Browsing by Author "Kortum, Alex"

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    Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus–Associated Anal Precancer in Persons Living With HIV
    (Wolters Kluwer, 2023) Brenes, David; Kortum, Alex; Carns, Jennifer; Mutetwa, Tinaye; Schwarz, Richard; Liu, Yuxin; Sigel, Keith; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Gaisa, Michael; Chiao, Elizabeth
    INTRODUCTION: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. METHODS: The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wt/vol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2+ for each HRME image. RESULTS: The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2+. At the AIN 2+ probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 (P = 0.68) and specificity of 0.60 (P = 0.48) when using histopathology as the gold standard. DISCUSSION: When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2+ treatment options by enabling real-time diagnosis.
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    Design and Evaluation of ScanCap: A Low-Cost, Reusable Tethered Capsule Endoscope with Blue-Green Illumination Imaging for Unsedated Screening and Early Detection of Barrett’s Esophagus
    (MDPI, 2024) Hicheri, Cheima; Azimuddin, Ahad M.; Kortum, Alex; Bailey, Joseph; Tang, Yubo; Schwarz, Richard A.; Rosen, Daniel; Jain, Shilpa; Mansour, Nabil M.; Groth, Shawn; Vasavada, Shaleen; Rao, Ashwin; Maliga, Adrianna; Gallego, Leslie; Carns, Jennifer; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca; Rice360 Institute for Global Health Technologies
    Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett’s Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett’s with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE in unsedated patients. The tethered capsule (12.8 mm diameter, 35.5 mm length) contains a color camera and rotating mirror and is designed to be swallowed; images are collected as the capsule is retracted manually via the tether. The tether provides electrical power and illumination at wavelengths of 415 nm and 565 nm and transmits data from the camera to a tablet. The ScanCap prototype capsule was used to image the oral mucosa in normal volunteers and ex vivo esophageal resections; images were compared to those obtained using an Olympus CV-180 endoscope. Images of superficial capillaries in intact oral mucosa were clearly visible in ScanCap images. Diagnostically relevant features of BE, including irregular Z-lines, distorted mucosa, and dilated vasculature, were clearly visible in ScanCap images of ex vivo esophageal specimens.
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    Development of a multimodal mobile colposcope for real-time cervical cancer detection
    (Optica Publishing Group, 2022) Coole, Jackson B.; Brenes, David; Possati-Resende, Júlio César; Antoniazzi, Márcio; Fonseca, Bruno de Oliveira; Maker, Yajur; Kortum, Alex; Vohra, Imran S.; Schwarz, Richard A.; Carns, Jennifer; Souza, Karen Cristina Borba; Santana, Iara Viana Vidigal; Kreitchmann, Regis; Salcedo, Mila P.; Salcedo, Mila P.; Ramanujam, Nirmala; Schmeler, Kathleen M.; Richards-Kortum, Rebecca
    Cervical cancer remains a leading cause of cancer death among women in low-and middle-income countries. Globally, cervical cancer prevention programs are hampered by a lack of resources, infrastructure, and personnel. We describe a multimodal mobile colposcope (MMC) designed to diagnose precancerous cervical lesions at the point-of-care without the need for biopsy. The MMC integrates two complementary imaging systems: 1) a commercially available colposcope and 2) a high speed, high-resolution, fiber-optic microendoscope (HRME). Combining these two image modalities allows, for the first time, the ability to locate suspicious cervical lesions using widefield imaging and then to obtain co-registered high-resolution images across an entire lesion. The MMC overcomes limitations of high-resolution imaging alone; widefield imaging can be used to guide the placement of the high-resolution imaging probe at clinically suspicious regions and co-registered, mosaicked high-resolution images effectively increase the field of view of high-resolution imaging. Representative data collected from patients referred for colposcopy at Barretos Cancer Hospital in Brazil, including 22,800 high resolution images and 9,900 colposcope images, illustrate the ability of the MMC to identify abnormal cervical regions, image suspicious areas with subcellular resolution, and distinguish between high-grade and low-grade dysplasia.
