Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy.

Abstract

Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients.
Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher's exact test, t-test, and one way analysis of variance were used to determine significance at corrected p < 0.05.
HPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P. On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients with MSA of either type had significantly higher MD values of putamen than normal subjects.
HPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of "normal." In doubtful cases, measurement of the MD values of nearby putamen may be valuable.

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RESEARCH ARTICLE Open Access
Hyperintense putaminal rim at 1.5 T: prevalence
in normal subjects and distinguishing features
from multiple system atrophy
Khin K Tha1*, Satoshi Terae2*, Akiko Tsukahara2, Hiroyuki Soma3, Ryo Morita2, Ichiro Yabe3, Yoichi M Ito4,
Hidenao Sasaki3and Hiroki Shirato1
Abstract
Background: Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for
multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at
3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether
HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and
the features which distinguish from HPR in MSA patients.
Methods: Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and
gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and
presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients
with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C)
were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal
subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher’s exact test, t-test, and one way
analysis of variance were used to determine significance at corrected p<0.05.
Results: HPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not
observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was
continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with
hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect
of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P.
On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients
with MSA of either type had significantly higher MD values of putamen than normal subjects.
Conclusions: HPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without
discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of
“normal.” In doubtful cases, measurement of the MD values of nearby putamen may be valuable.
Background
The term “hyperintense putaminal rim (HPR)” is com-
monly used to represent a linear hyperintensity at the
lateral margin of the putamen on T2-weighted or
proton-density-weighted images of the brain [1-10]. It
was first reported by Savoiardo et al. as an observation
inmultiplesystem atrophy(MSA) patientswith
extrapyramidal symptoms and autonomic failure [1].
Later studies suggested an association of HPR with bra-
dykinesia and contralateral rigidity [2,3]. The clinical ap-
plicability of HPR in distinguishing between MSA and
Parkinson’s disease (PD) has also been reported [2,6].
That is, because HPR is observed in MSA, but not in
PD, it can be used to distinguish between these two dis-
eases having similar clinical features [2,6].
Although HPR is widely accepted as a magnetic reson-
ance imaging (MRI) sign suggestive of MSA, consensus is
lacking among the previous studies in regard to whether it
* Correspondence: kktha@med.hokudai.ac.jp; saterae@med.hokudai.ac.jp
1Department of Radiobiology and Medical Engineering, Hokkaido University
Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan
Full list of author information is available at the end of the article
© 2012 Tha et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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is pathological [1-8]. While the mere presence of linear
hyperintensity at the lateral margin of the putamen had
been considered pathological in many studies [2,6-8], a
few studies have suggested that mild linear hyperintensity
is a finding of normal aging [4,5]. In the latter studies,
HPR was considered as abnormal only if it was moderate
to severe in degree and exhibited posterolateral predomin-
ance [4], or if it was associated with hypointensity of the
nearby putamen [5]. There has been large variation in the
reported sensitivity and specificity of HPR for the diagno-
sis of MSA [4,6-8]. Although slight variation in the scan
parameters can influence its appearance, it is considered
that this variation is generally attributed to a lack of con-
sensus about HPR. Although there have been suggestions
that mild linear hyperintensity may be a normal finding,
there is still a lack of statistically significant datum to sup-
port this conclusion [4,5].
In 2005, Lee et al. reported that HPR was observed in
normal subjects at 3 T, but found that it was not observ-
able in normal subjects at 1.5 T [9]. Two years later,
Fujii et al. examined HPR in a large number of subjects,
and found that HPR was prevalent in normal subjects
between 30 and 70 years of age, at 3 T [10]. Based on
their observations, Fujii et al. considered HPR in normal
subjects as a “pseudosign” — a perceived hyperintensity
due to hypointensity of the remainder of the putamen
induced by age-related iron deposition. They also com-
mented that HPR was clearly visible at 3 T, but not at
1.5 T, due to pronounced susceptibility effects at 3 T. In
light of the findings of these reports, a few recent studies
performed using 3 T have taken into account the possi-
bility of observing HPR in normal subjects [11,12].
Although there is general consensus that HPR is some-
times observed in normal subjects at 3 T, whether it can
be observed at 1.5 T has not been clearly documented.
The findings of existing reports are contradictory — a few
earlier studies have suggested the presence of HPR in nor-
mal subjects at 1.5 T [4,5], whereas the reports by Lee and
Fujii et al. do not support this conclusion [9,10]. It is thus
necessary to determine whether HPR can be observed in
normal subjects at 1.5 T, and, if so, to establish its MRI
characteristics, and the features which distinguish it from
HPR in MSA patients, at this lower signal strength.
In this study, we sought to determine whether HPR could
be observed in normal subjects at 1.5 T, and to establish its
prevalence, the MRI characteristics, and the distinguishing
features from HPR observed in MSA patients.
