This PDF file contains the front matter associated with SPIE Proceedings Volume 11215, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

Advances in image and signal processing and the miniaturisation of the medical devices have enabled the design of hybrid intravascular imaging catheters that have two probes on their tip which allow more complete assessment of plaque morphology physiology and biology than standalone intravascular imaging techniques. Histology studies have highlighted the superiority of hybrid intravascular imaging in assessing lesion characteristics; however the value of these techniques in the clinical arena and research is yet unclear. The aim of this presentation is to summarise the developments in the field, present the advantages and limitations of the existing prototypes and based on the existing evidence discuss the potential value of the established or emerging hybrid intravascular imaging probes in guiding percutaneous coronary intervention, assessing lesion pathology and detecting plaques that are a likely to progress and cause events.

A novel lipid sensitive OCT setup is presented, using light source with a central wavelength of 1280 nm and a spectral tuning range of 201 nm. A cholesterol plaque located in the aorta was imaged post mortem. Different spectral bands were chosen in post processing. Analyzing the signal attenuation of the different spectral bands enables us to see a clear difference between the lipid absorption in the plaque between the bands. In the normal tissue no clear separation of the signal attenuation can be found. This enables us to visualize the plaque on a three dimensional level.

Light attenuation has been used for a better understanding of plaque build-up in coronary arteries. The current analysis is only useful in diseased segments. We applied an automated detection using a deep-learning approach to identify the diseased areas. A U-net was trained to detect the lumen, the guide-wire structure, healthy vessel wall, and the diseased vessel wall. The trained network achieves an average Dice index of 0.88±0.02. Applying it to all images of the testing pullbacks, diseased areas were segmented. The attenuation was estimated in this area and can be visualized in a 3-D view reconstructed using the detected lumen regions.

Optical coherence tomography (OCT) is capable of resolving detailed features of human cardiac tissue. However, prior studies have not analyzed OCT-imaged tissue architecture with respect to medical history and demographics, which could enable insight on differences between patient populations. Therefore, the objective of this study was to extract quantitative features from cardiac OCT images and compare features based on donor characteristics. Fifty human hearts with varying cardiac disease were acquired and imaged with the TELESTO I OCT system (Thorlabs GmbH, Germany). Trichrome histology was obtained to verify tissue composition, and 573 matches were made between OCT b-scans and histology. Eight quantitative image features; attenuation coefficient, contrast, correlation, energy, homogeneity, standard deviation, skewness, and kurtosis; were extracted from 320 by 160 μm regions of interest (ROI) within each B-scan, such that each unique tissue type within a B-scan was included in one ROI. Afterwards, groups of tissue features, based on donor characteristics, were compared using Welch’s unpaired t-test with an alpha value of 0.05. Tissue features were also correlated to age and body mass index using Pearson’s correlation coefficient. For the majority of the data, no significant differences were found, and correlation to age and body mass index were low. The majority of significant differences were found between groups with and without history of hypertension, and groups with or without myocardial infarction. These results provide an initial investigation of the relationship between OCT image features of different tissue types in the human heart with patient medical history and demographics.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the western world. Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is frequently conducted to treat AF. However, current PVI procedures for lesion formation are guided only with indirect information, which may lead to non-transmural lesions, and contribute to the high recurrence of AF. Therefore, direct lesion quality feedback may potentially improve PVI efficacy. To study the real-time direct guidance capability of polarization sensitive optical coherence tomography (PSOCT), a custom-designed integrated PSOCT-RFA catheter was prototyped and tested in RFA procedures in the left atria of living swine.

Radiofrequency ablation (RFA) therapy is commonly used to treat cardiac arrythmias. To restore sinus rhythm, areas of myocardium that triggers abnormal electrical activity are ablated. However, patients require multiple procedures for treatment. Clinicians currently lack the intraoperative surgical tools to visualize and assess tissue during ablation. Real-time visualization of myocardial tissue and lesion formation in vivo could potentially help reduce relapses. In this work, a combined multispectral fiber bundle-RFA catheter is introduced to assess contact and directly visualize lesion formation during and after ablation.

Near infrared spectroscopy (NIRS) is used for a wide variety of applications due to its noninvasiveness, ease of use, quick acquisition time, and affordability. In this study we investigate the effectiveness of spatial frequency domain imaging (SFDI), a widefield noncontact quantitative NIRS technique, to assess peripheral artery disease progression in vivo. SFDI measures absolute (i.e. optical scattering-corrected) tissue concentrations of oxy- hemoglobin and deoxyhemoglobin, and therefore total hemoglobin concentration and tissue oxygen saturation. Female apolipoprotein E-deficient mice (n=9) underwent femoral artery ligation to induce unilateral ischemia in the left hindlimb. Brie y, the left femoral artery was exposed and ligated via suture midway between the aortic trifurcation and division into the saphenous and popliteal arteries. SFDI was acquired for both the ischemic and control limbs over 4 weeks to track changes in vascular perfusion. We also acquired high frequency pulsed-wave Doppler ultrasound images and performed histological analysis, both of which confirmed occlusion of the left femoral artery post-ligation. The ischemic to control ratio for tissue oxygen saturation was 0.96±0.06 at baseline and 0.86±0.10 at day 1, 0.94±0.06 at day 3, 0.95±0.14 at day 7, 0.91±0.09 at day 14, 0.90±0.09 at day 21, and 1.01±0.09 at day 28. These results demonstrate the ability of NIRS to detect a decrease in tissue oxygen saturation in the ischemic limb within a week of ischemic injury, followed by recovery at 4 weeks post-ligation. Our work provides evidence for the potential of SFDI to accurately and noninvasively quantify peripheral artery disease progression in a preclinical murine model.

Cardiovascular complication is a major health concern for diabetic patients. Elevated blood sugar levels lead to the formation of advanced glycation end products (AGEs), which are implicated in diabetic pathogenesis. In this study, we investigate the effect of prolonged exposure to elevated sugar level by studying the combined effect of diffusion and glycation rate in arteries from different commonly-consumed simple sugars. Since some AGEs are autofluorescent, we will perform multiphoton autofluorescence imaging to quantify the rates of fluorescent AGEs formation in elastic fibers and collagen fibers. Cross-section imaging of arteries and spatial and temporal profiles of autofluorescence of the blood vessel will be investigated.

Fluorescence Lifetime Imaging (FLIm) is a label-free technique that provides biochemical information from biological samples derived from tissue autofluorescence. Using a custom multispectral FLIm/IVUS catheter system, fluorescence lifetime data (n=33,980 locations) was collected from ex vivo human artery segments (n=32 samples). Our findings indicate that intravascular spectroscopy with FLIm supports the identification of early progression-prone lesions, characterized by the accumulation of extracellular lipids, as well as the quantification of inflammatory activity, characterized by macrophage foam cells accumulation. This information improves our understanding of plaque development, which may ultimately be used to improve risk assessment of acute coronary events.

Epicardial catheter ablation has been increasingly recognized as an important adjunct in treating ventricular arrhythmias unamenable by endocardial ablation alone. The presence of epicardial adipose tissue (EAT) is a primary cause for ineffective ablation energy delivery and electrogram misinterpretation. To address this need, we propose a catheter-based near-infrared spectroscopic technique for mapping EAT and lesion deposition, and validate it within excised human donor hearts. We introduce a new parameter, the adipose contrast index (ACI), for rapid lipid assessment. Strong correspondence was observed between values derived from interpolated 3-dimensional ACI maps and histologically-determined EAT layer thickness (Pearson’s, R = 0.903).

Fluorescence Lifetime Imaging (FLIm) is a label-free technique that reveals extracellular lipid and foam cells accumulation within atherosclerotic lesions, complementing the structural information provided by Optical Coherence Tomography (OCT). Successful intravascular implementation of FLIm-OCT requires high optical performances for both single and multimode beams, spanning the near UV to near IR range, out of reach of the current miniature optics (ball or gradient index lenses). Here, we present a 0.3 x 0.3 x 0.8 mm3 monolithic freeform optic that provides high optical performances over the UV-IR range (355-1360 nm), enabling high-performance intravascular FLIm-OCT imaging catheter designs.

We demonstrated the ability of fiber-based Fluorescence Lifetime Imaging (FLIm) guided Raman spectroscopy to monitor the quality of engineered vascular grafts with high speed and specificity. We report FLIm guided Raman imaging as an effective multimodal technique to evaluate scaffold cross-linking and localized calcification. Current results indicate that the lifetime of AR-BP shortens upon GA cross-linking,and Raman spectroscopy reveals secondary structural changes occurring in the Amide I region of cross-linked pericardia. GA fixed vascular grafts are prone to calcification, an effect linked to graft failure. The calcified regions exhibited shorter lifetimes in fluorescence spectral bands ranging from 380 to 455 nm and Raman spectra exhibited the specific hydroxyapatite signature at 960 cm-1 co-localized with these lower lifetime regions. We conclude that FLIm guided Raman imaging can detect cross-linking signatures and areas of calcification in tissue with biochemical specificity.

