Optical coherence tomography and convolutional neural networks can differentiate colorectal liver metastases from liver parenchyma ex vivo.

PURPOSE: Optical coherence tomography (OCT) is an imaging technology based on low-coherence interferometry, which provides non-invasive, high-resolution cross-sectional images of biological tissues. A potential clinical application is the intraoperative examination of resection margins, as a real-time adjunct to histological examination. In this ex vivo study, we investigated the ability of OCT to differentiate colorectal liver metastases (CRLM) from healthy liver parenchyma, when combined with convolutional neural networks (CNN). METHODS: Between June and August 2020, consecutive adult patients undergoing elective liver resections for CRLM were included in this study. Fresh resection specimens were scanned ex vivo, before fixation in formalin, using a table-top OCT device at 1310 nm wavelength. Scanned areas were marked and histologically examined. A pre-trained CNN (Xception) was used to match OCT scans to their corresponding histological diagnoses. To validate the results, a stratified k-fold cross-validation (CV) was carried out. RESULTS: A total of 26 scans (containing approx. 26,500 images in total) were obtained from 15 patients. Of these, 13 were of normal liver parenchyma and 13 of CRLM. The CNN distinguished CRLM from healthy liver parenchyma with an F1-score of 0.93 (0.03), and a sensitivity and specificity of 0.94 (0.04) and 0.93 (0.04), respectively. CONCLUSION: Optical coherence tomography combined with CNN can distinguish between healthy liver and CRLM with great accuracy ex vivo. Further studies are needed to improve upon these results and develop in vivo diagnostic technologies, such as intraoperative scanning of resection margins.

Optical coherence tomography combined with convolutional neural networks can differentiate between intrahepatic cholangiocarcinoma and liver parenchyma ex vivo.

PURPOSE: Surgical resection with complete tumor excision (R0) provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma (iCCA). A non-invasive imaging technology, which could provide quick intraoperative assessment of resection margins, as an adjunct to histological examination, is optical coherence tomography (OCT). In this study, we investigated the ability of OCT combined with convolutional neural networks (CNN), to differentiate iCCA from normal liver parenchyma ex vivo. METHODS: Consecutive adult patients undergoing elective liver resections for iCCA between June 2020 and April 2021 (n = 11) were included in this study. Areas of interest from resection specimens were scanned ex vivo, before formalin fixation, using a table-top OCT device at 1310 nm wavelength. Scanned areas were marked and histologically examined, providing a diagnosis for each scan. An Xception CNN was trained, validated, and tested in matching OCT scans to their corresponding histological diagnoses, through a 5 × 5 stratified cross-validation process. RESULTS: Twenty-four three-dimensional scans (corresponding to approx. 85,603 individual) from ten patients were included in the analysis. In 5 × 5 cross-validation, the model achieved a mean F1-score, sensitivity, and specificity of 0.94, 0.94, and 0.93, respectively. CONCLUSION: Optical coherence tomography combined with CNN can differentiate iCCA from liver parenchyma ex vivo. Further studies are necessary to expand on these results and lead to innovative in vivo OCT applications, such as intraoperative or endoscopic scanning.

Toward Rapid, Widely Available Autologous CAR-T Cell Therapy - Artificial Intelligence and Automation Enabling the Smart Manufacturing Hospital.

CAR-T cell therapy is a promising treatment for acute leukemia and lymphoma. CAR-T cell therapies take a pioneering role in autologous gene therapy with three EMA-approved products. However, the chance of clinical success remains relatively low as the applicability of CAR-T cell therapy suffers from long, labor-intensive manufacturing and a lack of comprehensive insight into the bioprocess. This leads to high manufacturing costs and limited clinical success, preventing the widespread use of CAR-T cell therapies. New manufacturing approaches are needed to lower costs to improve manufacturing capacity and shorten provision times. Semi-automated devices such as the Miltenyi Prodigy® were developed to reduce hands-on production time. However, these devices are not equipped with the process analytical technology necessary to fully characterize and control the process. An automated AI-driven CAR-T cell manufacturing platform in smart manufacturing hospitals (SMH) is being developed to address these challenges. Automation will increase the cost-effectiveness and robustness of manufacturing. Using Artificial Intelligence (AI) to interpret the data collected on the platform will provide valuable process insights and drive decisions for process optimization. The smart integration of automated CAR-T cell manufacturing platforms into hospitals enables the independent manufacture of autologous CAR-T cell products. In this perspective, we will be discussing current challenges and opportunities of the patient-specific but highly automated, AI-enabled CAR-T cell manufacturing. A first automation concept will be shown, including a system architecture based on current Industry 4.0 approaches for AI integration.