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.

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.

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%.

Near-infrared multispectral endoscopic imaging of deep artificial interproximal lesions in extracted teeth.

BACKGROUND AND OBJECTIVE: A safer alternative method to radiographic imaging is needed. We present a multispectral near-infrared scanning fiber endoscope (nirSFE) for dental imaging which is designed to be the smallest imaging probe with near-infrared (NIR) imaging (1200-2000 nm). MATERIALS AND METHODS: The prototype nirSFE is designed for wide-field forward viewing of scanned laser illumination at 1310, 1460, or 1550 nm. Artificial lesions with varying sizes and locations were prepared on proximal surfaces of extracted human teeth to examine capability and limitation of this new dental imaging modality. Nineteen artificial interproximal lesions and several natural occlusal lesions on extracted teeth were imaged with nirSFE, OCT, and microCT. RESULTS: Our nirSFE system has a flexible shaft as well as a probe tip with diameter of 1.6 mm and a rigid length of 9 mm. The small form factor and multispectral NIR imaging capability enables multiple viewing angles and reliable detection of lesions that can extend into the dentin. Among nineteen artificial interproximal lesions, the nirSFE reflectance imaging operating at 1460-nm and OCT operating at 1310-nm scanned illumination exhibited high sensitivity for interproximal lesions that were closer to occlusal surface. Diagnosis from a non-blinded trained user by looking at real-time occlusal-side nirSFE videos indicate true positive rate of 78.9%. There were no false positives. CONCLUSIONS: This study demonstrates that nirSFE may be used for detecting occlusal lesions and interproximal lesions located less than 4 mm under the occlusal surface. Major advantages of this imaging system include multiple viewing angles due to flexibility and small form factor, as well as the ability to capture real-time video. The multispectral nirSFE has the potential to be employed as a low-cost dental camera for detecting dental lesions without exposure to ionizing radiation. Lasers Surg. Med. 51:459-465, 2019. © 2019 Wiley Periodicals, Inc.

Near-Infrared Imaging of Artificial Enamel Caries Lesions with a Scanning Fiber Endoscope.

Several studies have shown that near-infrared imaging has great potential for the detection of dental caries lesions. A miniature scanning fiber endoscope (SFE) operating at near-infrared (NIR) wavelengths was developed and used in this study to test whether the device could be used to discriminate demineralized enamel from sound enamel. Varying depths of artificial enamel caries lesions were prepared on 20 bovine blocks with smooth enamel surfaces. Samples were imaged with a SFE operating in the reflectance mode at 1310-nm and 1460-nm in both wet and dry conditions. The measurements acquired by the SFE operating at 1460-nm show significant difference between the sound and the demineralized enamel. There was a moderate positive correlation between the SFE measurements and micro-CT measurements, and the NIR SFE was able to detect the presence of demineralization with high sensitivity (0.96) and specificity (0.85). This study demonstrates that the NIR SFE can be used to detect early demineralization from sound enamel. In addition, the NIR SFE can differentiate varying severities of demineralization. With its very small form factor and maneuverability, the NIR SFE should allow clinicians to easily image teeth from multiple viewing angles in real-time.

Three-dimensional measurement of small inner surface profiles using feature-based 3-D panoramic registration.

Rapid development in the performance of sophisticated optical components, digital image sensors, and computer abilities along with decreasing costs has enabled three-dimensional (3-D) optical measurement to replace more traditional methods in manufacturing and quality control. The advantages of 3-D optical measurement, such as noncontact, high accuracy, rapid operation, and the ability for automation, are extremely valuable for inline manufacturing. However, most of the current optical approaches are eligible for exterior instead of internal surfaces of machined parts. A 3-D optical measurement approach is proposed based on machine vision for the 3-D profile measurement of tiny complex internal surfaces, such as internally threaded holes. To capture the full topographic extent (peak to valley) of threads, a side-view commercial rigid scope is used to collect images at known camera positions and orientations. A 3-D point cloud is generated with multiview stereo vision using linear motion of the test piece, which is repeated by a rotation to form additional point clouds. Registration of these point clouds into a complete reconstruction uses a proposed automated feature-based 3-D registration algorithm. The resulting 3-D reconstruction is compared with x-ray computed tomography to validate the feasibility of our proposed method for future robotically driven industrial 3-D inspection.

Run-to-Run Optimization Control Within Exact Inverse Framework for Scan Tracking.

A run-to-run optimization controller uses a reduced set of measurement parameters, in comparison to more general feedback controllers, to converge to the best control point for a repetitive process. A new run-to-run optimization controller is presented for the scanning fiber device used for image acquisition and display. This controller utilizes very sparse measurements to estimate a system energy measure and updates the input parameterizations iteratively within a feedforward with exact-inversion framework. Analysis, simulation, and experimental investigations on the scanning fiber device demonstrate improved scan accuracy over previous methods and automatic controller adaptation to changing operating temperature. A specific application example and quantitative error analyses are provided of a scanning fiber endoscope that maintains high image quality continuously across a 20 °C temperature rise without interruption of the 56 Hz video.

Bound constrained bundle adjustment for reliable 3D reconstruction.

