European Radiology

, Volume 27, Issue 12, pp 5073–5079 | Cite as

Structural changes in Parkinson’s disease: voxel-based morphometry and diffusion tensor imaging analyses based on 123I-MIBG uptake

  • Kazufumi Kikuchi
  • Akio Hiwatashi
  • Osamu Togao
  • Koji Yamashita
  • Ryo Somehara
  • Ryotaro Kamei
  • Shingo Baba
  • Hiroo Yamaguchi
  • Jun-ichi Kira
  • Hiroshi Honda



Patients with Parkinson’s disease (PD) may exhibit symptoms of sympathetic dysfunction that can be measured using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. We investigated the relationship between microstructural brain changes and 123I-MIBG uptake in patients with PD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analyses.


This retrospective study included 24 patients with PD who underwent 3 T magnetic resonance imaging and 123I-MIBG scintigraphy. They were divided into two groups: 12 MIBG-positive and 12 MIBG-negative cases (10 men and 14 women; age range: 60–81 years, corrected for gender and age). The heart/mediastinum count (H/M) ratio was calculated on anterior planar 123I-MIBG images obtained 4 h post-injection. VBM and DTI were performed to detect structural differences between these two groups.


Patients with low H/M ratio had significantly reduced brain volume at the right inferior frontal gyrus (uncorrected p < 0.0001, K > 90). Patients with low H/M ratios also exhibited significantly lower fractional anisotropy than those with high H/M ratios (p < 0.05) at the left anterior thalamic radiation, the left inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, and the left uncinate fasciculus.


VBM and DTI may reveal microstructural changes related to the degree of 123I-MIBG uptake in patients with PD.

Key Points

Advanced MRI methods may detect brain damage more precisely.

Voxel-based morphometry can detect grey matter changes in Parkinson’s disease.

Diffusion tensor imaging can detect white matter changes in Parkinson’s disease.


Parkinson’s disease Magnetic resonance imaging Diffusion tensor imaging Radionuclide imaging Neurodegenerative diseases 



Diffusion tensor imaging


Fractional anisotropy




Mean diffusivity




Multiple system atrophy


Parkinson’s disease


Voxel-based morphometry


Compliance with ethical standards


The scientific guarantor of this publication is Hiroshi Honda.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.


The authors state that this work has not received any funding.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the institutional review board.

Ethical approval

Institutional review board approval was obtained.


