Fetal lung development via quantitative biomarkers from diffusion MRI and histological validation in rhesus macaques

Nara S. Higano, Xuefeng Cao, Jinbang Guo, Xiaojie Wang, Christopher D. Kroenke, Alyssa L. Filuta, James P. Bridges, Jason C. Woods

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To demonstrate sensitivity of diffusion-weighted MRI (DW-MRI) to pulmonary cellular-space changes during normal in utero development using fetal rhesus macaques, compared to histological biomarkers. Study design: In vivo/ex vivo DW-MRI was acquired in 26 fetal rhesus lungs (early-canalicular through saccular stages). Apparent diffusion coefficients (ADC) from MRI and tissue area density (H&E), alveolar type-II cells (ABCA3), and epithelial cells (TTF1) from histology were compared between gestational stages. Results: In vivo/ex vivo ADC correlated with each other (Spearman ρ = 0.47, P = 0.038; Bland–Altman bias = 0.0835) and with area-density (in vivo ρ = -0.56, P = 0.011; ex vivo ρ = −0.83, P < 0.0001). In vivo/ex vivo ADC increased exponentially toward saturation with gestational stage (R2 = 0.49/0.49), while area-density decreased exponentially (R2 = 0.53). ABCA3 and TTF1 stains demonstrated expected fetal cellular development. Conclusions: Fetal DW-MRI provides a non-invasive biomarker for pulmonary structural maturation, with a strong correlation to histological markers during tissue development in rhesus macaques. This method has strong potential for assessing human fetal development, particularly in patients with pulmonary hypoplasia.

Original languageEnglish (US)
JournalJournal of Perinatology
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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