This PDF file contains the front matter associated with SPIE Proceedings Volume 12819, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Accurate classification of plaque composition is essential for treatment planning. Deep learning (DL) methods have been introduced for this purpose, to analyze intravascular images and characterize in a fast and subjective manner plaque types. In this study, we compared the efficacy of two DL methods, designed to process data acquired by two intravascular–an optical coherence tomography (OCT) and a near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS)–catheters to assess plaque types using histology as the reference standard. We matched histology, OCT, and NIRS-IVUS images, compared their estimations, and found that the DL method developed for NIRS-IVUS analysis had a better correlation with histology for calcific and lipidic tissue as compared with the OCT-DL method while both methods had a moderate correlation with the estimations of histology for fibrotic tissue. These findings could be attributed to the fact that OCT due to its poor penetration especially in lesions with large plaque burden fails to identify the deep-seated plaque and also to the fact that the NIRS-IVUS-DL method was developed with the use of histology instead of experts’ analysis.

Histopathological information is critical to identify diseased region in coronary tissues, with great potential to guide the treatment of coronary artery disease. We develop a pathology-aware generative adversarial network (GAN) to generate virtual histology images from coronary optical coherence tomography (OCT) images. The proposed network integrates transformer network structure with a cycleGAN framework. Our algorithm advances existing cycleGAN-based method with a lower value of Frechet Inception distance, as demonstrated by a cross-validation experiment from a human coronary dataset. Our work incorporates histopathological visualization into real-time OCT imaging, holding great potential to assist diagnostic and therapeutic applications of cardiovascular diseases.

Acute coronary syndrome (ACS) is a common cardiovascular event with significant implications on global health. Degradation and remodelling of coronary plaques play a pivotal role in both the development of ACS, which can be visualized using intravascular PS-OCT, a high resolution, invasive imaging modality with contrast for collagen. In this work we adapt a machine-learning based segmentation pipeline to enable volumetric assessment of coronary plaques and automated evaluation of polarization properties. The utility of this framework is demonstrated through a case study investigating the fibrous caps of coronary plaques between unstable patients with ACS and stable patients with chronic coronary syndrome (CCS). Preliminary results show that ACS plaque caps exhibit significantly lower birefringence than the caps of lesions in CCS patients, while having comparable cap thickness. Our pipeline allows for automated volumetric coronary plaque analysis, paving the way toward prospective studies to determine whether volumetric properties measured with intravascular PS-OCT may improve risk stratification of patients with coronary artery disease.

Coronary artery plaque structural stress (PSS) is associated with plaque vulnerability and is quantifiable in vivo with optical coherence tomography (OCT) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) but the accuracy of these is unclear. This study explored the performance of the two modalities in measuring PSS using histology as reference standard. NIRS-IVUS and OCT images obtained in vessels under physiological pressure require transformation to a zero-pressure condition to estimate PSS. Two methods were examined to achieve this – uniform and non-uniform shrinkage (which may to be superior for eccentric plaques) followed by PSS computation which was compared to histology-derived PSS. NIRS-IVUS and OCT imaging were conducted ex vivo in cadaveric human coronaries prior to histological analysis. In 93 pairs of NIRS-IVUS-histology and 88 pairs of OCT-histology sections, the correlation between the PSS estimated by histology and NIRS-IVUS using the uniform shrinkage approach was higher than that derived by OCT. Non-uniform shrinkage resulted in a numerically lower correlation but no significant difference by Bland-Altman analysis compared to uniform shrinkage.

In the study, we design a real-time multimodal imaging system to identify and differentiate lipid-rich plaques from stable plaques. We have shown that IVPA is able to perform lipid detection in real time imaging mode. We also see potential lipid and calcified region in ex vivo human artery images. In the future, we plan to validate our study with more ex-vivo animal and human artery images to determine the safety and usefulness before moving on to the in-vivo studies.

