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. 2019 May 21;292(1):267–268. doi: 10.1148/radiol.2019190486

Is High-Spatial-Resolution Diffusion MRI Applicable for the Diagnosis of Parkinson Disease?

Young Hee Sung *, Eung Yeop Kim †,✉
PMCID: PMC7370928  PMID: 31112091

Editor:

We read with great interest the article by Zhong and colleagues in the April 2019 issue of Radiology titled “High-Spatial-Resolution Diffusion MRI in Parkinson Disease: Lateral Asymmetry of the Substantia Nigra” (1). The authors demonstrated asymmetric abnormality in the left substantia nigra (SN) in right-handed patients with Parkinson disease (PD) by using a sophisticated model with high-spatial-resolution diffusion MRI. Despite the intriguing results, we would like to raise a few concerns.

First, Zhong et al defined the SN as the hypointense region at the level of the red nucleus on images (b = 0 sec/mm2). However, it has been considered that this region represents the substantia nigra pars reticulata. The SN pars compacta, which is a region that contains dopaminergic neurons, is rather mainly located below the red nucleus (2). As PD is characterized by the death of dopaminergic neurons in the SN pars compacta, their definition of the SN may not be suitable for evaluating neuronal loss in PD.

Second, they only determined abnormality in the left SN. There is, however, no ground truth for their results. If their measurements are valid, the left striatum should be more affected at dopamine transporter imaging, which may serve as the reference standard. It would therefore be better to show the results of dopamine transporter imaging to prove their findings.

Third, it has been known that asymmetric symptoms do not change over the course of PD (3), and rest tremor of a limb is one of the supportive criteria for its diagnosis (4). In the study by Zhong et al, 17 of 27 patients with PD presented with left-sided symptoms. It is therefore expected that the right SN may be more affected than the left one. Unexpectedly, however, the authors only showed abnormality in the left SN.

Last, a recent meta-analysis of dorsal nigral hyperintensity at susceptibility-weighted imaging for PD showed a sensitivity of 94.6% and specificity of 94.4% (5). The study by Zhong and colleagues, however, had a sensitivity of 66.7% and specificity of 70.4%, with the best area under the receiver operating characteristic curve of 0.73. In this regard, their method may be limited for diagnosis of PD.

Footnotes

Disclosures of Conflicts of Interest: H.Y.S. disclosed no relevant relationships. E.Y.K. disclosed no relevant relationships.

References

  • 1.Zhong Z, Merkitch D, Karaman MM, et al. High-spatial-resolution diffusion MRI in Parkinson disease: lateral asymmetry of the substantia nigra. Radiology 2019;291(1):149–157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Langley J, He N, Huddleston DE, et al. Reproducible detection of nigral iron deposition in 2 Parkinson’s disease cohorts. Mov Disord 2019;34(3):416–419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Lee CS, Schulzer M, Mak E, Hammerstad JP, Calne S, Calne DB. Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis. Neurology 1995;45(3 Pt 1):435–439. [DOI] [PubMed] [Google Scholar]
  • 4.Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30(12):1591–1601. [DOI] [PubMed] [Google Scholar]
  • 5.Mahlknecht P, Krismer F, Poewe W, Seppi K. Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson’s disease. Mov Disord 2017;32(4):619–623. [DOI] [PubMed] [Google Scholar]
Radiology. 2019 May 21;292(1):267–268. doi: 10.1148/radiol.2019190486

Response

Zheng Zhong *,§, Douglas Merkitch ║, M Muge Karaman *,§, Jiaxuan Zhang *,#, Jennifer G Goldman ║,**, Xiaohong Joe Zhou *,†,‡,§,✉

We thank Drs Sung and Kim for their thoughtful letter, which gives us an opportunity to clarify our study (1). A point-by-point response is provided below.

First, we would like to clarify that the regions of interest in our study were not selected at the level of the red nucleus. As stated in our article, the structure of SN was identified in at least three contiguous sections. The middle section, which was typically inferior to the red nucleus, was chosen for analysis. We agree that the selected section may partially contain SN pars reticulata. To reduce the contribution of the SN pars reticulata, we repeated the analysis using the section immediately inferior to the middle section. The results showed a higher area under the curve (area under the receiver operating characteristic curve = 0.82) than what was reported in our article (area under the receiver operating characteristic curve = 0.73) when the combination of α and β on the left SN was used for differentiating patients with PD from healthy control participants. Similar improvements were also seen in other diffusion parameters and their combinations, suggesting the importance of SN pars compacta as compared with SN pars reticulata (2).

Second, we agree that another independent methodology, such as histopathologic analysis or dopamine transporter imaging, is needed to substantiate our observations. This was acknowledged in our article (1) and will be addressed in future studies.

Third, we reported that 17 of 27 patients with PD presented with left-side onset. These patients continued left-side dominance of symptoms at the time of study based on motor scores (data not presented), which is consistent with the report by Lee et al (3). However, over time, PD symptoms frequently become bilateral, which may partially explain the left SN abnormalities at imaging. Further study will be needed to advance our understanding regarding laterality, both clinically and radiologically.

Last, susceptibility-weighted imaging is sensitive to iron deposition (4), whereas high-b-value diffusion MRI can probe tissue microstructures (5). It was not our intent to compare the performance of these two techniques. Instead, our focus was on reporting lateral asymmetry of SN in quantitative diffusion parameters. This asymmetry may complement other imaging techniques such as susceptibility-weighted imaging to improve the characterization of PD.

Footnotes

Disclosures of Conflicts of Interest: Z.Z. disclosed no relevant relationships. D.M. Activities related to the present article: supported in part by grants from the National Institutes of Health (NIH K23NS060949) and the Michael J. Fox Foundation. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. M.M.K. Activities related to the present article: supported in part by a grant from the National Institutes of Health (NIH R01EB026716). Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. J.Z. disclosed no relevant relationships. J.G.G. Activities related to the present article: supported in part by grants from the National Institutes of Health (NIH K23NS060949) and the Michael J. Fox Foundation. Activities not related to the present article: is a paid consultant for Acadia, Aptinyx, Sunovion, and WorldwideMed; institution has grants/grants pending from Biogen, CHDI, and Consolidated Antiaging. Other relationships: disclosed no relevant relationships. X.J.Z. Activities related to the present article: supported in part by grants from the National Institutes of Health (NIH 1S10RR028898 and R01EB026716). Activities not related to the present article: is a paid consultant for Horizon Medical Physics Services; institution has grants from Abbvie; has a patent issued; receives royalties from Elsevier. Other relationships: disclosed no relevant relationships.

References

  • 1.Zhong Z, Merkitch D, Karaman MM, et al. High-spatial-resolution diffusion MRI in Parkinson disease: lateral asymmetry of the substantia nigra. Radiology 2019;291(1):149–157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Langley J, He N, Huddleston DE, et al. Reproducible detection of nigral iron deposition in 2 Parkinson’s disease cohorts. Mov Disord 2019;34(3):416–419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Lee CS, Schulzer M, Mak E, Hammerstad JP, Calne S, Calne DB. Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis. Neurology 1995;45(3 Pt 1):435–439. [DOI] [PubMed] [Google Scholar]
  • 4.Haacke EM, Xu Y, Cheng YC, Reichenbach JR. Susceptibility weighted imaging (SWI). Magn Reson Med 2004;52(3):612–618. [DOI] [PubMed] [Google Scholar]
  • 5.Tang L, Zhou XJ. Diffusion MRI of cancer: from low to high b-values. J Magn Reson Imaging 2019;49(1):23–40. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Radiology are provided here courtesy of Radiological Society of North America

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