We have recently developed a low-cost (material cost = $1,500), smartphone-compatible confocal endomicroscope. By using a custom, hyper-chromatic objective lens, the confocal endomicroscope generated cross-sectional confocal images over a depth range of 110 µm. The confocal endomicroscope achieved lateral resolution of 2 µm and axial resolution of 4 µm. The imaging speed was 4 fps. Preliminary results from the pilot study of imaging the human cervix in vivo in Uganda showed that the confocal endomicroscope could visualize distinctive, bright objects with a similar distribution to squamous epithelial cell nuclei.

Caries of the interdental space are usually difficult to detect with conventional bitewing radiography. We have developed an interdental probe for polarization-sensitive optical coherence tomography (PSOCT) that can distinguish between healthy and carious tooth structures. The development is based on a fiber optic probe with a compact motor design that allows volumetric imaging. In a clinical study, demineralization was detected using proximal PSOCT scans of premolars and molars, and compared with blind diagnoses from four dentists. The results show that PSOCT can detect both, early demineralization and advanced proximal caries, some of which could not be diagnosed with bitewing radiography.

Interstitial lung disease (ILD) is a group of lung conditions, characterized by inflammation and pulmonary fibrosis. High-resolution computed tomography (HRCT), is often insufficient to detect fibrosis, and acquisition of lung biopsies is needed. Polarization-sensitive optical coherence tomography (PS-OCT) provides high-resolution images of the airways and fibrotic tissue-specific contrast by assessing tissue birefringence in a minimally invasive way. We developed a distal scanning endoscope and performed in-vivo PS-OCT measurements by advancing the endoscope in the lungs of 16 ILD patients undergoing biopsy acquisition and in 3 asthma patients included as non-fibrotic controls. Fibrosis was quantified in the acquired PS-OCT images, in HRCT, and in biopsies. Results show excellent correlation of PS-OCT detected fibrosis with histologically confirmed fibrosis, while HRCT only showed a poor-moderate correlation with histology for fibrosis quantification.

Cystic fibrosis (CF) is a condition arising from a genetic disorder of the cystic fibrosis transmembrane conductance regulator (CFTR) protein traversing luminal organ epithelial lining. Nasal potential difference (NPD) measurement can be used to study CF through evaluation of CFTR channel activity. Salt-bridge-based probes in combination with calomel electrodes have been used to provide discriminative information between normal and CF patients. This setup is bulky and less convenient for use in a clinical setting. Thus, we have developed a small caliber NPD probe and validated it in 3 normal subjects, providing results consisted to those reported in literature.

Asthma is a widespread, potentially fatal disease characterized in part by airway smooth muscle (ASM) abnormality. In this work we present results using polarization sensitive optical coherence tomography (PS-OCT) to assess both ASM structure and function for the purpose of guiding treatment. We show imaging results from a longitudinal clinical study involving bronchial thermoplasty (BT) for the reduction of ASM, and we present our recent work on using a custom modified tissue bath apparatus to conduct imaging of airway segments in varied contractile states. By assessing both structure and function simultaneously, we could dramatically improve feedback obtained for prospective treatments.

Our lab has developed a 2-mm-diameter transnasal introduction tube (TNIT) that enables safe and rapid optical coherence tomography (OCT) imaging of the upper gastrointestinal tract in unsedated pregnant women. Here, we report our clinical experience with TNIT-based OCT imaging in unsedated pregnant women (n=5) at Mass General Hospital (MGH). Results show that OCT imaging of the esophagus, stomach, and duodenum can be safely and effectively conducted in pregnant women with this device.

The recent FDA approval of 5-aminolevulinic acid (5-ALA)/protoporphyrin IX (PpIX) for fluorescence-guided resection of gliomas has significantly improved surgeons’ ability to identify and remove bulk high-grade tumors using widefield imaging. However, the limited sensitivity of widefield fluorescence imaging makes it challenging to identify regions of sparse and low fluorophore accumulation, such as in low-grade gliomas and at the diffuse margins of all gliomas. Here we describe several improvements on a handheld confocal microscope designed to detect sparse PpIX fluorescence in vivo, with the goal of providing a quantitative method to guide glioma resections.

