This PDF file contains the front matter associated with SPIE Proceedings Volume 11621, including the Title Page, Copyright information, and Table of Contents.

Patients with cardiac arrythmia most commonly require radiofrequency ablation to destroy arrhythmogenic electrical pathways and restore normal heart rhythm. However, arrhythmia resurgence exists from limited means to directly confirm the extent of lesion progression during RFA procedure. Optical spectroscopy is sensitive to tissue optical properties and changes in biomolecular composition. We propose a simplified optical spectroscopy through a single fiber integrated catheter to predict irrigated endocardial lesion progression using deep neural network model on ex-vivo model.

Radiofrequency ablation procedures, such as pulmonary vein isolation for patients with atrial fibrillation, require detailed anatomical mapping of atrial structural substrate to identify AF substrate. Identification of structural substrates, such as scar tissue, pulmonary vein, collagen and adipose tissue can provide helpful guidance of RFA procedures. We demonstrate mapping of atrial substrates using optical spectral signatures from near-infrared spectroscopy. Using position tracking and interpolation algorithm, we assess the capability of NIRS to distinguish various tissue structures on a reconstructed 3D spatial maps of ex-vivo swine and human atriums.

Transseptal puncture (TSP) is commonly conducted under the guidance of fluoroscopy and/or intracardiac echocardiography (ICE) at the fossa ovalis (FO) to gain percutaneous access to the left atrium for intracardiac procedures. Issues with traditional TSP include: additional vascular access through a sheath, and fluoroscopy exposes patients to ionizing radiation. TSP, if not done appropriately can result in serious complications. We studied the feasibility of optical coherence tomography (OCT) guidance of TSP with ex vivo and in vivo experiments. Results show that OCT can provide detailed structure information to identify FO allowing for safe TSP.

Optical coherence tomography (OCT) has been applied for understanding heart development because of its capability of imaging both the structure and function of tiny beating embryonic hearts. Labeling endocardial cushions is necessary for quantifying morphological characteristics of the looping hearts. Since manual segmentation is time-consuming and prone to subjectivity, this study aims to use V-net to automatically segment endocardial cushions from OCT images. This will benefit research on heart development, especially studies requiring large cohorts of embryos, for example those investigating the teratogenic effects of ethanol or drugs and the prevention of these effects on the developing hearts.

In this project, we propose a deep learning based weakly supervised learning algorithm for cardiac adipose tissue segmentation using image-level labels. Based on ReLayNet, our proposed method can automatically segment the adipose tissue from normal myocardium tissue in pixel level. Compared with fully supervised learning methods, our model achieves competitive segmentation results on both accuracy and Dice coefficient within a database of OCT images of human cardiac tissue. Combined with the OCT image, the predicted adipose map could provide additional information for the guidance of cardiac radio frequency ablation.

A 1470-nm laser previously demonstrated faster sealing and cutting of blood vessels with lower thermal spread than radiofrequency and ultrasonic surgical devices. This study simulates laser sealing and cutting of vessels in a sequential two-step process, for low (< 25 W), medium (~ 100 W), and high (200 W) power lasers. Optical transport, heat transfer, and tissue damage simulations were conducted. The blood vessel was assumed to be compressed to 400 μm thickness, matching previous experimental studies. A wide range of linear beam profiles (1-5 mm widths and 8-9.5 mm lengths), incident powers (20-200 W) and irradiation times (0.5-5.0 s), were simulated. Peak seal and cut temperatures and bifurcated thermal seal zones were also simulated and compared with experimental results for model validation. Optimal low power laser parameters were: 24W/5s/8x2mm for sealing and 24W/5s/8x1mm for cutting, yielding thermal spread of 0.4 mm and corresponding to experimental vessel burst pressures (BP) of ~450 mmHg. Optimal medium-power laser parameters were: 90 W/1s/9.5x3mm for sealing and 90W/1s/9.5x1mm for cutting, yielding thermal spread of 0.9 mm for BP of ~1300 mmHg. Optimal high-power laser parameters were: 200W/0.5s/9x3mm for sealing and 200W/0.5s/9x1mm for cutting, yielding thermal spread of 0.9 mm and extrapolated to have BP of ~1300 mmHg. All lasers produced seal zones between 0.4-1.5 mm, correlating to high BP of 300-1300 mmHg. Higher laser powers enable shorter sealing and cutting times and higher vessel seal strengths.

