CoreView: fresh tissue biopsy assessment at the bedside using a millifluidic imaging chip.

Minimally invasive core needle biopsies for medical diagnoses have become increasingly common for many diseases. Although tissue cores can yield more diagnostic information than fine needle biopsies and cytologic evaluations, there is no rapid assessment at the point-of-care for intact tissue cores that is low-cost and non-destructive to the biopsy. We have developed a proof-of-concept 3D printed millifluidic histopathology lab-on-a-chip device to automatically handle, process, and image fresh core needle biopsies. This device, named CoreView, includes modules for biopsy removal from the acquisition tool, transport, staining and rinsing, imaging, segmentation, and multiplexed storage. Reliable removal from side-cutting needles and bidirectional fluid transport of core needle biopsies of five tissue types has been demonstrated with 0.5 mm positioning accuracy. Automation is aided by a MATLAB-based biopsy tracking algorithm that can detect the location of tissue and air bubbles in the channels of the millifluidic chip. With current and emerging optical imaging technologies, CoreView can be used for a rapid adequacy test at the point-of-care for tissue identification as well as glomeruli counting in renal core needle biopsies.

O-pH: Optical pH Monitor to Measure Dental Biofilm Acidity and Assist in Enamel Health Monitoring.

OBJECTIVE: Bacteria in the dental biofilm produceacid after consumption of carbohydrates which if left unmonitored leads to caries formation. We present O-pH, a device that can measure dental biofilm acidity and provide quantitative feedback to assist in oral health monitoring. METHOD: O-pH utilizes a ratiometric pH sensing method by capturing fluorescence of Sodium Fluorescein, an FDA approved chemical dye. The device was calibrated to a lab pH meter using buffered fluorescein solution with a correlation coefficient of 0.97. The calibration was further verified in vitro on additional buffered solution, artificial, and extracted teeth. An in vivo study on 30 pediatric subjects was performed to measure pH before (rest pH) and after (drop pH) a sugar rinse, and the resultant difference in pH (diff pH) was calculated. The study enrolled subjects with low (Post-Cleaning) and heavy (Pre-Cleaning) biofilm load, having both unhealthy/healthy surfaces. Further, we modified point-based O-pH to an image-based device using a multimode-scanning fiber endoscope (mm-SFE) and tested in vivo on one subject. RESULTS AND CONCLUSION: We found significant difference between Post-Cleaning and Pre-Cleaning group using drop pH and diff pH. Additionally, in Pre-Cleaning group, the rest and drop pH is lower at the caries surfaces compared to healthy surfaces. Similar trend was not noticed in the Post-Cleaning group. mm-SFE pH scope recorded image-based pH heatmap of a subject with an average diff pH of 1.5. SIGNIFICANCE: This work builds an optical pH prototype and presents a pioneering study for non-invasively measuring pH of dental biofilm clinically.

Cost-Efficient Video Synthesis and Evaluation for Development of Virtual 3D Endoscopy.

OBJECTIVE: 3D reconstruction of the shape and texture of hollow organs captured by endoscopy is important for the diagnosis and surveillance of early and recurrent cancers. Better evaluation of 3D reconstruction pipelines developed for such applications requires easy access to extensive datasets and associated ground truths, cost-efficient and scalable simulations of a range of possible clinical scenarios, and more reliable and insightful metrics to assess performance. METHODS: We present a computer-aided simulation platform for cost-effective synthesis of monocular endoscope videos and corresponding ground truths that mimic a range of potential settings and situations one might encounter during acquisition of clinical endoscopy videos. Using cystoscopy of the bladder as model case, we generated an extensive dataset comprising several synthesized videos of a bladder phantom. We then introduce a novel evaluation procedure to reliably assess an individual 3D reconstruction pipeline or to compare different pipelines. RESULTS: To illustrate the use of the proposed platform and evaluation procedure, we use the aforementioned dataset and ground truths to evaluate a proprietary 3D reconstruction pipeline (CYSTO3D) for bladder cystoscopy videos and compared it with a general-purpose 3D reconstruction pipeline (COLMAP). The evaluation results provide insight into the suggested clinical acquisition protocol and several potential areas for refinement of the pipeline to improve future performance. CONCLUSION: Our work proposes an endoscope video synthesis and reconstruction evaluation toolset and presents experimental results that illustrate usage of the toolset to efficiently assess performance and reveal possible problems of any given 3D reconstruction pipeline, to compare different pipelines, and to provide technically or clinically actionable insights.

