Hemodynamics of Saline Flushing in Endoscopic Imaging of Partially Occluded Coronary Arteries.

PURPOSE: Intravascular endoscopy can aid in the diagnosis of coronary atherosclerosis by providing direct color images of coronary plaques. The procedure requires a blood-free optical path between the catheter and plaque, and achieving clearance safely remains an engineering challenge. In this study, we investigate the hemodynamics of saline flushing in partially occluded coronary arteries to advance the development of intravascular forward-imaging catheters that do not require balloon occlusion. METHODS: In-vitro experiments and CFD simulations are used to quantify the influence of plaque size, catheter stand-off distance, saline injection flowrate, and injection orientation on the time required to achieve blood clearance. RESULTS: Experiments and simulation of saline injection from a dual-lumen catheter demonstrated that flushing times increase both as injection flow rate (Reynolds number) decreases and as the catheter moves distally away from the plaque. CFD simulations demonstrated that successful flushing was achieved regardless of lumen axial orientation in a 95% occluded artery. Flushing time was also found to increase as plaque size decreases for a set injection flowrate, and a lower limit for injection flowrate was found to exist for each plaques size, below which clearance was not achieved. For the three occlusion sizes investigated (90, 95, 97% by area), successful occlusion was achieved in less than 1.2 s. Investigation of the pressure fields developed during injection, highlight that rapid clearance can be achieved while keeping the arterial overpressure to < 1 mmHg. CONCLUSIONS: A dual lumen saline injection catheter was shown to produce clearance safely and effectively in models of partially occluded coronary arteries. Clearance was achieved across a range of engineering and clinical parameters without the use of a balloon occlusion, providing development guideposts for a fluid injection system in forward-imaging coronary endoscopes.

A temperature-sensitive, high-adhesion medical tape: a comparative, single-blind clinical trial.

OBJECTIVE: Medical adhesives are used to secure wound care dressings and other critical devices to the skin. While high peel-strength adhesives provide more secure skin attachment, they are difficult to remove from the skin and are correlated with medical adhesive-related skin injuries (MARSI), including skin tears, and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to dressing or device dislodgement and further medical complications. METHOD: This paper reports on the clinical testing of a new, high-adhesion medical tape, ThermoTape (University of Washington, US), designed for low skin trauma upon release. ThermoTape was benchmarked with Tegaderm (3M, US) and Kind Removal Tape (KRT) (3M, US). All three tapes were applied to both the left and right forearm of healthy volunteers and were removed 24 hours later-the right arm without applying heat and the left arm by applying a heat pack for 30 seconds before removal. Tape wear, self-reported pain (0-10 scale) and skin redness 15 minutes after removal were recorded. RESULTS: This was a 53-subject comparative, single-blind clinical trial. There were clinically and statistically significant results supporting reduced pain during removal of ThermoTape with warming, with an average 58% decrease in pain, paired with a statistically significant 45% reduction in skin redness (p<0.01 for both values). In contrast, there were statistically insignificant differences in pain and redness for removal of Tegaderm and KRT with warming. ThermoTape after warming, in comparison with Tegaderm without warming, produced a reduced pain score of >1 on the 0-10 Wong-Baker/Face pain scale, which was statistically significant (p<0.01). CONCLUSION: These results provide compelling evidence that warming ThermoTape prior to removal can reduce pain and injury when compared with standard medical tapes. This could allow for stronger attachment of wound care dressings and critical medical devices while reducing cases of MARSI.

Large field-of-view short-wave infrared metalens for scanning fiber endoscopy.

Significance: The scanning fiber endoscope (SFE), an ultrasmall optical imaging device with a large field-of-view (FOV) for having a clear forward view into the interior of blood vessels, has great potential in the cardiovascular disease diagnosis and surgery assistance, which is one of the key applications for short-wave infrared biomedical imaging. The state-of-the-art SFE system uses a miniaturized refractive spherical lens doublet for beam projection. A metalens is a promising alternative that can be made much thinner and has fewer off-axis aberrations than its refractive counterpart. Aim: We demonstrate a transmissive metalens working at 1310 nm for a forward viewing endoscope to achieve a shorter device length and better resolution at large field angles. Approach: We optimize the metalens of the SFE system using Zemax, fabricate it using e-beam lithography, characterize its optical performances, and compare them with the simulations. Results: The SFE system has a resolution of ∼ 140 µ m at the center of field (imaging distance 15 mm), an FOV of ∼ 70 deg , and a depth-of-focus of ∼ 15 mm , which are comparable with a state-of-the-art refractive lens SFE. The use of the metalens reduces the length of the optical track from 1.2 to 0.86 mm. The resolution of our metalens-based SFE drops by less than a factor of 2 at the edge of the FOV, whereas the refractive lens counterpart has a ∼ 3 times resolution degradation. Conclusions: These results show the promise of integrating a metalens into an endoscope for device minimization and optical performance improvement.

