Ischemic cerebral edema (CE) is a major cause of death in patients with ischemic stroke. Detecting CE and local cerebral blood perfusion (LCBP) simultaneously may offer valuable insights for treating ischemic stroke (IS). In this work, a swept-source optical coherence tomography (SS-OCT) system was established to evaluate the photo-thrombosis ischemia mouse model for a long time. The progressive state of CE and LCBP was quantified and analyzed. Preliminary studies revealed that edema significantly affected LCBP with a clear spatial dependence, the edema area increased sharply when the LCBP dropped to around 60% of the initial value.
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.
We demonstrate a quasinoncontact photoacoustic imaging method using a homodyne interferometer with a long coherence length laser. The generated photoacoustic signal is detected by a system that is locked at its maximum sensitivity through the use of balanced detection and zero-crossing triggering. The balanced detector is substantially equalized, so its output is zero when the system reaches the maximum sensitivity. The synchronization approach is used to trigger the excitation and detection of the photoacoustic signal. The system is immune to ambient vibrations. A thin water layer on the sample surface is used to reduce the effect of the rough tissue surface. The performance of the system is demonstrated by in vivo imaging of the microvasculature in mouse ears.
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.
We propose a random perturbation model to describe the variation of laser speckle patterns caused by moving particles in capillary vessels. When passing through probing volume, moving particles encode random perturbations into observed laser speckle patterns. We extract the perturbation envelopes of time-varying laser speckles for tracking the motion of single particle. And, the full-field transverse velocities of flowing particles are obtained by using cross-correlation between the perturbation envelopes. The proposed method is experimentally verified by the use of polymer-microsphere suspension in a glass capillary.
Unilateral carotid artery ligation which could induce adaptive improvement is a classic model that has been widely used to study pathology of ischemic disease. In those studies, blood flow is an important parameter to characterize the ischemia. Optical coherence tomography (OCT) is a powerful imaging modality which can provide depth resolved images in biological tissue with high spatial and temporal resolution. SPF rats was anesthetized with isoflurane and divided into two groups. In first group, bilateral carotid artery was surgically exposed, and then left carotid artery was ligated. Blood flow changes of the contralateral carotid artery was monitored using high speed spectral domain optical coherence tomography, including the absolute flow velocity and the flow volume. In the other group, skull window was opened at the ipsilateral cerebral cortex of ligation and blood supply of small artery was measured before and after the ligation. The measured results demonstrate the blood supply compensation process after unilateral carotid artery ligation. With the superiority of high resolution, OCT is an effective technology in monitoring results of carotid artery after ligation.
We demonstrate a noncontact photoacoustic imaging (PAI) system in which an optical interferometer is used for ultrasound detection. The system is based on a modified optical-fiber Michelson interferometer that measures the surface displacement caused by photoacoustic pressure. A synchronization method is utilized to keep its high sensitivity to reduce the influence of ambient vibrations. The system is experimentally verified by imaging of a phantom. The experimental results indicate that the proposed system can be used for noncontact PAI with high resolution and high bandwidth.
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.
We introduce a system for rapidly measuring the intraocular distances of human eyes in vivo with high sensitivity by using
Fourier domain low-coherence interferometry. The system mainly consisting of a rapid focus displacement unit and a
reference arm which has a variable optical path length. This system is capable of providing a complete biometrical
assessment of a human eye in a single measurement procedure, including cornea thickness, anterior chamber depth, lens
thickness, and axial length. The system is experimentally verified by measuring the four parameters of a human eye in
vivo.
KEYWORDS: Heart, Optical coherence tomography, Blood circulation, Mathematical modeling, Doppler effect, Finite element methods, In vivo imaging, Animal model studies, Systems modeling, Molybdenum
The heart undergoes remarkable changes during embryonic development due to genetic programming and epigenetic influences, in which mechanical loads is a key factor. As embryonic research development, an important goal is to develop mathematical models that describe the influence of mechanics on embryonic heart development. However, basic parameters for the modeling are difficult to acquire since the embryonic heart is tiny and beating fast in the early stages. Optical coherence tomography (OCT) technique provides depth-resolved image with high resolution and high acquisition speed in a noninvasive manner. In this paper, we performed 4D[(x,y,z) + t] scan on the outflow tract (OFT) of the chick embryonic heart at stage of HH18(~ 3 days of incubation) in vivo using spectral domain OCT (SDOCT). Parameters such as displacement and geometrical size of the OFT were extracted from the structural images of the SDOCT. Two-dimensional strain vector were solved using strain-displacement relations in curvilinear cylindrical coordinates based on kinetic theory of elasticity. Based on the geometrical size and other initial conditions, two-dimensional elasticity finite element model of the OFT myocardial wall deformation were established and then solved by direct frequency response method. Comparison between experimental data and simulation result shows the utility of the finite element models. Our results demonstrate that mathematical modeling based on parameters provided by SDOCT is a useful approach for studying cardiac development in early stage.
The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.
We present a 3D imaging system for simultaneously imaging the distributions of refractive index and optical absorption using a transmission Fourier-domain low-coherence interferometer. The forward-scattering light travelling through a sample interferes with a reference light beam. The projections of refractive index and optical absorption within the sample are calculated from measured interference fringes. We acquire the projections at sufficient angular views and reconstruct the distributions of refractive index and optical absorption using the filter back-projection algorithm. The proposed method is experimentally verified by using a plastic tube phantom.
We demonstrate a method for measuring the total velocity components of particle flow using optical coherence tomography. When passing through a probe volume, moving particles cause the intensity variation of backscattered light. The intensity signal contains the velocity information about the particle flow. Such variation is separated into a phase modulation and an amplitude modulation, from which the axial and transverse components of velocity are obtained. The proposed method is experimentally verified using polystyrene particle suspension flow.
A photoacoustic tomography imaging system using a low-coherence interferometer with rapid detection of phase modulation was designed, fabricated, and tested for biologic imaging. A noncontact probing technique was applied to improve the practicability of the system. The technique is experimentally verified by the image of a simulated tissue sample and the blood vessels within a mouse ear flap (pinna) in vivo. The system’s axial and lateral resolutions are evaluated at 45 and ~15 μm, respectively. The system’s imaging depth is 1mm in a special phantom. The results show that the system has the feasibility to be used as a photoacoustic tomography imaging method, and it may provide a kind of possibility of noncontact real-time PAT.
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