Methods
Participants
This retrospective study was approved by the Institu-
tional Review Board of Hokkaido University Hospital
(No. 010-0017 and No. 010-0286), and complied with
the ethical standards established in the Declaration of
Helsinki. Written informed consent for MRI was obtained
from all normal subjects. The requirement of informed
consent from the patients was waived (According to the
institutional regulations, written informed consent is not
necessary, provided the study is retrospective and ano-
nymity of the patients is maintained.).
To determine whether HPR could be observed in normal
subjects at 1.5 T, and to establish its prevalence and MRI
characteristics, the magnetic resonance (MR) images of the
brains of 130 normal healthy subjects (64 men and 66
women; mean age=43±13 years; age range=22–67 years),
who volunteered to participate in establishing a normal
brain database, were retrospectively reviewed. All MR
images were obtained over a 6-month period (May through
October, 2005). All subjects had no history of diseases
which might affect the integrity of the central nervous sys-
tem, such as hypertension or diabetes mellitus. Psychiatric
disorders were excluded by a questionnaire. The results of
neurological examination performed on the day of MRI
were normal. The MR images of the brain showed no obvi-
ous abnormalities.
To establish the distinguishing features of HPR observed
in MSA patients, the MR images of the brains of MSA
patients obtained over a 58-month period (October, 2005
through July, 2010) were also reviewed. Inclusion criteria
were probable or possible MSA according to the Consensus
criteria [13] and age below 70 years. Exclusion criteria were
MR images that were distorted by artifacts or MR images
showing the presence of abnormalities other than those
related to MSA (e.g., infarction or hemorrhage). Of the 24
MSA patients, the MR images of 6 MSA patients with pre-
dominant parkinsonian symptoms (MSA-P)(5 probable
MSA-P and 1 possible MSA-P; 2 men and 4 women; mean
age=58.7±4.7 years; age range=52–64 years) and 15 MSA
patients with predominant cerebellar symptoms (MSA-C)
(14 probable MSA-C and 1 possible MSA-C; 7 men and 8
women;meanage=59.2±4.4years;agerange=54–66years)
were eligible for the study. The average disease duration was
5±3.7 years (range=2–11 years) in MSA-P patients, and
4±2.6years(range=1–9years)inMSA-Cpatients.
MRI and image processing
MRI was performed using a 1.5 T imager (Magnetom
Symphony or Vision, Siemens Medical Solutions, Erlangen,
Germany) and a head coil. Axial fast spin-echo T2-
weighted imaging (T2WI) was performed, using the follow-
ing imaging parameters: repetition time (TR)=4500–
5010 ms; echo time (TE)=96–99 ms; effective echo train
length (ETLeff)=7; number of excitations (NEX)=2; slice
thickness=5 mm; interslice gap=1.5 mm; field of view
(FOV)=180×240 mm; and acquisition matrix size=177×
512. Axial fast spin-echo echo-planar diffusion tensor im-
aging (DTI) was performed in all normal subjects and 13
MSA patients (3 MSA-P, 10 MSA-C), using the following
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parameters:
(b)=1000 smm-2; NEX=2; number of gradient directions
=12; slice thickness=5 mm; interslice gap=1.5 mm;
FOV=240×240mm;andacquisitionmatrixsize=92×128.
Mean diffusivity (MD) maps were constructed from
the diffusion tensor images.
TR=5100 ms;TE=139ms;b-value
Evaluation of images
Visual analysis
The axial T2-weighted images were visually evaluated by
two radiologists (one with 22 years and one with 6 years
of experience in neuroimaging). The evaluations were
done independently, and disagreements were solved by
consensus. Image evaluation was conducted in two ses-
sions. In the first session, the T2-weighted images of nor-
mal subjects were evaluated. The raters were informed
that these subjects were normal. Six months later, the T2-
weighted images of all MSA patients admixed with those
of 24 patients with systemic diseases other than MSA were
evaluated. That is, the T2-weighted images of these 24
patients were used as dummy data, to limit potential bias;
the results of these images were not used in this study.
The raters were aware that the group belonged to a dis-
eased state, but were not informed of the name of the dis-
ease or other clinical information — a situation similar to
previous studies [4,14]. Evaluation was done at the for-
amen of Monro level, where the bilateral putamina exhib-
ited their largest surface area. For assessment of continuity
and dimension of HPR, the raters were allowed to view
adjacent slices and zoom the images. However, the raters
were not allowed to view images of the infratentorial
compartment.
The T2-weighted images of normal subjects were eval-
uated for the presence of HPR, its conspicuity, distribu-
tion among gender and age groups, and the MRI
characteristics {i.e., laterality, greatest dimensions (an-
teroposterior and transverse dimensions), association
with hypointensity of the nearby putamen, and presence
of discontinuity}. The conspicuity of HPR was classified
into absent, vague, and present, as in Fujii et al. [10].
This classification was used so as to allow comparison of
the prevalence between the two magnetic field strengths.
Representative examples of the different degrees of con-
spicuity of HPR are shown in Figure 1. Hypointensity of
the putamen was classified into mild (hyperintense to
globus pallidus), moderate (isointense to globus palli-
dus), and severe (hypointense to globus pallidus) — de-
pending on its signal intensity relative to globus pallidus.
