Three-Dimensional Nanoscale Nuclear Architecture Mapping of Rectal Biopsies Detects Colorectal Neoplasia in Patients with Inflammatory Bowel Disease

Abstract

Patients with inflammatory bowel disease (IBD) colitis are at an increased risk of developing colorectal cancer and are currently recommended to undergo extensive annual or biennial colonoscopy, a costly and invasive procedure. Most surveillance colonoscopies are negative with no existing objective measures for assessing their risk of developing cancer. We have recently developed a less invasive, cost-effective and objective method to assess cancer risk by detecting the presence of colonic neoplasia via 3-dimensional (3D) nanoscale nuclear architecture mapping (nanoNAM) of normal-appearing rectal biopsies. To establish its translational relevance, we prospectively recruited 103 patients with IBD colitis undergoing surveillance colonoscopy and measured submicroscopic alterations in aberrant intrinsic nuclear architecture of epithelial cells from normal-appearing rectal biopsies with nanoNAM. The results were correlated with the histologic diagnoses from all random biopsies obtained during initial and follow-up colonoscopy within 3 years. Using nanoNAM-based structural characterization as input features into a soft margin-based n-SVM risk classifier, we show that nanoNAM detects colonic neoplasia with AUC of 0.87 AE 0.04, sensitivity of 0.81 AE 0.09, and specificity of 0.82 AE 0.07 in the independent validation set. In addition, projecting nanoNAM features onto a 2-sphere reveals patients with low-risk and high-risk IBD colitis existing on separate hemispheres. Finally, we show that this ability to assess cancer risk translates to clinicallyrelevant estimation of individual-patient likelihood of being truly at risk. We demonstrate the potential of nanoNAM to identify patients with IBD at higher risk of developing cancer from normal-appearing rectum tissue, which may aid clinicians in patients with personalized IBD colitis surveillance.

Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions

“…Our literature search yielded only one study applying AI for the detection of colonic neoplasia in IBD. Uttam et al [ 60 ] employed support SVM to analyze 3-dimensional nanoscale nuclear architecture mapping (NanoNAM) of normal-appearing rectal biopsies in a prospective cohort of 103 IBD patients. In their study, NanoNAM detected colonic neoplasia with an AUC of 0.87 ± 0.04, sensitivity of 0.81 ± 0.09, and specificity of 0.82 ± 0.07 in the independent validation set.…”

Predicting Crohn’s disease severity in the colon using mixed cell nucleus density from pseudo labels

“…This process can be generally applied to images of tissue-containing slides and has been used on lung cancer tasks 8,9 . For IBD, sub-microscopic scale features from nuclei have been used to differentiate between high and low-risk samples for development of neoplasia 10 . Specifically for Crohn's disease, segmented nuclei have been used as a component in determining desirable anatomical locations for biopsies with respect to a present ulcer 11 .…”

Correlation of Serum CA242, CA724, and TPA Levels with Clinicopathological Features and Prognosis in Patients with Inflammatory Bowel Disease Complicated with Rectal Cancer

“…IBD mainly includes ulcerative colitis and Crohn's disease, with the pathogenic factors of environment, heredity, intestinal microorganism, immune dysfunction, etc. [ 1 , 2 ], which affects many races around the world. At present, the incidence of IBD in China is on the rise, and more and more patients are affected by chronic mucosal inflammation repeatedly.…”

“…(2) The relationship between serum tumor marker levels and clinicopathological features of patients with IBD and rectal cancer. The general data form was fulfilled to analyze the relationship between clinicopathological features and serum CA242, CA724, and TPA levels.…”