High-Resolution Rapid Diagnostic Imaging of Whole Prostate Biopsies Using Video-Rate Fluorescence Structured Illumination Microscopy.
Rapid assessment of prostate core biopsy pathology at the point-of-procedure could provide benefit in a variety of clinical situations. Even with advanced transrectal ultrasound guidance and saturation biopsy protocols, prostate cancer can be missed in up to half of all initial biopsy procedures. In addition, collection of tumor specimens for downstream histologic, molecular, and genetic analysis is hindered by low tumor yield due to inability to identify prostate cancer grossly. However, current point-of-procedure pathology protocols, such as frozen section analysis (FSA), are destructive and too time- and labor-intensive to be practical or economical. Ex vivo microscopy of the excised specimens, stained with fast-acting fluorescent histology dyes, could be an attractive nondestructive alternative to FSA. In this work, we report the first demonstration of video-rate structured illumination microscopy (VR-SIM) for rapid high-resolution diagnostic imaging of prostate biopsies in realistic point-of-procedure timeframes. Large mosaic images of prostate biopsies stained with acridine orange are rendered in seconds and contain excellent contrast and detail, exhibiting close correlation with corresponding hematoxylin and eosin histology. A clinically relevant review of VR-SIM images of 34 unfixed and uncut prostate core biopsies by two independent pathologists resulted in an area under the receiver operative curve (AUC) of 0.82-0.88, with a sensitivity ranging from 63% to 88% and a specificity ranging from 78% to 89%. When biopsies contained more than 5% tumor content, the sensitivity improved to 75% to 92%. The image quality, speed, minimal complexity, and ease of use of VR-SIM could prove to be features in favor of adoption as an alternative to destructive pathology at the point-of-procedure.
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
Mei
M
Wang
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Hillary Z
HZ
Kimbrell
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Andrew B
AB
Sholl
Bioinnovation Program, Tulane University, New Orleans, Louisiana.
David B
DB
Tulman
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
Katherine N
KN
Elfer
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
Tyler C
TC
Schlichenmeyer
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana.
Benjamin R
BR
Lee
Department of Mathematics, Tulane University, New Orleans, Louisiana.
Michelle
M
Lacey
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana. jqbrown@tulane.edu.
J Quincy
JQ
Brown
D000165:Acridine Orange; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D019540:Area Under Curve; D001707:Biopsy, Needle / Q000379:methods*; D004396:Coloring Agents; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods*; D018715:Microscopy, Video / Q000295:instrumentation / Q000379:methods*; D015588:Observer Variation; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D013997:Time Factors
D004396:Coloring Agents; D000165:Acridine Orange