Dynamic optical contrast imaging (DOCI) is an imaging method utilizing fluorescence lifetime that our team has developed for identification of margins in head & neck mucosal malignancies. In this paper we demonstrate the first utilization of DOCI in cutaneous melanoma. We utilized both a 530/30nm band pass filter, as well as a 400nm long pass filter to capture the autofluorescence of tissue fluorophores, after excitation with a 365nm wide field LED light source. Imaging was captured, processed via an established protocol in MatLab, and regions of interest were compared to corresponding histopathology. Patients with biopsy confirmed cutaneous melanoma who were undergoing surgical removal of their malignancy were recruited for in-vivo pre-operative DOCI imaging, intraoperative imaging, then ex-vivo imaging of the tumor after removal. Patients free of disease with benign moles were also recruited for in-vivo DOCI imaging to serve as controls. 11 patients with melanoma and 10 controls were included. DOCI distinguishes between melanoma vs. normal surrounding skin (sensitivity=94% specificity=88%, AUC=0.921) as well as benign nevi vs. melanoma (sensitivity=100% and specificity=80%, AUC=0.953), posing benefit opportunities for both melanoma diagnostics as well as margin determination.
Positive surgical margins in head and neck cancers (HNC) are associated with poor survival. Standard frozen section analysis for intraoperative assessment of margins is limited by processing time and sampling error. Optical imaging technologies may address these limitations. We identified the following techniques in a literature search of optical imaging modalities for the detection of head and neck tumor margins: autofluorescence imaging, dynamic optical contrast imaging, optical coherence tomography, narrow band imaging, hyperspectral imaging, Raman spectroscopy, near-infrared fluorescence imaging, confocal laser endomicroscopy, and high-resolution microendoscopy. Penetration depths range from surface level to 6mm, image acquisition times range from real-time to several minutes, and 3/9 require exogenous contrast agents. Reported sensitivity and specificity range from 71-100% and 43-100%, respectively. Each reviewed modality lends unique strengths such as fast image acquisition times, wide field of view, high native contrast, or seamless integration with existing endoscopes. However, none have yet to replace palpation and frozen section analysis in the operating room.
Scar formation in tissue is a healing process that inhibits normal tissue function through the deposition of predominantly disorganized type I collagen which is much more rigid than native collagen. Scarring in the vocal fold is especially debilitating as the vocal fold requires flexibility and freedom of movement to produce voicing. Furthermore the vocal fold has a very layered and organized structure with type I collagen in the basement membrane providing organ structural support, while type III collagen is in high concentration in the deep layer of the vocal fold. Using Dynamic Optical Contrast Imaging (DOCI) on unstained histological rabbit vocal fold slides (formalin fixed paraffin embedded tissue, FFPE), we were able to use subtle differences in fluorescence lifetime between native and scarred collagen types to image molecular evolution of scarring following injury. The degree of scarring and the DOCI fluorescence life time shift correlated with molecular and functional evaluations of scarring. Preliminary results demonstrates DOCI could be used as a prognostic tool useful to clinicians by depicting scar damage on vocal folds, (VF) not visible to the unaided eye or with white light endoscopic imaging.
Surgical excision of an adenomatous or hypercellular parathyroid gland is typically the treatment of choice for primary hyperparathyroidism. Intraoperative identification can be challenging due to potential variable location and indistinct features of these glands. In 115 ex-vivo specimens we evaluated the efficacy of DOCI in identifying hypercellular parathyroid glands. Significant imaging differences were seen between hypercellular vs normal parathyroid glands vs other adjacent healthy tissues across 8 spectral channels (p<0.05). Our classification result (100% sensitivity, 98.8% specificity) using a logistic regression classifier further corroborated that DOCI has the capacity to accurately identify and differentiate parathyroid glands from surrounding tissues. DOCI enables sensitive and specific mapping of parathyroid location, leading to improved accuracy of the surgical procedure, reduced time to successful completion, fewer risks and improved patient outcomes.
Due to the anatomic confines of the head and neck, resection of oropharyngeal squamous cell carcinoma (OPSCC) necessitates precise margins that balance oncologic outcomes with preservation of speech and swallowing. Dynamic Optical Contrast Imaging (DOCI) is a novel non-invasive imaging system that measures endogenous fluorescence decay rates. DOCI acquires images in real-time (<2 secs) with an operatively relevant wide field of view (6.5 cm2). After surgical excision, 10 OPSCC specimens were imaged using DOCI. In all 10 specimens, DOCI clearly differentiated healthy tissue from cancer (p<0.01). DOCI has the potential to improve patient oncologic and functional outcomes by allowing the surgeon to precisely determine margins intraoperatively.
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