First steps in imaging the right ventricle with iodine-123-metaiodobenzylguanidine (123I-MIBG) and cadmium-zinc-telluride technology

  • Anisiia Doytchinova
  • Myron GersonEmail author

Pulmonary hypertension is a physiologic condition defined as mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg measured on right heart catheterization. This can be caused by a variety of diseases, of which left -sided heart dysfunction being the most common.1,2 The two large groups of pulmonary hypertension are pre-capillary, characterized by end-expiratory pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg and peripheral vascular resistance > 3 Wood units; and post-capillary, defined as PCWP > 15 mm Hg. Despite the heterogeneity of conditions leading to elevated pulmonary pressures, pulmonary hypertension uniformly remains an indicator of poor prognosis. The clinical significance of mPAP values between 20 and 24 mm Hg remains under debate, with some studies also showing increased mortality in this group.3

Pulmonary arterial hypertension (PAH) is a small subset of pre-capillary pulmonary hypertension that occurs in the absence of lung disease, chronic thromboembolism or other rare conditions.4 This results from imbalance of secreted vasoactive substances, which favor vasoconstriction, thrombosis, and endothelial and smooth muscle proliferation.5,6 Even with the recent therapeutic advances, PAH remains a disease with significant morbidity and mortality.4,7 Mortality ranges up to 10% per year in patients with high-risk indicators such as right ventricular failure, repeated syncope, pericardial effusion, impaired 6-minute walk distances, low cardiac index and high levels of B-type natriuretic peptide (BNP), and right atrial pressures.4 Because right ventricular failure is the main cause of death in this population, patients with PAH are routinely followed with echocardiography to assess right ventricular function and guide therapy.8 However, each echocardiographic measure of right ventricular function has inherent limitations mainly due to the complex shape and structure of the right ventricle.9

It is postulated that patients who exhibit a maladaptive pattern of right ventricular remodeling with dilatation, fibrosis, and decreased contractility also demonstrate downregulation of α, β, and dopaminergic receptors and increased sympathetic activity.10,11 As such, nuclear imaging with iodine-123-metaiodobenzylguanidine (123I-MIBG) can potentially play an important role in the management and risk stratification of these patients. In support of this notion, data have suggested that sympathetic function is altered in patients with PAH. In a study of 55 patients with pulmonary hypertension including 28 with PAH, heart-to-mediastinal ratios (H/M) were lower in pulmonary hypertension compared to control subjects. In addition, H/M ratios > 2.0 were associated with improved survival.12 Takao et al. have also shown that right ventricle-to-left ventricle (RV/LV) uptake ratio of 123I-MIBG correlates well with mean pulmonary pressures.13 More recently in a small study of 21 patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH), patients with PAH had lower 123I-MIBG lung uptake compared to subjects with CTEPH and controls.14 Contrary to the above findings, clinical studies treating PAH patients with beta blockers have not demonstrated improved outcomes.15 It is possible that the right dose and/or type of beta blocker has not been tested.

In this issue of the Journal, Gimelli et al. studied 13 patients with newly diagnosed PAH and 11 patients with pulmonary hypertension associated with non-ischemic dilated cardiomyopathy (DCM) using 123I-MIBG uptake and cadmium-zinc-telluride (CZT) technology. The authors employed the 17-segment left ventricle model and scored the percent uptake in the right ventricle relative to the interventricular septum. For this purpose, a semi-quantitative software (Corridor4DM, INVIA; Ann Arbor, MI) was used after manual reconstruction of the right ventricular images. Due to artifacts in the inferior wall, only segments 1, 2, 3, 4, 8, 9, 13, and 14 were reported and those were designated to correspond to the lateral right ventricular wall. The authors found no difference in H/M ratios between the groups, but noted that patients with PAH had significantly lower lung-to-mediastinal (L/M) ratios. The study also demonstrated that right ventricular perfusion and early innervation were significantly higher in PAH than in DCM and that RV/LV perfusion and innervation ratios were directly correlated with right ventricular thickness and diameter.

Despite its small size, the study is novel and of potential clinical importance. Lung-to-mediastinal ratios in combination with H/M values are associated with all cause mortality and rate of events in patients with heart failure.16,17 Previous studies from the authors’ group have also shown the feasibility of performing simultaneous LV perfusion and innervation with a CZT camera.18 However, this is the first study to apply this concept to the right ventricle.

It is well established that possibly due to prolonged transit time, heart failure and/or elevated left ventricular filling pressure result in increased lung uptake of myocardial perfusion tracers.19 This is likely to be an important factor in the increased L/M ratios seen in the DCM patients in the present study as the NT pro-BNP levels averaged 13,213 pg/mL in the DCM patients and only 259 pg/mL in the PAH patients. As pulmonary transit time should also be elevated in the PAH patients, this would seem to further support the postulate that low L/M ratio in the PAH patients may reflect impaired pulmonary endothelial function.

The main limitations of the study are the small sample size, significantly higher body mass index in the DCM group, and the poor quality images in some of the cases. There are no prior data applying the 17-segment model of the left ventricle to the right heart. Further, all patients studied had some evidence of right ventricular hypertrophy and it is unknown if such analysis could be performed in those with normal thickness. Given some patients with PAH are diagnosed quite late into their course and there has been no improvement in time to diagnosis over the last two decades, a modality that can aid in earlier diagnosis may be of significant importance.20 Additional larger studies are needed to answer these questions, validate the findings presented by the authors, and demonstrate reproducibility.



