Friday, April 19, 2024
4/19/2024
Project Summary/Abstract Anal cancer incidence has been increasing, by four times over the last three decades. The incidence rate is unacceptably high among HIV-positive homosexual men, 131 per 100,000. The main challenge in anal cancer diagnosis and prevention is the lack of a standardized screening program. In vivo optical microscopy technologies such as confocal microscopy and optical coherence tomography have the potential to visualize cellular morphologic changes associated with the anal malignancy, but their clinical adaptation has been challenging. In this Trailblazer R21 project, we propose to develop a low-cost, scattering-based light sheet microscopy (sLSM) device that can aid accurate diagnosis of anal cancer, with the goal of ultimately reducing the anal cancer-associated morbidity and mortality. Our sLSM device will uniquely address the unmet needs in existing in vivo microscopy technologies (e.g., CM, OCT), simultaneously achieving i) high lateral resolution (1- 2 µm) for examining cellular nuclear features in the epithelium, ii) large FOV (~2.5 mm), iii) visualization of the entire epithelial thickness in a single image, and iv) low device cost (~$2,000). We expect that the sLSM device will reveal the key diagnostic cellular features in vivo, which will facilitate detection of early-stage anal malignancy and timely initiation of adequate treatment. The sLSM device will also guide the biopsy to malignant lesions with high sensitivity and specificity to increase the biopsy yield and reduce the morbidity and complication caused by the unnecessary biopsy of benign lesions. As the first step towards this goal, we will develop the prototype handheld sLSM device and evaluate the accuracy of diagnosing anal malignancy in the following aims: In Aim 1, we will develop a handheld sLSM probe for imaging anal mucosa. The sLSM device will provide cellular resolution in the epithelium and reveal architectural details in deeper regions in a single image. We will optimally design the illumination and detection optics to achieve the 1.4 µm lateral resolution over a 2.5-mm FOV, 6.5 ± 0.9 µm axial resolution for the epithelium, and 18 ± 8 µm axial resolution for the superficial lamina propria. In Aim 2, we will conduct a clinical study of imaging human anal tissues with the handheld sLSM device. One hundred anal biopsies concerning for anal cancer will be first imaged with the sLSM device. sLSM images will be compared with the corresponding histologic images to identify cellular and architectural features visualized in sLSM images and to develop the sLSM diagnostic criteria. The sensitivity and specificity of the sLSM for diagnosing anal malignancy will be evaluated. Automated image analysis algorithms will be developed to quantitatively evaluate the cellular and architectural features. In addition to providing a low-cost microscopy tool that aids accurate diagnosis of anal malignancy, the sLSM technology can be used for in vivo diagnosis of other cancers (e.g., cervical, oral, skin cancers), intra-operative assessment of the surgical margin, and quality assurance during the core needle biopsy.
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