We report the development and characterization of a multispectral FLIm/ polarization-sensitive OCT intravascular imaging catheter system. Key innovations include a high return loss rotary junction. The combined imaging contrasts target the improved characterization of inflammation and disruption of the extracellular matrix, two key contributors to atherosclerosis, by enabling the evaluation of biochemical signatures, birefringence, and depolarization in addition to lesion morphology. We present key aspects of the system’s design and performance and highlight challenges associated with the development of intravascular imaging systems suitable for clinical translation.

Atherosclerosis is a leading cause of global mortality. Current clinically available imaging techniques suffer from limited spatial resolution and lack the ability to identify biomolecular features of atherosclerotic plaques. To address this, our team has developed a bimodal imaging system which consists of optical coherence tomography (OCT) and fluorescence. In addition, a nanoparticle named porphysomes is used as a fluorescence contrast agent to target macrophages in the plaques of diseased mice. Results suggest that our intravascular imaging system is capable of detecting the fluorescence from nanoparticles which provides complementary biological information to the structural information obtained from simultaneously-acquired OCT images.

Coronary chronic total occlusions (CTOs) are severe blockages formed by lipid, fibrous, and calcific material within the artery, halting blood flow for at least three months. Treating CTOs using true-lumen crossing is challenging due to their composition and high tortuosity in coronary arteries. Our study uses intracardiac echocardiography (ICE) catheters to image coronary arteries, introducing a novel 2D and 3D outlining technique. This advancement may improve percutaneous coronary interventions (PCI) for CTOs by providing live imaging feedback during true-lumen crossing procedures, enhancing treatment outcomes.

This conference presentation was prepared for SPIE Photonics West BiOS 2024.

This conference presentation was prepared for SPIE Photonics West BiOS 2024.

This conference presentation was prepared for SPIE Photonics West BiOS 2024.

This conference presentation was prepared for SPIE Photonics West BiOS 2024.

The next-generation chip-on-tip surgical endoscopes require small footprint (1-3 French), hyperspectral imaging capability for multi-biomarker quantification with high frame rate to reduce motion artefacts. These innovations demand high data rate links, which could require twisted-pair cables if transmitted electrically. To eliminate bulky electrical wiring, we propose an all-optical powering and communication chip at the distal end consisting of a monolithically series interconnected Photonic Power Converter and a reflective electroabsorption modulator (REAM) based on a p-i-n diode structure with an embedded multiple quantum well (MQW) absorber. Optical sources for the power generator and reflective modulator are provided remotely over optical fiber, thus removing the need to host power-hungry lasers at the distal tip. To simplify the overall design, the communication scheme takes advantage of the REAM’s dual functionality as a modulator and detector. Here, we have used a commercial REAM designed to operate at 1550nm and a novel Time Division Duplexing (TDD) communication protocol to demonstrate bidirectional transmission at 500 Mb/s over a single-mode fiber on a benchtop in order to examine the feasibility of the scheme. We found that at shorter wavelength near the MQW band-edge, zero-bias operation of the REAM is possible and the required modulation voltage swing is reduced. Operating under zero-bias at 1520nm instead of 1550nm leads to negligible static energy consumption and about 47% reduction in dynamic energy consumption, reaching an 8dB extinction ratio. Additionally, at 1520nm, the photocurrent generation responsivity increases dramatically at zero-bias, allowing the Transimpedance Amplifier (TIA) to be removed from the receiver circuit. This results in reduced footprint and power consumption of the receiver front end circuit.

We have developed a prototype multiplexed fiber-optic system that enables real-time monitoring of hypoxia-sensing fluorophores in beating isolated rat hearts, providing dynamic data useful for the assessment of cardiac metabolism, with potential for cross-correlation and biological validation using parallel MR spectroscopy and PET or SPECT imaging. The system has been designed to suppress background and increase light efficiency. We have established a data analysis pipeline using nonnegative least-squares curve fitting allowing unmixing of overlapped fluorescence spectra and fluorophore quantification. In this first phase of our work, we demonstrate simultaneous detection of a mixture of fluorophores in isolated perfused hearts.

