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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 2  |  Page : 278-281

Effectiveness of QSM Over R2* in Assessment of Parkinson's Disease - A Systematic Review

Department of Medical Imaging Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India

Date of Web Publication15-May-2020

Correspondence Address:
Pendem Saikiran
Department of Medical Imaging Technology, School of Allied Health Sciences, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.284377

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 » Abstract 

The incidence and prevalence of Parkinson's (PD) are increasing rapidly in developing countries. PD is difficult to diagnose based on clinical assessment. Presently, magnetic resonance imaging (MRI) methods such as R2* and Quantitative Susceptibility Mapping (QSM) were found to be useful in diagnosing the PD based on the iron deposition in different regions of the brain. The objective of this review was to evaluate the efficacy of QSM over R2* in assessment of PD. A comprehensive literature search was made on PubMed-Medline, CINAHL, Science Direct, Scopus, Web of Science, and the Cochrane library databases for original research articles published between 2000 and 2018. Original articles that reported the efficacy of QSM and R2* in assessment of PD were included. A total of 327 studies were identified in the literature search. However, only ten studies were eligible for analysis. Of the ten studies, five studies compared the accuracy of QSM over R2* in measuring the iron deposition in different regions of brain in PD. Our review found that QSM has better accuracy in identifying iron deposition in PD patients compared to R2*. However, there is discrepancy in the results between MRI Imaging methods and Postmortem studies. Additional longitudinal research studies are needed to provide a strong evidence base for the use of MRI imaging methods such as R2*and QSM in accurately measuring iron deposition in different regions of brain and serve as biomarkers in PD.

Keywords: Iron deposition, Parkinson's disease, quantitative susceptibility mapping, R2* mapping, substantia nigra
Key Message: Usefulness of QSM and R2* mapping in measuring iron deposition in Parkinson's disease

How to cite this article:
Saikiran P, Priyanka. Effectiveness of QSM Over R2* in Assessment of Parkinson's Disease - A Systematic Review. Neurol India 2020;68:278-81

How to cite this URL:
Saikiran P, Priyanka. Effectiveness of QSM Over R2* in Assessment of Parkinson's Disease - A Systematic Review. Neurol India [serial online] 2020 [cited 2022 May 26];68:278-81. Available from: https://www.neurologyindia.com/text.asp?2020/68/2/278/284377

Parkinson's disease (PD) is a neurodegenerative disorder affecting 1--2 per 1000 of the population. Prevalence of PD is 1% of the population aged above 60 years. It is mainly associated with the degeneration of dopaminergic neurons in the substantia nigra (SN) and increased iron deposition.[1],[2],[3] The iron deposition has also been observed in other brain regions, such as red nuclei, globus pallidus, head of caudate, putamen, and thalamus.[4],[5],[6],[7] The diagnostic accuracy of PD based on clinical assessment was not satisfactory. Hence, in vivo imaging of brain content would serve as biomarker for PD diagnosis. With the advent of magnetic resonance imaging (MRI), the in vivo imaging of brain iron content had become possible. R2 and R2* relaxometry methods of MRI were useful in estimating the iron deposition in subtantia nigra and other gray matter nuclei in PD Patients. R2 and R2* maps were acquired using fast spin echo sequence (echo time msec, 8000/86; bandwidth, range, -62.5 to 62.5 kHz; four signals acquired) and a multiecho gradient echo sequence (45/4.0, 7.6, 11.2, 14.8, 18.4, 22.0, 25.6, 29.2, 32.8, 36.4, 40.0; bandwidth range, -62.5 to 62.5 kHz; flip angle, 15°).[8],[9],[10],[11],[12],[13] The relaxometry methods had disadvantage of considering both local and surrounding tissue susceptibilities. These inaccuracies had led to the development of novel technique called Quantitative Susceptibility Mapping (QSM). In QSM, the inhomogeneities from surrounding structures was removed by deconvolution method which helps in providing direct measure of local inhomogenities of the magnetic field. QSM maps were acquired using 3D multi Gradient Echo (GRE) data. The magnitude and phase images were obtained. The brain regions were segmented and finally QSM maps with suppressed streak artifacts were reconstructed from the background corrected phase images using morphology enabled dipole inversion (MEDI) sequence.[12],[13],[14],[15]

The objective of this review was to compare QSM and R2* values in multiple deep gray matter nuclei in patients with PD and to determine if QSM can provide a more direct and accurate measure of iron content than R2* mapping, and more sensitive than R2* mapping to PD-related tissue changes.

