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Apelian C.,ESPCI ParisTech | Apelian C.,LLTech SAS | Harms F.,LLTech SAS | Thouvenin O.,ESPCI ParisTech | And 2 more authors.
Biomedical Optics Express | Year: 2016

We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other OCTbased techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a wide range of organs in normal or pathological conditions. © 2016 Optical Society of America.


Bruhat A.,University of Pittsburgh | Combrinck M.,PathWest Laboratory MedicineWA | Dalimier E.,LLTech SAS | Harms F.,LLTech SAS | Fine J.L.,University of Pittsburgh
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2015

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.


Dalimier E.,LLTech SAS | Salomon D.,University of Monastir
Dermatology | Year: 2012

Background/Aims: Full-field optical coherence tomography (FFOCT) is a new imaging technology that can provide 3D micron-level resolution and is suited for high-resolution imaging of biological tissue. The aim of this study was to evaluate its capacity and potential for imaging human epidermis and dermis and various skin pathologies in ex vivo and in vivo conditions. Methods: Non-fixed and fixed samples of normal and pathological skin and normal in vivo skin were imaged with a FFOCT system and compared to histological slides. Results: The epidermis and adnexae, the collagen bundles of the dermis and the hypodermis could be identified through architectural and cellular details. The pathological structures were distinguished from the normal structures and corresponded to their histopathological organization. Conclusion: FFOCT is a novel technology in the field of skin imaging that has the potential to be a relevant complement to existing non-invasive imaging modalities for clinical and cosmetic applications. Copyright © 2012 S. Karger AG, Basel.


Grieve K.,Center Hospitalier National dOphtalmologie des Quinze Vingts | Palazzo L.,Clinique du Trocadero | Dalimier E.,LLTech SAS | Vielh P.,Translational Research Laboratory | Fabre M.,Translational Research Laboratory
Gastrointestinal Endoscopy | Year: 2015

Background Rapid on-site evaluation of cytologic specimens is a way of determining the adequacy of fine-needle aspiration (FNA). However, alternatives may be useful when the presence of a cytotechnologist and/or pathologist is not possible. Objective To evaluate the feasibility of using full-field optical coherence tomography (FFOCT) for FNA specimen quality assessment. Design FFOCT images were acquired on gastric, pancreatic, pelvic, and lymph-node formalin-fixed FNA specimens and were compared with histology of the same samples. Setting Pathology suite in a hospital. Patients Fourteen patients undergoing gastric, pancreatic, pelvic, or lymph-node EUS-guided FNA biopsy. Interventions FFOCT imaging on formalin-fixed samples before histologic procedures. Main Outcome Measurements FFOCT imaging feasibility and visibility of normal and abnormal features on images. Results FFOCT imaging was possible. Blood, mucus, muscle, collagen, and digestive mucosa could be identified as well as abnormal architectural features including infiltrative pancreatic ductal carcinoma and a neuroendocrine neoplasm. Lesions at the individual cell level could not be detected. Limitations The study was performed on a limited number of cases. Conclusion FFOCT offers rapid, noninvasive, nondestructive imaging of FNA biopsy specimens. In the future, it could be performed in the endoscopy suite to improve detection of satisfactory specimens and obviate the need for rapid on-site evaluation. © 2015 American Society for Gastrointestinal Endoscopy.


Lopater J.,University of Paris Descartes | Colin P.,University of Paris Descartes | Beuvon F.,University of Paris Descartes | Sibony M.,University of Paris Descartes | And 3 more authors.
World Journal of Urology | Year: 2016

Objectives: To evaluate the diagnostic accuracy (Acc) of full-field optical coherence tomography (FFOCT) for cancer detection on prostate biopsy. Materials and methods: 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. Results: 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. Conclusions: FFOCT of prostate biopsy cores may provide a diagnostic accuracy greater than 80 %, with a good reliability and a high NPV. Take home message: “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.” © 2015, Springer-Verlag Berlin Heidelberg.


