Investigation of the Healthy Nigrosome-1 for the Diagnosis of Parkinson’s Disease using Multiple Susceptibility based MRI Techniques
Kyung Mi Lee1 and Hyug-Gi Kim2

1Radiology, Kyung Hee University Hospital, Seoul, Korea, Republic of, 2Biomedical Engineering, College of Electronic Information Engineering, Kyung Hee University, Gyeonggi-do, Korea, Republic of

Synopsis

Nigrosome-1 region that is affected to the loss of dopaminergic neurons is one of the important characteristics of Parkinson’s disease (PD). To evaluate the early stage of PD and investigate the main mechanisms of nigrosome degeneration using MR images, the susceptibility based MRI techniques were performed: R2* (=1/T2*) map, SWI and QSM map in seven elderly healthy subjects that are reference subjects for PD.

Purpose

Parkinson’s disease (PD) is associated with motor symptoms largely attributable to loss of dopaminergic neurons1. Nigrosome-1 represent small clusters of dopaminergic cells within substantia nigra (SN)2. Recent studies to diagnosis PD have been introduced to visualize the nigrosome-1 in a clinical population by using SWI techniques3. However, previous studies do not reveal the obvious reason of visualizing nigrosome-1 to be in vivo biomarker for PD. It needs to exactly identify the reason and improve the image contrast to precisely diagnosis for PD using MRI. To investigate the usefulness of diagnosis of the healthy nigrosome-1 region using various MRI techniques including QSM, SWI, R2* (=1/T2*) map. We hypothesized that different imaging findings of nigrosome-1 could be present depending on the iron deposition and contents of nigrosome.

Materials and Methods

Seven elderly healthy subjects (mean age = 66.1, 5 females and 2 males) were participated. MR imaging was performed at 3T (Ingenia, Philips Healthcare, Best, Netherlands) with a head coil (dStream HeadSpine coil). The image acquisition was performed using a 3D gradient-echo (FFE) sequence was run with four echoes (first TE/△TE/final TE=7.2/10.0/37 ms). R2* map were generated with four-TEs magnitude images using linear regression of the logarithm of the MR signal. To generate SWI, the magnitude and phase images with longest TE (37ms) were selected from the multiple-TEs. Phase image were high-pass-filtered with a 64×64 low-spatial-frequency central kernel by using SPIN (MRI Institute for Biomedical Research, Detroit, Michigan) software to create high-pass-filtered phase images. QSM data were obtained with the morphology enabled dipole inversion (MEDI) software4.

All subjects were organized as groups according to the results of susceptibility based MR images. To evaluate between normal subject and PD patient, the quantitative susceptibility value of nigrosome-1 was measured by using drawing ROIs, respectively.

Results

Three Groups were organized for the degree of visualizing nigosome-1: group I-equivocal bad 2 subjects and group II-equivocal good 2 subjects for three susceptibility based MRI techniques, group III-best visualizing 3 subjects in QSM map compared to R2* map and SWI. Fig.1 demonstrates comparisons for visualizing nigrosome-1 of R2* map, SWI and QSM map in group III. Nigrosome-1 was visualized as low signal values in R2* map, as high signal values in SWI and as low signal values in QSM compared to around SN. From the comparison results among three techniques, the nigrosome-1 in QSM map was visualized equivocal better than other techniques. Fig.2 shows the results of comparison of normal subject and PD patient for QSM map. Nigrosome-1 in the PD subject was not visualized compared to the normal subject. The susceptibility value in nigrosome-1 in PD was increased 112.9 % compared to the normal subject.

Discussion

The loss of SN dopaminergic neurons is most prominent in sub-regions called nigrosome-1. There are two main possible mechanisms for visualizing nigrosome-1 in normal subjects and not visualizing in PD patients. Because of increased iron content or decreased neuromelanin contents with decreased iron storage capacity leading to more free iron with paramagnetic properties5. Until lately, however, there is no obvious reason to visualize nigrosome-1 in normal but not visualize in PD. In this study, we have investigated the nigrosome-1 of healthy elderly subjects which are to early diagnosis PD subjects using susceptibility effects based MRI techniques. In case of result of group I, no image could be visualized for nigrsome-1. One of the reasons may already be increased iron contents. Except for result of group I, QSM map was higher sensitivity to identify nigrosome-1 than other MRI techniques. From the results of comparison of the susceptibility value of nigrosome-1 in the normal subject and PD, the iron contents were increased in nigrosome-1 in PD by using QSM map. Nigrosome-1 can be detected by using magnetization transfer (MT) image that is mirrored the effects of neuromelanin contents. To clearly investigate the reason, it needs to evaluate not only susceptibility based MR images (e.g. QSM) but also neuromelanin based MR images (e.g. MT). The QSM map is more effective to evaluate the PD stage using visualizing nigrosome-1. Therefore, the QSM technique offers more efficiency information of the susceptibility effects for early diagnosis for PD than the R2* map or SWI estimation.

Conclusion

The QSM technique proved to be more effective to evaluate the early stage for PD than R2* map or SWI. Therefore, the susceptibility effects in the QSM can be used to an early diagnosis for PD. Furthermore, the QSM technique can be used as an imaging biomarker to evaluate disease progression for PD patients.

Acknowledgements

No acknowledgement found.

References

1. H. Braak et al. Neurobiol Aging, 2003 Mar-Apr, vol. 24, pp. 197-211. 2. Damier P et al, Brain J Neurol, 1999, 122(Pt 8): 1421-1436. 3. Schwarz ST, Afzal M, Auer DP et al, PLoS One, 2014 Apr 7;9(4):e93814. 4. Liu T, Wang Y et al, Magn Reson Med, 2011 Sep;66(3):777-83. 5. L. Zecca et al, J Neurochem, 2008 Aug vol. 106, pp.1866-75.

Figures

Fig.1 demonstrates comparisons for visualizing nigrosome-1 of R2* map, SWI and QSM map obtained from multiple echoes based FFE sequence for a subject in group III. Nigrosome-1 was visualized as low values compared to around SN in R2* map. For the result of SWI, nigrosome-1 was visualized as high signal values compared to around SN. For the result of QSM map, nigrosome-1 was visualized as low values compared to around SN.

Fig.2 shows the results of comparison of normal subject and PD patient for QSM map. Nigrosome-1 in the PD subject was not visualized compared to the normal subject. The susceptibility value in nigrosome-1 in PD was increased 112.9 % compared to the normal subject.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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