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.

Highlights

  • Allogeneic hematopoietic stem cell transplantation represents an important and potentially curative treatment option for patients suffering from malignant or benign hematologic diseases

  • Ultrasound-based diagnosis of acute GI graft-versus-host disease (GvHD) was either established by an experienced ultrasound examiner based on the combined evaluation of intestinal wall thickening in B-mode ultrasound, hypervascularization in color-coded doppler sonography and early arterial enhancement and transmural penetration of microbubbles in contrast-enhanced ultrasound (CEUS) as described before [10]

  • Since acute GI GvHD often presents with segmental rather than continuous intestinal affections, the inexperienced examiners received parametric images derived from all intestinal regions that could be imaged in each patient to enable as comprehensive as possible an evaluation by parametric imaging and excluding the potential bias of presenting to the inexperienced examiners only preselected areas that an experienced examiner might image because the areas showed sonomorphological alterations suspicious for acute GI GvHD

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Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an important and potentially curative treatment option for patients suffering from malignant or benign hematologic diseases. CEUS does not require ionizing radiation, and the microbubble-based contrast agent does not confer any risk of nephrotoxicity Since it allows for sensitive analysis of the vascularization and perfusion of the small and large bowel, CEUS enables detection of alterations of the intestinal wall by evaluation of the dynamic microvascularization of the intestine. Transmural penetration of microbubbles during CEUS can be utilized as a sonomorphological correlate of tissue damage of the intestinal epithelium conferred by donor derived alloreactive immune cells [2,6] Far, it has been reported, albeit with relatively low patient and control numbers, that CEUS can be a sensitive and very specific (75–100%) diagnostic tool for the detection of acute GI GvHD [5]. In this proof-of-concept study, we sought to evaluate if parametric analysis of CEUS by inexperienced examiners can be utilized to detect and determine activity of acute GI GvHD, establishing it as a diagnostic tool that facilitates CEUS-based diagnosis of GI GvHD

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