3D diagnosis of Hirschsprung disease using open-top light-sheet microscopy

使用开顶光片显微镜对先天性巨结肠进行 3D 诊断

• 批准号: 10484508
• 负责人: Nicholas Reder
• 金额: $ 25.25万
• 依托单位: ALPENGLOW BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484508
• 关键词: 3-Dimensional; Address; Affect; Antibodies; Biological Assay; Biopsy; Biopsy Specimen; CLIA certified; Cell Count; Chronic; Clinical; Clinical Trials; Complex; Congenital Abnormality; Congenital Megacolon; Constipation; Consumption; Data Set; Diagnosis; Diagnostic; Diagnostic Errors; Disease; Distal; Dysplasia; Enteral; Enteric Nervous System; Excision; Future; Ganglia; Gold; Harvest; Human; Hypertrophy; Image; Imaging Techniques; Individual; Infant; Intestines; Label; Laboratories; Length; Light; Machine Learning; Malignant neoplasm of prostate; Methods; Microscope; Microscopy; Mucous Membrane; Nature; Nerve; Nerve Fibers; Nervous system structure; Neurons; Pathologist; Pathology; Pathology processes; Patients; Phase; Positioning Attribute; Preparation; Process; Protocols documentation; Readiness; Rectum; Research; Sampling; Services; Small Business Innovation Research Grant; Specimen; Stains; Structure; Submucosa; Suction; Techniques; Technology; Testing; Three-Dimensional Imaging; Time; Tissues; Training; Translating; Work; analysis pipeline; automated analysis; density; disease diagnosis; ganglion cell; improved; lightspeed; machine learning algorithm; nerve supply; neuromuscular; novel; rectal

Abstract Hirschsprung disease is a congenital defect that affects an estimated 1:5000 liveborn infants. It is characterized by absent ganglion cells (neurons) in the distal rectum and a variable length of contiguous proximal bowel. The diagnosis of Hirschsprung disease relies upon subjective pathologist interpretation of up to 100 tissue sections from suction rectal biopsies to prove the absence of ganglion cells and the presence of hypertrophic nerves. Due to the labor-intensive and time-consuming nature of the current diagnostic process, there is a need to more efficiently and comprehensively diagnose Hirschsprung disease. Our team has pioneered the use of 3D open-top light-sheet (OTLS) microscopy, which enables rapid, high-throughput imaging of large clinical samples. In combination with cutting-edge machine learning techniques, we hypothesize that 3D OTLS microscopy can provide more accurate and consistent assessment of ganglion cells and hypertrophic nerves in suction rectal biopsies from patients with suspected Hirschsprung disease. We will test this hypothesis by developing a multiplex staining protocol and machine learning analysis pipeline, which will be piloted on 100 rectal biopsy specimens from fresh resection specimens.

摘要