Defining the relevance of surgical margins. Part two: Strategies to improve prediction of recurrence risk

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Due to the complex nature of tumour biology and the integration between host tissues and molecular processes of the tumour cells, a continued reliance on the status of the microscopic cellular margin should not remain our only determinant of the success of a curative-intent surgery for patients with cancer. Based on current evidence, relying on a purely cellular focus to provide a binary indication of treatment success provides an incomplete interpretation of potential outcomes. A more holistic analysis of the cancer margin may be required. If we are to move ahead from our current situation - and allow treatment plans to be more intelligently tailored to meet the requirements of each individual tumour - we need to improve our utilisation of techniques that either improve recognition of residual tumour cells within the surgical field or enable a more comprehensive interrogation of tumour biology that identifies a risk of recurrence. In the second article in this series on defining ...

Extracting Morphological and Sub-Resolution Features from Optical Coherence Tomography Images, a Review with Applications in Cancer Diagnosis

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Extracting Morphological and Sub-Resolution Features from Optical Coherence Tomography Images, a Review with Applications in Cancer Diagnosis Before they become invasive, early cancer cells exhibit specific and characteristic changes that are routinely used by a histopathologist for diagnosis. Currently, these early abnormalities are only detectable ex vivo by histopathology or, non-invasively and in vivo, by optical modalities that have not been clinically implemented due to their complexity and their limited penetration in tissues. Optical coherence tomography (OCT) is a noninvasive medical imaging technology with increasing clinical applications in areas such as ophthalmology, cardiology, gastroenterology, etc. In addition to imaging the tissue micro-structure, OCT can also provide additional information, describing the constituents and state of the cellular components of the tissue. Estimates of the nuclear size, sub-cellular morphological variations, dispersion and index of refraction can be extracted from the OCT images and can serve as diagnostically useful biomarkers. Moreover, the development of fully automated...

Multiscale Label-Free Imaging of Fibrillar Collagen in the Tumor Microenvironment

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With recent advances in cancer therapeutics, there is a great need for improved imaging methods for characterizing cancer onset and progression in a quantitative and actionable way. Collagen, the most abundant extracellular matrix protein in the tumor microenvironment (and the body in general), plays a multifaceted role, both hindering and promoting cancer invasion and progression. Collagen deposition can defend the tumor with immunosuppressive effects, while aligned collagen fiber structures can enable tumor cell migration, aiding invasion and metastasis. Given the complex role of collagen fiber organization and topology, imaging has been a tool of choice to characterize these changes on multiple spatial scales, from the organ and tumor scale to cellular and subcellular level. Macroscale density already aids in the detection and diagnosis of solid cancers, but progress is being made to integrate finer microscale features into the process. Here we review imaging modalities ranging f...

Deep learning-based optical coherence tomography image analysis of human brain cancer

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Real-time intraoperative delineation of cancer and non-cancer brain tissues, especially in the eloquent cortex, is critical for thorough cancer resection, lengthening survival, and improving quality of life. Prior studies have established that thresholding optical attenuation values reveals cancer regions with high sensitivity and specificity. However, threshold of a single value disregards local information important to making more robust predictions. Hence, we propose deep convolutional neural networks (CNNs) trained on labeled OCT images and co-occurrence matrix features extracted from these images to synergize attenuation characteristics and texture features. Specifically, we adapt a deep ensemble model trained on 5,831 examples in a training dataset of 7 patients. We obtain 93.31% sensitivity and 97.04% specificity on a holdout set of 4 patients without the need for beam profile normalization using a reference phantom. The segmentation maps produced by parsing the OCT volume an...

Weakly Supervised Melanoma Identification in Optical Coherence Tomography

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Purpose: Several noninvasive imaging techniques and computer-aided diagnosis systems have been developed to aid in the in-depth assessment of melanomas. However, the detection of thin melanomas (<1 mm) is difficult using current noninvasive imaging techniques, and the algorithms developed in previous studies are not capable of providing melanoma distribution. Experimental Design: Optical coherence tomography (OCT) was used to obtain depth-resolved volumetric data from spontaneous melanoma mice (20390 images for the induced group and 11616 images for the control group) in vivo. A weakly supervised deep-learning melanoma identification algorithm was developed that is capable of learning without the exact melanoma location. Results: The tumor thickness of melanocytic lesions predicted by the proposed algorithm was similar to that measured by histopathology. The proposed method achieves a correlation coefficient of 0.98 between the tumor area measured in the photograph and the area p...

Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery

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Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protoco...

Efficacy of optical coherence tomography in the diagnosing of oral cancerous lesion: systematic review and meta-analysis

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Non-invasive diagnostic tools that facilitate visualization of potentially malignant oral lesions and cancers have been introduced. Oral lesions detected by optical coherence tomography (OCT) were compared to reference results based on histological findings. The diagnostic odds ratio (DOR), along with summary receiver operating characteristic curve (SROC), area under SROC, sensitivity, specificity, and negative predictive values, were the outcomes. The DOR of OCT was 86.9190 (95% confidence interval [CI]: 38.7435, 194.9985), and the area under SROC was 0.951. OCT showed good sensitivity (0.9138; 95% CI: 0.8758, 0.9409) and specificity (0.9110; 95% CI: 0.8568, 0.9460), and a high negative predictive value (0.9225; 95% CI: 0.8863, 0.9478). Diagnostic sensitivity was higher when using artificial intelligence and automated algorithms compared to diagnoses made by clinicians. OCT is non-invasive, provides rapid results without radiation exposure, and can aid in the diagnosis and follow-u...

Diseased thyroid tissue classification in OCT images using deep learning: towards surgical decision support

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Intraoperative guidance tools for thyroid surgery based on optical coherence tomography (OCT) could aid distinguish between normal and diseased tissue. However, OCT images are difficult to interpret, thus, real-time automatic analysis could support the clinical decision making. In this study, several deep learning models were investigated for thyroid disease classification on 2D and 3D OCT data obtained from ex vivo specimens of 22 patients undergoing surgery and diagnosed with several thyroid pathologies. Additionally, two open-access datasets were used to evaluate the custom models. On the thyroid dataset, the best performance was achieved by the 3D vision transformer model with a Matthew's Correlation Coefficient (MCC) of 0.79 (accuracy 0.90) for the normal-vs-abnormal classification. On the open-access datasets, the custom models achieved the best performance (MCC>0.88, accuracy>0.96). Results obtained for the normal-vs-abnormal classification suggest OCT, complemented wit...

The Use of Optical Coherence Tomography for Gross Examination and Sampling of Fixed Breast Specimens: A Pilot Study

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Abstract Thorough gross examination of breast cancer specimens is critical in order to sample relevant portions for subsequent microscopic examination. This task would benefit from an imaging tool which permits targeted and accurate block selection. Optical coherence tomography (OCT) is a non-destructive imaging technique that visualizes tissue architecture and has the potential to be an adjunct at the gross bench. Our objectives were: (1) to familiarize pathologists with the appearance of breast tissue entities on OCT; and (2) to evaluate the yield and quality of OCT images of unprocessed, formalin-fixed breast specimens for the purpose of learning and establishment of an OCT-histopathology library. Methods: Firstly, 175 samples from 40 formalin-fixed, unprocessed breast specimens with residual tissue after final diagnosis were imaged with OCT and then processed into histology slides. Histology findings were correlated with features on OCT. Results: Residual malignancy was seen in ...

Extracellular Matrix Modulates Outgrowth Dynamics in Ovarian Cancer

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Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood due to the limited availability of cell culture models examining the behavior of cells that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components in human tissues, laminin and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths are developed. It is demonstrated that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53 and various OC cell lines. Outgrowths are initiated by cells that underwent outward translocation and retained the ability to intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography, and small amplitude oscillatory shear experiments reveal that increased ECM levels led to increased fibrous network thickness and hi...