Rapidly changing coagulation status is a major challenge in managing and preventing bleeding in patients on mechanical circulatory support. Here, we apply iCoagLab, a hand-held coagulation sensing instrument for timely and comprehensive blood coagulation assessment in patients undergoing cardiac pump implantation. Our results confirm the high accuracy and precision of iCoagLab tests in quantifying key clotting parameters including clotting time, clot stiffness and clotting rate. These studies will help pave the way towards addressing bleeding complications at the point of treatment to potentially manage and prevent hemorrhagic events during mechanical circulatory support.

A low degree of polarization uniformity (DOPU) and high double pass phase retardation (DPPR) values below the retinal-pigment epithelium – Bruch membrane’s (RPE-BM) complex in the human retina have been associated with the presence of melanin. Our polarimetry measurements (Cense et al, JBP, 2018) found no correlation between melanin and lower DOPU, because all young subjects had high DOPU values, but saw decreased DOPU in a subset of older subjects, who also have melanin. We hypothesize that this signal is not induced by melanin, but by a substance related to hypertension. Our measurements demonstrated a strong correlation between hypertensives and high DPPR values induced by the RPE-BM complex, suggesting that the induced retardance is the result of physiological changes associated with hypertension. This signal may be useful as a biomarker for screening of cardiovascular diseases.

We develop and characterize transgenic mouse models expressing ReaChR or NpHR specifically expressed in the heart tissue. Non-invasive pacing is achieved by shining red light from an LED array over a 10 mm diameter spot on the shaved mouse chest skin. We demonstrated that low power density (~1.2 mW/mm2) illumination is sufficient to induce tachycardia, bradycardia, and sustained arrhythmia, providing full control over the heart rhythm in live, anesthetized mice. This in vivo optogenetic pacing platform opens opportunities for future non-invasive studies on mammalian heart physiology, diseases, and therapies for arrhythmias without any surgical intervention.

The goal of this study is to explore the potential of pulsed and continuous wave light optogenetic stimulation on mouse embryonic cardiodynamics. Toward this goal, we engineered mouse embryos expressing the light-sensitive protein Channelrhodopsin-2 (ChR2) ubiquitously through the embryo. The embryos were dissected live and the optogenetic light stimulation of ChR2 at 473-nm was performed under imaging guidance. The pulsed stimulation allowed for a range of cardiodynamic behaviors and was overall found to have a milder effect on embryo viability, while the continuous wave stimulation provided an advantage in the faster mapping of optogenetic cardiac responses.

Cardiodynamics and hemodynamics are important factors regulating heart development, but dynamic 3D imaging of a beating embryonic heart has been challenging due to high requirements for both imaging scale and speed. Optical coherence tomography (OCT) has a unique imaging scale for 3D embryonic heart imaging in various animal models. However, the general imaging speed of OCT can only provide limited spatiotemporal sampling in direct volumetric acquisition of a beating heart. Here, we present an open-source, post-acquisition synchronization method that requires just a single, densely sampled linear 3D scan but generates superior 4D (3D+time) imaging quality with a high efficiency.

Biomechanical force exerted by early blood flow regulates heart development and alterations can result in congenital heart defects. To investigate dynamics during early cardiac development in mouse models of human disease, optical coherence tomography (OCT) based functional analysis methods are actively being developed. Here, by integrating and expanding recent OCT cardiodynamic techniques, we demonstrate a quantitative OCT angiography method capable of dynamic, volumetric flow analysis in embryonic vasculature and within the beating heart. The presented method will allow biomechanical studies of the role that early blood flow plays in regulating mammalian heart development.

