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.
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.
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.
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.
The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) and periodic stress (WPS) are the components which have been proved to influence the morphogenesis during early stages of cardiac development. The vessel wall will be deformed by the blood pressure and produce natural elastic force acting on the blood. Because blood flowing in different flow state and show different characteristics of fluid, which influence the calculation of WSS and WPS directly, it is necessary to study the blood flow state. In this paper, we introduce a method to quantify the blood flowing state 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. By processing the structural image, the geometric parameters were obtained. Blood flow velocity distribution in the OFT were calculated by Doppler OCT method. Hemodynamic parameters were obtained at different times during the cardiac cycle used biofluid mechanics theory, such as Reynolds number and Womersley number.
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.
Scale Invariant Feature Transform(SIFT)algorithm is widely used for ear feature matching and recognition. However, the application of the algorithm is usually interfered by the non-target areas within the whole image, and the interference would then affect the matching and recognition of ear features. To solve this problem, a combined image segmentation algorithm i.e. KRM was introduced in this paper, As the human ear recognition pretreatment method. Firstly, the target areas of ears were extracted by the KRM algorithm and then SIFT algorithm could be applied to the detection and matching of features. The present KRM algorithm follows three steps: (1)the image was preliminarily segmented into foreground target area and background area by using K-means clustering algorithm; (2)Region growing method was used to merge the over-segmented areas; (3)Morphology erosion filtering method was applied to obtain the final segmented regions. The experiment results showed that the KRM method could effectively improve the accuracy and robustness of ear feature matching and recognition based on SIFT algorithm.
NIRS analysis is considered to be a promising noninvasive detection technique. Existing research results show that optical properties of the human skin tissue will change with different contact pressures when contact survey mode is used for in vivo NIRS measurement. The impact of the contact pressure might be greater than the impact of glucose concentration on the spectral data of NIRS. The uncertainty caused by pressure in vivo, makes it extremely difficult to get the high SNR-spectrum. In this talk, the Monte Carlo simulation has been carried on under the condition of different contact pressure. Simulation results show that the diffused reflectance and transmittance increase with rising contact pressure. Moreover, the simulation results show that the effects of contact pressure are larger than the effects of glucose concentration. Therefore it is promising to make comprehensive utilization of diffused reflectance and transmittance to eliminate the interference which caused by contact pressure.
In this paper, we demonstrated the use of a spectral domain optical coherence tomography (OCT) in visualizing and
quantifying changes in cardiac wall strain and blood-flow velocities under normal and altered hemodynamic conditions in chicken embryos at an early stage of development, focusing on the heart outflow tract (OFT). OCT imaging allowed in vivo evaluation strain and strain rate of the myocardium of the OFT through analyzing the periodic variation of the myocardial wall thickness. We found that alterations in hemodynamic conditions, through OFT banding, Changed strain and blood-flow velocities through the OFT as expected.
We proposed and demonstrated a digital method of dispersion compensation suitable for spectral-domain optical coherence tomography. The wavelength coordinate of the coherence spectrum was calibrated digitally using a two-order polynomial. A software-based scheme was introduced to determine the polynomial coefficients of the polynomial fitting spectrum wavelength. Therefore, the spectrum deformation introduced by dispersion can be compensated effectively. This method was experimentally validated by in vivo imaging an early-stage chick embryonic heart.
Spectral OCT (SOCT), with high acquisition speed and high dynamic range, has been implemented by many research
groups in the world. However, SOCT image inherently has virtual image, including auto-correlation noise and mirror
image. The existence of the virtual image may deteriorate the quality of the image. In order to eliminate those virtual
images, some methods have been demonstrated effective, such as differential SOCT and complex SOCT. In this paper, a
novel method is proposed i.e. three-phase shifting method. The pathlength of the reference arm is changed for certain
distance by PZT controller. Three phase shifted coherence spectra are recorded for A-line. The reconstruction algorithm
can eliminate both auto-correlation noise and minor image, thus improve the signal-to-noise ratio of the SOCT image.
Furthermore, this method is also able to amplify the measuring range of SOCT by a factor of 2. An intact porcine cornea
tissue in vitro is further used to show the potential of this method for high-resolution biological imaging.
A three-phase shifting method is introduced to spectral OCT to eliminate mirror image and autocorrelation noise inherent in spectral OCT signal, thus improves the measurable range of spectral OCT by a factor of 2. The feasibility of such method is demonstrated using a mirror like object. Comparison between two-phase and three-phase shifting methods is performed using a 1mm slab as the object. An intact porcine cornea tissue in vitro is also used to show the potential of this method for biological imaging.
Optical coherence tomography (OCT) is a new imaging modality that is being actively used in a variety of medical applications. Optical coherence tomography performs cross sectional imaging by measuring the time delay and magnitude of optical echoes at different transverse positions, essentially by the use of a low coherence interferometry to obtain the depth resolved information of a sample. The interference can occur only when the optical path lengths of light in both the sample arm and reference arm are matched to within the coherence length of light source. The most commonly used light sources in the current OCT systems are the superluminescent diodes (SLD). However, the coherence lengths of SLD are typically 10-30 microns that are not sufficient to achieve the resolution required for many medical applications. In the meantime, the moderate irradiance offered by the SLD limits the real time applications for OCT system, which usually require a power with an order of at least 10 milliwatts. Recently the diode-pumped superfluorescent optical fibers sources has been used in a variety of communication and sensor applications. The superfluorescent rare-earth doped optical fibers source is also the very good OCT systematic light source, because of that have a wide bandwidth of fluorescence and high emission power.