This paper presents a respiratory phase prediction technique from an optical phonocardiograph (PCG) signal. The PCG acquisition was conducted using a speckle-based sensor which includes illumination of the inspected subjects by a laser beam and analyzing the temporal changes in the spatial distribution of the back scattered secondary speckle patterns. From the analysis of the 2D speckle patterns a 1D nano vibrations signal was extracted. Then, we performed an analysis of this 1D signal while relying on the PCG extracted features used in Naïve Bayes model. The performance accuracy for the respiratory phase prediction conducted over four subjects was 83%. The high accuracy made possible thanks to 9 spatial illumination spots used in our optical sensor and using a decision algorithm involving spots' combination (while each one of the 9 spots illuminating the chest of the inspected subjects was analyzed separately).

Non-invasive monitoring of cardiovascular diseases has been explored by means of laser Doppler vibrometry (LDV). In previous work, we have developed a handheld 6-beam on-chip LDV-device based on silicon photonics that can simultaneously measure the skin vibrations induced by cardiac action in multiple positions. This allows for the estimation of the pulse wave velocity (PWV), which is the current gold standard for evaluating arterial stiffness. The demonstrator has been used in a series of clinical feasibility studies. However, the system required the application of a retro-reflective (RR) patch to the skin prior to the measurement in order to enhance skin reflection. The use of the RR patch reduces the device usability and may also impact the measurement results. In this work, we bring the concept one step further by eliminating the need for the RR patch during the measurement. The diffuse reflection from the skin leads to the low intensity of the back-reflected light detected by the interferometric readout system of the LDV. In order to increase the reflection signal level, we propose to operate the LDV at 1310nm where skin reflection is relatively strong while still being insensitive to skin tones. Furthermore, the optical imaging system between LDV-chip and skin has been designed for optimal signal strength in combination with sufficient depth of focus. We report on LDV measurements without using RR patch, and on the details of the optimized optical system.

Photoactivation is a promising theranostic tool to image and stabilize the atherosclerotic plaque by apoptosis induction in macrophages or other vascular cells; however, lack of effective drugs and mechanistic understanding hinder its clinical application for cardiovascular disease. Here, we developed the macrophage targeted photosensitizer delivery strategy and demonstrated that imaging assisted light activation reduced inflammation and burden of atherosclerotic plaques. Mechanistically, targeted photoactivation induced autophagy and increased MerTK expression in carotid atheroma as early as 1 day, and had 2-fold increase in macrophage-associated apoptotic cells, indicating efferocytosis enhancement. This multifunctional photoactivatable theranostic strategy could confer a promising tool for high-risk plaques.

Classification of atherosclerotic plaques in vivo remains challenging, even with high-resolution optical techniques, such as intravascular optical coherence tomography (OCT). Plaques contain lipid-rich, fibrous, and calcified components with unique optical properties, enabling their discrimination by quantitative light scattering analysis. We present an approach for improved computation of depth-resolved attenuation coefficients in OCT capable of determining layer-resolved backscattering fractions, thus providing complementary quantitative scattering metrics descriptive of the tissue’s physical properties. We report preliminary findings showing meaningful lesion contrast in quantitative scattering parameters in clinical and cadaver heart pullbacks, which stand to provide additional tools for improved classification of atherosclerotic plaques.

Intravascular polarimetry complements the high-resolution images of conventional intravascular optical coherence tomography (OCT) with quantitative measures of tissue polarization properties that relate to tissue composition. Yet, additional metrics further complicate image interpretation, and leveraging the quantitative polarization metrics currently relies on tedious manual segmentation. Here, we developed a customized convolutional neural network multi-class segmentation model to detect the intima-media boundary whenever visible and otherwise identify the presence of attenuating plaque that masks this boundary. Combined with the IV-OCT backscatter signal, the polarization metrics that enhance the discrimination of targeted features, thereby improving the accuracy and robustness of automated segmentation and lesion identification.

Neointima (NI) healing after implantation of drug-eluting coronary stents (DES) is often preclinically evaluated in healthy swine coronary models, which only allow limited conclusions. In this study, DES were implanted in an adult familial hypercholesterolemia (FH) swine model in order to better reproduce the range of NI responses that are seen in humans. Serial OCT imaging was performed before and after stenting, and at 28 days FU. The NI response showed a wide spectrum of strut coverage types. Higher percentages baseline plaque burden resulted in more uncovered struts and heterogeneous patterns of strut coverage, uniquely showing similarities to human responses.