During mouse embryonic development cardiac tissue derives from the mesoderm to form the cardiac crescent. Within 24 hours the heart morphs from a flat crescent into a linear elongated tube that will fold on itself to carry out cardiac looping and position itself to form future cardiac chambers. Through out this entire process the heart is continuously contracting—adding more cardiomyocytes and organizing their layout to generate a contractile force that efficiently pushes blood plasma through the embryonic circulation. During this stage, the embryonic heart is composed of cardiac progenitor cells that are in the process of differentiating into mature cardiac cells. It is suspected that cardiac contraction may provide mechanical information that guides cell behavior and influences cell fate decisions. In this work, we have utilized volumetric, high-speed OCT imaging in conjunction with live mouse embryo culture to characterize how cardiac contraction patterns in the mid-gestation embryo, as the heart progresses from the cardiac crescent to the linear heart tube stage. To accomplish this, we set timed matings to obtain mouse embryos of the desired stage. Mouse embryos are live dissected and are allowed to recover in media supplemented with serum at 37°C and gassed with 5% CO2. To image these embryos, we have utilized a commercial fourier domain mode lock (FDML) OCT system to image the live embryonic mouse heart at 19 volumes/second with a 512x128 voxel element 3D OCT data set. In our approach, we customized the sample arm of the FDML system so that it may be placed within an incubator to maintain physiological conditions through the entire imagining session. At a 19Hz volume rate, single acquisitions only last several seconds and make this approach ideal for high throughput imaging. With a central wavelength of 1318nm and an axial resolution of 8.33um in air, we are able to reconstruct high resolution structural images of the mouse embryo with great temporal resolution to visualize the cardiac contraction cycle and the flow of blood cells through the lumen of the heart. We will use these datasets to characterize the patterning of contraction as the heart develops. This information will be resourceful by indicating which regions of the heart are adopting a cardiomyocyte identity and will help inform future hypothesis that attempt to determine how cardiac progenitor cells make cell fate decisions.

This conference presentation was prepared for SPIE Photonics West BiOS 2024.

Atrial fibrillation (AF) is the most common arrhythmia worldwide. An increasingly common treatment option is catheter ablation. During this procedure, the clinician steers a catheter into the left atrium and ablates a lesion fence around the pulmonary veins, a common source of ectopic signals. This lesion fence blocks arrhythmogenic tissue from initiating an erroneous heartbeat. However, if the disease has progressed from paroxysmal to persistent, pathogenic tissue exists throughout the atrium, and common ablation schemes are not as effective. In this case, technologies exist to electroanatomically map the atrium and guide clinicians in targeting adjunctive AF ablation targets. Low voltages mapped in vivo are a well-documented way of identifying atrial fibrosis, an important substrate for AF. Ablating low voltage zones in patients with a more developed disease can help terminate AF and improve long-term outcomes, but low voltage measurements are not specific to fibrosis. Treatment results vary because the targeting that electroanatomical mapping provides is incomplete. Our group has shown that polarization-sensitive optical coherence tomography (PSOCT) and near infrared spectroscopy (NIRS) can monitor lesion formation in vivo and differentiate tissue types in the atrium. Now, we are investigating the technology’s utility in identifying AF targets prior to ablation. We have collaborated in developing a swine model of AF that shows the atria remodels during the diseased state. Because of this, we can electroanatomically map these diseased hearts in vivo to measure low voltage zones. Subsequently, we examine the left atrium ex vivo using benchtop PSOCT, NIRS, and optical mapping (OM) and register these optical measurements to the in vivo low voltage zones. We show that OM confirms abnormal conduction, while PSOCT- and NIRS-derived metrics have promise for identifying low voltage zones. We confirm these measures with histological identification of fibrosis. This suggests the feasibility of using PSOCT-NIRS at the catheter tip to detect AF ablation targets.

Near-infrared reflectance spectroscopy can serve as a complementary imaging tool that accurately provides endocardial substrates through optical mapping and improves the quality of ablation therapy. Optical indices were extracted from spectrum response, visualized similarity of blood and PBS maps interpolated from those indices were evaluated. Statistical analysis between blood and PBS optical indices were performed for each substrate type, and classification algorithms were developed using key features to classify pulmonary vein, lesion, and fibrosis with high accuracy. The results indicate NIRS mapping catheters can serve as a complementary imaging tool to the current EAM systems to improve treatment efficacy.