Bundle adjustment (BA) is a common estimation algorithm that is widely used in machine vision as the last step in a feature-based three-dimensional (3D) reconstruction algorithm. BA is essentially a non-convex non-linear least-square problem that can simultaneously solve the 3D coordinates of all the feature points describing the scene geometry, as well as the parameters of the camera. The conventional BA takes a parameter either as a fixed value or as an unconstrained variable based on whether the parameter is known or not. In cases where the known parameters are inaccurate but constrained in a range, conventional BA results in an incorrect 3D reconstruction by using these parameters as fixed values. On the other hand, these inaccurate parameters can be treated as unknown variables, but this does not exploit the knowledge of the constraints, and the resulting reconstruction can be erroneous since the BA optimization halts at a dramatically incorrect local minimum due to its non-convexity. In many practical 3D reconstruction applications, unknown variables with range constraints are usually available, such as a measurement with a range of uncertainty or a bounded estimate. Thus to better utilize these pre-known, constrained, but inaccurate parameters, a bound constrained bundle adjustment (BCBA) algorithm is proposed, developed and tested in this study. A scanning fiber endoscope (the camera) is used to capture a sequence of images above a surgery phantom (the object) of known geometry. 3D virtual models are reconstructed based on these images and then compared with the ground truth. The experimental results demonstrate BCBA can achieve a more reliable, rapid, and accurate 3D reconstruction than conventional bundle adjustment.

Rapid scanning catheterscope for expanded forward-view volumetric imaging with optical coherence tomography.

We demonstrate a novel catheterscope, based on scanning fiber endoscopy, for volumetric imaging with optical coherence tomography (OCT), which possesses a high resonance frequency (>2 kHz) and a small outer diameter (OD) (1.07 mm). Our design is the fastest volumetric-scanning, forward-viewing catheterscope for OCT, and the scanning package has the smallest OD of any such OCT package published to date. Using a proof-of-operation catheterscope with commercial lenses, we demonstrate high-quality in vivo and ex vivo volumetric imaging and extend the 1.1 mm diameter field of view more than 200-fold by mosaicking. Due to its small OD, short rigid tip length, and fast scan rate, this scope is the leading candidate design to enable early detection and staging of bladder cancer during flexible white light cystoscopy.

Advances in engineering of high contrast CARS imaging endoscopes.

The translation of CARS imaging towards real time, high resolution, chemically selective endoscopic tissue imaging applications is limited by a lack of sensitivity in CARS scanning probes sufficiently small for incorporation into endoscopes. We have developed here a custom double clad fiber (DCF)-based CARS probe which is designed to suppress the contaminant Four-Wave-Mixing (FWM) background generated within the fiber and integrated it into a fiber based scanning probe head of a few millimeters in diameter. The DCF includes a large mode area (LMA) core as a first means of reducing FWM generation by ~3 dB compared to commercially available, step-index single mode fibers. A micro-fabricated miniature optical filter (MOF) was grown on the distal end of the DCF to block the remaining FWM background from reaching the sample. The resulting probe was used to demonstrate high contrast images of polystyrene beads in the forward-CARS configuration with > 10 dB suppression of the FWM background. In epi-CARS geometry, images exhibited lower contrast due to the leakage of MOF-reflected FWM from the fiber core. Improvements concepts for the fiber probe are proposed for high contrast epi-CARS imaging to enable endoscopic implementation in clinical tissue assessment contexts, particularly in the early detection of endoluminal cancers and in tumor margin assessment.

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.

Experimental and theoretical analysis for improved microscope design of optical projection tomographic microscopy.

We present theoretical and experimental results of axial displacement of objects relative to a fixed condenser focal plane (FP) in optical projection tomographic microscopy (OPTM). OPTM produces three-dimensional, reconstructed images of single cells from two-dimensional projections. The cell rotates in a microcapillary to acquire projections from different perspectives where the objective FP is scanned through the cell while the condenser FP remains fixed at the center of the microcapillary. This work uses a combination of experimental and theoretical methods to improve the OPTM instrument design.

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.

Computational modeling of optical projection tomographic microscopy using the finite difference time domain method.

We present a method for modeling image formation in optical projection tomographic microscopy (OPTM) using high numerical aperture (NA) condensers and objectives. Similar to techniques used in computed tomography, OPTM produces three-dimensional, reconstructed images of single cells from two-dimensional projections. The model is capable of simulating axial scanning of a microscope objective to produce projections, which are reconstructed using filtered backprojection. Simulation of optical scattering in transmission optical microscopy is designed to analyze all aspects of OPTM image formation, such as degree of specimen staining, refractive-index matching, and objective scanning. In this preliminary work, a set of simulations is performed to examine the effect of changing the condenser NA, objective scan range, and complex refractive index on the final reconstruction of a microshell with an outer radius of 1.5 µm and an inner radius of 0.9 µm. The model lays the groundwork for optimizing OPTM imaging parameters and triaging efforts to further improve the overall system design. As the model is expanded in the future, it will be used to simulate a more realistic cell, which could lead to even greater impact.

Design and preliminary study of custom laser scanning cystoscope for automated bladder surveillance.

BACKGROUND: The current gold standard of bladder cancer surveillance, endoscopic visualization, is manually manipulated and still has significant room for improvement in performance and controls. METHODS: This paper reports our developments toward automated bladder surveillance that employs a shape memory alloy-based machine-controlled scanning mechanism. In conjunction with the electro-mechanical advances, we use modified commercial post-processing computer vision software capable of converting cystoscopic video of the bladder into stitched panoramas. RESULTS: Experimental results conducted on a synthetic bladder demonstrate that this computer-aided scanning tool can help 82% of the entire bladder surface being scanned. Although the panoramic stitching algorithm increases the field of view and generates reasonable results in many cases, some image matching failures result in incompleteness in its full panoramic reconstruction. CONCLUSION: Our current study ensures that the automated steering mechanism can follow the desired trajectory to scan the surface of the bladder but must be improved. The current reconstruction algorithm needs further modification. Our methodology may constitute a first step in suggesting a new automated and computer-aided bladder surveillance system.

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.

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.

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.