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Imaging Brain Iron and Diffusion Patterns

Posted Dec 31, 2013 Updated Apr 10, 2023
By Maija Elina Rossi PhD , Hanna Ruottinen MD PhD , Tiia Saunamäki MD PhD , Irina Elovaara MD PhD , Prasun Dastidar MD PhD
12 min read

Rationale and Objectives

The aim of this study was to examine changes of brain iron content and diffusion patterns longitudinally in early-stage Parkinson’s disease (PD) patients using T2- and T2*-based magnetic resonance imaging (MRI) over 2-year follow-up.

Materials and Methods

We imaged 32 PD patients with tremor and 19 healthy controls. A follow-up study (median 25 months, range 22–31 months) was accomplished for 25 patients (men:women = 11:14; age range 44–87 years, median 73 years). All patients and healthy volunteers underwent clinical, neuropsychological, and MRI examinations on the same day. Three different MRI sequences were used and their results were compared: T2-weighted imaging, susceptibility-weighted imaging, and T2* mapping. Additionally, we evaluated diffusion tensor data between groups using tract-based spatial statistics.

Results

Over the 2-year follow-up, the iron-related relaxation increased in the globus pallidus anterior and the caudate nucleus and slightly in the substantia nigra pars compacta (SNc). In the globus pallidus anterior and medial SNc, the change was associated with mild cognitive impairment. In the caudate nucleus, the increase was pronounced in patients with disease onset at 67 years or older. In the SNc, medial transverse relaxation was increased, and in the thalamus, it was decreased, in patients with PD compared with healthy volunteers at 2-year follow-up. Tract-based spatial statistical data did not differ between groups based on gender or Unified Parkinson’s Disease Rating Scale, but a slight tendency to decreasing fractional anisotropy ( P < .10) in the genu of corpus callosum and bilaterally in corona radiata was seen over 2 years.

Conclusions

PD-related changes were found in putative iron content over 2 years. Although mild in the initial stages, these changes were consistent over MRI sequences. Rather than correlating with disease duration, the rate of changes was associated with individual characters, such as cognitive decline and age.

Parkinson’s disease (PD) is a neurodegenerative disease that is characterized by tremor, rigidity, bradykinesia, and postural instability . These motor symptoms are the basis of the diagnosis. Although the disease is incurable, various treatment options are available to enhance the quality of life, and new neuroprotective agents are constantly being developed . Depending on treatment, early initiation of therapy may provide benefit for the patient . Therefore, early diagnosis and initiation of therapy including follow-up are urgently needed. An accurate diagnosis of PD is challenging and increasingly complemented by imaging .

Imaging findings in PD patients are limited, but slight changes may be found with improving imaging techniques. Imaging of PD patients has made the most progress in the area of imaging dopamine transporters using positron emission tomography and various techniques of magnetic resonance imaging (MRI) . In addition to spectroscopy, diffusion tensor imaging (DTI), and functional imaging, one of the aspects investigated with MRI is the brain iron content, which is increased in the substantia nigra pars compacta (SNc) of PD patients . The brain iron content is associated with the loss of dopamine, and their concentrations seem to correlate as earlier shown in putamen . Therefore, because diagnostically promising results on the loss of dopamine have been reported with positron emission tomography , the results may be indirectly repeated by imaging iron with nonionizing MRI.

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Materials and methods

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MRI Protocol and Analysis

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c=(Sa−SgCC)(Sa+SgCC) c

=

(

S

a

−

S

g

C

C

)

(

S

a

+

S

g

C

C

)

where S a and S gCC are the signal intensities of the concerned structure and gCC, respectively, as previously described in Rossi et al . In T2* mapping, the quantitative T2* (ms) was used. Representative images are shown in Figure 1 .

