Chonnam Med J.  2016 Sep;52(3):145-150. 10.4068/cmj.2016.52.3.145.

¹²³I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases

• Nakajima K
• Yamada M

• KMID: 2432264
• DOI: http://doi.org/10.4068/cmj.2016.52.3.145

Abstract

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

Keyword

Lewy Body Disease; Parkinson Disease; Dementia; Nuclear Medicine; Quantitation

MeSH Terms

3-Iodobenzylguanidine
Cardiology
Dementia
Diagnosis
Japan
Lewy Bodies
Lewy Body Disease
Neurology
Nuclear Medicine
Parkinson Disease
Parkinsonian Disorders
Quality Control
3-Iodobenzylguanidine

Figure

• 

  FIG. 1 Semiautomatic method of setting ROI. Circular heart and rectangular mediastinal ROI (height, 30%; width, 10% of the mediastinum) are automatically determined after pointing towards the center of the heart.

• 

  FIG. 2 Typical calibration phantom images with low-energy high-resolution (LEHR) and medium-energy low-penetration (MELP) collimators. Contrast between heart and mediastinal counts is notable in both images. Regions of interest are automatically selected and positioned by smartMIBG software.

• 

  FIG. 3 123I-MIBG H/M ratio in control, Alzheimer's disease (AD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and pure autonomic failure (PAF). Regions of interest were positioned using smartMIBG software. H/M ratios are 2.9, 3.7, 3.0, 1.2, 1.7 and 1.2, respectively.

• 

  FIG. 4 Late H/M ratios in patients with probable Alzheimer's disease (AD), possible dementia with Lewy bodies (DLB), and probable DLB. Differences are significant among groups (p < 0.0001). Data are from Reference 26.

• 

  FIG. 5 Imaging with 123I-MIBG and 123I-ioflupane from a 72-year-old man with progressive supra-nuclear palsy (PSP). Uptake is normal on MIBG image (left) and obviously decreased on both sides of striatum on ioflupane image (right).

Reference

1. Tamaki N. Guidelines for clinical use of cardiac nuclear medicine (JCS 2005). Circ J. 2005; 69(Suppl IV):1125–1202.

2. Nakajima K, Nakata T. Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan. J Nucl Med. 2015; 56(Suppl 4):11S–19S. PMID: 26033897.

3. McKeith IG. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis. 2006; 9(3 Suppl):417–423. PMID: 16914880.

4. Nakajima K, Okuda K, Yoshimura M, Matsuo S, Wakabayashi H, Imanishi Y, et al. Multicenter cross-calibration of I-123 metaiodobenzylguanidine heart-to-mediastinum ratios to overcome camera-collimator variations. J Nucl Cardiol. 2014; 21:970–978. PMID: 24942608.

5. Slomka PJ, Mehta PK, Germano G, Berman DS. Quantification of I-123-meta-iodobenzylguanidine heart-to-mediastinum ratios: not so simple after all. J Nucl Cardiol. 2014; 21:979–983. PMID: 25005347.

6. Nakajima K, Yoshita M, Matsuo S, Taki J, Kinuya S. Iodine-123-MIBG sympathetic imaging in Lewy-body diseases and related movement disorders. Q J Nucl Med Mol Imaging. 2008; 52:378–387. PMID: 19088692.

7. Flotats A, Carrió I, Agostini D, Le Guludec D, Marcassa C, Schäfers M, et al. Proposal for standardization of ¹²³I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging. 2010; 37:1802–1812. PMID: 20577740.

8. Verberne HJ, Feenstra C, de Jong WM, Somsen GA, van Eck-Smit BL, Busemann Sokole E. Influence of collimator choice and simulated clinical conditions on ¹²³I-MIBG heart/mediastinum ratios: a phantom study. Eur J Nucl Med Mol Imaging. 2005; 32:1100–1107. PMID: 15902438.

9. Nakajima K, Matsubara K, Ishikawa T, Motomura N, Maeda R, Akhter N, et al. Correction of iodine-¹²³-labeled meta-iodobenzylguanidine uptake with multi-window methods for standardization of the heart-to-mediastinum ratio. J Nucl Cardiol. 2007; 14:843–851. PMID: 18022111.

10. Nakajima K, Matsumoto N, Kasai T, Matsuo S, Kiso K, Okuda K. Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database. Ann Nucl Med. 2016; 30:188–199. PMID: 26897008.

11. Okuda K, Nakajima K, Hosoya T, Ishikawa T, Konishi T, Matsubara K, et al. Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac Iodine-¹²³ MIBG imaging. J Nucl Cardiol. 2011; 18:82–89. PMID: 21104360.

