, "Deep convolutional neural networks for classifying head and neck cancer using hyperspectral imaging," J. Biomed. Opt. 22(6), 060503 (2017), doi: 10.1117/1.JBO.22.6.060503. Abstract. Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.

Purpose This study intends to investigate the feasibility of using hyperspectral imaging (HSI) to detect and delineate cancers in fresh, surgical specimens of patients with head and neck cancers. Experimental Design A clinical study was conducted in order to collect and image fresh, surgical specimens from patients (N = 36) with head and neck cancers undergoing surgical resection. A set of machine-learning tools were developed to quantify hyperspectral images of the resected tissue in order to detect and delineate cancerous regions which were validated by histopathologic diagnosis. More than two million reflectance spectral signatures were obtained by HSI and analyzed using machine-learning methods. The detection results of HSI were compared with autofluorescence imaging and fluorescence imaging of two vital-dyes of the same specimens. Results Quantitative HSI differentiated cancerous tissue from normal tissue in ex vivo surgical specimens with a sensitivity and specificity of 91% and 91%, respectively, and which was more accurate than autofluorescence imaging (P < 0.05) or fluorescence imaging of 2-NBDG (P < 0.05) and proflavine (P < 0.05). The proposed quantification tools also generated cancer probability maps with the tumor border demarcated and which could provide real-time guidance for surgeons regarding optimal tumor resection. Conclusions This study highlights the feasibility of using quantitative HSI as a diagnostic tool to delineate the cancer boundaries in surgical specimens, and which could be translated into the clinic application with the hope of improving clinical outcomes in the future.

Abstract. A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube ðx; y; λÞ, consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90% AE 8%, sensitivity of 89% AE 9%, and specificity of 91% AE 6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94% AE 6%, sensitivity of 94% AE 6%, and specificity of 95% AE 6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.

Surgical resection of head and neck (H and N) squamous cell carcinoma (SCC) may yield inadequate surgical cancer margins in 10 to 20% of cases. This study investigates the performance of label-free, reflectance-based hyperspectral imaging (HSI) and autofluorescence imaging for SCC detection at the cancer margin in excised tissue specimens from 102 patients and uses fluorescent dyes for comparison. Fresh surgical specimens (n = 293) were collected during H and N SCC resections (n = 102). The tissue specimens were imaged with reflectance-based HSI and autofluorescence imaging and afterwards with two fluorescent dyes for comparison. A histopathological ground truth was made. Deep learning tools were developed to detect SCC with new patient samples (inter-patient) and machine learning for intra-patient tissue samples. Area under the curve (AUC) of the receiver-operator characteristic was used as the main evaluation metric. Additionally, the performance was estimated in mm increments circumferentially from the tumor-normal margin. In intra-patient experiments, HSI classified conventional SCC with an AUC of 0.82 up to 3 mm from the cancer margin, which was more accurate than proflavin dye and autofluorescence (both p < 0.05). Intra-patient autofluorescence imaging detected human papilloma virus positive (HPV+) SCC with an AUC of 0.99 at 3 mm and greater accuracy than proflavin dye (p < 0.05). The inter-patient results showed that reflectance-based HSI and autofluorescence imaging outperformed proflavin dye and standard red, green, and blue (RGB) images (p < 0.05). In new patients, HSI detected conventional SCC in the larynx, oropharynx, and nasal cavity with 0.85–0.95 AUC score, and autofluorescence imaging detected HPV+ SCC in tonsillar tissue with 0.91 AUC score. This study demonstrates that label-free, reflectance-based HSI and autofluorescence imaging methods can accurately detect the cancer margin in ex-vivo specimens within minutes. This non-ionizing optical imaging modality could aid surgeons and reduce inadequate surgical margins during SCC resections.

Primary management for head and neck cancers, including squamous cell carcinoma (SCC), involves surgical resection with negative cancer margins. Pathologists guide surgeons during these operations by detecting cancer in histology slides made from the excised tissue. In this study, 381 digitized, histological whole-slide images (WSI) from 156 patients with head and neck cancer were used to train, validate, and test an inception-v4 convolutional neural network. The proposed method is able to detect and localize primary head and neck SCC on WSI with an AUC of 0.916 for patients in the SCC testing group and 0.954 for patients in the thyroid carcinoma testing group. Moreover, the proposed method is able to diagnose WSI with cancer versus normal slides with an AUC of 0.944 and 0.995 for the SCC and thyroid carcinoma testing groups, respectively. For comparison, we tested the proposed, diagnostic method on an open-source dataset of WSI from sentinel lymph nodes with breast cancer metastases, CAMELYON 2016, to obtain patch-based cancer localization and slide-level cancer diagnoses. The experimental design yields a robust method with potential to help create a tool to increase efficiency and accuracy of pathologists detecting head and neck cancers in histological images.

