Structured illumination microscopy as a diagnostic tool for nephrotic disease

Jonathan Nylk, James M. Pullman, Elaine C. Campbell, Frank J. Gunn-Moore, Michael B. Prystowsky, Kishan Dholakia

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Nephrotic disease is a group of debilitating and sometimes lethal diseases affecting kidney function, specifically the loss of ability to retain vital proteins in the blood while smaller molecules are removed through filtration into the urine. Treatment routes are often dictated by microscopic analysis of kidney biopsies. Podocytes within the glomeruli of the kidney have many interdigitating projections (foot processes), which form the main filtration system. Nephrotic disease is characterised by the loss of this tightly interdigitating substructure and its observation by electron microscopy (EM) is necessitated as these structures are typically 250􀀀500nm wide, with 40nm spacing. Diagnosis by EM is both expensive and time consuming; it can take up to one week to complete the preparation, imaging, and analysis of a single sample. We propose structured illumination microscopy (SIM) as an alternative, optical diagnostic tool. Our results show that SIM can resolve the structure of fluorescent probes tagged to podocin, a protein localised to the periphery of the podocyte foot processes. Three-dimensional podocin maps were acquired in healthy tissue and tissue from patients diagnosed with two different nephrotic disease states; minimal change disease and membranous nephropathy. These structures correlated well with EM images of the same structure. Preparation, imaging, and analysis could be achieved in several hours. Additionally, the volumetric information of the SIM images revealed morphological changes in disease states not observed by EM. This evidence supports the use of SIM as a diagnostic tool for nephrotic disease and can potentially reduce the time and cost per diagnosis.

Original languageEnglish
Title of host publicationAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XV
EditorsWarren S. Grundfest, Tuan Vo-Dinh, Anita Mahadevan-Jansen
Place of PublicationBellingham, WA
PublisherSPIE-International Society for Optical Engineering
Number of pages7
Volume10054
ISBN (Electronic)9781510605503
ISBN (Print)9781510605497
DOIs
Publication statusPublished - 2017
EventAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XV - San Francisco, United States
Duration: 29 Jan 201731 Jan 2017

Publication series

NameProceedings of SPIE
ISSN (Print)1605-7422
ISSN (Electronic)2410-9045

Conference

ConferenceAdvanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XV
CountryUnited States
CitySan Francisco
Period29/01/1731/01/17

Keywords

  • Kidney disease
  • Nephrology; Optical pathology
  • SIM
  • Structured illumination microscopy
  • Superresolution

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