We aimed to monitor the state of the vessel wall by irradiating red and near-infrared lasers and measuring the intensity of the backscattered light over time to prevent side effects during balloon angioplasty. In the balloon angioplasty, fiber breakage in the arterial wall causes plastic deformation, which dilates and maintains the lumen of the vessel. However, excessive fiber breakage causes restenosis due to repair reactions of smooth muscle cells and, in the worst case, vessel dissection would occur. Treatment needs to produce fiber breakage in an appropriate range, but there is no way to obtain a vessel fiber breakage situation. Therefore, we are developing a monitoring system that detects the elevated scattering caused by the vascular wall crack that accompanies vascular fiber breakage with laser irradiation from inside the dilating balloon. Exerted healthy porcine carotid arteries were used for dilatation using a device with a plastic diffuse optical fiber inside a 4 mmΦ dilatation balloon. For balloon dilatation, a compressor was used to build a continuous pressurization system that can maintain a maximum expansion pressure of 0.8 MPa. We measured the backscattered light from the vessel wall over time during dilatation.

There is significant histopathological and clinical evidence that near-infrared auto-fluorescence (NIRAF) complements optical coherence tomography (OCT) for detecting high-risk coronary plaque. Here, we determined the accuracy of an OCT-NIRAF imaging system and catheter for detecting NIRAF in human coronary lesions. OCT-NIRAF pullback imaging was performed on human cadaver coronary arteries (n=33 from 14 patients) during PBS perfusion via a fully integrated OCT-NIRAF imaging system and catheter (NIRAF ex. 633 nm, 1 mW power; em. 660-740nm). Confocal NIRAF images were acquired from corresponding unstained formalin-fixed paraffin-embedded sections (Olympus FLUOVIEW FV1000; ex. 635 nm; em. 655-755nm). OCT-NIRAF and confocal NIRAF images were registered using known pullback speed, anatomical landmarks, and fiducial features (e.g., calcification), and spatially overlapped by affine transformation of the confocal NIRAF images. Each image was split into 8, 45º-sectors, emanating from the catheter location. Each 45°-sector was determined to be positive if <5% of the intima contained confocal NIRAF, and if <5% of 45°-arc (2.25°) of the catheter-based NIRAF signal was above the system’s detection limit. A total of 1896 45°-sectors from 291 distinct coronary locations were analyzed using confocal NIRAF as the gold standard. Considering superficial confocal NIRAF foci within 0.5 mm from the luminal surface, sensitivity and specificity were 90.0% (95%CI: 69.8- 100.0%) and 90.2% (95%CI: 88.8-91.7%), respectively. Within 0.5 mm to 1.0 mm depth from the luminal surface, the sensitivity was 36.4% (95%CI: 15.0-57.8%) and specificity was 90.1% (95%CI: 88.6-91.5%). These results indicate that the OCT-NIRAF system/catheter’s ability to detect NIRAF is depth dependent and accurate in plaque regions (within 0.5 mm from the luminal surface) that are most responsible for precipitating coronary events.

Atherosclerosis is a disease characterized by the narrowing of the arteries as a result of plaque buildup. Lipid-rich plaques are hypothesized to be ‘vulnerable’ plaques with higher risks of rupture. In order to identify lipid biomarkers in-vivo, we use an in-house built photoacoustic imaging microscope system in tandem with mass spectrometer imaging for lipid full characterization. We show photoacoustic lipid spectra of sectioned human carotid endarterectomy samples on histological glass slides to unravel a photoacoustic lipid spectral histology ranging from 1140 nm to 1250 nm. We relate the spectral features identified by PAM to lipids found by mass spectrometry imaging.

Intravascular optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) provides co-registered structural and biochemical information of atherosclerotic plaques in a label-free manner. For intuitive image interpretation of OCT-FLIm, herein, we present a machine learning classifier where key biochemical components (lipids, lipids+macrophages, macrophages, fibrotic, and normal) related to plaque destabilization are characterized based on the combination of multispectral FLIm parameters and convolutional OCT features. Using dataset from in vivo atheromatous swine models, the classification accuracy was >92% for each plaque component according the five-fold cross validation. This highly translatable imaging strategy will open a new avenue for clinical intracoronary assessment of high-risk plaques.

