Colorectal cancer (CRC) ranks third globally in terms of prevalence, accounting for 10% of cancer cases and deaths each year. Irreversible electroporation (IRE) offers promise for treating CRC by selectively destroying tumor cells while minimizing harm to healthy tissue. However, the lack of effective guidance and evaluation methods hampers the achievement of complete tumor ablation. To address this, integrated OCT, US, and NIRF endoscopy enable real-time imaging of colorectal tumors, facilitating precise IRE treatment and evaluation of outcomes. In this study, we used an integrated imaging system to precisely guide and evaluate the implementation of IRE therapy in CRC.

Fluorescence imaging has been widely used in fields like (pre)clinical imaging, as well as in other domains. With advancements in imaging technology and the development of new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the CAPS camera, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700-900nm) region. Incorporating fluorescence lifetime into endoscopy would further differentiate malignant and benign cells based on their distinct lifetimes. Therefore, the capabilities of the system are demonstrated using a rigid endoscope involving various phantoms and various lifetime processing approaches to get the uniform lifetime image because of the independence of fluorescence lifetime to the intensity when the intensity image is not.

No diagnostic method is currently available to visualize and measure the airway smooth muscle (ASM) within a living patient. Endoscopic Polarization Sensitive Optical Coherence Tomography (PS-OCT) might enable quantification of ASM mass in vivo, by assessing tissue birefringence. We performed in vivo PS-OCT on patients (n=17) with airway diseases (asthma and interstitial lung disease) and one healthy volunteer. An in-house built distal scanning catheter (1.35 mm) was used to circumferentially scan the airways at 52 fps B-scan rate. We demonstrated PS-OCT to be a minimally invasive technique to assess ASM thickness in diseased airways relative to healthy subjects.

We conducted a first-in-human study using a fluorescent slurry comprised of 10 ml Methylene Blue (50 mg dissolved in water) and 10 ml Agave nectar. Preliminary data from the first patient indicates that at 20 minutes Barrett's Esophagus (esophageal pre-cancer) can be discriminated from normal tissue with a target-to-background ratio of 1.96 and an effect size > 5 (Cohen's D). We further show a dose modification pathway to high-TBR imaging shortly after swallowing the slurry.

Screening of Barrett’s Esophagus (BE) for progression to esophageal adenocarcinoma with standard endoscopic biopsy is expensive, invasive, and imprecise due to sampling error and the limited value of histomorphology for predicting cancer risk. We have developed a technology called in vivo laser capture microdissection (IVLCM) that overcomes these issues by using OCT tethered capsule endomicroscopy (OCT-TCE) to image the entire esophagus at the microscopic level. Pilot clinical study results show that IVLCM samples provide sufficient DNA material for genetic sequencing. The comparison of sequencing quality and gene mapping of IVLCM samples and conventional FFPE biopsy samples will be analyzed in the ongoing clinical study.

We extend the resolution of our 2p autofluorescence imaging probe by incorporation of custom designed and fabricated optics. We will add an NA extender piece, inserted at excitation fiber tip to boost the beam divergence at the excitation optics input. The new custom designed miniaturized objective will achieve a resolution of 0.5 μm, without any changes to the diameter of the objective design. Custom design objective also will allow us to perform autofluorescence imaging at two colors. This will enable the optical redox ratio characterization of tissues, which is an important hallmark in diagnosis of cancers at early stages.

Atherosclerosis is characterised by the buildup of plaque in the inner lining of vessels. Unstable atherosclerotic plaques are prone to rupture, which can lead to heart attacks or strokes. Current clinically available imaging techniques cannot accurately identify unstable plaques based on their structural features. It has been previously reported that unstable plaques may emit autofluorescence. Therefore, our team has developed a dual modality optical coherence tomography and fluorescence intravascular imaging system, and a miniaturised fibre-optic probe incorporating a 3D printed lens. The 3D printed lens is designed to correct the astigmatism that arises from the intravascular catheter, and to reduce stray light. Although the 3D printed lens is made by a polymer photoresist, it has low background fluorescence. We are using our novel fibre probe to explore the autofluorescence present in unstable human plaques.

