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Schmeler, K. M.

Publications and source records attributed to Schmeler, K. M..

2 recordsLinked to original sources

Dual-modality, deep-learning-enabled endomicroscope with large field-of-view and depth-of-field for real-time in vivo imaging of epithelial hallmarks of cancer

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep-learning-enabled endomicroscope that breaks these constrains and achieves 20 mm2 FOV and 500 {micro}m DOF with 4 {micro}m resolution, representing approximately 5x increase in FOV and 8x larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep-learning optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1-3 cm2) co-registered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point-of-care.

bioengineering↗

Dynamic evolution of cervical cancer mutations during chemoradiation using novel sampling approach

ObjectiveThe aim of this study was to validate a whole exome sequencing approach to longitudinally characterize the tumor mutational profile of cervical cancer patients undergoing chemoradiation (CRT). Experimental DesignCervical cancer tumor specimens from twenty-seven patients undergoing chemoradiation were collected before and throughout CRT and whole exome sequencing (WES) was performed to characterize individual mutations and alterations in unique genes. WES data were analyzed from cervical cancer patients in The Cancer Genome Atlas (TCGA) as a comparison group. ResultsOver 93% of mutated genes detected at baseline were present in TCGA. Tumor purity from collected swabs correlated with MRI tumor volumes during the course of treatment (R2=0.969). CDK4/CDK6/cyclin D1-related gene mutations involved in the ERK1/2, p16INK4, and p53 pathway and G1/S checkpoint most commonly persisted at the end of CRT. ConclusionThis non-invasive swab technique to serially sample tumor during CRT will allow new discoveries of dynamic tumor mutational profile changes during chemoradiation for mucosal tumors. Mutations that survived or increased during the initial weeks of radiation treatment are potential drivers of radiation resistance including the CDL4/CDK6/cyclin D1-related pathway. Statement of Translational RelevanceThere are no established biomarkers to predict chemoradiation (CRT) response for cervical cancer patients. Serial biopsies cannot be performed due to risks of bleeding and fistula. We used a novel non-invasive swab-based biopsy technique to obtain serial samples from a cohort of twenty-seven patients through the course of treatment, and validated this approach to obtain whole exome sequencing data. We analyzed dynamic tumor mutation profiles during CRT. Results from this study show that mutations in CDK4/CDK6/cyclin D1-related genes increased at the end of CRT, suggesting this pathway as a potential driver of radiation resistance.

cancer biology↗