The Value of Optical Coherence Tomography Angiography in Pituitary Adenomas

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Objective : This study aims to explore the value of retinal vessel density (VD) in diagnosing optic nerve injuries in patients with pituitary adenomas using optical coherence tomography angiography (OCTA). Methods : In this cross-sectional retrospective study, 100 patients with pituitary adenomas and 71 participants for normal controls, who visited the Beijing Tiantan Hospital from January 2019 to May 2021, were enrolled. The OCTA was used to measure retinal thickness and VD, and the correlation of these parameters with visual field (VF) factors was analyzed. Receiver operating characteristic curves were used to compare the value of the above parameters in diagnosing VF abnormalities in the patients with pituitary adenomas; the differences in retinal VD between 41 patients with pituitary adenomas who had normal retinal thicknesses and 41 patients in the normal control group with no statistical differences in gender and age were compared. Results : The radial peripapillary capillary ...

Research progress on the application of optical coherence tomography in the field of oncology

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Optical coherence tomography (OCT) is a non-invasive imaging technique which has become the "gold standard" for diagnosis in the field of ophthalmology. However, in contrast to the eye, nontransparent tissues exhibit a high degree of optical scattering and absorption, resulting in a limited OCT imaging depth. And the progress made in the past decade in OCT technology have made it possible to image nontransparent tissues with high spatial resolution at large (up to 2mm) imaging depth. On the one hand, OCT can be used in a rapid, noninvasive way to detect diseased tissues, organs, blood vessels or glands. On the other hand, it can also identify the optical characteristics of suspicious parts in the early stage of the disease, which is of great significance for the early diagnosis of tumor diseases. Furthermore, OCT imaging has been explored for imaging tumor cells and their dynamics, and for the monitoring of tumor responses to treatments. This review summarizes the recent advances in...

Michelson Diagnostics OCT points to reduced invasive biopsies

A clinical study published in The Lancet Oncology has evaluated the potential value of OCT technology in the treatment and care of basal cell carcinomas (BCC). The trial compared OCT-guided diagnosis of skin lesions with the standard punch biopsies in which small tissue samples are removed using a circular surgical instrument. The VivoSight OCT platform from Michelson Diagnostics was employed in the study, which involved 598 enrolled participants in the Netherlands. VivoSight is a multi-beam OCT platform employing light beams focused at different depths, designed to provide clinicians with continuous images of the epidermis and superficial dermis of the skin. The swept-source frequency-domain architecture operates at 1305 nanometers and achieves optical resolution of 7.5 microns in lateral and 5 microns in axial directions, according to the developers. The platform scans a 6 x 6 millimeter patch of skin and produces up to 500 cross-sectional slices per scan. The recent trial builds ...

66% of diagnostic biopsies for common skin cancer can be avoided using Michelson Diagnostics’ VivoSight OCT laser scanner

A major study published in leading cancer journal, The Lancet Oncology 1 have ground-breaking findings on Michelson Diagnostics, the UK based medical device company that use multi-beam Optical Coherence Tomography ('OCT') technology, which can transform patient's treatment and care of basal cell carcinomas (BCC). It was concluded that OCT-guided diagnosis, when compared to a standard punch biopsy could reduce the number of consultations and invasive procedures by a massive 66%. Professor Klara Mosterd performing an OCT scan on a patient’s lesion. Stitched skin biopsy wound Approximately 75% of skin cancers diagnosed in the UK are basal cell carcinomas 2 . It is the most common form of skin cancer that is rapidly increasing, with it affecting one in five people in the white population in their lifetime 3 . Annually, there are at least 150,000 cases in the UK and the number is growing, due to an aging population and sun exposure trends, creating a major burden on the NHS. OCT is an ad...

Pairing imaging, AI may improve colon cancer screening, diagnosis

A research team from the lab of Quing Zhu, the Edwin H. Murty Professor of Engineering at the McKelvey School of Engineering at Washington University in St. Louis, has combined optical coherence tomography (OCT) and machine learning to develop a colorectal cancer imaging tool that may one day improve the traditional endoscopy currently used by doctors. The results were published in the June issue of the Journal of Biophotonics, with an image featured on the inside cover. ( Read Full Article )


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