nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

09.12.2019 | Original Article

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

verfasst von: 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2020

Einloggen, um Zugang zu erhalten

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 (V_T), 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 V_T 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 V_T (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 V_T. Regional partial-volume correction degraded repeatability of both the global and regional V_T 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 V_T. 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.

Nur mit Berechtigung zugänglich

Zelt JGE, DeKemp RA, Rotstein BH, Nair GM, Narula J, Ahmadi A, et al. Nuclear imaging of the cardiac sympathetic nervous system: a disease-specific interpretation in heart failure. JACC Cardiovasc Imaging 2019.

Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, et al. Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982;307:205–11.PubMedCrossRef

Fallavollita JA, Luisi AJ, Michalek SM, Valverde AM, Haka MS, Hutson AD, et al. Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods. Contemp Clin Trials. 2006;27:374–88.PubMedCrossRef

Bengel FM, Schwaiger M. Assessment of cardiac sympathetic neuronal function using PET imaging. J Nucl Cardiol. 2004;11:603–16.PubMedCrossRef

Boschi S, Lodi F, Boschi L, Nanni C, Chondrogiannis S, Colletti PM, et al. 11C-meta-hydroxyephedrine: a promising PET radiopharmaceutical for imaging the sympathetic nervous system. Clin Nucl Med. 2015;40:e96–103.PubMedCrossRef

Allman KC, Wieland DM, Muzik O, Degrado TR, Wolfe ER, Schwaiger M. Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans. J Am Coll Cardiol. 1993;22:368–75.PubMedCrossRef

Barber MJ, Mueller TM, Henry DP, Felten SY, Zipes DP. Transmural myocardial infarction in the dog produces sympathectomy in noninfarcted myocardium. Circulation. 1983;67:787–96.PubMedCrossRef

Fallavollita JA, Heavey BM, Luisi AJ, Michalek SM, Baldwa S, Mashtare TL, et al. Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. J Am Coll Cardiol. 2014;63:141–9.PubMedCrossRef

Lautamaki R, Sasano T, Higuchi T, Nekolla SG, Lardo AC, Holt DP, et al. Multiparametric molecular imaging provides mechanistic insights into sympathetic innervation impairment in the viable infarct border zone. J Nucl Med. 2015;56:457–63.PubMedCrossRef

10.

Hiroshima Y, Manabe O, Naya M, Tomiyama Y, Magota K, Obara M, et al. Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET. J Nucl Cardiol. 2017:1–8.

11.

Harms HJ, Lubberink M, de Haan S, Knaapen P, Huisman MC, Schuit RC, et al. Use of a single 11C-meta-hydroxyephedrine scan for assessing flow–innervation mismatches in patients with ischemic cardiomyopathy. J Nucl Med. 2015;56:1706–11.PubMedCrossRef

12.

Münch G, Nguyen NTB, Nekolla S, Ziegler S, Muzik O, Chakraborty P, et al. Evaluation of sympathetic nerve terminals with [11C] epinephrine and [11C] hydroxyephedrine and positron emission tomography. Circulation. 2000;101:516–23.PubMedCrossRef

13.

Raffel DM, Chen W, Sherman PS, Gildersleeve DL, Jung Y-W. Dependence of cardiac 11C-meta-hydroxyephedrine retention on norepinephrine transporter density. J Nucl Med. 2006;47:1490–6.PubMed

14.

DeGrado TR, Hutchins GD, Toorongian SA, Wieland DM, Schwaiger M. Myocardial kinetics of carbon-11-meta-hydroxyephedrine: retention mechanisms and effects of norepinephrine. J Nucl Med. 1993;34:1287–93.PubMed

15.

Fricke E, Eckert S, Dongas A, Fricke H, Preuss R, Lindner O, et al. Myocardial sympathetic innervation in patients with symptomatic coronary artery disease: follow-up after 1 year with neurostimulation. J Nucl Med. 2008;49:1458–64.PubMedCrossRef

16.

Harms HJ, de Haan S, Knaapen P, Allaart CP, Rijnierse MT, Schuit RC, et al. Quantification of [11 C]-meta-hydroxyephedrine uptake in human myocardium. EJNMMI Res. 2014;4:52.PubMedPubMedCentralCrossRef

17.

Thackeray JT, Renaud JM, Kordos M, Klein R, Beanlands RSB, DaSilva JN. Test–retest repeatability of quantitative cardiac 11C-meta-hydroxyephedrine measurements in rats by small animal positron emission tomography. Nucl Med Biol. 2013;40:676–81.PubMedCrossRef

18.

Wang T, Wu KY, Miner RC, Renaud JM, Beanlands RSB. Reproducible quantification of cardiac sympathetic innervation using graphical modeling of carbon-11-meta-hydroxyephedrine kinetics with dynamic PET-CT imaging. EJNMMI Res. 2018;8:63.PubMedPubMedCentralCrossRef

19.

Hall AB, Ziadi MC, Leech JA, Chen S-Y, Burwash IG, Renaud J, et al. Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study. Circulation. 2014;130:892–901.PubMedCrossRef

20.

Wu KY, Dinculescu V, Renaud JM, Chen S-Y, Burwash IG, Mielniczuk LM, et al. Repeatable and reproducible measurements of myocardial oxidative metabolism, blood flow and external efficiency using 11 C-acetate PET. J Nucl Cardiol. 2018;25(6):1912–25 1–14.PubMedCrossRef

21.

Rosenspire KC, Haka MS, Van Dort ME, Jewett DM, Gildersleeve DL, Schwaiger M, et al. Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging. J Nucl Med. 1990;31:1328–34.PubMed

22.

