Parametric Imaging of Contrast-Enhanced Ultrasound (CEUS) for the Evaluation of Acute Gastrointestinal Graft-Versus-Host Disease

Abstract

In recent years contrast-enhanced ultrasound (CEUS) has been an emerging diagnostic modality for the detection of acute gastrointestinal (GI) graft-versus-host disease (GvHD) in patients after allogeneic stem cell transplantation. However, broad clinical usage has been partially limited by its high dependence on the expertise of an experienced examiner. Thus, the aim of this study was to facilitate detection of acute GI GvHD by implementing false color-coded parametric imaging of CEUS. As such, two inexperienced examiners with basic knowledge in abdominal and vascular ultrasound analyzed parametric images obtained from patients with clinical suspicion for acute GvHD in a blinded fashion. As diagnostic gold standard, histopathological GvHD severity score on intestinal biopsies obtained from lower GI tract endoscopy was performed. The evaluation of parametric images by the two inexperienced ultrasound examiners in patients with histological confirmation of acute GI GvHD was successful in 17 out of 19 patients (89%) as opposed to analysis of combined B-mode ultrasound, strain elastography, and CEUS by an experienced examiner, which was successful in 18 out of 19 of the patients (95%). Therefore, CEUS with parametric imaging of the intestine was technically feasible and has the potential to become a valuable diagnostic tool for rapid and widely accessible detection of acute GvHD in clinical practice.

Keywords: CEUS; GvHD; allogeneic stem cell transplantation; dynamic vascularization; parametric imaging.

Figure 1

Ultrasound images of a patient with histological confirmation of acute intestinal GvHD. A + C: B-mode ultrasound showing intestinal wall thickening. B: CEUS image showing early arterial hyperenhancement of the intestinal wall (red arrows) and transmural penetration of microbubbles (white arrows). D: Soft tissue edema as a correlate of acute inflammation examined by strain elastography.

Figure 2

CEUS parametric imaging for the detection of acute GI GvHD. Parametric images of the same patient showing a region of the small intestine with early arterial hyperenhancement color coded in red and transmural penetration of microbubbles (white arrows).

Figure 3

Ultrasound findings of another patient with acute GI GvHD and also an example of severe histopathological findings in GI GvHD. (A–D): B-mode and CEUS findings, including parametric imaging. Early arterial hyperenhancement of the intestinal wall (white arrows in A) and progressive transmural penetration of microbubbles (white arrows in B and C) compared with parametric images with early arterial hyperenhancement color coded in red and transmural penetration of microbubbles (white arrows). (E,F): Histology of colonic mucosa with severe acute GvHD (Lerner grade IV): denudation of mucosal epithelium, ulceration, and loss of crypts with abundant apoptosis in basal crypts (white arrows in F). (H&E staining, E: 50×, F: 200×).

Figure 4

Evaluation of treatment success with parametric imaging of CEUS. B-mode and parametric images of CEUS were evaluated (A) before and (B) 4 weeks after treatment initiation. In comparison with A, B shows a regression of arterial hyperenhancement reflected by the change of color coding to the higher degree green and blue nuances and the diminished amount of red and yellow and reduced occurrence of transmural penetration.