High resolution ultrasound imaging for repeated measure of wound tissue morphometry, biomechanics and hemodynamics under fetal, adult and diabetic conditions.

Surya C. Gnyawali,Mithun Sinha,Brian Wulff,Mohamed S. El Masry,Fidel Soto-Gonzalez,Subhadip Ghatak,Sashwati Roy,Chandan K. Sen,Traci A. Wilgus,Gordon Niall Stevenson

doi:10.1371/journal.pone.0241831

Abstract

Non-invasive, repeated interrogation of the same wound is necessary to understand the tissue repair continuum. In this work, we sought to test the significance of non-invasive high-frequency high-resolution ultrasound technology for such interrogation. High-frequency high-resolution ultrasound imaging was employed to investigate wound healing under fetal and adult conditions. Quantitative tissue cellularity and elastic strain was obtained for visualization of unresolved inflammation using Vevo strain software. Hemodynamic properties of the blood flow in the artery supplying the wound-site were studied using color Doppler flow imaging. Non-invasive monitoring of fetal and adult wound healing provided unprecedented biomechanical and functional insight. Fetal wounds showed highly accelerated closure with transient perturbation of wound tissue cellularity. Fetal hemodynamics was unique in that sharp fall in arterial pulse pressure (APP) which was rapidly restored within 48h post-wounding. In adults, APP transiently increased post-wounding before returning to the pre-wounding levels by d10 post-wounding. The pattern of change in the elasticity of wound-edge tissue of diabetics was strikingly different. Severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of the non-diabetic group. Wound bed of adult diabetic mice (db/db) showed persistent hypercellularity compared to littermate controls (db/+) indicative of prolonged inflammation. Normal skin strain of db/+ and db/db were asynchronous. In db/db, severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of non-diabetics. This study showcases a versatile clinically relevant imaging platform suitable for real-time analyses of functional wound healing.

Highlights

Non-invasive interrogation of the functional aspects of cutaneous wound healing is highly powerful in helping to understand the tissue repair continuum through repeated measurements of the same wound [1]
Such approach is powerful in discriminating cell populations within the skin based on morphological features, it must rely on invasive tissue biopsy interrupting the tissue repair process [4]
We show the first evidence for animal studies using ultrasound in monitoring fetal wound healing

Summary

Introduction

Non-invasive interrogation of the functional aspects of cutaneous wound healing is highly powerful in helping to understand the tissue repair continuum through repeated measurements of the same wound [1]. Onset of injury marks the beginning of wound healing which, through a number of inter-dependent mechanisms, advances as one continuous process [2] Any interruption of such processes by invasive measures such as tissue biopsy may be viewed as a confounding factor that complicates the original cascade of event elicited by another injury on an already wounded tissue [3]. Histological quantification of skin and its appendages has been accepted as a standard method to demarcate epidermal and dermal thickness [4] Such approach is powerful in discriminating cell populations within the skin based on morphological features, it must rely on invasive tissue biopsy interrupting the tissue repair process [4]. At a more macroscopic scale, imaging approaches may provide critically important functional data that may act as a temporal reference line to enhance histological data interpretation [2]

Objectives

Methods

Results

Conclusion