 » Methods Top


This review was conducted according to the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The PRISMA includes a checklist to ensure transparent reporting of systematic reviews and a four-phase diagram.[16]

Literature search strategy

A comprehensive literature searches for relevant original research studies published between 2000 and 2018 was performed using PubMed-Medline, CINHAL, Science Direct, Scopus, and the Cochrane Library. The following keywords were used in the search: 'Parkinson's disease', 'R2* mapping', 'Quantitative Susceptibility Mapping', 'iron deposition', 'substantia nigra', 'red nucleus', 'Globus pallidus', 'Putamen,' and 'Head of Caudate nucleus'. Searches were limited to the English language and adult populations. Detailed methods of study retrieval from each database are shown in [Table 1]. References from retrieved studies were scanned for additional relevant studies, but none were identified.
Table 1: Detailed methods of study retrieval from each database

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Inclusion criteria

Studies were included in this review if they fulfilled the below-mentioned selection criteria:

Type of study

  • Original research studies that were published in English between 2000 and 2018
  • Case control studies that included QSM and R2* values in PD patients
  • The studies compared with QSM and R2* values in patients with PD.

Type of participants

The studies involved adult patients (above 18 years) with PD who underwent MRI brain which included QSM and R2*.

Types of outcome

Primary and secondary outcomes of effectiveness were assessed.

Primary outcomes

* Measurement of iron content in the regions of brain using MRI techniques such as R2* and QSM value.

Secondary outcomes

* Comparison of sensitivity between QSM and R2* values between PD and controls.

Data extraction

Two authors individually extracted data from each included study and any dissimilarity were resolved following a discussion.

Data synthesis

Data were assessed for quality of methods and outcomes.

 » Results Top

A total of 327 studies were identified through the literature. Seven duplicate articles were removed. After assessment of titles and abstract, 310 studies were excluded because they did not meet the inclusion criteria. An additional five studies were excluded after assessing the full text because they did not meet the review criteria. The exclusion criteria were studies comparing iron content measured in brain using MRI (QSM and R2*) and postmortem, studies measuring iron content by QSM and R2* in other pathologies. Finally, five studies were included in the data extraction [Figure 1].
Figure 1: Flow diagram showing study selection process

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Sample characteristics

The six reviewed studies involved 226 PD patients and 218 controls and the age group was 21–75. Both genders were included in all the studies. The majority of the patients were male. [Table 2] summarizes the sample characteristics of the reviewed studies.
Table 2: Patient characteristics in reviewed studies

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Quality assessment

Newcastle–Ottawa scale were utilized by two independent authors to assess the methodological qualities of the included studies. In the case of a disagreement a final decision was made by consensus with a third reviewer. Among the five studies none received the maximum quality score of nine points. Among five, one reviewed study had a methodological quality score of six, four had a score of five. All reviewed studies were case–control, specified patient characteristics, and reported inclusion and exclusion criteria. The detailed quality assessment is listed in [Table 3].
Table 3: The Characteristics of the 5 studies included for review

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Structure by structure analyses of results from individual studies

Substantia nigra

An elevation of iron concentration was found in both R2* and QSM measurements in all the studies. Three studies also noted elevated in the iron concentration in pars compacta[17],[18],[19] and one study noted elevation in pars reticulate.[19]

Red nucleus

An elevation of iron concentration was found in QSM measurement of one study.[20] There was no significant iron content detected in R2* and QSM measurements in the other studies.

Globus pallidus

An elevation of iron concentration was found in QSM measurement of one study.[20] There was no significant iron content detected in R2* and QSM measurements in the other studies.


There was no significant iron content detected in R2* and QSM measurements in all the studies.

Caudate nucleus

There was no significant iron content detected in R2* and QSM measurements in all the studies.


An elevation of iron concentration was found in QSM measurement of one study.[20] There was no significant iron content detected in R2* and QSM measurements in the other studies.

