Aligning Small Datasets Using Domain Adversarial Learning: Applications in Automated in Vivo Oral Cancer Diagnosis.

Deep learning approaches for medical image analysis are limited by small data set size due to factors such as patient privacy and difficulties in obtaining expert labelling for each image. In medical imaging system development pipelines, phases for system development and classification algorithms often overlap with data collection, creating small disjoint data sets collected at numerous locations with differing protocols. In this setting, merging data from different data collection centers increases the amount of training data. However, a direct combination of datasets will likely fail due to domain shifts between imaging centers. In contrast to previous approaches that focus on a single data set, we add a domain adaptation module to a neural network and train using multiple data sets. Our approach encourages domain invariance between two multispectral autofluorescence imaging (maFLIM) data sets of in vivo oral lesions collected with an imaging system currently in development. The two data sets have differences in the sub-populations imaged and in the calibration procedures used during data collection. We mitigate these differences using a gradient reversal layer and domain classifier. Our final model trained with two data sets substantially increases performance, including a significant increase in specificity. We also achieve a significant increase in average performance over the best baseline model train with two domains (p = 0.0341). Our approach lays the foundation for faster development of computer-aided diagnostic systems and presents a feasible approach for creating a robust classifier that aligns images from multiple data centers in the presence of domain shifts.

Clinical label-free endoscopic imaging of biochemical and metabolic autofluorescence biomarkers of benign, precancerous, and cancerous oral lesions.

Early detection is critical for improving the survival rate and quality of life of oral cancer patients; unfortunately, dysplastic and early-stage cancerous oral lesions are often difficult to distinguish from oral benign lesions during standard clinical oral examination. Therefore, there is a critical need for novel clinical technologies that would enable reliable oral cancer screening. The autofluorescence properties of the oral epithelial tissue provide quantitative information about morphological, biochemical, and metabolic tissue and cellular alterations accompanying carcinogenesis. This study aimed to identify novel biochemical and metabolic autofluorescence biomarkers of oral dysplasia and cancer that could be clinically imaged using novel multispectral autofluorescence lifetime imaging (maFLIM) endoscopy technologies. In vivo maFLIM clinical endoscopic images of benign, precancerous, and cancerous lesions from 67 patients were acquired using a novel maFLIM endoscope. Widefield maFLIM feature maps were generated, and statistical analyses were applied to identify maFLIM features providing contrast between dysplastic/cancerous vs. benign oral lesions. A total of 14 spectral and time-resolved maFLIM features were found to provide contrast between dysplastic/cancerous vs. benign oral lesions, representing novel biochemical and metabolic autofluorescence biomarkers of oral epithelial dysplasia and cancer. To the best of our knowledge, this is the first demonstration of clinical widefield maFLIM endoscopic imaging of novel biochemical and metabolic autofluorescence biomarkers of oral dysplasia and cancer, supporting the potential of maFLIM endoscopy for early detection of oral cancer.

Prevalence and patterns of maxillofacial trauma: a retrospective descriptive study.

INTRODUCTION: We aimed to describe the prevalence and pattern of maxillofacial trauma in Qatar. METHODS: This is a retrospective study of trauma registry data at Hamad General Hospital during the period from January 2011 to December 2014. The study included all traumatic maxillofacial patients who underwent CT scan and were admitted during the study period. RESULTS: A total of 1187 patients with maxillofacial injuries were included in the study and 18.5% of all trauma admissions were related to maxillofacial injuries. Young age and males were predominantly affected. Mechanisms of injury were mainly traffic-related and fall. Orbital injuries were the commonest followed by maxillary injuries. The median and range face abbreviated injury score (AIS) was 2 [1-3] with 66% had a score of 2. Maxillofacial fractures were frequently associated with traumatic brain injuries. One out of five patients was managed with surgery and had median length of stays in ICU and hospital 5 and 7 days, respectively. Overall, in-hospital mortality was 8.3%. Mortality in isolated maxillofacial was low (0.3%) in comparison to 15% in polytrauma patients (p = 0.001). Multivariable regression analysis showed that Injury Severity Score, face AIS and Glasgow Coma Scale were predictors of mortality with age-adjusted odd ratio of 1.15, 2.48 and 0.82; respectively. CONCLUSIONS: Maxillofacial trauma requiring admission is not uncommon in our trauma center and mostly it is mild to moderate in severity. Associated injuries are present in most of the maxillofacial injured patients and further diagnostic investigations should be part of the assessment in maxillofacial injuries.

End-to-End Neural Network for Feature Extraction and Cancer Diagnosis of In Vivo Fluorescence Lifetime Images of Oral Lesions.

In contrast to previous studies that focused on classical machine learning algorithms and hand-crafted features, we present an end-to-end neural network classification method able to accommodate lesion heterogeneity for improved oral cancer diagnosis using multispectral autofluorescence lifetime imaging (maFLIM) endoscopy. Our method uses an autoencoder framework jointly trained with a classifier designed to handle overfitting problems with reduced databases, which is often the case in healthcare applications. The autoencoder guides the feature extraction process through the reconstruction loss and enables the potential use of unsupervised data for domain adaptation and improved generalization. The classifier ensures the features extracted are task-specific, providing discriminative information for the classification task. The data-driven feature extraction method automatically generates task-specific features directly from fluorescence decays, eliminating the need for iterative signal reconstruction. We validate our proposed neural network method against support vector machine (SVM) baselines, with our method showing a 6.5%-8.3% increase in sensitivity. Our results show that neural networks that implement data-driven feature extraction provide superior results and enable the capacity needed to target specific issues, such as inter-patient variability and the heterogeneity of oral lesions.Clinical relevance- We improve standard classification algorithms for in vivo diagnosis of oral cancer lesions from maFLIm for clinical use in cancer screening, reducing unnecessary biopsies and facilitating early detection of oral cancer.

