NmMRI~SNc~
We found that the contrast ratio of the lateral SNc was significantly decreased in early-PD and late-PD and that of the medial SNc gradually and stage-dependently decreased in PD,
which corresponded to the pathological lesions.
These findings indicate that SNc lesions extend from the lateral to the medial regions as PD progresses.
Tanaka et al.
reported that a reduction in neuromelanin contrast started ventrolaterally and advanced medially in the substantia nigra based on a visual assessment of NmMR images18.However,
the present study is the first effort to quantify medial and lateral SNc using NmMRI to the best of our knowledge.
NmMRI~LC~
Braak et al.
proposed that alpha-synuclein-immunopositive Lewy neuritis and the accumulation of Lewy bodies that are characteristic pathological features of PD emerge from the inferior brain stem and ascend to the nuclear gray and cortical areas19.
However,
some studies have also indicated that Lewy bodies and neural cell loss are irrelevant in some regions of the brain in patients with PD.
Noradrenergic neurons are relatively well-preserved in the LC of patients with early-PD and they undergo different intracellular changes from the SN20.
Reports indicate that the signal intensity of the LC on NmMR images is significantly reduced in PD8.
We identified significant signal reductions in the LC of patients with late-PD,
which suggests that lesions emerge in the LC during late-PD.
These findings are compatible with the findings of others indicating that the LC plays a compensatory role for the substantia nigra during early-PD21,22.
Noradrenergic neurons containing neuromelanin in the LC are disrupted in AD,
but the clinical or functional importance of such disruption remains unclear.
Some reports suggest that a reduction in the number of noradrenergic neurons affects the accumulation of beta-amyloid,
inflammation or microcirculation in the LC23,24.
Our NmMRI study could not identify a significant signal reduction in the LC of patients with AD.
Busch et al.
reported that the LC starts to lose cells only during the later stages of AD25.
Therefore,
we consider that this result can be attributed to the relatively short duration (2.5 years) of the disease and the small number of patients with AD in this study.
Signals were significantly more reduced in the medial and lateral SNc of patients with late-PD compared with AD,
which is useful for differentiating these diseases.
MIBG
The neurological diseases with significant reduction in MIBG scintigraphy uptake include PD,
dementia with Lewy bodies and pure autonomic failure,
and they are recognized as characteristic findings of Lewy-body diseases.
Sympathetic nerves in patients with PD are generally disturbed and Lewy bodies are found in sinoatrial nodal ganglia,
the myocardium,
and paravertebral ganglia26,27.
A pathological investigation has revealed that sympathetic nerve fibers are significantly reduced in patients with PD and well preserved in those with AD28.
Although the heart-to-mediastinum count ratio is reduced on MIBG scintigrams of early-PD,
its relationship with progression remains controversial28,29.
We found here that the heart-to mediastinum count ratio was significantly lower in late-PD than early-PD,
indicating that signal reduction is stage-dependent.
On the other hand,
we could not exclude the effect of a possible relationship between heart-to-mediastinum signal reduction and duration.
The heart-to-mediastinum count ratio was well-preserved in patients with AD,
which helped to differentiate it from late-PD.
NmMRI vs.
MIBG
To the best of our knowledge,
this is the first comparison of brain NmMRI and MIBG scintigraphy of PD and AD.
We identified a weak correlation in the SNc,
implying that the findings of both modalities can serve as indicators of progressive PD,
which involves both the central and peripheral autonomic nervous systems.
Our results revealed that the autonomic nervous system gradually becomes disturbed over time.
Limitation
The limitations of the present study are as follows.
Because the study comprised very few patients with AD,
further studies of a large population are required to validate our findings.
Second,
iron concentrations in the SNc that increase with age can mask signal alterations on NmMR images3.
Therefore,
we could not exclude this effect when evaluating neuromelanin in elderly individuals.
Third,
the low spatial resolution of NmMRI did not allow three-dimensional image acquisition.
Therefore,
measurement errors might have arisen due to partial volume effects particularly when assessing changes in the LC.
Conclusions
The SNc becomes disturbed from the lateral to the medial region on NmMR images of the SNc as PD progresses and the LC is also disturbed in late-PD.
The sympathetic nerves in the left cardiac ventricle are also disturbed in MIBG scintigrams of PD.
Thus,
NmMRI and MIBG scintigraphy can be helpful tools to evaluate PD progression and to differentiate PD from AD.