Tissue-clearing technique and cutaneous nerve biopsies: Quantification of the intraepidermal nerve-fiber density using active clarity technique-pressure related efficient and stable transfer of macromolecules into organs

Dai Hyun Kim, Se Jeong Lee, Eunsoo Lee, Ji Hyuck Hong, Soo-Hong Seo, Hyo Hyun Ahn, Byung Jo Kim, Woong Sun, Im Joo Rhyu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background and Purpose Cutaneous nerve biopsies based on two-dimensional analysis have been regarded as a creditable assessment tool for diagnosing peripheral neuropathies. However, advancements in methodological imaging are required for the analysis of intact structures of peripheral nerve fibers. A tissue-clearing and labeling technique facilitates three-dimensional imaging of internal structures in unsectioned, whole biological tissues without excessive time or labor costs. We sought to establish whether a tissue-clearing and labeling technique could be used for the diagnostic evaluation of peripheral neuropathies. Methods Five healthy individuals and four patients with small-fiber neuropathy (SFN) and postherpetic neuralgia (PHN) were prospectively enrolled. The conventional methods of indirect immunofluorescence (IF) and bright-field immunohistochemistry (IHC) were adopted in addition to the tissue-clearing and labeling method called active clarity technique-pressure related efficient and stable transfer of macromolecules into organs (ACT-PRESTO) to quantify the intraepidermal nerve-fiber density (IENFD). Results The mean IENFD values obtained by IF, bright-field IHC, and ACT-PRESTO in the healthy control group were 6.54, 6.44, and 90.19 fibers/mm2, respectively; the corresponding values in the patients with SFN were 1.99, 2.32, and 48.12 fibers/mm2, respectively, and 3.06, 2.87, and 47.21 fibers/mm2, respectively, in the patients with PHN. Conclusions This study has shown that a tissue-clearing method provided not only rapid and highly reproducible three-dimensional images of cutaneous nerve fibers but also yielded reliable quantitative IENFD data. Quantification of the IENFD using a tissue-clearing and labeling technique is a promising way to improve conventional cutaneous nerve biopsies.

Original languageEnglish
Pages (from-to)537-544
Number of pages8
JournalJournal of Clinical Neurology (Korea)
Volume15
Issue number4
DOIs
Publication statusPublished - 2019 Oct

Keywords

  • ACT-PRESTO
  • Intraepidermal nerve-fiber density
  • Peripheral neuropathy
  • Tissue-clearing and labeling technique
  • ‌Cutaneous nerve biopsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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