The role of biomechanical signaling is well accepted as a modulator of cardiac cell behavior and a requirement for cardiac morphogenesis. However, the small, fragile nature of the embryonic heart makes it difficult to determine transient mechanical homeostasis during heart development and search for causal links between biomechanical forces and cardiac cell behavior in vivo. Our work focuses on characterizing the regulatory role of biomechanical signals to direct cardiac morphogenesis and cell behavior. Towards this end, we have successfully established cardiac optogenetics to control heartbeat frequency in the embryonic mouse heart for the first time. We will combine this approach with second harmonic generation, an unbiased imaging approach to detect collagen deposition. Using optogenetic cardiac pacing and second harmonic generation imaging, we will look at how changes in heart biomechanics are consequential in the deposition and organization of cardiac collagen.

Extracorporeal life support (ECLS) is used in intensive care units (ICUs) as heart-lung bypass for critically ill patients to support either inadequate heart or lung function. Decisions to discontinue ECLS are typically based on clinical judgment and patient trajectory during trial-off support. We investigated an optical measurement of muscle oxygenation (MOx) as an indicator for adequacy of circulatory function during trials-off ECLS. Clinicians were queried prior to trial-off as to whether the patient was deemed: ready, might be ready, or not likely ready to discontinue ECLS. MOx was determined using an optical analysis developed in our laboratory. Optical spectra were acquired from infants using a fiber-optic probe affixed to the arm or leg. Five infants were studied during 6 trials-off ECLS. Mean initial MOx was 96.6+/-8.5% (n=6). In trials resulting in discontinuation of ECLS, MOx was > 94%. In those remaining on ECLS, MOx was lower during the trial off at all time points. Mean MOx trended lower (75.1+/-23.5%), in the first 6 minutes for those not removed from ECLS, compared with those for whom ECLS was subsequently discontinued (97.2+/-3.8%). Lactate trended higher in subjects remaining on ECLS (3.4+/-0.8) compared with those removed from support (1.7+/-0.7). Clinician predictions prior to trial-off did not correlate with ultimate decision for discontinuing ECLS. Although preliminary, we believe that MOx may be useful to assist in objectively assessing adequacy of circulatory function and may be helpful in the early determination of readiness for discontinuation of ECLS.

New techniques are needed to study the coronary microvasculature in the embryo and to quantify the differences between healthy and diseased coronary development. We combine our custom optical clearing method (LIMPID), fluorescent staining with DiI and DAPI, and 3D confocal microscopy to visualize the coronary vasculature at two developmental stages (day 9, 13) in quails. We discovered a highly organized coronary vessel network that is aligned with surrounding myocardium cells even at early developmental stages. By characterizing the normal heart vasculature, this experiment provides a baseline for future studies on how diseases affect coronary and myocardial orientation in the embryo.

Myocardial fiber orientation is closely related to the functions of the heart. The development of imaging tools for depicting myocardial fiber orientation is important. We developed a polarized hyperspectral imaging microscope (PHSIM) for cardiac fiber orientation imaging, which is capable of polarimetric imaging and hyperspectral imaging. Polarimetric imaging is realized by the integration of two polarizers. Hyperspectral imaging is realized by snapscan Preliminary imaging experiments were implemented on an unstained paraffin embedded tissue slides of a chicken heart. We also set up a Monte Carlo simulation program based on the cylinder optical model to simulate the cardiac fiber structure of the sample and the optical setup of the PHSIM system, in which we can calculate the system output light intensity related to cardiac fiber orientation. According to the imaging and simulation results, there exists a variation of intensity of acquired images with the polar angles from the maximum to the minimum under different wavelengths, which should relate to the orientation of cardiac fibers. In addition, there is a shift of the polar angle where the maximum intensity appears when a rotation of the sample happened both in the simulation and imaging experiments. Further work is required for imaging more types of myocardial tissues at different parts and the design of a complete quantitative model to describe the relations among polar angles, wavelengths, and cardiac fiber orientations.