The authors have no conflicts of interest to declare.


  1. 1.
    Hoeper MM, Humbert M, Souza R, Idrees M, Kawut SM, Sliwa-Hahnle K, Jing ZC, Gibbs JS. A global view of pulmonary hypertension. Lancet Respir Med. 2016;4:306–22.CrossRefGoogle Scholar
  2. 2.
    Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D42–50.CrossRefGoogle Scholar
  3. 3.
    Maron BA, Hess E, Maddox TM, Opotowsky AR, Tedford RJ, Lahm T, Joynt KE, Kass DJ, Stephens T, Stanislawski MA, Swenson ER, Goldstein RH, Leopold JA, Zamanian RT, Elwing JM, Plomondon ME, Grunwald GK, Baron AE, Rumsfeld JS, Choudhary G. Association of borderline pulmonary hypertension with mortality and hospitalization in a large patient cohort: Insights from the veterans affairs clinical assessment, reporting, and tracking program. Circulation. 2016;133:1240–8.CrossRefGoogle Scholar
  4. 4.
    Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M and Group ESCSD. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37:67–119.Google Scholar
  5. 5.
    Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004;351:1655–65.CrossRefGoogle Scholar
  6. 6.
    Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT. Pulmonary arterial hypertension: the clinical syndrome. Circ Res. 2014;115:115–30.CrossRefGoogle Scholar
  7. 7.
    Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jais X, Montani D, Souza R, Simonneau G. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156–63.CrossRefGoogle Scholar
  8. 8.
    van Wolferen SA, Marcus JT, Boonstra A, Marques KM, Bronzwaer JG, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007;28:1250–7.CrossRefGoogle Scholar
  9. 9.
    Satriano A, Pournazari P, Hirani N, Helmersen D, Thakrar M, Weatherald J, White JA, Fine NM. Characterization of right ventricular deformation in pulmonary arterial hypertension using three-dimensional principal strain analysis. J Am Soc Echocardiogr. 2019;32:385–93.CrossRefGoogle Scholar
  10. 10.
    Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res. 2014;115:176–88.CrossRefGoogle Scholar
  11. 11.
    Drake JI, Bogaard HJ, Mizuno S, Clifton B, Xie B, Gao Y, Dumur CI, Fawcett P, Voelkel NF, Natarajan R. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol. 2011;45:1239–47.CrossRefGoogle Scholar
  12. 12.
    Sakamaki F, Satoh T, Nagaya N, Kyotani S, Oya H, Nakanishi N, Kuribayashi S, Ishida Y. Correlation between severity of pulmonary arterial hypertension and 123I-metaiodobenzylguanidine left ventricular imaging. J Nucl Med. 2000;41:1127–33.Google Scholar
  13. 13.
    Morimitsu T, Miyahara Y, Sinboku H, Ikeda S, Naito T, Nishijima K, Takao M. Iodine-123-metaiodobenzylguanidine myocardial imaging in patients with right ventricular pressure overload. J Nucl Med. 1996;37:1343–6.Google Scholar
  14. 14.
    Higo K, Kubota K, Miyanaga S, Miyata M, Nakajo M, Jinguji M, Ohishi M. Impairment of iodine-123-metaiodobenzylguanidine ((123)I-MIBG) uptake in patients with pulmonary artery hypertension. Int Heart J. 2018;59:112–9.CrossRefGoogle Scholar
  15. 15.
    Perros F, de Man FS, Bogaard HJ, Antigny F, Simonneau G, Bonnet S, Provencher S, Galie N, Humbert M. Use of beta-blockers in pulmonary hypertension. Circ Heart Fail. 2017;10(4):e003703.Google Scholar
  16. 16.
    Gerson MC, Dwivedi AK, Abdallah M, Shukla R, Jacobson AF. Significance of I-123 metaiodobenzylguanidine ((1)(2)(3)I-MIBG) lung activity in subjects with heart failure in comparison to healthy control subjects. J Nucl Cardiol. 2013;20:592–9.CrossRefGoogle Scholar
  17. 17.
    Kamiyoshi Y, Yazaki Y, Urushibata K, Koizumu T, Kasai H, Izawa A, Kinoshita O, Hongo M, Ikeda U. Risk stratification assessed by combined lung and heart iodine-123 metaiodobenzylguanidine uptake in patients with idiopathic dilated cardiomyopathy. Am J Cardiol. 2008;101:1482–6.CrossRefGoogle Scholar
  18. 18.
    Gimelli A, Liga R, Giorgetti A, Genovesi D, Marzullo P. Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium-zinc-telluride camera: first clinical experience. Eur Heart J Cardiovasc Imaging. 2014;15:575–85.CrossRefGoogle Scholar
  19. 19.
    Boucher CA, Zir LM, Beller GA, Okada RD, McKusick KA, Strauss HW, Pohost GM. Increased lung uptake of thallium-201 during exercise myocardial imaging: clinical, hemodynamic and angiographic implications in patients with coronary artery disease. Am J Cardiol. 1980;46:189–96.CrossRefGoogle Scholar
  20. 20.
    Brown LM, Chen H, Halpern S, Taichman D, McGoon MD, Farber HW, Frost AE, Liou TG, Turner M, Feldkircher K, Miller DP, Elliott CG. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest. 2011;140:19–26.CrossRefGoogle Scholar

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© American Society of Nuclear Cardiology 2019

Authors and Affiliations

  1. 1.Division of Cardiovascular Health and DiseaseUniversity of Cincinnati Medical CenterCincinnatiUSA

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