For patients undergoing surgical cancer resection of squamous cell carcinoma (SCCa), cancer-free surgical margins are essential for good prognosis. We developed a method to use hyperspectral imaging (HSI), a noncontact optical imaging modality, and convolutional neural networks (CNNs) to perform an optical biopsy of ex-vivo, surgical gross-tissue specimens, collected from 21 patients undergoing surgical cancer resection. Using a cross-validation paradigm with data from different patients, the CNN can distinguish SCCa from normal aerodigestive tract tissues with an area under the receiver operator curve (AUC) of 0.82. Additionally, normal tissue from the upper aerodigestive tract can be subclassified into squamous epithelium, muscle, and gland with an average AUC of 0.94. After separately training on thyroid tissue, the CNN can differentiate between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multinodular goiter (MNG) with an AUC of 0.93. Classical-type papillary thyroid carcinoma is differentiated from MNG with an AUC of 0.91. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multicategory diagnostic information for normal and cancerous head-and-neck tissue, and more patient data are needed to fully investigate the potential and reliability of the proposed technique.

Total laparoscopic hysterectomy has been shown to be an equally effective and safe technique when compared with conventional abdominal surgery for endometrial carcinoma. The procedure, as performed at our institution, involves the use of a uterine balloon manipulator (RUMI manipulator and Koh Colpotomizer system) for optimal surgical control. The fallopian tubes are cauterized to prevent transtubal spread of the tumor. The balloon manipulator thus creates a positive closed pressure system within the uterine cavity. After observing extensive displacement of tumor into small and large blood vessels in 1 case of grade 1, stage 1b endometrial carcinoma, we reviewed slides from 37 hysterectomy specimens (7 for endometrial carcinoma or atypical hyperplasia and 30 for benign conditions) performed laparoscopically between August 2004 and March 2006 at Emory University and Crawford Long Hospitals. We reviewed all slides for the presence or absence of endometrial tumor/tissue in vascular spaces. Patients with endometrial carcinoma/atypical complex hyperplasia included 6 FIGO grade I endometrioid carcinomas (3 stages 1A; 3 stages 1B) and 1 patient with atypical complex hyperplasia. Tumor within blood vessels was noted in 5 of 7 (71%) cases. In 3 cases, including the case of atypical complex hyperplasia, the number of vessels containing tumor were too numerous to count small and large caliber blood vessels. In the remainder, 1 case had 2 small vessels involved and in the other 7 small vessels showed tumor within vascular lumina. Benign endometrial glands and stromal tissue were noted within vascular spaces in 4 of 30 (13%) hysterectomy specimens removed for benign conditions. We describe a hitherto unreported artifact of vascular pseudo invasion in hysterectomy specimens obtained using the technique of total laparoscopic abdominal hysterectomy. We postulate that the creation of a closed pressure system generated as part of the operative technique is likely responsible for this phenomenon. Pathologists need to be aware of this artifact to avoid misinterpretation of vascular invasion in these cases with its associated therapeutic and prognostic implications.

The performance of hyperspectral imaging (HSI) for tumor detection is investigated in ex-vivo specimens from the thyroid (N = 200) and salivary glands (N = 16) from 82 patients. Tissues were imaged with HSI in broadband reflectance and autofluorescence modes. For comparison, the tissues were imaged with two fluorescent dyes. Additionally, HSI was used to synthesize three-band RGB multiplex images to represent the human-eye response and Gaussian RGBs, which are referred to as HSI-synthesized RGB images. Using histological ground truths, deep learning algorithms were developed for tumor detection. For the classification of thyroid tumors, HSI-synthesized RGB images achieved the best performance with an AUC score of 0.90. In salivary glands, HSI had the best performance with 0.92 AUC score. This study demonstrates that HSI could aid surgeons and pathologists in detecting tumors of the thyroid and salivary glands.