12. Okuda K, Nakajima K, Sugino S, Kirihara Y, Matsuo S, Taki J, et al. Development and validation of a direct-comparison method for cardiac ¹²³I-metaiodobenzylguanidine washout rates derived from late 3-hour and 4-hour imaging. Eur J Nucl Med Mol Imaging. 2016; 43:319–325. PMID: 26298280.

13. Verberne HJ, Habraken JB, van Eck-Smit BL, Agostini D, Jacobson AF. Variations in ¹²³I-metaiodobenzylguanidine (MIBG) late heart mediastinal ratios in chronic heart failure: a need for standardisation and validation. Eur J Nucl Med Mol Imaging. 2008; 35:547–553. PMID: 17922122.

14. Nakajima K, Okuda K, Matsuo S, Yoshita M, Taki J, Yamada M, et al. Standardization of metaiodobenzylguanidine heart to mediastinum ratio using a calibration phantom: effects of correction on normal databases and a multicentre study. Eur J Nucl Med Mol Imaging. 2012; 39:113–119. PMID: 22009380.

15. Nakajima K, Nakata T, Yamada T, Yamashina S, Momose M, Kasama S, et al. A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging. Eur J Nucl Med Mol Imaging. 2014; 41:1673–1682. PMID: 24663289.

16. Nakajima K, Nakata T, Matsuo S, Jacobson AF. Creation of mortalityrisk charts using ¹²³I meta-iodobenzylguanidine heart-to-mediastinum ratio in patients with heart failure: 2- and 5-year risk models. Eur Heart J Cardiovasc Imaging. 2015; [Epub ahead of print]. DOI: 10.1093/ehjci/jev322.

17. Hakusui S, Yasuda T, Yanagi T, Tohyama J, Hasegawa Y, Koike Y, et al. A radiological analysis of heart sympathetic functions with meta-[¹²³I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst. 1994; 49:81–84. PMID: 7963268.

18. Iwasa K, Nakajima K, Yoshikawa H, Tada A, Taki J, Takamori M. Decreased myocardial ¹²³I-MIBG uptake in Parkinson's disease. Acta Neurol Scand. 1998; 97:303–306. PMID: 9613559.

19. Yoshita M. Differentiation of idiopathic Parkinson's disease from striatonigral degeneration and progressive supranuclear palsy using iodine-¹²³ meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci. 1998; 155:60–67. PMID: 9562324.

20. Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. ¹²³I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999; 67:189–194. PMID: 10406987.

21. Orimo S, Suzuki M, Inaba A, Mizusawa H. ¹²³I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2012; 18:494–500. PMID: 22321865.

22. Yoshita M, Taki J, Yamada M. A clinical role for [¹²³I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2001; 71:583–588. PMID: 11606666.

23. Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, et al. Cardiac ¹²³I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2001; 70:781–783. PMID: 11385013.

24. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005; 65:1863–1872. PMID: 16237129.

25. Hanyu H, Shimizu S, Hirao K, Kanetaka H, Iwamoto T, Chikamori T, et al. Comparative value of brain perfusion SPECT and [¹²³I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2006; 33:248–253. PMID: 16328506.

26. Sakamoto F, Shiraishi S, Yoshida M, Tomiguchi S, Hirai T, Namimoto T, et al. Diagnosis of dementia with Lewy bodies: diagnostic performance of combined ¹²³I-IMP brain perfusion SPECT and ¹²³I-MIBG myocardial scintigraphy. Ann Nucl Med. 2014; 28:203–211. PMID: 24363079.

27. Yoshita M, Arai H, Arai H, Arai T, Asada T, Fujishiro H, et al. Diagnostic accuracy of ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study. PLoS One. 2015; 10:e0120540. PMID: 25793585.

28. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-¹²³ meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010; 55:2212–2221. PMID: 20188504.

29. Nakata T, Nakajima K, Yamashina S, Yamada T, Momose M, Kasama S, et al. A pooled analysis of multicenter cohort studies of ¹²³I-mIBG imaging of sympathetic innervation for assessment of long-term prognosis in heart failure. JACC Cardiovasc Imaging. 2013; 6:772–784. PMID: 23845574.

30. Agostini D, Verberne HJ, Burchert W, Knuuti J, Povinec P, Sambuceti G, et al. I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study. Eur J Nucl Med Mol Imaging. 2008; 35:535–546. PMID: 18043919.

31. King AE, Mintz J, Royall DR. Meta-analysis of ¹²³I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord. 2011; 26:1218–1224. PMID: 21480373.

32. Tossici-Bolt L, Hoffmann SM, Kemp PM, Mehta RL, Fleming JS. Quantification of [¹²³I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio. Eur J Nucl Med Mol Imaging. 2006; 33:1491–1499. PMID: 16858570.