This conference presentation was prepared for the Diagnostic and Therapeutic Applications of Light in Cardiology 2023 conference at SPIE BiOS, SPIE Photonics West 2023.

Preclinical studies and clinical diagnostics increasingly rely on optical techniques to visualize internal organs. Miniaturised catheters or endoscopes are necessary for imaging small and/or delicate arteries. However, current lens fabrication methods limit the performance of these ultrathin devices, resulting in a poor combination of resolution, depth of focus and multimodal imaging capability. This talk will introduce our latest research to address these combined challenges. In particular, we have utilized 3D micro-printing technology to fabricate freeform optics directly onto an optical fiber to achieve freeform designs for aberration-corrected optical coherence tomography (OCT) and to enable highly-sensitive multimodal fluorescence+OCT imaging in vivo.

Optical coherence tomography offers the highest spatial resolution for clinical intravascular imaging. Optical coherence polarimetry additionally measures polarization effects that afford insight into the microstructure and physical orientation of collagen or smooth muscle cells and the scattering properties of lipid-rich plaques. We have been making progress with simplifying the integration of optical coherence polarimetry into existing clinical instruments, with using the polarization contrast to enable AI-based segmentation facilitating automated lesion analysis, and with compensating the polarization effects of the rotating catheter. These efforts will empower clinical investigations that expand on the findings from our initial clinical pilot trials.

We report the development and characterization of a multispectral FLIm/ polarization-sensitive OCT intravascular imaging catheter system. This system targets the improved characterization of two key contributors to atherosclerosis disease development: inflammation and disruption of the extracellular matrix, by enabling the evaluation of biochemical signature, 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.

Patients with atrial fibrillation (AF) require detailed mapping of the left atrium (LA) during radiofrequency ablation (RFA) procedures. Identifying the lesion gaps can provide helpful guidance for complete conduction blocks, reducing the probability of recurrence. We implement anatomical mapping using an integrated optical probe with a combined modality of near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT). Both spectral signatures are captured simultaneously, with the sample-sites located by a magnetic tracking sensor. With increased sampling density and speed, we are able to recognize small gaps between lesions LA, and reconstruct atrial substrate and lesion maps with the tissue underneath PBS and blood.

Prolonged cardiopulmonary bypass (CPB) exposure and excessive anticoagulation during cardiac surgical procedures frequently cause acute bleeding. Here we investigated the accuracy and precision of a novel optical sensor, iCoaglab, that utilizes a small volume of whole blood to comprehensively monitor blood coagulation in patients. Our results showed coagulation metrics, activated clotting times (ACT), maximum clot stiffness (MA), and fibrinolysis were highly correlated with standard-reference tests. In conclusion, iCoaglab uniquely affords comprehensive profiling of whole blood coagulation, potentially enabling the capability to identify coagulation impairments and predict bleeding during CPB.

Combined intravascular ultrasound-optical coherence tomography (IVUS-OCT) enables more accurate coronary plaque tissue classification compared to single modality systems. Automated solutions are needed to that take advantage of information from both modalities to speed such analysis. This study aimed to train and validate a deep learning (DL) model for tissue classification in combined IVUS-OCT images. Coronary segments from 8 arteries from cadaveric human hearts were studied with the Novasight Hybrid imaging catheter. IVUS-OCT images were matched with histological sections and tissue types annotated. These regions of interest were used train and test a DL-classifier for plaque composition (949 matched histological and IVUS-OCT frames from 8 patients for training, 306 frames from 2 patients for testing). The accuracy of the classifier for regional classification was 78.8% suggesting that the trained DL-model is capable of accurate tissue type classification in combined IVUS-OCT images.

Sensing cardiac contractility on the single cell level and deep inside the heart remains a challenging task. Here, we interface microscopic whispering gallery mode lasers with cardiac cells and tissue to extract contractility profiles with cellular resolution and high temporal dynamics. To demonstrate advantages over imaging-based approaches, we characterise cardiac contractility in vivo in zebrafish embryos and in thick cardiac slices. We further present the development of nanolasers with improved spectral characteristics for sub-cellular sensing. Finally, we present new microlasers that extend the range of detectable biomechanical parameters, opening new avenues for future applications of microlasers in cardiovascular research.

Understanding mammalian cardiogenesis requires high-resolution imaging to assess changes in cardiac structure, morphology, dynamics, and function during embryonic development. Optical coherence tomography (OCT) shows promise for advanced studies due to superior imaging scale and speed for 4D imaging of the early mouse embryonic heart. Building on this, and enabled by prolonged embryo culture, efficient reconstruction, and multi-dimensional visualization strategy, we present the first longitudinal, 4D, dual-contrast OCT imaging of the beating mouse embryonic heart over development for up to ~12 hours, termed as 5D cardiodynamic and hemodynamic imaging. This paves the way to study early developmental dynamics of the heart.

Spatially resolving the molecular expression of multiple probes in 3D can help us understand complex biological processes. For instance, our group has linked abnormal shear stress patterns caused by regurgitant blood flow with resultant congenital heart defects (CHDs). Abnormal shear stress mapped on images of molecular expression gives additional context to developmentally critical pathways such as epithelial-mesenchymal transition (EMT). However, highly multiplexed 3D imaging is needed to accurately identify regions of interest in the looping heart. In this study, we demonstrate a sequential imaging of a library of HCR FISH probes.

Advances in three-dimensional (3D) microscopy are providing never-before-seen images of coronary microvasculature organization. However, it remains inaccessible to researchers due to difficult sample preparation and image analysis. We present a deep learning network that can segment the coronary microvasculature in 3D microscopy without vessel staining. The network is based on 3D U-net and accepts DAPI (nuclei) and autofluorescence (tissue structure) volumes as inputs. The network detects vessels with high accuracy when compared to the ground truth obtained from isolectin staining. Contrast-free segmentation of vessels simplifies sample preparation, frees fluorescent channels during imaging and opens the door toward user-friendly 3D microscopy.

Heart function is governed by three dynamic systems that control excitation-Ca2+ signaling-contraction in cardiac muscle cells. Dysregulation of these systems lead to cardiac arrhythmias, sudden death, and heart failure. We develop and use photonics technologies to shine light deep into the cellular and molecular details to investigate these dynamic systems. We use epi-fluorescence microscopy and voltage-sensitive indicator to study electrophysiology, confocal-fluorescence imaging and Ca2+ indicator to study Ca2+ signaling system, and second harmonic generation and 2-photon fluorescence microscopy to study the Ca2+ and contraction coupling in sub-cellular microdomains. I will present our research using photonics to decipher heart disease mechanisms.

This conference presentation was prepared for the Diagnostic and Therapeutic Applications of Light in Cardiology 2023 conference at SPIE BiOS, SPIE Photonics West 2023.

In atherosclerosis, lipid accumulation and inflammation over time may lead to blockage of the arteries or even stroke. Lipids are involved in all stages of atherosclerosis, and some lipids are linked to plaque vulnerability. It has been found that plaque lipid optoacoustic signals exhibit distinct spectral features, which allows for identification of different lipid plaque signatures. In this study we will present the ex vivo spectral optoacoustic results of different advanced atherosclerotic plaques, measured with multispectral optoacoustic tomography (inVision 128, iThera Medical GmbH, 850-1250nm). The found spectral features might be used in in vivo detection of advanced atherosclerotic plaque features of instability.