Flexible fiber cholangioscope for detection of near-infrared fluorescence.

Video 1Flexible fiber cholangioscope for detection of near-infrared fluorescence.

The Scanning Fiber Endoscope: A Novel Surgical and High-Resolution Imaging Device for Intracranial Neurosurgery.

BACKGROUND: The scanning fiber endoscope (SFE) is a novel medical imaging device that has been used in various vascular beds as a form of angioscopy, as well as in tracts and duct systems for endoluminal imaging. Owing to its miniaturized form, high resolution, and flexibility, it has demonstrated success in imaging across a wide range of diagnostic applications. OBJECTIVE: To demonstrate, by performing a third ventriculostomy and visualizing the cranial nerves and brainstem anatomy, that, without modification, the SFE can be used through a transcranial approach in a therapeutic intraventricular neurosurgical application. METHODS: A 3.7 French SFE system was used without modification on a live porcine model to perform a third ventriculostomy and acquire high-resolution images of the animal's ventricular system, cranial nerves, and brainstem. A side-by-side comparison was made with one of the current standard-of-care rigid endoscopes as a context for size and image quality. RESULTS: High-resolution video-rate imaging was used to assist the successful, uncomplicated performance of a third ventriculostomy. High-resolution endoscopic images of the brainstem and cranial nerves were acquired. CONCLUSION: Although the SFE has been shown to be a superior device for imaging, here we demonstrate its first use as a potential therapeutic device in intracranial neurosurgery.

Deep-Learning-Based Real-Time and Automatic Target-to-Background Ratio Calculation in Fluorescence Endoscopy for Cancer Detection and Localization.

Esophageal adenocarcinoma (EAC) is a deadly cancer that is rising rapidly in incidence. The early detection of EAC with curative intervention greatly improves the prognoses of patients. A scanning fiber endoscope (SFE) using fluorescence-labeled peptides that bind rapidly to epidermal growth factor receptors showed a promising performance for early EAC detection. Target-to-background (T/B) ratios were calculated to quantify the fluorescence images for neoplasia lesion classification. This T/B calculation is generally based on lesion segmentation with the Chan-Vese algorithm, which may require hyperparameter adjustment when segmenting frames with different brightness and contrasts, which impedes automation to real-time video. Deep learning models are more robust to these changes, while accurate pixel-level segmentation ground truth is challenging to establish in the medical field. Since within our dataset the ground truth contained only a frame-level diagnosis, we proposed a computer-aided diagnosis (CAD) system to calculate the T/B ratio in real time. A two-step process using convolutional neural networks (CNNs) was developed to achieve automatic suspicious frame selection and lesion segmentation for T/B calculation. In the segmentation model training for Step 2, the lesion labels were generated with a manually tuned Chan-Vese algorithm using the labeled and predicted suspicious frames from Step 1. In Step 1, we designed and trained deep CNNs to select suspicious frames using a diverse and representative set of 3427 SFE images collected from 25 patient videos from two clinical trials. We tested the models on 1039 images from 10 different SFE patient videos and achieved a sensitivity of 96.4%, a specificity of 96.6%, a precision of 95.5%, and an area under the receiver operating characteristic curve of 0.989. In Step 2, 1006 frames containing suspicious lesions were used for training for fluorescence target segmentation. The segmentation models were tested on two clinical datasets with 100 SFE frames each and achieved mean intersection-over-union values of 0.89 and 0.88, respectively. The T/B ratio calculations based on our segmentation results were similar to the manually tuned Chan-Vese algorithm, which were 1.71 ± 0.22 and 1.72 ± 0.28, respectively, with a p-value of 0.872. With the graphic processing unit (GPU), the proposed two-step CAD system achieved 50 fps for frame selection and 15 fps for segmentation and T/B calculation, which showed that the frame rejection in Step 1 improved the diagnostic efficiency. This CAD system with T/B ratio as the real-time indicator is designed to guide biopsies and surgeries and to serve as a reliable second observer to localize and outline suspicious lesions highlighted by fluorescence probes topically applied in organs where cancer originates in the epithelia.

Prototype Development of a Temperature-Sensitive High-Adhesion Medical Tape to Reduce Medical-Adhesive-Related Skin Injury and Improve Quality of Care.

