Patients
We investigated patients who were initially suspected of PD and were finally confirmed PD or AD between December 2008 and April 2012.
Both MR imaging and MIBG scintigraphy performed within 1 year thereafter were retrospectively evaluated.
Probable PD and AD were diagnosed according to the criteria of the United Kingdom Brain Bank and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association,
respectively.
Patients with PD were assigned to groups with either early-PD or late-PD based on Hoehn and Yahr staging.15 Early-PD comprised stages I and II,
and late-PD comprised stages III,
IV and V.
Patients with symptomatic cerebrovascular diseases and other central nervous system disorders were strictly excluded from the NmMRI evaluation and those with cardiac diseases,
diabetes mellitus and/or medications that can interfere with MIBG uptake,
were excluded from the MIBG scintigraphy assessment.
We finally enrolled 13 (5 men and 8 women),
31 (14 men and 17 women) and 6 (3 men and 3 women) patients with early-PD,
late-PD and AD,
respectively (Table 1).
The age of each group of early-PD,
late-PD and AD ranged from 59 to 85 years (mean±SD,
68.3±5.88),
59 to 83 years (mean±SD,
71.8±8.95),
and 58 to 84 years (mean±SD,
75.7±9.52),
respectively.
The duration of the illness for early-PD,
late-PD,
and AD ranged from 0 to 9 years (mean±SD,
4.30±5.37),
2 to 27 years (mean±SD,
9.48±6.86),
and 1 to 3 years (mean±SD,
2.5±3.00),
respectively.
We used the Hasegawa dementia scale revised (HDS-R) 16 to determine cognitive impairment or dementia,
which is similar to mini-mental state examination (MMSE) and has a total score of 30.
HDS-R in patients with AD ranged from 6 to 17 (mean±SD,
12.8±4.76).
The control group of NmMRI comprised 20 age-matched patients (5 men and 15 women,
64 to 87 years (mean±SD,
74.8±5.4)) without a history of motor and cognitive impairment and brain lesions on MR images during the same period.
However,
we did not obtain MIBG scintigraphy from the same age-matched patients during this period.
Our institutional review board approved the study and written,
informed consent was waived.
Table 1: Clinical characteristics of patient and control groups
Age does not differ between patient and control groups (p = 0.082; one-way analysis of variance).
Image acquisition
All MR images were acquired using a clinical 3T MR scanner (Signa EXCITE HD,
GE,
Milwaukee,
WI,
USA).
Axial images were acquired parallel to the anterior commissure-posterior commissure line.
T1-weighted fast spin echo sequences were applied to NmMRI with the following parameters: TR/TE,
600/13 msec; echo train length,
2; slice thickness,
2.5 mm with 1- mm intersection gaps; matrix size,
512 × 512; FOV,
220 mm; acquisition time,
12 min.
The scan covered the area from the upper border of the midbrain to the inferior border of the pons.
We excluded other coexisting central nervous system disorders using axial T1- and T2-weighted images,
fluid attenuated inversion recovery images and diffusion-weighted images of the entire brain according to the following standard protocol for adult brain imaging at our hospital: T1-weighted spin-echo sequence,
TR/TE,
600/15 msec; section thickness,
5 mm; FOV 220 mm; matrix 512 × 512; T2-weighted fast spin-echo sequence,
TR/TE,
4000/90 msec; section thickness,
5 mm; FOV 220 mm; matrix 512 × 512; fluid attenuated inversion recovery sequence,
TR/TE/IR,
4000/90/20; section thickness,
5 mm; FOV 220 mm; matrix 512 × 512; and diffusion-weighted imaging sequence,
TR/TE,
4000/90 msec; section thickness,
5 mm; FOV 220 mm; matrix 512 × 512; maximum b factor,
1000 mm2/s.
The patients received an intravenous injection of 111 MBq of 123I-MIBG,
and static planar images of the chest were acquired 30 min later for 4 min in a 256 × 256 matrix using a dual-head gamma camera with a large field of view and a low-energy,
high-resolution collimator (E-CAM; Siemens,
Erlangen,
Germany).
Image analysis
Signal intensity was measured for quantitative NmMRI by setting ROIs.
We equally divided into medial and lateral SNc at the level of the inferior colliculus and defined the ROIs in areas including the high signal intensity on NmMRI.
We also defined the ROIs symmetrically in the ventral tegmentum as control located in the anterolateral part of aqueduct.
Concerning LC,
we defined the ROIs in the anterolateral areas around the fourth ventricle at the level of upper pons and also defined the ROIs symmetrically in the tegmentum as control located just behind the medial lemniscus.
The sizes of the ROI were 8,
2 and 10 mm2 on the SNc,
LC and tegmentum of the midbrain and pons,
respectively.
We calculated the contrast ratios of the three bilateral portions by dividing their signal intensity by that of control areas such as the tegmentum of midbrain and pons.
A ROI was drawn manually over the whole heart on MIBG scintigrams to assess the global myocardial kinetics of MIBG.
A second rectangular ROI over the upper mediastinum served as a background reference region.
The density of the MIBG count in the heart and the mediastinum and heart-to-mediastinum count ratios were calculated for the images.
Statistical analysis
Differences in contrast ratios between early-PD,
late-PD,
AD and controls in the medial SNc,
lateral SNc and LC on NmMRI and between early-PD,
late-PD and AD on MIBG scintigraphy were then statically analyzed.
The medial SNc,
lateral SNc,
and MIBG scintigram were analyzed using a one-way analysis of variance and the Bonferroni post hoc test,
and the LC was analyzed using the Kruskal-Wallis and Dunn post hoc tests.
The level of statistical significance was defined as p < 0.05 for all tests.
The contrast ratios of NmMRI and MIBG scintigram in early-PD,
late-PD and AD were analyzed using Spearman’s rank-order correlation coefficient test.