Optical coherence tomography (OCT) is a new modality used to image biological tissues that weakly scatter and absorb light. It was demonstrated that this technique provides image with micrometer resolution in a noncontact and noninvasive way. Traditional OCT is time domain OCT (TDOCT). In this method the length of the reference arm in an interferometer is rapidly scanned over a distance corresponding to the imaging depth range. The mechanism of scanning largely limits the acquisition speed and makes real-time imaging impossible. In recent years a new model OCT based on Fourier domain interferometry is emerged, we called it spectral OCT (SOCT) or Fourier domain OCT (FDOCT). SOCT can avoid scanning of the reference, thus can reach very high acquisition speed. In this paper, spectral OCT related theories and techniques are reviewed. This paper consists of three sections: principle of SOCT, different sep-ups, recent progress and advance.
Optical coherence tomography (OCT) is a new imaging modality that is being actively used in a variety of medical applications. Currently, most of the OCT systems operate in the time domain, which requires scanning the optical path length in the reference arm in order to obtain the in-depth profile, i.e. A scan. This however limits the system scanning speed. To avoid the axial scanning and therefore improve the system scanning speed, a novel OCT system is recently proposed by a number of groups that operates in the frequency domain, i.e. the spectral OCT. In this paper, we report the spectral OCT system being constructed at Tianjin University. The system has a dynamic range at 78dB and is capable of scanning speed at 12 seconds per image, largely limited by the bottleneck of data transferring from the CCD camera currently employed to the computer. The SOCT imaging results obtained from the animal tissues (cornea from an intact porcine eye) in vitro will be presented.
Clustered microcalcifications (MCCs) in mammograms are an important sign in the detection of breast cancer. Nevertheless, it is a complex and difficult task for radiologists to detect the clustered MCCs from the tissue background of mammograms only by naked eyes. This paper presents a prototype of a computer-aided detection system to automatically detect MCCs in mammograms. The detection algorithm mainly comprises three modules. The first module, called the mammogram pre-progressing module, inputs and digitizes mammograms into 8-bit images of size 2048x2048, normalizes the images, manually extracts the breast region from the background. The second module, called the feature extraction module, is achieved by using mixed features consisting of two wavelet features and two gray level statistical features. The wavelet features are generated by a five-level wavelet decomposition and reconstruction algorithm. The gray level statistical features used in this paper are median contrast and normalized gray level value. Finally, the third module, called the MCCs detection module, discovers MCCs in the images by using a classifier. This paper uses a three-layer artificial neural network (ANN) as a classifier to segment MCCs from the processing image. The ANN takes these four features generated in the second module as inputs. The output of the ANN corresponding to the true MCC pixels is then thresholded to segment out the true MCC pixels. One advantage of the designed system is that each module is a separate component that can be individually upgraded to improve the whole system. The algorithm is tested with a series of clinical mammograms. A sensitivity of more than 78% is obtained at a relatively low false-positive (FP) detection of 2.09 per image. The results are compared with the judgement of radiological experts, and they are very encouraging.
KEYWORDS: Mammography, Breast, Image filtering, Electronic filtering, Gaussian filters, Computing systems, Detection and tracking algorithms, Signal detection, Signal to noise ratio, Digital imaging
Clustered microcalcifications (MCCs) on mammograms are an important early sign of breast cancer. An intelligent computer-aided diagnosis system can be very helpful for radiologist in detecting and diagnosing MCCs earlier than typical screening programs. In this paper, the detection algorithm is able to extract high-frequency signal and remove low-frequency background by exploiting a difference-image technique in which a signal-suppressed image is subtracted from a signal-enhanced image to remove the structured background in a mammogram. The difference image is thresholded to detect these MCCs in mammograms. The algorithm is tested with a series of clinical mammograms. A true positive rate ofmore than 75.5% is obtained at a false-positive (FP) detection of 2.18 per image
Clustered microcalcifications (MCCs) on mammograms are important hints of breast cancer. Nevertheless, it is a complex and difficult task for radiologists to detect the clustered MCCs from the tissue background of mammograms only by naked eyes. This paper presents a method for computer-aided detection of MCCs in digital mammograms. The detection algorithm mainly consists of two different methods. The first one, based on the difference-image technique, recognizes high-frequency signals and very high-frequency noise. The second one is able to extract high-frequency signal by exploiting a wavelet based noise suppression and neural network (NN) classification. In the false-positive reduction step, false signals are separated from MCCs by means of an AND operation on signals from two methods. The algorithm is tested with a series of clinical mammograms. A sensitivity ofmore than 90% is obtained at a relatively low false-positive (FP) detection of 2.18 per image. The results are compared with thejudgement ofradiological experts, and they are very encouraging.
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