33 research outputs found
Functional transcranial brain imaging by optical-resolution photoacoustic microscopy
Optical-resolution photoacoustic microscopy (OR-PAM) is applied to functional brain imaging in living mice. A near-diffraction-limited bright-field optical illumination is employed to achieve micrometer lateral resolution, and a dual-wavelength measurement is utilized to extract the blood oxygenation information. The variation in hemoglobin oxygen saturation (sO_2) along vascular branching has been imaged in a precapillary arteriolar tree and a postcapillary venular tree, respectively. To the best of our knowledge, this is the first report on in vivo volumetric imaging of brain microvascular morphology and oxygenation down to single capillaries through intact mouse skulls. It is anticipated that: (i) chronic imaging enabled by this minimally invasive procedure will advance the study of cortical plasticity and neurological diseases; (ii) revealing the neuroactivity-dependent changes in hemoglobin concentration and oxygenation will facilitate the understanding of neurovascular coupling at the capillary level; and (iii) combining functional OR-PAM and high-resolution blood flowmetry will have the potential to explore cellular pathways of brain energy metabolism
Whisker's Directional Selectivity: Orientation Columns in the Barrel Field?
Using voltage-sensitive dye optical imaging methods, we visualized neural activity in the rat barrel cortex in response to the deflection of a single whisker in different directions. Obtained data indicates that fast movements of single whiskers in varying directions correlate with different patterns of activation in the somatosensory cortex. A functional map was created based on the voltage-sensitive dye optical signal. This supports prior research that vibrissae deflections cause responses in different cortical neurons within the barrel field according to the direction of the deflection. By analogy with the orientation columns in the visual cortex, directionally-biased single whisker responses to different directions of deflection could be a possible mechanism for the directional selectivity of this important sensory response
Photoacoustic and optical coherence tomography of epilepsy with high temporal and spatial resolution and dual optical contrasts
Epilepsy mapping with high spatial and temporal resolution has great significance for both fundamental research on epileptic neurons and the clinical management of epilepsy. In this communication, we demonstrate for the first time in vivo epilepsy mapping with high spatial and temporal resolution and dual optical contrasts in an animal model. Through the variations of a depthresolved optical coherence tomography signal with optical scattering contrast, we observed that epileptic neuron activities modulated the optical refractive index of epileptic neurons and their surrounding tissue. Simultaneously, through neurovasculature coupling mechanisms and optical absorption contrast, we used photoacoustic signals to document the hemodynamic changes of the microvasculature surrounding the epileptic neurons. The epilepsy mapping results were confirmed by a simultaneously recorded electroencephalogram signal during epileptic seizure. Our new epilepsy mapping tool, with high temporal and spatial resolution and dual optical contrasts, may find many applications, such as drug development and epilepsy surgery
Optical Imaging of Interaural Time Difference Representation in Rat Auditory Cortex
We used in vivo voltage-sensitive dye optical imaging to examine the cortical representation of interaural time difference (ITD), which is believed to be involved in sound source localization. We found that acoustic stimuli with dissimilar ITD activate various localized domains in the auditory cortex. The main loci of the activation pattern shift up to 1 mm during the first 40 ms of the response period. We suppose that some of the neurons in each pool are sensitive to the definite ITD and involved in the transduction of information about sound source localization, based on the ITD. This assumption gives a reasonable fit to the Jeffress model in which the neural network calculates the ITD to define the direction of the sound source. Such calculation forms the basis for the cortex's ability to detect the azimuth of the sound source
Functional transcranial brain imaging by optical-resolution photoacoustic microscopy
