SignificanceAntiamyloid β (Aβ) immunotherapy is a promising therapeutic strategy for Alzheimer’s disease (AD) but generates large amounts of soluble Aβ peptides that could overwhelm the clearance pathway, leading to serious side effects. Direct implications of Aβ in glymphatic drainage transport for cerebral vasculature and tissue are not well known. Studies are needed to resolve this issue and pave the way to better monitoring abnormal vascular events that may occur in Aβ-modifying therapies for AD.AimThe objective is to characterize the modification of cerebral vasculature and tissue induced by soluble Aβ abundantly present in the glymphatic clearance system.ApproachAβ1 − 42 peptide was injected intracerebroventricularly and swept-source optical coherence tomography (SS-OCT) was used to monitor the progression of changes in the brain microvascular network and tissue in vivo over 14 days. Parameters reflecting vascular morphology and structure as well as tissue status were quantified and compared before treatment.ResultsVascular perfusion density, vessel length, and branch density decreased sharply and persistently following peptide administration. In comparison, vascular average diameter and vascular tortuosity were moderately increased at the late stage of monitoring. Endpoint density gradually increased, and the global optical attenuation coefficient value decreased significantly over time.ConclusionsAβ burden in the glymphatic system directly contributes to cerebrovascular structural and morphological abnormalities and global brain tissue damage, suggesting severe deleterious properties of soluble cerebrospinal fluid-Aβ. We also show that OCT can be used as an effective tool to monitor cerebrovascular dynamics and tissue property changes in response to therapeutic treatments in drug discovery research.
KEYWORDS: Optical coherence tomography, Brain, In vivo imaging, Tissues, Arteries, Magnetic resonance imaging, Blood vessels, Signal attenuation, Scattering, Tissue optics
Cerebral edema is a severe complication of ischemic cerebrovascular disease, which can lead to microcirculation compression resulting in additional ischemic damage. Real-time and continuous in vivo imaging techniques for edema detection are of great significance to basic research on cerebral edema. We attempted to monitor the cerebral edema status in rats with middle cerebral artery occlusion (MCAO) over time, using a wide field-of-view swept-source optical coherence tomography (SS-OCT) system. Optical attenuation coefficients (OACs) were calculated by an optimized depth-resolved estimation method, and en face OAC maps covering the whole cortex were obtained. Then, the tissue affected by edema was segmented from the OAC maps, and the cortical area affected by edema was estimated. Both magnetic resonance image (MRI) and brain water content measurements were used to verify the presence of cerebral edema. The results showed that the average OAC of the ischemic area gradually decreased as cerebral edema progressed, and the edema area detected by SS-OCT had high similarity in position and shape to that obtained by MRI. This work extends the application of OCT and provides an option for detecting cerebral edema in vivo after ischemic stroke.
The optical attenuation coefficient (OAC) reflects the optical properties of various tissues or tissues of the same type under different physiological conditions. Quantitative measurement of OAC from optical coherence tomography (OCT) signals can provide additional information and can increase the potential for OCT applications. We present an optimized depth-resolved estimation (ODRE) method that derives a precise mapping between the measured OCT signal and the OAC. In contrast to previous depth-resolved estimation (DRE) methods, the optimized method can estimate the OAC in any depth range and ignore whether the light is completely attenuated. Numerical simulations and phantom experiments are used to verify its validity, and this method is applied to detect cerebral damage. In combination with OCT angiography, real-time observation of the change of blood perfusion and the degree of cerebral damage in mice with focal cerebral ischemia provides important information to help us understand the temporal relationship between brain damage and ischemia.
A blockage of the middle cerebral artery (MCA) on the cortical branch will seriously affect the blood supply of the cerebral cortex. Real-time monitoring of MCA hemodynamic parameters is critical for therapy and rehabilitation. Optical coherence tomography (OCT) is a powerful imaging modality that can produce not only structural images but also functional information on the tissue. We use OCT to detect hemodynamic changes after MCA branch occlusion. We injected a selected dose of endothelin-1 (ET-1) at a depth of 1 mm near the MCA and let the blood vessels follow a process first of occlusion and then of slow reperfusion as realistically as possible to simulate local cerebral ischemia. During this period, we used optical microangiography and Doppler OCT to obtain multiple hemodynamic MCA parameters. The change trend of these parameters from before to after ET-1 injection clearly reflects the dynamic regularity of the MCA. These results show the mechanism of the cerebral ischemia-reperfusion process after a transient middle cerebral artery occlusion and confirm that OCT can be used to monitor hemodynamic parameters.
Activity of brain neurons will lead to changes in local blood flow rate (BFR). Thus, it is important to measure the local BFR of cerebral cortex on research of neuron activity in vivo, such as rehabilitation evaluation after stroke, etc. Currently, laser Doppler flowmetry is commonly used for blood flow measurement, however, relatively low resolution limits its application. Optical coherence tomography (OCT) is a powerful noninvasive 3D imaging modality with high temporal and spatial resolutions. Furthermore, OCT can provide flow distribution image by calculating Doppler frequency shift which makes it possible for blood flow rate measurement. In this paper, we applied OCT to measure the blood flow rate of the primary motor cortex in rats. The animal was immobilized and anesthetized with isoflurane, an incision was made along the sagittal suture, and bone was exposed. A skull window was opened on the primary motor cortex. Then, blood flow rate changes in the primary motor cortex were monitored by our homemade spectral domain OCT with a stimulation of the passive movement of the front legs. Finally, we established the relationship between blood flow rate and the test design. The aim is to demonstrate the potential of OCT in the evaluation of cerebral cortex function.
It is important to measure embryonic heart myocardial wall strain and strain rate for understanding the mechanisms of embryonic heart development. Optical coherence tomography (OCT) can provide depth resolved images with high spatial and temporal resolution, which makes it have the potential to reveal the complex myocardial activity in the early stage embryonic heart. We develop a novel method to measure strain in embryonic chick heart based on spectral domain OCT images and subsequent image processing. We perform 4D(x,y,z,t) scanning on the outflow tract (OFT) of chick embryonic hearts in HH18 stage (~3 days of incubation). Only one image sequence acquired at the special position is selected based on the Doppler blood flow information where the probe beam penetrates through the OFT perpendicularly. For each image of the selected sequence, the cross-section of the myocardial wall can be approximated as an annulus. The OFT is segmented with a semi-automatic boundary detection algorithm, thus the area and mean circumference of the annular myocardial wall can be achieved. The myocardial wall thickness was calculated using the area divided by the mean circumference, and then the strain was obtained. The results demonstrate that OCT can be a useful tool to describe the biomechanical characteristics of the embryonic heart.
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