Vascular biomechanics and molecular disease activity in the thoracic aorta: a novel imaging method

Savine Minderhoud, Alexander J. Fletcher, Gillian MacNaught, Sebastien Cadet, SA (Suze-Anne) Korteland, Isabella Kardys, Dimitris Rizopoulos, Piotr Slomka, David E. Newby, Jolien Hesselink, Niki Walker, Alexander Hirsch, Marc R. Dweck*, Jolanda Wentzel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

AIMS: The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET). METHODS AND RESULTS: As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland-Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44-55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age. CONCLUSION: Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity.

Original languageEnglish
Article numberjaec090
Pages (from-to)1698-1707
Number of pages10
JournalEuropean Heart Journal Cardiovascular Imaging
Volume23
Issue number12
Early online date6 Jun 2022
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
Conflict of interest: The authors have no relationships relevant to the content of this paper to disclose. D.E.N. was supported by Toshiba, M.R.D. has received speaker fees from Pfizer and Novartis. He has received consultancy fees from Novartis, Jupiter Bioventures and Silence therapeutics. S.S. has received consultancy fee and research funding from GlaxoSmithKline. Siemens gave institutional support.

Funding Information:
The authors wish to thank Dr. Ning Jin (Siemens Medical Solutions, USA) for providing the 4D flow prototype sequence. This study was supported by the Thorax Foundation, British Heart Foundation and Siemens. M.R.D. is supported by the British Heart Foundation (FS/SCRF/21/32010) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). D.E.N. is supported by the British Heart Foundation (FS/19/15/34155, CH/09/002, RG/16/10/32375, RE/18/5/34216) and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

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