Medical adhesives are used to secure wound care dressings and other critical devices to the skin. Without means of safe removal, these stronger adhesives are difficult to painlessly remove from the skin and may cause medical-adhesive-related skin injuries (MARSI), including skin tears and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to device dislodgement and further medical complications. This paper outlines the development of a high-adhesion medical tape designed for low skin trauma upon release. By warming the skin-attached tape for 10-30 s, a significant loss in adhesion was achieved. A C14/C18 copolymer was developed and combined with a selected pressure-sensitive adhesive (PSA) material. The addition of 1% C14/C18 copolymer yielded the largest temperature-responsive drop in surface adhesion. The adhesive film was characterized using AFM, and distinct nanodomains were identified on the exterior surface of the PSA. Our optimized formulation yielded 67% drop in adhesion when warmed to 45 °C, perhaps due to melting nanodomains weakening the adhesive-substrate boundary layer. Pilot clinical testing resulted in a significant decrease in pain when a heat pack was used for removal, giving an average pain reduction of 66%.

Unifying theory of carotid plaque disruption based on structural phenotypes and forces expressed at the lumen/wall interface.

OBJECTIVES: To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption. MATERIALS AND METHODS: First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14). RESULTS: In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these 'rupture' phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption. CONCLUSIONS: Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.

Detection of Barrett's neoplasia with a near-infrared fluorescent heterodimeric peptide.

BACKGROUND: Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects. METHODS: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett's esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions. RESULTS: The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett's neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens. CONCLUSIONS: This "first-in-human" clinical study demonstrates the feasibility of detection of early Barrett's neoplasia using a NIR-labeled peptide heterodimer.

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.

Intensity-Mosaic: automatic panorama mosaicking of disordered images with insufficient features.

Purpose: Handling low-quality and few-feature medical images is a challenging task in automatic panorama mosaicking. Current mosaicking methods for disordered input images are based on feature point matching, whereas in this case intensity-based registration achieves better performance than feature-point registration methods. We propose a mosaicking method that enables the use of mutual information (MI) registration for mosaicking randomly ordered input images with insufficient features. Approach: Dimensionality reduction is used to map disordered input images into a low dimensional space. Based on the low dimensional representation, the image global correspondence can be recognized efficiently. For adjacent image pairs, we optimize the MI metric for registration. The panorama is then created after image blending. We demonstrate our method on relatively lower-cost handheld devices that acquire images from the retina in vivo, kidney ex vivo, and bladder phantom, all of which contain sparse features. Results: Our method is compared with three baselines: AutoStitch, "dimension reduction + SIFT," and "MI-Only." Our method compared to the first two feature-point based methods exhibits 1.25 (ex vivo microscope dataset) to two times (in vivo retina dataset) rate of mosaic completion, and MI-Only has the lowest complete rate among three datasets. When comparing the subsequent complete mosaics, our target registration errors can be 2.2 and 3.8 times reduced when using the microscopy and bladder phantom datasets. Conclusions: Using dimensional reduction increases the success rate of detecting adjacent images, which makes MI-based registration feasible and narrows the search range of MI optimization. To the best of our knowledge, this is the first mosaicking method that allows automatic stitching of disordered images with intensity-based alignment, which provides more robust and accurate results when there are insufficient features for classic mosaicking methods.

Implementation and evaluation of team science training for interdisciplinary teams in an engineering design program.

INTRODUCTION: Interdisciplinary academic teams perform better when competent in teamwork; however, there is a lack of best practices of how to introduce and facilitate the development of effective learning and functioning within these teams in academic environments. METHODS: To close this gap, we tailored, implemented, and evaluated team science training in the year-long Engineering Innovation in Health (EIH) program at the University of Washington (UW), a project-based course in which engineering students across several disciplines partner with health professionals to develop technical solutions to clinical and translational health challenges. EIH faculty from the UW College of Engineering and the Institute of Translational Health Sciences' (ITHS) Team Science Core codeveloped and delivered team science training sessions and evaluated their impact with biannual surveys. A student cohort was surveyed prior to the implementation of the team science trainings, which served as a baseline. RESULTS: Survey responses were compared within and between both cohorts (approximately 55 students each Fall Quarter and 30 students each Spring Quarter). Statistically significant improvements in measures of self-efficacy and interpersonal team climate (i.e., psychological safety) were observed within and between teams. CONCLUSIONS: Tailored team science training provided to student-professional teams resulted in measurable improvements in self-efficacy and interpersonal climate both of which are crucial for teamwork and intellectual risk taking. Future research is needed to determine long-term impacts of course participation on individual and team outcomes (e.g., patents, start-ups). Additionally, adaptability of this model to clinical and translational research teams in alternate formats and settings should be tested.