Table 1

Imaging Parameters

Parameter T2WI SWI MapIt DTI Slice thickness (mm) 3.0 1.5 4.0 3.0 Slice gap (mm) 0 0 0.8 3.9 Field of view 172.5 × 230.0 172.5 × 230.0 220.0 × 220.0 230.0 × 230.0 Acquisition matrix 384 × 290 256 × 182 384 × 384 128 × 128 Interpolated matrix 768 × 768 Repetition time (ms) 3200 27 422 5043 Echo time (ms) 354 20 4.18: 94 11.32: 18.46: 25.60: 32.74

DTI, diffusion tensor imaging; MapIt, multiple echo sequence for T2* measurement; SWI, susceptibility-weighted imaging; T2WI, T2-weighted imaging.

Figure 1, T2* map (a) , T2-weighted imaging (b) , and susceptibility-weighted imaging (c) of a 59-year-old male patient with 3-month duration of symptoms of Parkinson's disease at the baseline.

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Analysis for Iron Content

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Figure 2, Regions of interest in a T2-weighted imaging of a 54-year-old female patient with 3.5-year duration of symptoms at the 2-year follow-up. (a) Red nucleus (1), substantia nigra pars compacta medial (2) and lateral (3), and pars reticulata medial (4) and lateral (5), and cerebral peduncle (6). (b) caudate nucleus (7), putamen anterior (8) and posterior (9), globus pallidus anterior (10) and posterior (11), and thalamus (12).

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TBSS Analysis

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Statistical Analysis

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Results

Longitudinal MRI Analysis of Iron Content

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Figure 3, Tissue contrast against the genu of corpus callosum in T2 -weighted imaging (T2WI) (a) , susceptibility-weighted imaging (SWI) (b) , and R 2 * (c) in healthy volunteers ( n = 19) and patients ( n = 25) at the baseline and at the 2-year follow-up. The bars represent 95% confidence interval. CN, caudate nucleus; CP, cerebral peduncle; GPa, globus pallidus anterior; SNc, substantia nigra pars compacta. * P < .10, ** P < .05 between baseline and follow-up.

Table 2

P Values for Comparison between the Baseline and 2-Year Follow-up of PD Patients

Region T2WI SWI R2* GP anterior.003 ∗ .127 ∗ .056 ∗ Caudate nucleus .489 ∗ .599 ∗ .081 ∗ SNc lateral .749 ∗ .847 ∗ 1.000 † SNc medial.031 ∗ .322 ∗ .943 † Cerebral peduncle .073 † 1.000 † .095 †

GP, globus pallidus; PD, Parkinson’s disease; SNc, substantia nigra compacta; SWI, susceptibility-weighted imaging; T2WI, T2-weighted imaging.

Student’s t -test for paired samples. The values have been corrected for multiple comparisons.

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Comparison with Clinical Data

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Figure 4, Longitudinal changes in groups based on (a) age as younger (Y) or older (O) than 67 years at disease onset, (b) gender as male (M) or female (F), (c) cognitive status as cognitively intact (CI) or with mild cognitive impairment (MCI), and (d) Unified Parkinson's Disease Rating Scale score as higher (H) or lower (L) than 20 at the baseline. CN, caudate nucleus; CP, cerebral peduncle; GPa, globus pallidus anterior; SNcl, substantia nigra pars compacta lateral; SNcm, SNc medial; SWI, susceptibility-weighted imaging; T2WI, T2-weighted imaging. * P < .05, ** P < .10.

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Comparison with Healthy Volunteers

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TBSS Data

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Figure 5, Mean fractional anisotropy image of all patients ( grayscale ) at the 2-year follow-up MRI, overlapped with the mean skeleton ( green ), on base of which the statistical group comparisons are calculated. Significant differences between groups are presented in red-yellow . The image showing differences based on patient age at disease onset ( P < .05) is focused on the right thalamus (a) and that based on MCI ( P < .1) is focused on the left capsula externa (b) , both structures marked with an arrow. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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Discussion

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Conclusion

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Academic Radiology, Volume 21, Issue 1
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