Yoshinaga K, Burwash IG, Leech JA, Haddad H, Johnson CB, Garrard L, et al. The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll Cardiol. 2007;49:450–8.PubMedCrossRef

23.

Klein R, Renaud JM, Ziadi MC, Thorn SL, Adler A, Beanlands RS. Intra-and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program. J Nucl Cardiol. 2010;17:600–16.PubMedCrossRef

24.

Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533–9.PubMedCrossRef

25.

Sander CY, Mandeville JB, Wey H-Y, Catana C, Hooker JM, Rosen BR. Effects of flow changes on radiotracer binding: simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation. J Cereb Blood Flow Metab. SAGE Publications Sage UK: London, England; 2019;39:131–146.

26.

Logan J, Volkow ND, Fowler JS, Wang G-J, Dewey SL, MacGregor R, et al. Effects of blood flow on [11C] raclopride binding in the brain: model simulations and kinetic analysis of PET data. J Cereb Blood Flow Metab. SAGE Publications Sage UK: London, England; 1994;14:995–1010.

27.

Holthoff VA, Koeppe RA, Frey KA, Paradise AH, Kuhl DE. Differentiation of radioligand delivery and binding in the brain: validation of a two-compartment model for [11C] flumazenil. J Cereb Blood Flow Metab. SAGE Publications Sage UK: London, England; 1991;11:745–52.CrossRef

28.

Thackeray JT, Beanlands RS, DaSilva JN. Presence of specific 11C-meta-hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue. J Nucl Med. 2007;48:1733–40.PubMedCrossRef

29.

Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.PubMedCrossRef

30.

Burwash IG, Forbes AD, Sadahiro M, Verrier ED, Pearlman AS, Thomas R, et al. Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis. Am J Physiol Circ Physiol. 1993;265:H1734–43.CrossRef

31.

Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86:420.PubMedCrossRef

32.

Koo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med. 2016;15:155–63.PubMedPubMedCentralCrossRef

33.

Klein R, Ocneanu A, Renaud JM, Ziadi MC, Beanlands RSB. Consistent tracer administration profile improves test–retest repeatability of myocardial blood flow quantification with 82 Rb dynamic PET imaging. J Nucl Cardiol. 2016;25(3):929–41 1–13.PubMedCentralCrossRef

34.

Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud. 2010;47:931–6.CrossRef

35.

Nordstokke DW, Zumbo BD. A new nonparametric Levene test for equal variances. Psicológica. 2010;31:401–30.

36.

Bateman TM, Ananthasubramaniam K, Berman DS, Gerson M, Gropler R, Henzlova M, et al. Reliability of the 123I-mIBG heart/mediastinum ratio: results of a multicenter test–retest reproducibility study. J Nucl Cardiol. 2018;26:1555–65.PubMedCrossRef

37.

van den Hoff J, Burchert W, Börner A-R, Fricke H, Kühnel G, Meyer GJ, et al. [1-11C] Acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med. 2001;42:1174–82.PubMed

38.

Schäfers M, Dutka D, Rhodes CG, Lammertsma AA, Hermansen F, Schober O, et al. Myocardial presynaptic and postsynaptic autonomic dysfunction in hypertrophic cardiomyopathy. Circ Res. 1998;82:57–62.PubMedCrossRef

39.

Thackeray JT, Beanlands RS, DaSilva JN. Insulin restores myocardial presynaptic sympathetic neuronal integrity in insulin-resistant diabetic rats. J Nucl Cardiol. 2013;20:845–56.PubMedCrossRef

40.

Thackeray JT, Radziuk J, Harper M-E, Suuronen EJ, Ascah KJ, Beanlands RS, et al. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol. 2011;10:75.PubMedPubMedCentralCrossRef

41.

Hutchins GD, Caraher JM, Raylman RR. A region of interest strategy for minimizing resolution distortions in quantitative myocardial PET studies. J Nucl Med. 1992;33:1243–50.PubMed

42.

Sasano T, Abraham MR, Chang KC, Ashikaga H, Mills KJ, Holt DP, et al. Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol. 2008;51:2266–75.PubMedCrossRef

43.

Fallavollita JA, Dare JD, Carter RL, Baldwa S, Canty JM. Denervated myocardium is preferentially associated with sudden cardiac arrest in ischemic cardiomyopathy. Circ Cardiovasc Imaging. 2017;10:e006446.PubMedPubMedCentralCrossRef

44.

Aikawa T, Naya M, Obara M, Oyama-Manabe N, Manabe O, Magota K, et al. Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study. Eur J Nucl Med Mol Imaging. 2017;44:1897–905.PubMedCrossRef

45.

Zelt JGE, Mielniczuk LM, Orlandi C, Robinson S, Hadizad T, Walter O, et al. PET imaging of sympathetic innervation with [18F]Flurobenguan vs [11C]mHED in a patient with ischemic cardiomyopathy. J Nucl Cardiol 2018;1–3.

46.

Zelt J, Renaud J, Mielniczuk L, Garrard L, Orlandi C, Beanlands R, et al. Tracer kinetics of fluorine-18 LMI1195 compared to carbon-11 hydroxyephedrine for PET imaging of sympathetic innervation. Can J Cardiol. 2018;34:S117–8.CrossRef

Titel: Reliable quantification of myocardial sympathetic innervation and regional denervation using [11C]meta-hydroxyephedrine PET
verfasst von: 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
Publikationsdatum: 09.12.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04629-5

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2020

Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation

PET imaging of COVID-19: the target and the number

Relationship between coronary arterial 18F-sodium fluoride uptake and epicardial adipose tissue analyzed using computed tomography

Facing a disruptive threat: how can a nuclear medicine service be prepared for the coronavirus outbreak 2020?

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden