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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 7/2020

01-07-2020 | Neurotomy | Original Article

Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET

Authors: Kai Yi Wu, Jason G.E. Zelt, Tong Wang, Vincent Dinculescu, Robert Miner, Catherine Lapierre, Nicole Kaps, Aaryn Lavallee, Jennifer M. Renaud, James Thackeray, Lisa M. Mielniczuk, Shin-Yee Chen, Ian G. Burwash, Jean N. DaSilva, Rob S.B. Beanlands, Robert A. deKemp

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2020

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Abstract

Purpose

Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [11C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF).

Methods

Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VT), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values < 75% of the LV-maximum. Test-retest repeatability and observer reproducibility were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient of repeatability (NPC).

Results

Intra- and inter-observer correlations of both VT and RI were excellent (ICC = 0.93–0.99). Observer reproducibility (NPC = 3–13%) was lower than test-retest repeatability (NPC = 12–61%). Both regional (%LV defect size) and global (LV-mean) measures of sympathetic innervation were more repeatable using the simple RI model compared to VT (NPC = 12% vs. 19% and 30% vs. 54%). Using either model, quantification of regional denervation (defect size) was consistently more reliable than the global LV-mean values of RI or VT. Regional partial-volume correction degraded repeatability of both the global and regional VT measures by 2–12%. Test-retest repeatability of MBF estimation was relatively poor (NPC = 30–61%) compared with the RI.

Conclusions

Quantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex VT. Observer variability was significantly lower than the test-retest repeatability using a highly automated analysis program. These results support the use of the simple RI method for reliable analysis of HED PET images in clinical research studies for future evaluation of new therapies and for risk stratification in patients with heart failure.
Appendix
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Metadata
Title
Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET
Authors
Kai Yi Wu
Jason G.E. Zelt
Tong Wang
Vincent Dinculescu
Robert Miner
Catherine Lapierre
Nicole Kaps
Aaryn Lavallee
Jennifer M. Renaud
James Thackeray
Lisa M. Mielniczuk
Shin-Yee Chen
Ian G. Burwash
Jean N. DaSilva
Rob S.B. Beanlands
Robert A. deKemp
Publication date
01-07-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04629-5

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