Optimization Study of the Hemodynamics of Saline Flushing in Endoscopic Imaging of Chronic Total Occlusions (CTOs).

PURPOSE: In this study, in vitro experiments and computational fluid dynamic (CFD) simulations are used to expand the understand of the physics of saline flushing of a blocked artery to enable optical imaging. This process involves saline injection, mixing with blood, and advection of the mixture away from the region of interest to provide a clear optical path for imaging. METHODS: CFD simulations are used as a rapid turn-around tool for the evolutionary design process of an endovascular catheter that combines imaging forward-viewing element with saline flushing lumens. RESULTS: A novel design and control technique is developed that provides the method to regulate the pressure in a blocked artery during saline flushing, so only small deviations from physiological pressure values are exerted on the damaged artery wall at any time, minimizing risk of rupture. In vitro experiments demonstrate the optical clearing process in phantoms simulating chronic total occlusions (CTOs) in coronary arteries with an opaque blood surrogate being removed by saline flushing. With the CFD compared by the experiments, parametric analyses of artery diameter and curvature, and flushing lumen diameter size were conducted to understand their impact on flushing times and pressures. Different plaque morphologies were studied to explore the feasibility of saline flushing in different CTO conditions. CONCLUSIONS: A new catheter design is demonstrated to safely and effectively produce saline flushing, leading to a clear optical imaging field, and an improved technique is outlined that overcomes some practical challenges and limitations commonly encountered in angioscopy.

Intraductal Tissue Sampling Device Designed for the Biliary Tract.

Clinical sampling of tissue that is read by a pathologist is currently the gold standard for making a disease diagnosis, but the few minimally invasive techniques available for small duct biopsies have low sensitivity, increasing the likelihood of false negative diagnoses. We propose a novel biopsy device designed to accurately sample tissue in a biliary stricture under fluoroscopy or endoscopic guidance. The device consists of thin blades organized around the circumference of a cylinder that are deployed into a cutting annulus capable of comprehensively sampling tissue from a stricture. A parametric study of the device performance was done using finite element analysis; this includes the blade deployment under combined axial compression and torsion followed by an axial 'cutting' step. The clinical feasibility of the device is determined by considering maximum deployment forces, the radial expansion achieved and the cutting stiffness. We find practical parameters for the device operation to be an overall length of 10 mm and a diameter of 3.5 mm for a [Formula: see text] blade thickness, which allow the device to be safely deployed with a force of 10N and achieve an expansion over 3x its original diameter. A model device was fabricated with these parameters and a [Formula: see text] thickness out of a NiTi superalloy and tested to validate the performance. The device showed strong agreement with an equivalent numerical model, reaching a peak force within 2% of that predicted numerically and fully recovering after compression to 20% of its length. Clinical and Translational Impact Statement -This pre-clinical research conceptually demonstrates a novel expandable device to biopsy tissue in narrow strictures during an ERCP procedure. It can greatly improve diagnostic tissue yield compared to existing methods.

Optical pH measurement system using a single fluorescent dye for assessing susceptibility to dental caries (Erratum).

The erratum corrects a grant number listed in Acknowledgments section of the original article.

Miniature gastrointestinal endoscopy: Now and the future.

Since its original application, gastrointestinal (GI) endoscopy has undergone many innovative transformations aimed at expanding the scope, safety, accuracy, acceptability and cost-effectiveness of this area of clinical practice. One method of achieving this has been to reduce the caliber of endoscopic devices. We propose the collective term "Miniature GI Endoscopy". In this Opinion Review, the innovations in this field are explored and discussed. The progress and clinical use of the three main areas of miniature GI endoscopy (ultrathin endoscopy, wireless endoscopy and scanning fiber endoscopy) are described. The opportunities presented by these technologies are set out in a clinical context, as are their current limitations. Many of the positive aspects of miniature endoscopy are clear, in that smaller devices provide access to potentially all of the alimentary canal, while conferring high patient acceptability. This must be balanced with the costs of new technologies and recognition of device specific challenges. Perspectives on future application are also considered and the efforts being made to bring new innovations to a clinical platform are outlined. Current devices demonstrate that miniature GI endoscopy has a valuable place in investigation of symptoms, therapeutic intervention and screening. Newer technologies give promise that the potential for enhancing the investigation and management of GI complaints is significant.