Machine-Learning Assisted Discrimination of Precancerous and Cancerous from Healthy Oral Tissue Based on Multispectral Autofluorescence Lifetime Imaging Endoscopy.

Multispectral autofluorescence lifetime imaging (maFLIM) can be used to clinically image a plurality of metabolic and biochemical autofluorescence biomarkers of oral epithelial dysplasia and cancer. This study tested the hypothesis that maFLIM-derived autofluorescence biomarkers can be used in machine-learning (ML) models to discriminate dysplastic and cancerous from healthy oral tissue. Clinical widefield maFLIM endoscopy imaging of cancerous and dysplastic oral lesions was performed at two clinical centers. Endoscopic maFLIM images from 34 patients acquired at one of the clinical centers were used to optimize ML models for automated discrimination of dysplastic and cancerous from healthy oral tissue. A computer-aided detection system was developed and applied to a set of endoscopic maFLIM images from 23 patients acquired at the other clinical center, and its performance was quantified in terms of the area under the receiver operating characteristic curve (ROC-AUC). Discrimination of dysplastic and cancerous from healthy oral tissue was achieved with an ROC-AUC of 0.81. This study demonstrates the capabilities of widefield maFLIM endoscopy to clinically image autofluorescence biomarkers that can be used in ML models to discriminate dysplastic and cancerous from healthy oral tissue. Widefield maFLIM endoscopy thus holds potential for automated in situ detection of oral dysplasia and cancer.

Clinical label-free biochemical and metabolic fluorescence lifetime endoscopic imaging of precancerous and cancerous oral lesions.

INTRODUCTION: Incomplete head and neck cancer resection occurs in up to 85% of cases, leading to increased odds of local recurrence and regional metastases; thus, image-guided surgical tools for accurate, in situ and fast detection of positive margins during head and neck cancer resection surgery are urgently needed. Oral epithelial dysplasia and cancer development is accompanied by morphological, biochemical, and metabolic tissue and cellular alterations that can modulate the autofluorescence properties of the oral epithelial tissue. OBJECTIVE: This study aimed to test the hypothesis that autofluorescence biomarkers of oral precancer and cancer can be clinically imaged and quantified by means of multispectral fluorescence lifetime imaging (FLIM) endoscopy. METHODS: Multispectral autofluorescence lifetime images of precancerous and cancerous lesions from 39 patients were imaged in vivo using a novel multispectral FLIM endoscope and processed to generate widefield maps of biochemical and metabolic autofluorescence biomarkers of oral precancer and cancer. RESULTS: Statistical analyses applied to the quantified multispectral FLIM endoscopy based autofluorescence biomarkers indicated their potential to provide contrast between precancerous/cancerous vs. healthy oral epithelial tissue. CONCLUSION: To the best of our knowledge, this study represents the first demonstration of label-free biochemical and metabolic clinical imaging of precancerous and cancerous oral lesions by means of widefield multispectral autofluorescence lifetime endoscopy. Future studies will focus on demonstrating the capabilities of endogenous multispectral FLIM endoscopy as an image-guided surgical tool for positive margin detection during head and neck cancer resection surgery.

Recombinant human bone morphogenetic protein-7 and bone marrow as a substitute for bone graft in reconstruction defect of rabbit mandible.

OBJECTIVE: To obtain information on the feasibility of employing recombinant human bone morphogenetic protein-7 (rhBMP-7), mixed with bone marrow as a substitute for autologous bone graft. METHODS: We carried out the study in the University Clinic Center, Sarajevo, Bosnia and Herzegovina, from February 2002 to January 2004. Six New Zealand rabbits underwent hemiresection of the mandible. We placed rhBMP-7 in a concentration of 100 micrograms and collagen (ACS) as carrier mixed with bone marrow in the defects in 3 animals. In another group of 3, we restored the defect by placement of autologous bone graft harvested from the iliac crest. We evaluated the results by the activity of the alkaline phosphatase enzyme (ALP), CT assessment with bone mineral density (BMD) analysis, and clinical and histologic examinations. RESULTS: The ALP activity was significantly higher after 14 days, in the rhBMP7/ACS sites than the bone graft sites (30th day). Mean BMD of tissue induced by rhBMP-7/ACS on the 30th day was 510 mg/cm3 in caudal, and 553 mg/cm3 in sagittal plane, and bone graft tissue was 510 mg/cm3 in caudal and 530 mg/cm3 in sagittal plane. Clinical inspection and histologic examination on the 60th day showed complete bridged defects with abundant woven bone in 2 of 3 rhBMP-7/ACS sites (67%), and no incorporation of the autologous bone graft into the other groups treated sites. CONCLUSION: The rhBMP-7/ACS mixed with bone marrow was very effective in establishing complete bone regeneration into the defects, indicating that it could be an adequate alternative for autologous bone transplantation.