Light for Life Technologies (France)

DFFOCT allows for the visualization and characterization of cellular dynamics, providing future direction for cell-targeted therapeutics. In this work, we analyze the potential of DFFOCT to increase understanding of dynamic cellular processes under varying conditions.

Full Field OCT (FFOCT) is a shot noise limited interferometric microscopy technique that uses incoherent light and has proved to be an effective diagnostic tool in terms of sensitivity and specificity. We have used the FFOCT setup built by LLTech for the analysis of various cancerous tissues corresponding to the following organs: breast, skin, prostate, lungs, ENT, bladder, brain etc. The scores obtained were found in the range between 80 and 98%. To do better and to provide informations that the histology does not carry we have studied, using the same setup, the temporal dependence of our signals which we found to be related to the cellular metabolism. We have used the new high speed and high full well capacity of the Adimec camera to achieve a time analysis ranging between 2 and a few thousands of ms. We thus obtain a new contrast which constitutes a biomarker at the sub-cellular scale. We monitor the characteristic frequencies and amplitude of the signal and display them on the images of the tissues using a new processing code of the time series. This metabolic contrast also reveal the evolution of the activity of cancer cells under treatments such as chemotherapy. We will illustrate this new approach through examples of cancer tissues that are planned to be used as intraoperative tools.

Non-melanoma skin cancer is the most common cancer. On cosmetically sensitive areas, Mohs micrographic surgery is the standard of care; intra-operative margin assessment minimizes the surgical defect while helping to reduce the recurrence rate by a factor of 3 compared to surgical excision. The current Mohs technique relies on frozen section tissue slide preparation, which significantly lengthens operative time and requires on-site trained histotechnicians. Full-field micro-tomography is a novel optical imaging technique based on interferometry. It allows the extraction of a full-field optical coherence tomography (FFOCT) image, representative of the morphology of the tissue, and the dynamic cell information, representative of the intra-cellular metabolic activity. Both images are calculated at the micron-level in a few minutes and without tissue preparation. This multi-centric study aimed to evaluate these combined new imaging modalities for the analysis of skin cancer margins during Mohs surgery. Over 200 Mohs specimens were imaged in Drexel University College of Medicine, USA, and GHR Mulhouse Sud Alsace, France. An atlas was established of FFOCT images and corresponding histological slides to reveal FFOCT reading criteria of normal and cancerous structures. Dynamic cell information enhanced visualization of cancerous cells and surrounding immune cells, and yielded metabolic quantification of cancerous area versus benign areas. Finally, deep learning algorithms were developed for preliminary results for the automatic detection of cancerous tissue. Hybrid morphologic and metabolic micro-tomography techniques hold great potential for skin cancer margin assessment. They can potentially reduce recurrence rates and surgery times, optimize clinical workflow, and decrease healthcare costs.

IntroductionTumor detection and visualization plays a key role in the clinical workflow of a patient with suspected cancer, both in the diagnosis and treatment. Several optical imaging techniques have been evaluated for guidance during oncological interventions. Optical coherence tomography (OCT) is a technique which has been widely evaluated during the past decades. This review aims to determine the clinical usefulness of OCT during cancer interventions focussing on qualitative features, quantitative features and the diagnostic value of OCT.MethodsA systematic literature search was performed for articles published before May 2018 using OCT in the field of surgical oncology. Based on these articles, an overview of the clinical usefulness of OCT was provided per tumor type.ResultsA total of 785 articles were revealed by our search, of which a total of 136 original articles were available for analysis, which formed the basis of this review. OCT is currently utilised for both preoperative diagnosis and intraoperative detection of skin, oral, lung, breast, hepatobiliary, gastrointestinal, urological, and gynaecological malignancies. It showed promising results in tumor detection on a microscopic level, especially using higher resolution imaging techniques, such as high-definition OCT and full-field OCT.ConclusionIn the near future, OCT could be used as an additional tool during bronchoscopic or endoscopic interventions and could also be implemented in margin assessment during (laparoscopic) cancer surgery if a laparoscopic or handheld OCT device will be further developed to make routine clinical use possible.

