Significance: Current approaches to stimulating and recording from the brain have combined electrical or optogenetic stimulation with recording approaches, such as two-photon, electrophysiology (EP), and optical intrinsic signal imaging (OISI). However, we lack a label-free, all-optical approach with high spatial and temporal resolution.
Aim: To develop a label-free, all-optical method that simultaneously manipulates and images brain function using pulsed near-infrared light (INS) and functional optical coherence tomography (fOCT), respectively.
Approach: We built a coregistered INS, fOCT, and OISI system. OISI and EP recordings were employed to validate the fOCT signals.
Results: The fOCT signal was reliable and regional, and the area of fOCT signal corresponded with the INS-activated region. The fOCT signal was in synchrony with the INS onset time with a delay of ∼30 ms. The magnitude of fOCT signal exhibited a linear correlation with the INS radiant exposure. The significant correlation between the fOCT signal and INS was further supported by OISI and EP recordings.
Conclusions: The proposed fiber-based, all-optical INS-fOCT method allows simultaneous stimulation and mapping without the risk of interchannel cross-talk and the requirement of contrast injection and viral transfection and offers a deep penetration depth and high resolution.
The brain experiences alterations including cerebral ischemia and tissue damage after focal ischemic stroke. A thorough understanding of the spatiotemporal dynamics of blood perfusion and tissue damage is of great importance in stroke research. In chronic rat photothrombotic (PT) stroke model, a parallel study of both vascular and cellular responses to regional ischemia was performed with optical coherence tomography (OCT) in a label-free and depth-resolved manner. OCT revealed that vessels of different types and depth presented various spatial and temporal dynamics. In the ischemic core area, the distal middle cerebral arteries (dMCAs) were blocked gradually with laser irradiation and a spontaneous recanalization was observed at Day 5. In the chronic recovery period, the blocked small pial microvessels presented an apparent neovascularization progressing from the peripheral into the core area, with the final blood flow volume exceeding the baseline before PT. While the cortical capillary perfusion of the core area totally disappeared at Day 3 after PT and never recovered in the core area till the end of observation. The results demonstrated that blood reperfusion mainly occurred in the dMCAs vessels and pial microvessels of the superficial layer, but not in capillaries located deep in the cortex. The response of the cellular scattering and tissue damage showed a high spatial and temporal correlation with the capillary perfusion. On the whole, ischemic area and lesion area from attenuation coefficient are not exactly the same but complentary, with great help in understanding stroke mechanism comprehensively.
KEYWORDS: Optical coherence tomography, Angiography, Image resolution, Tissues, Brain, Medical imaging, Imaging systems, In vivo imaging, Visualization, 3D image processing
Optical coherence tomography angiography (OCTA) is a promising imaging modality that enables an in vivo label-free, high-resolution and high-contrast visualization of three-dimensional biological microvasculature. The blood flow contrast in OCTA is achieved by mathematically distinguishing the dynamic flow from the static surrounding tissue. However, the residual surrounding tissue remains as the background in the angiogram, which severely hinders the interpretation and quantification of the angiographic outcomes. The current temporal, wavelength, angular and spatial averaging approaches have been employed to enhance the flow contrast by trading imaging time and resolution for multiple independent measurements. Our study has further demonstrated that these averaging approaches are equivalent in principle, offering almost the same flow contrast improvement as the number of averages increases. Given a sufficient number, an ideal flow contrast can be achieved, while the cost of imaging time or resolution is unaffordable for any individual averaging approach alone. Thus, we have proposed a hybrid averaging strategy for a desired flow contrast by cost apportionment. It is demonstrated that, compared with any individual approach, hybrid averaging is able to offer a desired flow contrast without severe degradation of imaging time and resolution. In addition, making use of the extended range of a VCSEL based swept source OCT, an angular averaging approach by path length encoding is also demonstrated for flow contrast enhancement. This study is beneficial to providing useful guidance for the design of OCTA and facilitating the interpretation of OCT angiograms in clinical applications.
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