Clinical correlation of R2* and QSM

Out of five, three studies correlated R2* and QSM values with clinical parameters. One study found R2* values not correlated with any of the clinical parameters. QSM values in the substantia nigra pars compacta were highly correlated with the disease duration, levodopa equivalent daily dose [LEDD], unified Parkinson's disease rating scale (UPDRS).[18] Another longitudinal study found R2* values in substantia nigra correlated with UPDRS I and QSM values in substantia nigra got correlated with UPDRS III.[19] One study found several correlations R2* and QSM values in substantia nigra for UPDRS I, UPDRS II. The H–Y scale, LEDD was correlated with R2* and QSM values in substantia nigra.[20] Two studies did not correlate MRI measurements with clinical parameters.[17],[21]

Correlation of R2* and QSM

Three studies found that the accuracy was significantly higher for QSM than for R2*. The sensitivity of QSM compared to R2* in detecting the iron content deposition in substantia nigra of PD patients with controls with much larger dynamic range.[17],[18],[21]

 » Discussion Top

Excessive Iron deposition is frequently associated with pathogenesis of PD.[22],[23],[24] Our study represents the first systemic review that analysis iron levels in various brain regions of PD patients by R2* and QSM. Our review confirmed that there is increase in iron deposition in substantia nigra and suggests iron deposition may also occur in the red nucleus, globus pallidus, and thalamus. Our study shows that QSM was sensitive in detecting the iron deposition in substantia nigra compared to R2*. R2* weighting depends on the varying magnetic field generated by both local tissue magnetic susceptibility and surrounding tissue susceptibility. These inaccuracies led to reduced sensitivity of predicting iron deposition levels.[25] Our review found that QSM values were highly correlated with disease condition especially with UPDRS II and UPDRS III which determine the motor activity and more sensitive measure for disease motor progression. Several postmortem studies had done in evaluation of iron deposition in Parkinson's disease. There is discrepancy in the results of R2* and QSM methods and postmortem results, the reason could be because post mortem measurements are usually done at late stages of PD.[7],[26] Hence, there is need for longitudinal studies using MRI methods to accurately assess the iron deposition in other brain regions apart from substantia nigra. The review showed that the limitations of R2* methods (disruptions due to calcifications, micro bleeds, and myelinated fiber's had been overcome by QSM and highly accurate in severing as diagnostic marker for PD.

 » Limitations Top

Our study has few limitations. First, limited number of longitudinal studies involved in the review. Second, small sample size used.

 » Conclusion Top

Our review concludes that QSM has better accuracy than R2* method in detecting the iron deposition in different regions of brain in PD. However, due to discrepancies between QSM, R2* and postmortem results, large number of longitudinal studies in MRI would be required to confirm iron deposition in brain regions as biomarker for PD.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

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Fearnley JM, Lees AJ. Ageing and Parkinson's disease: Substantia nigra regional selectivity. Brain 1991;114:2283-301.  Back to cited text no. 2
Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999;122:1437-48.  Back to cited text no. 3
Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, Daniel SE, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain1991;114:1953-75.  Back to cited text no. 4
Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, et al. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J Neurochem 1989;52:1830-6.  Back to cited text no. 5
Lewis MM, Du G, Kidacki M, Patel N, Shaffer ML, Mailman RB, et al. Higher iron in the red nucleus marks Parkinson's dyskinesia. Neurobiol Aging2013;34:1497-503.  Back to cited text no. 6
Wang JY, Zhuang QQ, Zhu LB, Zhu H, Li T, Li R, et al. Meta-analysis of brain iron levels of Parkinson's disease patients determined by postmortem and MRI measurements. Sci Rep 2016;6:36669.  Back to cited text no. 7
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Gorell JM, Ordidge RJ, Brown GG, Deniau JC, Buderer NM, Helpern JA. Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. Neurology 1995;45:1138-43.  Back to cited text no. 11
Ulla M, Bonny JM, Ouchchane L, Rieu I, Claise B, Durif F. Is R2* a new MRI biomarker for the progression of Parkinson's disease? A longitudinal follow-up. PLoS One 2013;8:e57904.  Back to cited text no. 12
Wieler M, Gee M, Martin WR. Longitudinal midbrain changes in early Parkinson's disease: Iron content estimated from R*/MRI. Parkinsonism Relat Disord 2015;21:179-83.  Back to cited text no. 13
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Barbosa JH, Santos AC, Tumas V, Liu M, Zheng W, Haacke EM, et al. Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2*. Magn Reson Imaging 2015;33:559-65.  Back to cited text no. 17
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  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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