Optical coherence tomography (OCT) is an established technique that provides noninvasive, volumetric, and real-time in vivo images of tissue microstructure.¹ One longstanding criticism of traditional OCT images (i.e., B-scans), however, is that they only provide morphological information about the tissue.^2,3 Quantitative analysis of tissue properties would facilitate more accurate differentiation between diseased tissue and normal tissue. Several researchers have proposed that the optical attenuation coefficient (AC), which measures how quickly incident light is attenuated when passing through a medium, may enable such analysis. Indeed, analysis of the AC has been used for quantitative assessment and differentiation of several tissue types:⁴ for example, quantification of the AC from OCT data enables in vivo diagnostic applications, such as imaging of atherosclerotic plaques,³ assessment of glaucoma,⁵ identification of axillary lymph nodes,⁶ differentiation between normal and cancerous tissue in the bladder⁷ and colon,⁸ and imaging of the cerebral cortex after stroke.⁹ In addition, measurement of the AC also serves to assess vascularity in human burn scars¹⁰ and development of acne scars,¹¹ as well as to monitor the effect of photodynamic therapy in skin lesions.¹²

Appropriate testing platforms are essential to characterize, optimize, and validate new clinical systems and procedures.^1,2 The testing of devices and procedures can be performed on a variety of platforms, including calibrated test targets, ex vivo human or animal tissues, in vivo animal models, tissue-mimicking phantoms, and human subjects. In the early stages of device development, tissue phantoms are often preferred to the alternatives of ex vivo tissues and animal models due to their notable advantages of being low cost, easily accessible, non-perishable, free of ethical or legal considerations, and most important, designed with known properties, allowing for repeated and reliable assessment of instruments. As a result, creating realistic tissue substitutes for biomedical applications has been the focus of many ongoing research efforts.

Background Bladder cancer is the 10^th most common malignancy and carries the highest treatment cost among all cancers. The elevated cost stems from its high recurrence rate, which necessitates frequent surveillance. White light cystoscopy (WLC), the standard of care surveillance tool to examine the bladder for lesions, has limited sensitivity for early-stage bladder cancer. Blue light cystoscopy (BLC) utilizes a fluorescent dye to induce contrast in cancerous regions, improving the sensitivity of detection by 43%. Nevertheless, the added equipment cost and lengthy dwell time of the dye limits the availability of BLC. Methods Here, we report the first demonstration of digital staining as a promising strategy to convert WLC images collected with standard-of-care clinical equipment into accurate BLC-like images, providing enhanced sensitivity for WLC without the associated labor or equipment cost. Results By introducing key pre-processing steps to circumvent color and brightness variations in clinical datasets needed for successful model performance, the results achieve a staining accuracy of 80.58% and show excellent qualitative and quantitative agreement of the digitally stained WLC (dsWLC) images with ground truth BLC images, including color consistency. Conclusions In short, dsWLC can affordably provide the fluorescent contrast needed to improve the detection sensitivity of bladder cancer, thereby increasing the accessibility of BLC contrast for bladder cancer surveillance. The broader implications of this work suggest digital staining is a cost-effective alternative to contrast-based endoscopy for other clinical scenarios outside of urology that can democratize access to better healthcare.

Borrelia burgdorferi sensu lato family of spirochetes causes Lyme disease (LD) in animals and humans. As geographic territory of ticks expands across the globe, surveillance measures are needed to measure transmission rates and provide early risk testing of suspected bites. The current standard testing of LD uses an indirect two-step serological assay that detects host immune reactivity. Early detection remains a challenge because the host antibody response develops several weeks after infection. A microneedle (MN) device was developed to sample interstitial fluid (ISF) and capture spirochetes directly from skin. After sampling, the MN patch is easily dissolved in water or TE buffer, and the presence of spirochete DNA is detected by PCR. Performance was tested by spiking porcine ear skin with inactivated Borrelia burgdorferi, which had an approximate recovery of 80% of spirochetes. With further development, this simple direct PCR method could be a transformative approach for early detection of the causative agent of Lyme disease and enable rapid treatment to patients when infection is early, and numbers of systemic spirochetes are low.

Blue light cystoscopy (BLC) has been demonstrated to detect bladder tumors with better sensitivity than white light cystoscopy (WLC); however, the use of BLC is limited to the operating room. In this study, we aim to bring BLC to the clinic by transforming WLC frames into digitally-stained BLC-like frames. We collected region-matched WLC and BLC videos from TURBT procedures and generated BLC-like frames, using WLC frames as input and the matched BLC frames as target. We will discuss the staining performances with perfectly registered WLC-BLC datasets, as well as WLC and BLC video clips collected with commercial clinical systems.

Bladder cancer is 10 ^th most common malignancy and carries the highest treatment cost among all cancers. The high cost of bladder cancer treatment stems from its high recurrence rate, which necessitates frequent surveillance. White light cystoscopy (WLC), the standard of care surveillance tool to examine the bladder for lesions, has limited sensitivity for early-stage bladder cancer. Blue light cystoscopy (BLC) utilizes a fluorescent dye to induce contrast in cancerous regions, improving the sensitivity of detection by 43%. Nevertheless, the added cost and lengthy administration time of the dye limits the availability of BLC for surveillance. Here, we report the first demonstration of digital staining on clinical endoscopy videos collected with standard-of-care clinical equipment to convert WLC images to accurate BLC-like images. We introduce key pre-processing steps to circumvent color and brightness variations in clinical datasets needed for successful model performance; the results show excellent qualitative and quantitative agreement of the digitally stained WLC (dsWLC) images with ground truth BLC images as measured through staining accuracy analysis and color consistency assessment. In short, dsWLC can provide the fluorescent contrast needed to improve the detection sensitivity of bladder cancer, thereby increasing the accessibility of BLC contrast for bladder cancer surveillance use without the cost and time burden associated with the dye and specialized equipment.