• retrospective

• diagnostic or prognostic study

• performed at one institution


  1. 1.
    de Lau LM, Breteler MM (2006) Epidemiology of Parkinson's disease. Lancet Neurol 5:525–535CrossRefPubMedGoogle Scholar
  2. 2.
    Obeso JA, Rodriguez-Oroz MC, Rodriguez M et al (2000) Pathophysiology of the basal ganglia in Parkinson's disease. Trends Neurosci 23:S8–S19CrossRefPubMedGoogle Scholar
  3. 3.
    Hattori T, Orimo S, Hallett M et al (2014) Relationship and factor structure in multisystem neurodegeneration in Parkinson's disease. Acta Neurol Scand 130:347–353CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sisson JC, Shapiro B, Meyers L et al (1987) Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 28:1625–1636PubMedGoogle Scholar
  5. 5.
    Mantysaari M, Kuikka J, Mustonen J et al (1992) Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine. Diabetes 41:1069–1075CrossRefPubMedGoogle Scholar
  6. 6.
    Yoshita M (1998) Differentiation of idiopathic Parkinson's disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155:60–67CrossRefPubMedGoogle Scholar
  7. 7.
    Hakusui S, Yasuda T, Yanagi T et al (1994) A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst 49:81–84CrossRefPubMedGoogle Scholar
  8. 8.
    Orimo S, Takahashi A, Uchihara T et al (2007) Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson's disease. Brain Pathol 17:24–30CrossRefPubMedGoogle Scholar
  9. 9.
    Orimo S, Kanazawa T, Nakamura A et al (2007) Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol 113:81–86CrossRefPubMedGoogle Scholar
  10. 10.
    Gattellaro G, Minati L, Grisoli M et al (2009) White matter involvement in idiopathic Parkinson disease: a diffusion tensor imaging study. AJNR Am J Neuroradiol 30:1222–1226CrossRefPubMedGoogle Scholar
  11. 11.
    Schrag A, Good CD, Miszkiel K et al (2000) Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 54:697–702CrossRefPubMedGoogle Scholar
  12. 12.
    Vymazal J, Righini A, Brooks RA et al (1999) T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 211:489–495CrossRefPubMedGoogle Scholar
  13. 13.
    Burton EJ, McKeith IG, Burn DJ, Williams ED, O'Brien JT (2004) Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. Brain 127:791–800CrossRefPubMedGoogle Scholar
  14. 14.
    Rae CL, Correia MM, Altena E, Hughes LE, Barker RA, Rowe JB (2012) White matter pathology in Parkinson's disease: the effect of imaging protocol differences and relevance to executive function. Neuroimage 62:1675–1684CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Karagulle Kendi AT, Lehericy S, Luciana M, Ugurbil K, Tuite P (2008) Altered diffusion in the frontal lobe in Parkinson disease. AJNR Am J Neuroradiol 29:501–505CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang K, Yu C, Zhang Y et al (2011) Voxel-based analysis of diffusion tensor indices in the brain in patients with Parkinson's disease. Eur J Radiol 77:269–273CrossRefPubMedGoogle Scholar
  17. 17.
    Salsone M, Cerasa A, Arabia G et al (2014) Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: volumetric study. Parkinsonism Relat Disord 20:1004–1008CrossRefPubMedGoogle Scholar
  18. 18.
    Postuma RB, Berg D, Stern M et al (2015) MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 30:1591–1601CrossRefPubMedGoogle Scholar
  19. 19.
    Webster DD (1968) Critical analysis of the disability in Parkinson's disease. Mod Treat 5:257–282PubMedGoogle Scholar
  20. 20.
    Yonezawa M, Nagao M, Abe K et al (2013) Relationship between impaired cardiac sympathetic activity and spatial dyssynchrony in patients with non-ischemic heart failure: assessment by MIBG scintigraphy and tagged MRI. J Nucl Cardiol 20:600–608CrossRefPubMedGoogle Scholar
  21. 21.
    Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38:95–113CrossRefPubMedGoogle Scholar
  22. 22.
    Smith SM, Jenkinson M, Johansen-Berg H et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505CrossRefPubMedGoogle Scholar
  23. 23.
    Smith SM, Jenkinson M, Woolrich MW et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23:S208–S219CrossRefPubMedGoogle Scholar
  24. 24.
    Mori S, Oishi K, Jiang H et al (2008) Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage 40:570–582CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98CrossRefPubMedGoogle Scholar
  26. 26.
    Palma JA, Kaufmann H (2014) Autonomic disorders predicting Parkinson's disease. Parkinsonism Relat Disord 20:S94–S98CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Cubo E, Martin PM, Martin-Gonzalez JA, Rodriguez-Blazquez C, Kulisevsky J, Members EG (2010) Motor laterality asymmetry and nonmotor symptoms in Parkinson's disease. Mov Disord 25:70–75CrossRefPubMedGoogle Scholar
  28. 28.
    Sakakibara R, Tateno F, Kishi M, Tsuyusaki Y, Terada H, Inaoka T (2014) MIBG myocardial scintigraphy in pre-motor Parkinson's disease: a review. Parkinsonism Relat Disord 20:267–273CrossRefPubMedGoogle Scholar
  29. 29.
    Cacciola A, Milardi D, Anastasi GP et al (2016) A Direct Cortico-Nigral Pathway as Revealed by Constrained Spherical Deconvolution Tractography in Humans. Front Hum Neurosci 10:374CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290:213–242CrossRefPubMedGoogle Scholar
  31. 31.
    Kunzle H (1978) An autoradiographic analysis of the efferent connections from premotor and adjacent prefrontal regions (areas 6 and 9) in macaca fascicularis. Brain Behav Evol 15:185–234CrossRefPubMedGoogle Scholar
  32. 32.
    Kwon HG, Jang SH (2014) Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain. Front Hum Neurosci 8:41PubMedPubMedCentralGoogle Scholar
  33. 33.
    Peran P, Cherubini A, Assogna F et al (2010) Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature. Brain 133:3423–3433CrossRefPubMedGoogle Scholar
  34. 34.
    Hattori T, Orimo S, Aoki S et al (2012) Cognitive status correlates with white matter alteration in Parkinson's disease. Hum Brain Mapp 33:727–739CrossRefPubMedGoogle Scholar
  35. 35.
    Song SK, Lee JE, Park HJ, Sohn YH, Lee JD, Lee PH (2011) The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status. Mov Disord 26:289–296CrossRefPubMedGoogle Scholar
  36. 36.
    Nishio Y, Hirayama K, Takeda A et al (2010) Corticolimbic gray matter loss in Parkinson's disease without dementia. Eur J Neurol 17:1090–1097CrossRefPubMedGoogle Scholar
  37. 37.
    Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-Keil D, Rub U (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol 249:III/1–III/5CrossRefGoogle Scholar
  38. 38.
    Chan LL, Rumpel H, Yap K et al (2007) Case control study of diffusion tensor imaging in Parkinson's disease. J Neurol Neurosurg Psychiatry 78:1383–1386CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300Google Scholar
  40. 40.
    Woo CW, Krishnan A, Wager D (2014) Cluster-extent based thresholding in fMRI analyses: Pitfalls and recommendations. Neuroimage 91:412–419CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  1. 1.Department of Clinical Radiology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Neurology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Personalised recommendations