A5019766816- Optical Imaging and Spectroscopy Techniques
- Photoacoustic and Ultrasonic Imaging
- Traumatic Brain Injury and Neurovascular Disturbances
- Advanced MRI Techniques and Applications
- Optical Coherence Tomography Applications
- Advanced Fluorescence Microscopy Techniques
- Photoreceptor and optogenetics research
- Analytical Chemistry and Sensors
- Functional Brain Connectivity Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Advanced Neuroimaging Techniques and Applications
- Acute Ischemic Stroke Management
- Plasma Diagnostics and Applications
- Intracerebral and Subarachnoid Hemorrhage Research
- Thermoregulation and physiological responses
- Neurological Disease Mechanisms and Treatments
- MRI in cancer diagnosis
- Thermal Regulation in Medicine
- Nitric Oxide and Endothelin Effects
- Non-Invasive Vital Sign Monitoring
- Cerebrovascular and Carotid Artery Diseases
- Cardiovascular Health and Disease Prevention
- Cell Image Analysis Techniques
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Athinoula A. Martinos Center for Biomedical Imaging
2016-2025
Mass General Brigham
2024
Zero to Three
2023
HKUST Shenzhen Research Institute
2021
Medical University of the Americas
2020
VA Boston Healthcare System
2019
Harvard University Press
2011
University of Pennsylvania
2009
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes volume and rather than activity per se. Therefore, understanding transformation of microscopic vascular behavior into macroscopic signals foundation physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure BOLD-relevant...
Identification of the cellular players and molecular messengers that communicate neuronal activity to vasculature driving cerebral hemodynamics is important for (1) basic understanding cerebrovascular regulation (2) interpretation functional Magnetic Resonance Imaging (fMRI) signals. Using a combination optogenetic stimulation 2-photon imaging in mice, we demonstrate selective activation cortical excitation inhibition elicits distinct vascular responses identify vasoconstrictive mechanism as...
Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent this hypothesis, intact stimulus-induced was observed inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knock-out (KO) mice, which the primary mechanism astrocytic calcium increase-the from intracellular stores following activation an IP3-dependent pathway-is lacking. Further, our results wild-type (WT) mice indicate that...
Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies pathophysiology. Currently no accepted method exists for vivo longitudinal monitoring CBF with high resolution rats and mice. Using three-dimensional Doppler Optical Coherence Tomography cranial window preparations, we present methods algorithms regional the rat cortex. Towards this end, develop validate a quantitative statistical model to describe effect static tissue on velocity sensitivity. This is...
Oxygen levels in biological systems can be measured by the phosphorescence quenching method using probes with controllable parameters and defined biodistributions. We describe a general approach to construction of phosphorescent nanosensors tunable spectral characteristics, variable degrees quenching, high selectivity for oxygen. The are based on bright Pt Pd complexes porphyrins symmetrically π-extended (tetrabenzoporphyrins tetranaphthoporphyrins). π-Extension core macrocycle allows tuning...
In vivo imaging of cerebral tissue oxygenation is important in defining healthy physiology and pathological departures associated with disease. We used a recently developed two-photon microscopy method, based on novel phosphorescent nanoprobe, to image the rat primary sensory cortex response stimulation. Our measurements showed that stimulus-evoked increase pO 2 depended baseline level. particular, during sustained stimulation, steady-state at low-baseline locations remained baseline,...
Diffuse correlation spectroscopy (DCS) measurements of blood flow rely on the sensitivity temporal autocorrelation function diffusively scattered light to red cell (RBC) mean square displacement (MSD). For RBCs flowing with convective velocity [Formula: see text], is expected decay exponentially where text] delay time. also experience shear-induced diffusion a coefficient and an MSD text]. Surprisingly, experimental data primarily reflect diffusive behavior. To provide quantitative estimates...
Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations autofluorescence lifetime as a biomarker exposed rat cortices. We describe customized two-photon imaging system with time correlated single photon counting detection and specialized software modeling multiple-component fits fluorescence decay monitoring their transient behaviors. In NADH suggests the presence four...
Ever since the introduction of thrombolysis and subsequent expansion endovascular treatments for acute ischemic stroke, it remains to be identified why actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging capillary circulation in mice, we introduce pathological phenomenon dynamic flow stalls cerebral capillaries, occurring persistently salvageable penumbra after reperfusion. These stalls, which different from permanent cellular plugs...
Optical coherence tomography (OCT) and optical microscopy (OCM) have demonstrated the ability to investigate cyto- myelo-architecture in brain. Polarization-sensitive OCT provides sensitivity additional contrast mechanisms, specifically birefringence of myelination and, therefore, is advantageous for investigating white matter fiber tracts. In this Letter, we developed a polarization-sensitive microscope (PS-OCM) with 3.5 μm axial 1.3 transverse resolution organization orientation at finer...
Our understanding of how capillary blood flow and oxygen distribute across cortical layers to meet the local metabolic demand is incomplete. We addressed this question by using two-photon imaging resting-state microvascular partial pressure (PO2) in whisker barrel cortex awake mice. measurements I-V show that red-blood-cell flux oxygenation heterogeneity, intracapillary resistance delivery, all decrease with depth, reaching a minimum around layer IV, while depth-dependent extraction fraction...
There is an increasing need for quantitative and computationally affordable models analyzing tissue metabolism hemodynamics in microvascular networks. In this work, we develop a hybrid model to solve the time-varying oxygen advection-diffusion equation vessels tissue. To obtain three-dimensional temporal evolution of concentration realistic complex vessel networks, used graph-based advection combined with finite-element based diffusion implicit time-advancing scheme. We validated algorithm...
We report a group of optical imaging probes, comprising upconverting lanthanide nanoparticles (UCNPs) and polyanionic dendrimers. Dendrimers with rigid cores multiple carboxylate groups at the periphery are able to tightly bind surfaces UCNPs pretreated NOBF 4 , yielding stable, water-soluble, biocompatible nanomaterials. Unlike conventional linear polymers, dendrimers adhere by donating only fraction their peripheral UCNP–surface interactions. The remaining termini make up an interface...
Evaluating cerebral energy metabolism at microscopic resolution is important for comprehensively understanding healthy brain function and its pathological alterations. Here, we resolve specific alterations in vivo Sprague Dawley rats utilizing minimally-invasive 2-photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence. Time-resolved enable distinction different components contributing to NADH autofluorescence. Ostensibly,...
Progress in experimental stroke and translational medicine could be accelerated by high-resolution vivo imaging of disease progression the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury using intrinsic scattering properties cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal ischemic mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In acute stages, spatiotemporal...
Functional hyperemia reduces oxygen extraction efficacy unless counteracted by a reduction of capillary transit-time heterogeneity blood. We adapted bolus tracking approach to estimation for two-photon microscopy and then quantified changes in plasma mean transit time during forepaw stimulation anesthetized mice (C57BL/6NTac). In addition, we analyzed coefficient variance = heterogeneity/mean time, which expect remain constant passive, compliant microvascular networks. Electrical reduced,...