Conventional laser scanning mechanisms, such as MEMS mirrors and piezoelectric tubes, are often complex to fabricate and limited in their fields of view. We developed a distal laser scanning platform that is scalable for both high performance and low resource settings given its low cost and low voltage requirements. Our platform enabled a customisable array of resonantly scanning optical fibers to be mounted on the top and/or bottom of a piezoelectric bender. Parallel scans were combined to generate multiplexed multi-millimeter fields of view at low voltage drives. We explored the bender’s potential as an endomicroscopic scanning platform by demonstrating its use in the depth-multiplexed OCT imaging of a fingertip and 3D cell culture.

Improving the sensitivity of endoscopic optical coherence tomography (OCT) to pre-cancerous esophageal lesions stands to improve patient outcomes. Although nuclei-level features relevant to dysplasia diagnoses are below conventional OCT systems’ resolution, tissue scattering properties report local particle size and concentration, indirectly accessing nuclei diameter and nuclear-cytoplasmic ratio (NCR). Recently, we have shown that acquiring co-registered images of a sample at different numerical aperture (NA) enhances scattering property measurements through angular diversity. We present preliminary results for a custom-designed, catheter-based, dual-NA endoscopic probe demonstrating improved characterization of phantoms and tissue with histological validation, and potential utility for more sensitive dysplasia diagnoses.

Circular-ranging OCT methods overcome data bandwidth barriers to high-speed and long-range laparoscopic imaging. As such, the beam-scan engine within the laparoscopic probe has become the critical speed and field limiting component within these systems. MEMs devices are an attractive strategy for beam-scanning but they offer limited scan fields when operated at high speeds. We demonstrate a high-speed and large-field MEMs-scanner-based laparoscopic probe based on a parallelized 32-beam design. The design and performance of this laparoscopic probe are presented, and volumetric OCT imaging at near video-rate speeds is demonstrated.

Cochlear implant is by far the most successful treatment for sensorineural hearing loss (SNHL) - the most common sensory deficit in the world. Although it was generally prescribed, the understanding of the etiology and the cellular structural abnormalities of SNHL is still limited due to the lack of direct imaging of the interior of the inner ear of living human patients. We have developed a micro-OCT probe that can serve as the stylet of a cochlear implant, which can perform cellular-level imaging through the cochlear implant during the surgery, providing diagnostic information and guidance to the surgeons.

Endoscopic imaging enables label free microscopy on the surface of organs, yet relies on spectral absorption information for contrast. The image in a scanning free system is formed using a tiny metalens, or graded index at the tip of the endoscope fiber bundle. However chromatic aberrations often lead to images being distorted between the color channels. In this paper we propose a phase imaging method that utilizes different color channels to encode different depth planes using the chromatic aberrations inherent in small metaoptics or grin leness. The metalens that make the image on the coherent fiber bundle has size dependent chromatic aberration that shifts the focal plane for different wavelengths. We present a phase imaging method that utilizes the chromatic defocusing in endoscope to compute the shape of transparent surfaces at video rate (for transparent lesion detection where the absorption changes are slight or minimal). The phase is solved in a single shot using RGB data.

Micro-optical coherence tomography (µOCT), is an emerging optical imaging approach enabling visualization of tissue microstructures at near cellular level. Small form-factor fiber-optic probes are needed to enable uOCT devices for minimally invasive diagnostic procedures such as coronary catheterization for atherosclerosis evaluation. Manufacturing complexities associated with miniaturizing current fiber-optic probes limit their optical and mechanical performance. We will present details of the design and construction of these miniaturized µOCT probes comprising TPL-based 3D printed optics, along with pre-clinical imaging results from an animal model. This probe is capable of lateral resolution of 5 µm and EDOF exceeding 850 µm in tissue.

Metasurfaces possess vast potential for flexible beam shaping with reduced physical footprint compared to traditional refractive bulk optics. In our group we have recently investigated two applications for metasurfaces in optical coherence tomography (OCT): a compact metalens possessing wavefront shaping properties significantly improved over lens designs typically employed in endoscopic OCT; and a metasurface design in which the separation of the illumination and collection channels allows a narrow point spread function to be maintained over a large depth range. In this work we show OCT results obtained using these metasurfaces and discuss the future role of metasurfaces in endoscopic OCT.

This conference presentation was prepared for the Endoscopic Microscopy XVIII conference at SPIE BiOS, SPIE Photonics West 2023.

We demonstrate a tethered capsule endoscope (TCE), which uses double-clad fiber and reflective optics for multimodal imaging in the esophagus without undesirable chromatic effects, such as focal shifts or back-reflections. We use a single, custom ellipsoidal mirror to focus the light from the fiber tip onto the sample. We describe the mechanical and optical designs and the fabrication and assembly protocols necessary for optimal performance. We demonstrate the implementation of the capsule by performing combined optical coherence tomography and spectral imaging in ex-vivo esophagus.