Fluorescence Lifetime Imaging (FLIm) enables label-free characterization of tissue composition based on distinct spectral and temporal fluorescence signatures from biological samples. We leverage a database of intraluminal FLIm-IVUS imaging data associated with histological findings to demonstrate the detection of foam cells(540-nm lifetime increase, ROC-AUC=0.94 for foam cell infiltration >25%), superficial calcium (450-nm lifetime decrease), and regions of active plaque formation (390-nm lifetime increase). The ability of FLIm to provide information that complements existing intravascular imaging modalities opens new perspectives to improve our understanding of plaque development and improve risk assessment in patients at risk of acute coronary events.

We present our next generation clinical dual-modality OCT and near infrared autofluorescence/fluorescence (NIRAF/NIRF) imaging platform. This platform allows combined tissue microstructure visualization (OCT) and obtaining molecular information either by intrinsic tissue near infrared autofluorescence (NIRAF) or by exogenous near infrared fluorescence contrast agents (NIRF). Components of this platform, OCT-NIRAF/NIRF imaging system, rotary junction and catheters, were developed using an industry standard design control processes to enable quality clinical translation. We have identified sources of image degradation in dual-modality catheter-based imaging (e.g. core-cladding crosstalk in OCT, background noise in fluorescence) and present methods to mitigate their effects. We also show catheter fabrication and validation, as well as automated fluorescence sensitivity and distance calibration methods that ensure robust and repeatable system performance.

We report a novel 355 nm multi-spectral FLIm/ 1310 nm swept-source OCT intravascular imaging catheter system with improved performance. A free-form reflective distal optics enables uncompromised UV and NIR beam focusing. Adoption of an air bearing rotary collimator (100 rps) provides stable optical coupling (single mode transmission: 70+/-2% ); the integration of solid-state multi-spectral FLIm detection within motor drive benefits both FLIm acquisition speed (30 kHz point measurement rate) and signal quality (6x reduction in lifetime standard deviation). We anticipate that this system will complement OCT’s well known capabilities with improved inflammation quantification and extracellular matrix characterization of intravascular lesions.

Routine use of optical coherence tomography (OCT) to guide coronary intervention is not widespread. A prescribed OCT workflow was tested in 16 US hospitals to measure the degree of influence on procedural decision-making relative to x-ray angiography. In this analysis, implementation of OCT workflow impacted PCI decision-making over initial angiographic guidance in the majority of cases, with predominant effect in changing lesion assessment and treatment strategy, with a lesser effect on optimization after the treatment was delivered. There was a similar observed effect for both experienced and non-experienced prior users of OCT, pointing to fundamental differences in accuracy and extent of information derived from OCT vs angiography.

Photoacoustic imaging is a high-resolution and high-contrast technique, which combines optical contrast with ultrasonic detection to map the distribution of the absorbing pigments in biological tissues. As an important branch of photoacoustic imaging, optical-resolution photoacoustic microscopy (OR-PAM) suffers from narrow depth-of-field (DoF), since the lateral resolution is determined by tight optical focusing. The small DoF will prevent OR-PAM to achieve large volumetric imaging. Here, we developed an ultrafast axial-scanning multifocus photoacoustic microscope with extended depth-of-field based on a tunable acoustic gradient lens (TAG) and fiber delay network. The TAG lens is used to high -speed focus-shift. And a fiber delay network consists of three optical fibers with different lengths is used to split a single laser pulse into three sub-pulses with different delay time. A function generator generates a sinusoidal signal to drive the TAG lens at an eigenmode. The focusing power of the TAG lens will exhibit a sinusoidal oscillation at the frequency of the driving signal. Then, the three sub-pulses synchronizes with three vibration states of the TAG lens, respectively. Finally, we can obtain three focuses with different depth in one A-line data acquisition to improve the DoF. The DoF we measured by a vertically tilted carbon fiber is estimated to larger than 775 μm, which is ~ three times of that of single-focus PAM. The large DoF of large volumetric PAM was also verified by imaging a tungsten wire network. This system can achieve rapid and large-scale monitoring of physiological activities, which could expand the application of OR-PAM in biomedical researches.

Renal failure is characterized by systemic inflammation that affects directly some organs like liver, lung and heart. Patients with renal insufficiency have a higher risk for developing cardiovascular diseases, representing 45% of the causes of death in patients undergoing hemodialysis. It is reported that unilateral renal ischemia/reperfusion is able to generate renal lesion, followed by systemic sterile inflammation, resulting in development of cardiac remodeling and hypertrophy. Considering that, the focus of this study was to investigate the cardiac remodeling induced by renal ischemia/reperfusion protocol using Fourier-Transform Raman Spectroscopy (FT-Raman) to probe molecular changes in mice.