Ayaka Yokota1, Yasuhiro Fujiwara2, Tetsuyoshi Hirai3, Nobutaka Sakae4, Naokazu Sasagasako4, Takahisa Izumi5, Kuniharu Ohi5, and Hiroyuki Kumazoe5
1Graduated School of Health Sciences, Kumamoto University, Kumamoto, Japan, 2Department of Medical Image Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan, 3Faculty of Medicine, Saga University, Saga, Japan, 4Department of Neurology, National Hospital Organization Omuta National Hospital, Omuta, Japan, 5Department of Radiology, National Hospital Organization Omuta National Hospital, Omuta, Japan
Synopsis
We evaluated the
T1 values of the whole and subregions of the substantia nigra (SN) in patients with Parkinson's disease (PD) to identify an imaging
biomarker for the early diagnosis of PD. T1 values of the SN of patients with PD
were significantly shorter than those of healthy controls and tended to be longer in the
lateral part for both groups. T1 values may reflect the pathology of the SN and
help assess the degeneration of the SN caused by PD.
INTRODUCTION
Parkinson's
disease (PD) is a neurodegenerative disease that causes motor and cognitive
deficits due to degeneration and loss of neurons in the substantia nigra (SN) of
the midbrain. The diagnosis of PD is based on the clinical course, symptoms,
and neurological findings, and magnetic resonance imaging (MRI) is used to exclude
other diseases.
Neuromelanin-sensitive imaging (NMI)
can be used to assess SN degeneration. However, it is challenging to detect
small signal changes in the SN because the signal acquired by NMI depends on
the scanner and imaging parameters.
Recently, quantitative imaging techniques
for the
evaluation of the SN, such as R2*, QSM, and fractional anisotropy, have been
proposed as imaging biomarkers. A multiparametric
evaluation, rather than using a single parameter, is needed to accurately
diagnose early SN degeneration and differentiate it from other diseases. Due to the
fact that neuromelanin deposited in the SN has paramagnetic properties, the use
of the T1 value may be applicable for assessing SN degeneration.
We previously evaluated the T1 value of the SN in healthy subjects
and compared it with the NMI contrast. However, the relationship between SN
degeneration and changes in T1 values is unclear. Thus, the purpose of this
study was to investigate whether T1 values can be used as biomarkers to assess
SN degeneration in PD.MATERIALS AND METHODS
This study was performed
using a 3.0-T MRI with a phased-array coil (Ingenia, Philips Healthcare, Best,
The Netherlands). Fifteen healthy controls (HCs) (mean age, 59.4 years; age
range, 55–69 years) and 15 patients with PD
(mean age, 73.5 years; age range, 45–85 years) were enrolled. All subjects were
imaged using a 3D phase-sensitive inversion recovery (PSIR) sequence to obtain
the T1 map of the SN. The 3D PSIR sequence consists of a non-selective inversion
pulse and turbo field echo readouts at two inversion times. The T1 value was calculated voxel-by-voxel using two TI images
(PSIR and reference images). The specific method used was the same as that
previously reported. Regions of interest (ROIs) of both
SNs were manually placed on the magnitude image obtained by the PSIR
sequence. The T1 value and the high-signal area in both SNs were measured for
all subjects. Furthermore, the T1 values of three
subregions of the SN (central, medial, and lateral parts) were measured. Three
circular ROIs were set on the SN ROIs with equal spaces. The T1 value and area
of the SN
were compared between the HC and PD groups. The relationship between the Hoehn and Yahr stage and their measurements was also investigated in
patients with PD.RESULTS
Figure 1 shows
representative magnitude images and T1 maps for the volunteers and patients
with PD. There was no significant difference in the SN area between the HC and PD
groups (p = 0.29) (Fig. 2). The T1 value of the SN in
the PD group was significantly shorter than that in the HC group (p = 0.04)
(Fig. 3). The T1 values of the different regions of the SN tended to be longer,
from medial to lateral, in both the HC and PD groups (Fig. 4). The
T1 values of the SN for PD were shorter in patients with a higher Hoehn and
Yahr stage (r = -0.42) (Fig. 5). DISCUSSION
In the HC group, the T1 value of the SN was prolonged toward the lateral side
(medial < central < lateral). These results suggest that the amount of
local neuromelanin is related to the T1 value. On the other hand, the T1 value
of the SN for PD was significantly shorter than that for HC. Moreover, the
shortening of T1 in patients with PD was substantial in the central and lateral areas
among all regions. Given that the lateral part of the SN is more vulnerable,
and that degeneration proceeds in the earlier stage, the SN T1 value in the
lateral region may be an imaging biomarker for assessing SN degeneration.
However, the mechanism of T1 shortening associated with SN degeneration remains unclear. Excessive iron deposition due to abnormal iron
metabolism may shorten the T1 value of the SN, and further investigation is
needed.CONCLUSION
Quantification of
the T1 value of the SN may be a valuable biomarker for assessing SN
degeneration.Acknowledgements
No Acknowledgements.References
- Sasaki M, Shibata E, Tohyama K, et al. Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson's disease. Neuroreport. 2006;17(11):1215-1218.
- Baudrexel S, Nürnberger L, Rüb U, et al. Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson's disease. Neuroimage. 2010;51(2):512-520.
- Fujiwara Y, Hirai T, Ueda T, et al. Quantitative T1 mapping of the substantia nigra using phase-sensitive inversion recovery sequence at 3.0-T: a healthy volunteer study. Acta Radiologica. 2020;62(2):243-250
- Sulzer D, Cassidy C, Horga G, et al. Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease. npj Parkinson’s disease. 2018;11.
- Gibb WRG, Lees AJ. Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra and differential cell death in Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry. 1991;54:388-396.