In this work, we present a significant step toward in vivo ophthalmic optical coherence tomography and angiography on a photonic integrated chip. The diffraction gratings used in spectral-domain optical coherence tomography can be replaced by photonic integrated circuits comprising an arrayed waveguide grating. Two arrayed waveguide grating designs with 256 channels were tested, which enabled the first chip-based optical coherence tomography and angiography in vivo three-dimensional human retinal measurements. Design 1 supports a bandwidth of 22 nm, with which a sensitivity of up to 91 dB (830 µW) and an axial resolution of 10.7 µm was measured. Design 2 supports a bandwidth of 48 nm, with which a sensitivity of 90 dB (480 µW) and an axial resolution of 6.5 µm was measured. The silicon nitride-based integrated optical waveguides were fabricated with a fully CMOS-compatible process, which allows their monolithic co-integration on top of an optoelectronic silicon chip. As a benchmark for chip-based optical coherence tomography, tomograms generated by a commercially available clinical spectral-domain optical coherence tomography system were compared to those acquired with on-chip gratings. The similarities in the tomograms demonstrate the significant clinical potential for further integration of optical coherence tomography on a chip system.

The cutaneous vasculature is involved in many diseases. Current clinical examination techniques, however, cannot resolve the human vasculature with all plexus in a non-invasive manner. By combining an optical coherence tomography system with angiography extension and an all optical photoacoustic tomography system, we can resolve in 3D the blood vessels in human skin for all plexus non-invasively. With a customized imaging unit that permits access to various parts of patients’ bodies, we applied our multimodality imaging system to investigate several different types of skin conditions. Quantitative vascular analysis is given for each of the dermatological conditions to show the potential diagnostic value of our system in non-invasive examination of diseases and physiological processes. Improved performance of our system over its previous generation is also demonstrated with an updated characterization.

We present a combination of optical coherence tomography (OCT) and Raman spectroscopy (RS) for improved diagnosis and discrimination of different stages and grades of bladder cancer ex vivo by linking the complementary information provided by these two techniques. Bladder samples were obtained from biopsies dissected via transurethral resection of the bladder tumor (TURBT). As OCT provides structural information rapidly, it was used as a red-flag technology to scan the bladder wall for suspicious lesions with the ability to discriminate malignant tissue from healthy urothelium. Upon identification of degenerated tissue via OCT, RS was implemented to determine the molecular characteristics via point measurements at suspicious sites. Combining the complementary information of both modalities allows not only for staging, but also for differentiation of low-grade and high-grade cancer based on a multivariate statistical analysis. OCT was able to clearly differentiate between healthy and malignant tissue by tomogram inspection and achieved an accuracy of 71% in the staging of the tumor, from pTa to pT2, through texture analysis followed by k-nearest neighbor classification. RS yielded an accuracy of 93% in discriminating low-grade from high-grade lesions via principal component analysis followed by k-nearest neighbor classification. In this study, we show the potential of a multi-modal approach with OCT for fast pre-screening and staging of cancerous lesions followed by RS for enhanced discrimination of low-grade and high-grade bladder cancer in a non-destructive, label-free and non-invasive way.

Significance: After three decades, more than 75,000 publications, tens of companies being involved in its commercialization, and a global market perspective of about USD 1.5 billion in 2023, optical coherence tomography (OCT) has become one of the fastest successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.Aim: Our perspective focuses on disruptive forward-looking innovations and key technologies to further boost OCT performance and therefore enable significantly enhanced medical diagnosis.Approach: A comprehensive review of state-of-the-art accomplishments in OCT has been performed. Results:The most disruptive future OCT innovations include imaging resolution and speed (single-beam raster scanning versus parallelization) improvement, new implementations for dual modality or even multimodality systems, and using endogenous or exogenous contrast in these hybrid OCT systems targeting molecular and metabolic imaging. Aside from OCT angiography, no other functional or contrast enhancing OCT extension has accomplished comparable clinical and commercial impacts. Some more recently developed extensions, e.g., optical coherence elastography, dynamic contrast OCT, optoretinography, and artificial intelligence enhanced OCT are also considered with high potential for the future. In addition, OCT miniaturization for portable, compact, handheld, and/or cost-effective capsule-based OCT applications, home-OCT, and self-OCT systems based on micro-optic assemblies or photonic integrated circuits will revolutionize new applications and availability in the near future. Finally, clinical translation of OCT including medical device regulatory challenges will continue to be absolutely essential.Conclusions: With its exquisite non-invasive, micrometer resolution depth sectioning capability, OCT has especially revolutionized ophthalmic diagnosis and hence is the fastest adopted imaging technology in the history of ophthalmology. Nonetheless, OCT has not been completely exploited and has substantial growth potential-in academics as well as in industry. This applies not only to the ophthalmic application field, but also especially to the original motivation of OCT to enable optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching that of histology but without the need for tissue excision.

In this paper, we present a novel concept for a multi-channel swept source optical coherence tomography (OCT) system based on photonic integrated circuits (PICs). At the core of this concept is a low-loss polarization dependent path routing approach allowing for lower excess loss compared to previously shown PIC-based OCT systems, facilitating a parallelization of measurement units. As a proof of concept for the low-loss path routing, a silicon nitride PIC-based single-channel swept source OCT system operating at 840 nm was implemented and used to acquire in-vivo tomograms of a human retina. The fabrication of the PIC was done via CMOS-compatible plasma-enhanced chemical vapor deposition to allow future monolithic co-integration with photodiodes and read-out electronics. A performance analysis using results of the implemented photonic building blocks shows a potential tenfold increase of the acquisition speed for a multi-channel system compared to an ideal lossless single-channel system with the same signal-to-noise ratio.