title: Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology.
abstract: This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (>0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: Derek
authors.initials: D
authors.lastname: Ho
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: Tyler K
authors.initials: TK
authors.lastname: Drake
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Smith-McCune
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Darragh
authors.affiliation: Department of Pediatrics, Division of Adolescent Medicine, University of California, San Francisco, San Francisco, CA.
authors.forename: Loris Y
authors.initials: LY
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: Adam
authors.initials: A
authors.lastname: Wax
mesh_terms: D000465:Algorithms; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure*; D004847:Epithelial Cells / Q000648:ultrastructure*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007368:Interferometry / Q000295:instrumentation / Q000379:methods*; D011237:Predictive Value of Tests; D012372:ROC Curve; D018401:Sample Size; D012680:Sensitivity and Specificity; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000000981:diagnostic imaging / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000000981:diagnostic imaging* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology
keywords: a/LCI; cancer nuclear morphology; cancer screening; cervical cancer; optical biopsy