Browsing by Author "Hunt, Brady"
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Item Diagnosing Cervical Neoplasia in Rural Brazil: Clinical Trial Outcomes and a Next-generation Point-of-care Imaging System(2020-06-22) Hunt, Brady; Richards-Kortum, RebeccaThis work contains a series of clinical studies conducted at a Brazilian cancer hospital to validate a low-cost, portable, high-resolution microendoscope (HRME) for real-time diagnostic evaluation of cervical lesions. Findings from these clinical studies led me to explore two approaches to further improve HRME: 1) improved image analysis algorithms and 2) improved optical instrumentation. In total, five studies are presented: three clinical studies and two technical studies. Taken altogether, these studies provide strong evidence for the potential of HRME to improve cervical cancer prevention in low-resource healthcare settings.Item 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, RebeccaHigh-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.Item Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report(Wiley, 2018) Pantano, Naitielle; Hunt, Brady; Schwarz, Richard A.; Parra, Sonia; Cherry, Katelin; Possati‐Resende, Júlio César; Longatto‐Filho, Adhemar; Fregnani, José Humberto Tavares Guerreiro; Castle, Philip E.; Schmeler, Kathleen; Richards‐Kortum, RebeccaProflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.Item Towards a point-of-care strip test to diagnose sickle cell anemia(Public Library of Science, 2017) Bond, Meaghan; Hunt, Brady; Flynn, Bailey; Huhtinen, Petri; Ware, Russell; Richards-Kortum, RebeccaA rapid test to identify patients with sickle cell disease could have important benefits in low-resource settings. Sickle cell anemia (SCA) affects about 300,000 newborns each year, the majority of whom are born in sub-Saharan Africa. Low-cost therapies are available to treat SCA, but most countries in sub-Saharan Africa lack robust neonatal screening programs needed to identify patients in need of treatment. To address this need, we developed and evaluated a competitive lateral flow assay that identifies patients with SCA (genotype HbSS) in 15 minutes using undiluted whole blood. A small volume of blood (0.5 μL– 3 μL) is mixed with antibody-coated blue latex beads in a tube and applied to the strip. Strips are then placed in a well of running buffer and allowed to run for 10 minutes. Laboratory evaluation with samples containing different proportions of hemoglobin A (HbA) and hemoglobin S (HbS) indicated that the test should enable identification of SCA patients but not persons with sickle cell trait (SCT). We evaluated the test using 41 samples from individuals with SCA, SCT, and normal blood. With visual inspection or quantitative analysis, we found a 98% accuracy when differentiating SCA from normal and SCT samples as a group (90% sensitivity and 100% specificity for identifying SCA). This work demonstrates important steps towards making a lateral flow test for hemoglobinopathies more appropriate for point-of-care use; further work is needed before the test is appropriate for clinical use.