Optical Coherence Tomography of Tumor Spheroids Identifies Candidates for Drug Repurposing in Ovarian Cancer.

OBJECTIVE: Multicellular tumor spheroids (MCTs) are indispensable models for evaluating drug efficacy for precision cancer therapeutic strategies as well as for repurposing FDA-approved drugs for ovarian cancer. However, current imaging techniques cannot provide effective monitoring of pathological responses due to shallow penetration and experimentally operative destruction. We plan to utilize a noninvasive optical imaging tool to achieve in vivo longitudinal monitoring of the growth of MCTs and therapeutic responses to repurpose three FDA-approved drugs for ovarian cancer therapy. METHODS: A swept-source optical coherence tomography (SS-OCT) system was used to monitor the volume growth of MCTs over 11 days. Three inhibitors of 2-Methoxyestradiol (2-ME), AZD1208, and R-Ketorolac (R-keto) with concentrations of 1, 10, and 25 µM were employed to treat ovarian MCTs on day 5. Three-dimensional (3D), intrinsic optical attenuation contrast, and degree of uniformity were applied to analyze the therapeutic effect of these inhibitors on ovarian MCTs. RESULTS: We found that 2-ME, AZD1208, and R-keto with concentration of 10 and 25 µM significantly inhibited the volume growth of ovarian MCTs. There was no effect to necrotic tissues from all concentrations of 2-ME, AZD1208, and R-keto inhibitors from our OCT results. 2-ME and AZD1208 inhibited the growth of high uniformity tissues within MCTs and higher concentrations provided more significant inhibitory effects. CONCLUSION: Our results indicated that OCT was capable and reliable to monitor the therapeutic effect of inhibitors to ovarian MCTs and it can be used for the rapid characterization of novel therapeutics for ovarian cancers in the future.

Epidural anesthesia needle guidance by forward-view endoscopic optical coherence tomography and deep learning.

Epidural anesthesia requires injection of anesthetic into the epidural space in the spine. Accurate placement of the epidural needle is a major challenge. To address this, we developed a forward-view endoscopic optical coherence tomography (OCT) system for real-time imaging of the tissue in front of the needle tip during the puncture. We tested this OCT system in porcine backbones and developed a set of deep learning models to automatically process the imaging data for needle localization. A series of binary classification models were developed to recognize the five layers of the backbone, including fat, interspinous ligament, ligamentum flavum, epidural space, and spinal cord. The classification models provided an average classification accuracy of 96.65%. During puncture, it is important to maintain a safe distance between the needle tip and the dura mater. Regression models were developed to estimate that distance based on the OCT imaging data. Based on the Inception architecture, our models achieved a mean absolute percentage error of 3.05% ± 0.55%. Overall, our results validated the technical feasibility of using this novel imaging strategy to automatically recognize different tissue structures and measure the distances ahead of the needle tip during the epidural needle placement.

Computer-aided Veress needle guidance using endoscopic optical coherence tomography and convolutional neural networks.

During laparoscopic surgery, the Veress needle is commonly used in pneumoperitoneum establishment. Precise placement of the Veress needle is still a challenge for the surgeon. In this study, a computer-aided endoscopic optical coherence tomography (OCT) system was developed to effectively and safely guide Veress needle insertion. This endoscopic system was tested by imaging subcutaneous fat, muscle, abdominal space, and the small intestine from swine samples to simulate the surgical process, including the situation with small intestine injury. Each tissue layer was visualized in OCT images with unique features and subsequently used to develop a system for automatic localization of the Veress needle tip by identifying tissue layers (or spaces) and estimating the needle-to-tissue distance. We used convolutional neural networks (CNNs) in automatic tissue classification and distance estimation. The average testing accuracy in tissue classification was 98.53 ± 0.39%, and the average testing relative error in distance estimation reached 4.42 ± 0.56% (36.09 ± 4.92 µm).

Visually guided chick ocular length and structural thickness variations assessed by swept-source optical coherence tomography.

Chicks are an excellent model for studying myopia. To study the change of the ocular structures in chicks, ultrasound is mostly used. However, it suffers from limited spatial resolution. In this study, we investigated the axial length (AL) and the thickness of different ocular structures in chicks' eye undergoing visually induced changes using a swept-source optical coherence tomography (SS-OCT) system in vivo. Two groups of chicks wore a translucent plastic goggle (n = 6) over the right eye to induce form-deprivation myopia. Following 12 days of form deprivation, goggles were removed in one group of chicks (n = 3), and they were allowed to experience 5 days of unrestricted vision (recovery). Goggles remained in place for a total of 17 days for the remaining 3 chicks. A separate group of 3 chicks were untreated and served as normal control. Ocular dimensions were measured in control, myopic, and recovered eyes using an SS-OCT system. We found myopic chick eyes had significantly thicker AL, lens thickness (LT), anterior chamber depth (ACD), and vitreous chamber depth (VCD), but significantly thinner retina thickness (RT) and choroid thickness (ChT) compared to the control eyes. Following 5 days of recovery, the cornea thickness (CT), retina pigment epithelium thickness (RPET), and ChT were significantly thicker, while the ACD and LT became significantly thinner compared to that of myopic eyes. SS-OCT can serve as a promising tool to provide measurements of the entire ocular structures, for evaluating the change of thickness and depth of different ocular structures in chicks in vivo. The change of AL in the myopic and recovered chick eyes can be attributed to the thickness alterations of different ocular structures. Altogether, this work demonstrated the feasibility of SS-OCT in chick myopic research and exhibited new insights into the changes of ocular structures in chicks experiencing myopia after unrestricted vision recovery.