Optical Characterization of Neurosurgical Operating Microscopes: Quantitative Fluorescence and Assessment of PpIX Photobleaching.

Protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) is increasingly used as a fluorescent marker for fluorescence-guided resection of malignant gliomas. Understanding how the properties of the excitation light source and PpIX fluorescence interact with the surgical microscope is critical for effective use of the fluorescence-guided tumor resection technique. In this study, we performed a detailed assessment of the intensity of the emitted blue light and white light and the light beam profile of clinical grade operating microscopes used for PpIX visualization. These measurements revealed both recognized fluorescence photobleaching limitations and unrecognized limitations that may alter quantitative observations of PpIX fluorescence obtained with the operating microscope with potential impact on research and clinical uses. We also evaluated the optical properties of a photostable fluorescent standard with an excitation-emission profile similar to PpIX. In addition, we measured the time-dependent dynamics of 5-ALA-induced PpIX fluorescence in an animal glioma model. Finally, we developed a ratiometric method for quantification of the PpIX fluorescence that uses the photostable fluorescent standard to normalize PpIX fluorescence intensity. This method increases accuracy and allows reproducible and direct comparability of the measurements from multiple samples.

New endoscopic and cytologic tools for cancer surveillance in the digestive tract.

Cancer surveillance is an increasing part of everyday practice in gastrointestinal Endoscopy due to the identification of high-risk groups from genetic and biomarker testing, genealogic and epidemiologic studies, and the increasing number of cancer survivors. An efficient surveillance program requires a cost-effective means for image-guided cancer detection and biopsy. A laser-based tethered-capsule endoscope with enhanced spectral imaging is introduced for unsedated surveillance of the lower esophagus. An ultrathin version of this same endoscope technology provides a 1.2-mm guidewire with imaging capability and cannula-style tools are proposed for image-guided biopsy. Advanced three-dimensional cell visualization techniques are described for increasing the sensitivity of early cancer diagnosis from hematoxylin-stained cells sampled from the pancreatic and biliary ducts.

Tethered capsule endoscopy, a low-cost and high-performance alternative technology for the screening of esophageal cancer and Barrett's esophagus.

Esophageal cancer is currently the fastest growing cancer in the United States. To help combat the recent rise in morbidity, our laboratory has developed a low-cost tethered capsule endoscope system (TCE) aimed at improving early detection of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.6 mm O.D.) which fits into 6.4-mm easy-to-swallow capsule at the distal tip. The tethered portion contains a single mode optical fiber multiplexed to three laser diodes at the proximal end. This design offers two main advantages over current endoscope technology. First, because of its small size, the TCE can be swallowed with minimal patient discomfort, thereby obviating sedation. Second, by imaging via directed laser light, the TCE is strategically positioned to employ several burgeoning laser-based diagnostic technologies, such as narrow-band, hyperspectral, and fluorescence imaging. It is believed that the combination of such imaging techniques with novel biomarkers of dysplasia will greatly assist in identifying precancerous conditions such as Barrett's esophagus (BE). As the probe is swallowed, the fiber scanner captures high resolution, wide-field color images of the gastroesophageal junction (500 lines at 0.05-mm resolution) currently at 15-Hz frame rate. Video images are recorded as the capsule is slowly retracted by its tether. Accompanying software generates panoramic images from the video output by mosaicing individual frames to aid in pattern recognition. This initial report describes the rationale for the unique TCE system design, results from preliminary testing in vitro and in vivo, and discussion on the merits of this new platform technology as a basis for developing a low-cost screening program for esophageal cancer.