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    High frame rate video mosaicking microendoscope to image large regions of intact tissue with subcellular resolution
    (Optical Society of America, 2021) Hunt, Brady; Coole, Jackson; Brenes, David; Kortum, Alex; Mitbander, Ruchika; Vohra, Imran; Carns, Jennifer; Schwarz, Richard; Richards-Kortum, Rebecca
    High-resolution microendoscopy (HRME) is a low-cost strategy to acquire images of intact tissue with subcellular resolution at frame rates ranging from 11 to 18 fps. Current HRME imaging strategies are limited by the small microendoscope field of view (∼0.5 mm2); multiple images must be acquired and reliably registered to assess large regions of clinical interest. Image mosaics have been assembled from co-registered frames of video acquired as a microendoscope is slowly moved across the tissue surface, but the slow frame rate of previous HRME systems made this approach impractical for acquiring quality mosaicked images from large regions of interest. Here, we present a novel video mosaicking microendoscope incorporating a high frame rate CMOS sensor and optical probe holder to enable high-speed, high quality interrogation of large tissue regions of interest. Microendoscopy videos acquired at >90 fps are assembled into an image mosaic. We assessed registration accuracy and image sharpness across the mosaic for images acquired with a handheld probe over a range of translational speeds. This high frame rate video mosaicking microendoscope enables in vivo probe translation at >15 millimeters per second while preserving high image quality and accurate mosaicking, increasing the size of the region of interest that can be interrogated at high resolution from 0.5 mm2 to >30 mm2. Real-time deployment of this high-frame rate system is demonstrated in vivo and source code made publicly available.
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    Multimodal optical imaging with real-time projection of cancer risk and biopsy guidance maps for early oral cancer diagnosis and treatment
    (SPIE, 2023) Coole, Jackson B.; Brenes, David R.; Mitbander, Ruchika; Vohra, Imran S.; Hou, Huayu; Kortum, Alex; Tang, Yubo; Maker, Yajur; Schwarz, Richard A.; Carns, Jennifer L.; Badaoui, Hawraa; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca
    Significance: Despite recent advances in multimodal optical imaging, oral imaging systems often do not provide real-time actionable guidance to the clinician who is making biopsy and treatment decisions. Aim: We demonstrate a low-cost, portable active biopsy guidance system (ABGS) that uses multimodal optical imaging with deep learning to directly project cancer risk and biopsy guidance maps onto oral mucosa in real time. Approach: Cancer risk maps are generated based on widefield autofluorescence images and projected onto the at-risk tissue using a digital light projector. Microendoscopy images are obtained from at-risk areas, and multimodal image data are used to calculate a biopsy guidance map, which is projected onto tissue.ResultsRepresentative patient examples highlight clinically actionable visualizations provided in real time during an imaging procedure. Results show multimodal imaging with cancer risk and biopsy guidance map projection offers a versatile, quantitative, and precise tool to guide biopsy site selection and improve early detection of oral cancers. Conclusions: The ABGS provides direct visible guidance to identify early lesions and locate appropriate sites to biopsy within those lesions. This represents an opportunity to translate multimodal imaging into real-time clinically actionable visualizations to help improve patient outcomes.
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    Simple differential digital confocal aperture to improve axial response of line-scanning confocal microendoscopes
    (Optical Society of America, 2019) Tang, Yubo; Kortum, Alex; Vohra, Imran; Carns, Jennifer; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca
    Line-scanning confocal microendoscopy offers video-rate cellular imaging of scattering tissue with relatively simple hardware, but its axial response is inferior to that of point-scanning systems. Based on Fourier optics theory, we designed differential confocal apertures with a simple subtraction technique to improve the line-scanning sectioning performance. Taking advantage of digital slit apertures on a digital light projector and a CMOS rolling shutter, we demonstrate real-time optical sectioning performance comparable to point scanning in a dual-camera microendoscope (<$6,000). We validate the background rejection capability when imaging porcine columnar epithelium stained with fluorescent contrast agents with different uptake mechanisms and staining properties.