We have developed a new µOCT tethered Capsule Endomicroscopy imaging system for the diagnosis of Inflammatory bowel disease and Gastrointestinal cancer with micrometer resolution. The capsule we built measures 30 mm in length and 11 mm in diameter. By employing an optical design that incorporates the mirror tunnel design, we achieved a lateral resolution of less than 4 µm across a depth of field of 450 µm. The spectrometer we designed provides a resolution of 1.8 µm over a 4 mm imaging range, with an A-scan rate of up to 300 kHz. Imaging performance is demonstrated by beam profiling and imaging esophagus ex vivo.

Optical Coherence Tomography (OCT) acquires micron-resolution depth information on the superficial layers of tissues, but lacks in molecular specificity. Near Infrared Fluorescence (NIRF) imaging in combination with fluorescently labelled monoclonal antibodies can provide micron-resolution molecular contrast (Immuno-OCT). Here, a novel capsule endoscope design is presented, which facilitates circumferential imaging in the gastrointestinal tract. The endoscope is fitted with a double clad fiber coupler to enable dual-modality imaging. We present preliminary endoscopic data for both imaging modalities, for which phantoms were used to validate the capsule endoscope as an Immuno-OCT imaging device.

We demonstrate an all-reflective tethered capsule endoscope (RTCE) utilizing double-clad fiber and reflective optics for achromatic multimodal imaging of the esophagus. This device uses a custom ellipsoidal mirror to focus the light from the fiber tip onto the sample. In this work, we first describe key design parameters and highlight important assembly steps. We then demonstrate several data processing/analysis methods for signal multiplexing, rotation stabilization, and image analysis. Finally, we demonstrate the implementation of the capsule by performing combined OCT and spectral imaging in ex-vivo biological samples.

In our first clinical experience, we have found that Retrograde Tethered Capsule Endomicroscopy (R-TCE) was able to be advanced ~ 30 cm in 3 minutes in the colon of an unsedated study subject. R-TCE imaging enabled full circumferential OCT visualization of 96.60 ± 0.22 (95% CI) of the human colon wall. 3D rendered flythroughs of R-TCE OCT images demonstrate comprehensive visualization behind colonic folds where pre-neoplastic lesions may be missed by colonoscopy. The R-TCE procedure was well-tolerated, there were no complications, and a sigmoidoscopy conducted after the procedure did not show any R-TCE-related mucosal damage.

Conventional endoscopic probes have a field-of-view (FOV) limited by the aperture size, hindering imaging of larger areas. We propose a non-contact approach combined with a non-telecentric design expanding the FOV to several times the probe diameter, which enables to capture the entire region of interest. Our implementation utilizes 3D-printed micro-lenses fabricated via two-photon polymerization, allowing precise control of lens parameters and a simplified integration onto a fiber tip resulting in a compact OCT system with expanded FOV in the cm-scale, surpassing conventional probe limitations.

Metasurfaces possess vast potential for flexible beam shaping with reduced physical footprint compared to traditional refractive bulk optics. Such devices have the potential to revolutionize catheter-based biomedical imaging modalities such as optical coherence tomography (OCT) by enabling smaller catheter designs with enhanced performance and functionality compared to traditional ball lens or GRIN based designs. Previously our group demonstrated the first-ever integration of a metalens into a fully functioning OCT catheter. Here we present the continuation of that work, discussing refinements in both design and fabrication, and our overall efforts to develop metalens catheters as a complete replacement for traditional design.

Collection of biopsies from the most pathologically advanced region is critical for histopathological assessment of potentially cancerous sites in the lung. However, current applications are limited in their ability to simultaneously image and collect samples in subsegmental airways. We demonstrate a suction-snare device guided with optical coherence tomography and autofluorescence imaging (OCT-AFI) to improve diagnostic yield in these airways. Biopsies collected in healthy ex-vivo porcine airways are shown to retain structural and functional information. Feasibility is demonstrated in an ex-vivo porcine model to assess tissue abnormality prior to biopsy collection.