables superficial blood flow quantification. LSI is normally performed in a mounted configuration to decrease the likelihood of motion artifact. However, mounted LSI systems are cumbersome and difficult to transport quickly in a clinical setting for which portability is essential in providing bedside patient care.

High-speed spatial frequency domain imaging of rat cortex detects dynamic optical and physiological properties following cardiac arrest and resuscitation.

Quantifying rapidly varying perturbations in cerebral tissue absorption and scattering can potentially help to characterize changes in brain function caused by ischemic trauma. We have developed a platform for rapid intrinsic signal brain optical imaging using macroscopically structured light. The device performs fast, multispectral, spatial frequency domain imaging (SFDI), detecting backscattered light from three-phase binary square-wave projected patterns, which have a much higher refresh rate than sinusoidal patterns used in conventional SFDI.

Cerebral blood flow is decoupled from blood pressure and linked to EEG bursting after resuscitation from cardiac arrest.

In the present study, we have developed a multi-modal instrument that combines laser speckle imaging, arterial blood pressure, and electroencephalography (EEG) to quantitatively assess cerebral blood flow (CBF), mean arterial pressure (MAP), and brain electrophysiology before, during, and after asphyxial cardiac arrest (CA) and resuscitation. Using the acquired data, we quantified the time and magnitude of the CBF hyperemic peak and stabilized hypoperfusion after resuscitation. Furthermore, we assessed the correlation between CBF and MAP before and after stabilized hypoperfusion.

Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a neurovascular disease that is strongly associated with an increase in the number and size of spontaneous microbleeds. Conventional methods of magnetic resonance imaging for detection of microbleeds, and positron emission tomography with Pittsburgh Compound B imaging for amyloid deposits, can separately demonstrate the presence of microbleeds and CAA in affected brains in vivo; however, there still is a critical need for strong evidence that shows involvement of CAA in microbleed formation. Here, we show in a Tg2576 mouse model of Alzheimer's disease, that the combination of histochemical staining and an optical clearing method called optical histology, enables simultaneous, co-registered three-dimensional visualization of cerebral microvasculature, microbleeds, and amyloid deposits.