OCT-based tethered capsule endomicroscopy (TCE) is an emerging tool for unsedated Barrett’s Esophagus (BE) screening. Cancer progression risk is best determined by acquiring and analyzing a BE tissue sample. We report a TCE device with a biopsy channel capable of extracting tissue samples in an unsedated platform. We show in swine studies (n=2) the biopsy capsule can locate simulated targets and visualize the extraction of biopsies. Owing to its capacity to be utilized in patients without requiring sedation, this new technology could be useful for screening for BE subjects who have an elevated risk of developing cancer.

To address the need for less invasive and more accurate upper gastrointestinal biopsy, we have developed a swallowable optical-coherence tomography (OCT) tethered capsule endomicroscopy (TCE) device with image-targeted biopsy capabilities. The laser-captured biopsy can be used for histopathology and genetic analysis that could potentially improve the accuracy and reduce the cost of GI disease surveillance. Ex-vivo and in-vivo experiments on swine were conducted to optimize laser parameters, coating thickness, DNA isolation protocol, and histology of IVLCM samples. Results show that >200 ng of dsDNA can be isolated from the captured sample, which is sufficient for genetic analysis.

We present the compact SECM system with a 3D-printed tethered endoscopic capsule with a 1060 nm center wavelength. Compared to the previously presented 1310 nm SECM system, the present SECM system theoretically provides 15% improved lateral resolution, 5.2 times faster imaging speed, and two times faster fabrication times. We performed in vivo imaging on the swine esophagus and the SECM images clearly visualized squamous cell nuclei as a bright dot surrounded by dark cytoplasm and bright cell borders. These results indicate that our new SECM endoscopic system making it easier to conduct cellular-level diagnosis of upper GI tract.

Many neurological and digestive diseases have been linked to dysfunctions of the Enteric Nervous System (ENS) or gut microbiome imbalances. However, to this day, no tool allows a comprehensive in-vivo interrogation of the ENS. To address this lack of such technology, we performed a complete characterization and monitoring of the ENS to design an optogenetic endomicroscope based on Optical Coherence Tomography, capable of in-vivo mapping the ENS's morphology and functionality as well as in-situ microbiota sampling. We anticipate that researchers and clinicians would benefit from such a device to gain new insights into the microbiota-gut-brain axis and improve standards of care.

Calcium imaging has been widely employed in neuroscience research. A major challenge of calcium imaging is that the optical access depth in the mammalian brain is limited. Miniature optical imaging probes have been employed to image the deep brain regions. However, their imaging field-of-view is very small, which limits the number of neurons accessible and the overall experiment success rate. Recently, we have developed the Clear Optically Matched Panoramic Access Channel Technique (COMPACT), which effectively converts deep brain imaging into endoscopic microscopy. We will present the latest work of 0.5 mm COMPACT for in vivo functional imaging of mouse brain.

Optical coherence tomography combined with autofluorescence imaging (OCT-AFI) has shown potential for cancer detection. However, signal-to-background ratio (SBR) of the fluorescence modality is limited by low endogenous fluorophore signal, which is often similar in magnitude to system background fluorescence. We propose a double-clad fiber endoscope using time-resolved detection and index matching fluids at high reflection interfaces to improve SBR such that low-signal fluorophores can be visualized. Zemax and experimental measurements are used to assess device performance. Replacing air gaps with index matching fluid provides four orders of magnitude performance improvement. Time-resolved detection allows discrimination of system and target fluorescence.

This conference presentation was prepared for the Endoscopic Microscopy XVIII conference at SPIE BiOS, SPIE Photonics West 2023.

Coherent fiber bundles with their small diameter (less than 300 microns) pave the way towards ultra-thin holographic endoscopes. However, holographic imaging through CFBs suffers from random phase distortions due to the light transport through the fiber cores. We use two-wavelength digital holography, exploiting spectral correlations to eliminate the detrimental effects introduced by the fibre bundle. We use two-photon-polymerization to print our micro optics directly onto both the imaging fiber bundle and illumination fiber. Using an off-axis holographic setup and two lasers we are able to perform single-shot 3D holographic shape measurement.

This conference presentation was prepared for the Endoscopic Microscopy XVIII conference at SPIE BiOS, SPIE Photonics West 2023.