Cells shape or density is an important marker of tissues pathology. However, individual cells are difficult to observe in thick tissues frequently presenting highly scattering structures such as collagen fibers. Endogenous techniques struggle to image cells in these conditions. Moreover, exogenous contrast agents like dyes, fluorophores or nanoparticles cannot always be used, especially if non-invasive imaging is required. Scatterers motion happening down to the millisecond scale, much faster than the still and highly scattering structures (global motion of the tissue), allowed us to develop a new approach based on the time dependence of the FF-OCT signals. This method reveals hidden cells after a spatiotemporal analysis based on singular value decomposition and wavelet analysis concepts. It does also give us access to local dynamics of imaged scatterers. This dynamic information is linked with the local metabolic activity that drives these scatterers. Our technique can explore subcellular scales with micrometric resolution and dynamics ranging from the millisecond to seconds. By this mean we studied a wide range of tissues, animal and human in both normal and pathological conditions (cancer, ischemia, osmotic shock…) in different organs such as liver, kidney, and brain among others. Different cells, undetectable with FF-OCT, were identified (erythrocytes, hepatocytes…). Different scatterers clusters express different characteristic times and thus can be related to different mechanisms that we identify with metabolic functions. We are confident that the D-FFOCT, by accessing to a new spatiotemporal metabolic contrast, will be a leading technique on tissue imaging and for better medical diagnosis.

FFOCT (Full Field Optical Coherence Tomography) is a novel optical technology that gives access to very high resolution tomography images of biological tissues within minutes, non-invasively. This makes it an attractive tool to bridge the gap between medical imaging modalities (MRI, ultrasound, CT) used for cancer lesion identification or targeting and histological diagnosis. Clinical tissue specimens, such as surgical cancer margins or biopsies, can potentially be assessed rapidly, by the clinician, in the aim to help him decide on the course of action. A fast FFOCT prototype was built, that provides 1cm2 images with 1 µm resolution in 1 minute, and can accommodate samples up to 50mm diameter. Specific work was carried out to implement a large sample holder, high-speed image acquisition system, optimized scanning, and accelerated GPU tiles stitching. Results obtained on breast, urology, and digestive tissues show the efficiency of the technique for the detection of cancer on clinical tissue specimens, and reinforce the clinical relevance of the technique. The technical and clinical results show that the fast FFOCT system can successfully be used for a fast assessment of cancer excision margins or biopsies providing a very valuable tool in the clinical environment.

To evaluate the diagnostic accuracy (Acc) of full-field optical coherence tomography (FFOCT) for cancer detection on prostate biopsy. Thirty-eight consecutive patients with elevated PSA and/or suspicious digital rectal examination were prospectively included. For each patient, 1-10 cores were randomly selected and imaged with FFOCT immediately after sampling. The images obtained were de-identified and analyzed by three pathologists blinded to the results of pathological evaluation. The overall average Acc was measured, as well as sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV). The Acc learning curve was assessed by multivariate logistic regression, and inter-reader concordance was assessed by Kappa index. One hundred and nineteen cores were imaged. Of them, 40 (33.6%) were involved with cancer. The overall average Acc of FFOCT for cancer detection was of 70.6%. Se, Sp, PPV, and NPV were of 63, 74, 55.5, and 80%, respectively. A substantial agreement was observed among pathologists (κ = 0.6, p < 0.001). On multivariate analysis, Acc was associated with the number of previously interpreted cases, with a predicted Acc of 82% at the end of learning curve. The overall average accuracy for high Gleason score (>3 + 3) determination was of 72%, although results were limited by the small amount of cases. FFOCT of prostate biopsy cores may provide a diagnostic accuracy greater than 80%, with a good reliability and a high NPV. "Full-field optical coherence tomography is a novel imaging modality that could have a potential value in real-time diagnosis of prostate cancer during prostate biopsy procedures."

Full-field optical coherence tomography (FFOCT) quickly produces images that resemble conventional pathology images. We examined endometrium in an intra-operative like fashion (more than forty samples). FFOCT-imaged endometrium was recognizable to pathologists and compared favorably with microscopy of the same samples. Additional image enhancements and acquisition techniques were explored and may improve interpretation accuracy. Wider evaluation of images is ongoing, using more pathologist subjects. FFOCT may revolutionize pathology practice in the future by permitting rapid diagnosis and in vivo diagnosis; this is potentially a disruptive new diagnostic technique in pathology.