Assayag O.,ESPCI ParisTech | Antoine M.,Tenon Hospital APHP | Sigal-Zafrani B.,University Pierre and Marie Curie | Riben M.,University of Houston | And 7 more authors.
Technology in Cancer Research and Treatment | Year: 2014

We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) was used to image human breast tissue and is evaluated to assess its ability to aid the pathologist's management of intra-operative diagnoses. FF-OCT imaging safety was investigated and agreement between FF-OCT and routinely prepared histopathological images was evaluated. The compact setup used for this study provides 1 mm3 resolution and 200 mm imaging depth, and a 2.25 cm2 specimen is scanned in about 7 minutes.75 breast specimens were imaged from 22 patients (21 women, 1 man) with a mean age of 58 (range: 25-83). Pathologists blind diagnosed normal/benign or malignant tissue based on FF-OCT images alone, diagnosis from histopathology followed for comparison. The contrast in the FF-OCT images is generated by intrinsic tissue scattering properties, meaning that no tissue staining or preparation is required. Major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts were characterized. Subsequently, features resulting from pathological modification were characterized and a diagnosis decision tree was developed. Using FF-OCT images, two breast pathologists were able to distinguish normal/benign tissue from lesional with a sensitivity of 94% and 90%, and specificity of 75% and 79% respectively. © Adenine Press (2014).


PubMed | LLTech SAS, Hopital Tenon and Laue Langevin Institute
Type: Journal Article | Journal: Technology in cancer research & treatment | Year: 2016

Current techniques for the intraoperative analysis of sentinel lymph nodes during breast cancer surgery present drawbacks such as time and tissue consumption. Full-field optical coherence tomography is a novel noninvasive, high-resolution, fast imaging technique. This study investigated the use of full-field optical coherence tomography as an alternative technique for the intraoperative analysis of sentinel lymph nodes. Seventy-one axillary lymph nodes from 38 patients at Tenon Hospital were imaged minutes after excision with full-field optical coherence tomography in the pathology laboratory, before being handled for histological analysis. A pathologist performed a blind diagnosis (benign/malignant), based on the full-field optical coherence tomography images alone, which resulted in a sensitivity of 92% and a specificity of 83% (n = 65 samples). Regular feedback was given during the blind diagnosis, with thorough analysis of the images, such that features of normal and suspect nodes were identified in the images and compared with histology. A nonmedically trained imaging expert also performed a blind diagnosis aided by the reading criteria defined by the pathologist, which resulted in 85% sensitivity and 90% specificity (n = 71 samples). The number of false positives of the pathologist was reduced by 3 in a second blind reading a few months later. These results indicate that following adequate training, full-field optical coherence tomography can be an effective noninvasive diagnostic tool for extemporaneous sentinel node biopsy qualification.


PubMed | Clinique du Trocadero, Translational Research Laboratory, Center Hospitalier National dOphtalmologie des Quinze Vingts and LLTech SAS
Type: Journal Article | Journal: Gastrointestinal endoscopy | Year: 2015

Rapid on-site evaluation of cytologic specimens is a way of determining the adequacy of fine-needle aspiration (FNA). However, alternatives may be useful when the presence of a cytotechnologist and/or pathologist is not possible.To evaluate the feasibility of using full-field optical coherence tomography (FFOCT) for FNA specimen quality assessment.FFOCT images were acquired on gastric, pancreatic, pelvic, and lymph-node formalin-fixed FNA specimens and were compared with histology of the same samples.Pathology suite in a hospital.Fourteen patients undergoing gastric, pancreatic, pelvic, or lymph-node EUS-guided FNA biopsy.FFOCT imaging on formalin-fixed samples before histologic procedures.FFOCT imaging feasibility and visibility of normal and abnormal features on images.FFOCT imaging was possible. Blood, mucus, muscle, collagen, and digestive mucosa could be identified as well as abnormal architectural features including infiltrative pancreatic ductal carcinoma and a neuroendocrine neoplasm. Lesions at the individual cell level could not be detected.The study was performed on a limited number of cases.FFOCT offers rapid, noninvasive, nondestructive imaging of FNA biopsy specimens. In the future, it could be performed in the endoscopy suite to improve detection of satisfactory specimens and obviate the need for rapid on-site evaluation.


PubMed | LLTech SAS and University of Paris Descartes
Type: Journal Article | Journal: World journal of urology | Year: 2016

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 ( = 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.


PubMed | Mouse Clinical Institute, Institute of Image Guided Surgery, University of Strasbourg, LLTech SAS and 3 more.
Type: | Journal: Scientific reports | Year: 2016

The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.

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