Research Article: Identification of two distinct hereditary hemorrhagic telangiectasia patient subsets with different hepatic perfusion properties by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification

Date Published: April 11, 2019

Publisher: Public Library of Science

Author(s): Roland C. Schelker, Kornelia Andorfer, Franz Putz, Wolfgang Herr, Ernst-Michael Jung, Gianfranco D. Alpini.


Hereditary hemorrhagic telangiectasia (HHT) is marked by arteriovenous fusion comprising hepatic vascular malformations (HVaMs) with the chance of bleeding.

We investigated HVaMs in HHT patients by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification to be able to sub-classify a high risk cohort of asymptomatic HHT patients.

The imaging characteristics on CEUS in 34 patients (aged 21–84 years; mean 58.9) with HHT were retrospectively evaluated. Real-time contrast harmonic imaging, sulfur hexafluoride-filled microbubbles and motion adjustment were utilized. Cine loops of the liver were digital stored, perfusion was quantified using a software reading DICOM data`s.

HVaMs were diagnosed in 31 out of 34 patients. Significant uppermost peak enhancement (PE), wash-in area under the curve (WiAUC) and wash-in perfusion index (WiPI) were identified in the shunt region (100%), next in the hilar region (PE 32.6%; WiAUC 33.9%; WiPI 34.1%), and the lowest in the hepatic parenchyma (PE 10.2%; WiAUC 12.0%; WiPI 9.5%). The perfusion parameters in the shunt region compared to the other regions were significantly increased in one subgroup of patients. Consistent with this, the intrahepatic portal vein diameter and Buscarini grading was significantly higher, while portal vein peak velocity was significantly lower in this patient subset. By statistical analysis, we could correlate PE and WiPI to these clinical parameters, while WiAUC showed no clinical association.

For the first time we combined CEUS findings with motion adjustment software to quantitative determine perfusion parameters of a cohort of HHT patients. Hereby, we could identify a subset of HHT patients with two markedly increased parameter values in the shunt region compared to the hilus/hepatic parenchyma. This could contribute to sub-classify a high-risk group of HHT patients with therapeutic indication.

Partial Text

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominantly transmitted disorder affecting small mucocutaneous blood vessels and/or the vasculature of various viscera [1, 2].

The patients were 11 men and 23 women, with a mean age of 59.3 years (range, 21–84 years) at the moment of HVaM diagnosis. HVaMs could be proved in 31 out of 34 patients. Malignant lesions were not detectable in any of the cases (Table 1).

HHT is an uncommon autosomal dominantly transmitted disorder characterized by systemic vascular dilatation leading to arteriovenous fusion in the form of telangiectases or major vascular malformations, implying the chance of hemorrhagic incidents [20].

The expertise about US properties of HVaMs augmented in the last years, particularly by applying CCDS- and PD-US but there is few knowledge about quantitative perfusion characteristics. Our study showed significant differences in PE, WiAUC and WiPI values in the three determined areas: shunt region, hilus and hepatic parenchyma. Besides, the relative perfusion parameter values in the shunt region compared to other areas were significantly elevated in one subset of patients. As to that, we could correlate PE and WiPI to clinical parameters (portal vein diameter, portal vein peak velocity, Buscarini grading). These novel results could be utilized to sub-classify a high risk cohort of asymptomatic patients with therapeutic indication. Moreover, with novel upcoming therapeutic modalities like angiogenesis inhibitor bevacizumab, treatment of HVaMs and their complications will get more appealing in future. Thus, CEUS investigation is able to fill the hole of necessary precise cost-effective screening methods in HHT patients with HVaMs.