Optical-resolution photoacoustic microscopy (OR-PAM) is applied to functional brain imaging in living mice. A near-diffraction-limited bright-field optical illumination is employed to achieve micrometer lateral resolution, and a dual-wavelength measurement is utilized to extract the blood oxygenation information. The variation in hemoglobin oxygen saturation (sO_2) along vascular branching has been imaged in a precapillary arteriolar tree and a postcapillary venular tree, respectively. To the best of our knowledge, this is the first report on in vivo volumetric imaging of brain microvascular morphology and oxygenation down to single capillaries through intact mouse skulls. It is anticipated that: (i) chronic imaging enabled by this minimally invasive procedure will advance the study of cortical plasticity and neurological diseases; (ii) revealing the neuroactivity-dependent changes in hemoglobin concentration and oxygenation will facilitate the understanding of neurovascular coupling at the capillary level; and (iii) combining functional OR-PAM and high-resolution blood flowmetry will have the potential to explore cellular pathways of brain energy metabolism
Photoacoustic microscopy of microvascular responses to cortical electrical stimulation
Advances in the functional imaging of cortical hemodynamics have greatly facilitated the understanding of neurovascular coupling. In this study, label-free optical-resolution photoacoustic microscopy (OR-PAM) was used to monitor microvascular responses to direct electrical stimulations of the mouse somatosensory cortex through a cranial opening. The responses appeared in two forms: vasoconstriction and vasodilatation. The transition between these two forms of response was observed in single vessels by varying the stimulation intensity. Marked correlation was found between the current-dependent responses of two daughter vessels bifurcating from the same parent vessel. Statistical analysis of twenty-seven vessels from three different animals further characterized the spatial-temporal features and the current dependence of the microvascular response. Our results demonstrate that OR-PAM is a valuable tool to study neurovascular coupling at the microscopic level
Beyond life: Exploring hemodynamic patterns in postmortem mice brains
We utilize Laser Speckle Contrast Imaging (LSCI) for visualizing cerebral blood flow in mice during and post-cardiac arrest. Analyzing LSCI images, we noted temporal blood flow variations across the brain surface for hours postmortem. Fast Fourier Transform (FFT) analysis depicted blood flow and microcirculation decay post-death. Continuous Wavelet Transform (CWT) identified potential cerebral hemodynamic synchronization patterns. Additionally, non-negative matrix factorization (NMF) with four components segmented LSCI images, revealing structural subcomponent alterations over time. This integrated approach of LSCI, FFT, CWT, and NMF offers a comprehensive tool for studying cerebral blood flow dynamics, metaphorically capturing the ‘end of the tunnel’ experience. Results showed primary postmortem hemodynamic activity in the olfactory bulbs, followed by blood microflow relocations between somatosensory and visual cortical regions via the superior sagittal sinus. This method opens new avenues for exploring these phenomena, potentially linking neuroscientific insights with mysteries surrounding consciousness and perception at life's end
In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog
Accurately locating epileptic foci has great importance in advancing the treatment of epilepsy. In this study, epileptic seizures were first induced by intracortical injection of 4-aminopyridine in rats. A fluorescent deoxyglucose substitute, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), was then continuously injected via the tail vein. Brain glucose metabolism was subsequently monitored by fluorescence imaging of 2-NBDG. The initial uptake rate of 2-NBDG at the injection site of 4-aminopyridine significantly exceeded that of the control injection site, which indicated local hypermetabolism induced by seizures. Our results show that 2-NBDG can be used for localizing epileptic foci
Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo
We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood–brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism
Invasive and transcranial photoacoustic imaging of the vascular response to brain electrical stimulation
Advances in the brain functional imaging greatly facilitated the understanding of neurovascular coupling. For monitoring of the microvascular response to the brain electrical stimulation in vivo we used optical-resolution photoacoustic microscopy (OR-PAM) through the cranial openings as well as transcranially. Both types of the vascular response, vasoconstriction and vasodilatation, were clearly observed with good spatial and temporal resolution. Obtained results confirm one of the primary points of the neurovascular coupling theory that blood vessels could present vasoconstriction or vasodilatation in response to electrical stimulation, depending on the balance between inhibition and excitation of the different parts of the elements of the neurovascular coupling system