Introduction
Excessive pain during medical procedures is a widespread problem but is especially problematic during daily wound care of patients with severe burn injuries.
Methods
Burn patients report ...35–50% reductions in procedural pain while in a distracting immersive virtual reality, and fMRI brain scans show associated reductions in pain-related brain activity during VR. VR distraction appears to be most effective for patients with the highest pain intensity levels. VR is thought to reduce pain by directing patients’ attention into the virtual world, leaving less attention available to process incoming neural signals from pain receptors.
Conclusions
We review evidence from clinical and laboratory research studies exploring Virtual Reality analgesia, concentrating primarily on the work ongoing within our group. We briefly describe how VR pain distraction systems have been tailored to the unique needs of burn patients to date, and speculate about how VR systems could be tailored to the needs of other patient populations in the future.
We present a small, lightweight two-photon fiberscope and demonstrate its suitability for functional imaging in the intact brain. Our device consists of a hollow-core photonic crystal fiber for ...efficient delivery of near-IR femtosecond laser pulses, a spiral fiber-scanner for resonant beam steering, and a gradient-index lens system for fluorescence excitation, dichroic beam splitting, and signal collection. Fluorescence light is remotely detected using a standard photomultiplier tube. All optical components have 1 mm dimensions and the microscope's headpiece weighs only 0.6 grams. The instrument achieves micrometer resolution at frame rates of typically 25 Hz with a field-of-view of up to 200 microns. We demonstrate functional imaging of calcium signals in Purkinje cell dendrites in the cerebellum of anesthetized rats. The microscope will be easily portable by a rat or mouse and thus should enable functional imaging in freely behaving animals.
Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have ...sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM).
5-Aminolevulinic acid–induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared.
SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching.
SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes.
•The scanning fiber endoscope (SFE) was developed and optimized for PpIX detection.•Unlike the OPMI, the SFE can visualize PpIX in individual tumor cells.•SFE has significantly higher PpIX fluorescence detection sensitivity than OPMI.•We mapped PpIX accumulation in glioma border and normal mouse brain regions.•Tumor PpIX bleached fast under OPMI, but imaging time increased >6 times with SFE.
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In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable ...histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.
Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies.
LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease (
= .042), and 61.3% for patients with stage III/IV disease (
= .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%).
Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.
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%.
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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.
For daily burn wound care and therapeutic physical therapy skin stretching procedures, powerful pain medications alone are often inadequate. This feasibility study provides the first evidence that ...entering an immersive virtual environment using very inexpensive (∼$400) wide field of view Oculus Rift Virtual Reality (VR) goggles can elicit a strong illusion of presence and reduce pain during VR. The patient was an 11-year-old male with severe electrical and flash burns on his head, shoulders, arms, and feet (36 percent total body surface area (TBSA), 27 percent TBSA were third-degree burns). He spent one 20-minute occupational therapy session with no VR, one with VR on day 2, and a final session with no VR on day 3. His rating of pain intensity during therapy dropped from severely painful during no VR to moderately painful during VR. Pain unpleasantness dropped from moderately unpleasant during no VR to mildly unpleasant during VR. He reported going "completely inside the computer generated world", and had more fun during VR. Results are consistent with a growing literature showing reductions in pain during VR. Although case studies are scientifically inconclusive by nature, these preliminary results suggest that the Oculus Rift VR goggles merit more attention as a potential treatment for acute procedural pain of burn patients. Availability of inexpensive but highly immersive VR goggles would significantly improve cost effectiveness and increase dissemination of VR pain distraction, making VR available to many more patients, potentially even at home, for pain control as well as a wide range of other VR therapy applications. This is the first clinical data on PubMed to show the use of Oculus Rift for any medical application.
Flexible cystoscopy is frequently performed for recurrent bladder cancer surveillance, making it the most expensive cancer to treat over the patient's lifetime. An automated bladder surveillance ...system is being developed to robotically scan the bladder surface using an ultrathin and highly flexible endoscope. Such a system would allow cystoscopic procedures to be overseen by technical staff while urologists could review cystoscopic video postoperatively. In this paper, we demonstrate a method for reconstructing the surface of the whole bladder from endoscopic video using structure from motion. Video is acquired from a custom ultrathin and highly flexible endoscope that can retroflex to image the entire internal surface of the bladder. Selected frames are subsequently stitched into a mosaic and mapped to a reconstructed surface, creating a 3-D surface model of the bladder that can be expediently reviewed. Our software was tested on endoscopic video of an excised pig bladder. The resulting reconstruction possessed a projection error of 1.66 pixels on average and covered 99.6% of the bladder surface area.
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.
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