title: Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia.
abstract: Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histologic evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histologic detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images showed a striking similarity to the results of H&E staining, as shown by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions.
authors.affiliation: Department of Medicine, Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Makino
authors.forename: Manu
authors.initials: M
authors.lastname: Jain
authors.forename: David C
authors.initials: DC
authors.lastname: Montrose
authors.forename: Amit
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Joshua
authors.initials: J
authors.lastname: Sterling
authors.forename: Brian P
authors.initials: BP
authors.lastname: Bosworth
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Milsom
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.forename: Maria M
authors.initials: MM
authors.lastname: Shevchuk
authors.forename: Kathy
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Brown
authors.forename: David R
authors.initials: DR
authors.lastname: Rivera
authors.forename: Wendy O
authors.initials: WO
authors.lastname: Williams
authors.forename: Chris
authors.initials: C
authors.lastname: Xu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
authors.forename: Sushmita
authors.initials: S
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D001706:Biopsy / Q000379:methods*; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology; D018450:Disease Progression; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D025321:Surgery, Computer-Assisted / Q000379:methods; D014054:Tomography / Q000379:methods*