Longitudinal imaging of a 3D model of calcific aortic valve disease, which consisted of co-cultured GFP+ Valve Endothelial Cells (VEC) and Valve Interstitial Cells (VIC), was performed with a combined Optical Coherence Microscopy (OCM), confocal reflectance and fluorescence microscopy system. The acquired confocal volumes depicted the VEC morphological changes and migration as well as collagen fiber alignment. With the aid of computational refocusing and multi-volume processing, the OCM datasets could visualize VIC cell bodies, matrix remodeling, nodule formation and calcific deposits. The complementary information derived using this combined approach could help unravel the cellular mechanisms leading to aortic valve calcification.

Bacterial infections inside the heart, called infective endocarditis, result in high mortality. The bacteria encase themselves within a biofilm, which shields them from treatment by drugs or devices, and makes it challenging to diagnose and confirm infection, despite technological advances. In this study, we investigate the use of optical coherence microscopy (OCM), a non-invasive imaging modality, as a potential tool to visualize biofilms on heart valves. Biofilms were grown on porcine heart valves in human plasma using clinical isolates of Staphylococcus aureus or Streptococcus gordonii. S. aureus biofilms were treated with a fibrinolytic to degrade and remove biofilms. Valves were imaged before and after biofilm growth using OCM followed by subsequent confocal laser scanning microscopy using fluorescent staining. The resolutions and imaging areas of the two microscopes were matched. A comparative analysis of the two techniques showed that OCM can accurately differentiate between areas with and without biofilm. Our findings highlight OCM as a tool for non-contact, label free imaging that can provide key morphological information for infection diagnosis and therapy guidance.

All-optical ultrasound is emerging as an imaging modality well-suited to use in minimally invasive surgical procedures. With this paradigm, ultrasound is both generated and received using light. Recent studies have demonstrated intraluminal ultrasound imaging using a fibre optic device. In this work acoustic simulations were carried out for optimisation of device design. Two device setups were considered; a separate optical fibre for the ultrasound transmitter and receiver and an ultrasound transmitter and receiver combined on a single optical fibre. The image resolution and signal-to-noise ratio were used to evaluate the simulated devices and two parameters were studied, the separation between the transmitter and receiver for the two-fibre device, and the transmitter element size for both device setups. The results demonstrated how device dimensions affect the resulting imaging performance and show the efficacy of using simple acoustic simulations to inform all-optical ultrasound transducer design.

The Drosophila Melanogaster is a powerful tool for cardiac research due to its ability for disease modeling. OCM provides cross-sectional images of its beating heart tube, which can be segmented to quantify heart parameters. Here, we expanded upon an optimized LSTM U-Net model introduced in 2023, by Fishman et al., to improve segmentation performance when artifacts are present. We incorporated attention gates via skip connections between each level of the LSTM U-Net model. This model increases the prediction intersection over union (IOU) from 0.86 to 0.89 for images with reflection artifacts and from 0.81 to 0.89 for those depicting frequent heart movement.

In hearts, self-replicating reentrant spiral waves can cause deadly tachycardia. In vitro cardiac tissue models can benefit both fundamental research and patient-specific disease modeling. Here, cardiac optogenetics allows damage-free control of tissue activity. We present a system for digital control and observation of excitation wavefronts in human stem-cell-derived cardiomyocytes expressing f-ChRimson-YFP. Holographic light shaping enables patterned illumination, observing the 5x5 mm² sample at 250Hz frame rate. A fast data evaluation scheme accesses spatially resolved stimulus-induced sample activity and the propagation of action potential wavefronts in in vitro cell cultures. Experiments with varied illumination patterns control wavefront direction and timing, paving the way for patient-specific disease modeling.

We describe a substantially improved NIRF-IVUS imaging system to overcome current technical limitations. We have implemented a hybrid rotary joint capable of rotational speeds up to 6,000rpm and developed a NIRF-IVUS imaging catheter with a robust dual-layer drive shaft and a reduced rigid length of 2mm with a catheter size <3.6F. NIRF-IVUS processing software was also improved by implementing a high-speed acquisition trigger and data streaming for fast recording speeds. NIRF-IVUS imaging at speeds of at least 30 fps in phantoms and in vivo arterial disease models will demonstrate the unique capabilities of IVUS-NIRF imaging of plaque pathobiology.