The MRI characteristics were determined from HPR
classified as “present.”
The T2-weighted images of all MSA patients were also
evaluated for the presence of HPR, its conspicuity, the
MRI characteristics, and association with nearby abnor-
malities such as putaminal atrophy. To establish the
distinguishing features of HPR, the MRI characteristics
of HPR (i.e., HPR classified as “present”) were compared
between the patients with MSA of the either type and
age-matched normal subjects.
Quantitative analysis
All measurements were performed by a radiologist
with 9 years experience in neuroimaging. The MD
values of the putamen were measured, using manually
drawn regions-of-interest (ROIs). Measurement was
performed at the foramen of Monro level. ROIs were
drawn so as to include the whole putamen while
avoiding inclusion of cerebrospinal fluid (CSF) or
nearby structures. ROIs were drawn manually on the
echo-planar images with no diffusion weighting, and
superimposed directly onto the MD maps. An ex-
ample of the ROIs is shown in Figure 2. The MD
values of the putamen were compared between nor-
mal subjects with (i.e., HPR classified as “present”)
and without HPR (i.e., HPR classified as “absent”),
and between MSA patients and age-matched normal
subjects with HPR.
Statistical analysis
The MRI characteristics of HPR observed in normal
subjects and the distinguishing features of HPR between
normal subjects and MSA patients were established by
using Fisher’s exact test. Results were considered statisti-
cally significant at p<0.05. The MD values of the puta-
men were compared between normal subjects with HPR
and those without HPR, by using a t-test. Results were
considered statistically significant at p<0.05. The MD
values of the putamen were compared between MSA
patients and age-matched normal subjects with HPR, by
using one way analysis of variance (ANOVA) and post
hoc Bonferroni tests. Results were considered statisti-
cally significant at p<0.0167, corrected for multiple
comparisons.
Figure 1 Axial T2-weighted images of normal subjects showing
different degrees of conspicuity of HPR. HPR results classified
as absent (A), vague (B), and present (C) are shown.
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Results
Visual analysis
Table 1 shows the overall prevalence of HPR in normal
subjects. The prevalences of HPR in each age group are
summarized in Figure 3. The prevalence of HPR did not
vary significantly among the age groups (p=0.49). The
characteristics of HPR (HPR classified as “present”)
observed in normal patients are summarized in Table 2.
Neither gender predilection nor laterality in the distribu-
tion of HPR was observed. Majority of HPR were con-
tinuous throughout its length. HPR occupied nearly full
or full length or the anterior aspect of the lateral margin
of the putamen. All HPR measured less than 2 mm in
the maximum transverse dimension. There was no sig-
nificant association between the presence of HPR and
hypointensity of the nearby putamen.
Representative examples of HPR observed in MSA-P
and MSA-C patients are shown in Figure 4. HPR (i.e.,
HPR classified as “present”) was observed in 83.3% of
MSA-P (2 men and 3 women; mean age=57.9±4.7 years;
age range=52–64 years; disease duration=5.3±3.7 years;
range=2–11 years) and 60% of MSA-C patients (4 men
and 6 women; mean age=59.1±4.2 years; age range=54–
66 years; disease duration=3.1±1.8 years; range=1–
7 years). The results of the comparison of HPR among the
three groups (i.e., MSA-P patients, MSA-C patients, and
age-matched normal subjects) are summarized in Table 3.
Compared to normal subjects and MSA-C patients, HPR
was observed predominantly at a posterior location in
MSA-P patients. Discontinuity of HPR and atrophy of the
nearby putamen were also more frequently observed in
MSA-P patients. Although not statistically significant,
HPR tended to be more frequently associated with
hypointensity of the nearby putamen, in MSA-P patients.
The maximum transverse dimension of HPR also tended
to be larger. The findings of visual analysis were similar
between the normal subjects and MSA-C patients.
Quantitative analysis
The results of quantitative analysis are summarized in
Table 4 and Figure 5. There was no significant differ-
ence in the MD values of the putamen between the
normal subjects with and without HPR. The mean
MD values of the putamen were significantly higher
in MSA-P patients than the MSA-C patients and
normal subjects. Those of MSA-C patients were sig-
nificantly higher than normal subjects. These differ-
encesremained statistically
removal of outliers.
significanteven after
Figure 2 Examples of regions-of-interest (ROIs) used in the
measurement of MD values of the putamen. The ROIs were
drawn manually on the echo-planar images with no diffusion
weighting, and superimposed onto the MD maps. ROIs drawn on an
echo-planar image with no diffusion weighting are shown.
Table 1 The overall prevalence of hyperintense putamen
rim (HPR) in the normal subjects on the axial
T2-weighted images
LocationConspicuity of HPR
PresentVague Absent
Average38.5 40.8 20.8
Right37.743.119.2
Left39.238.5 22.3
Note: Data are presented in percentage (%).
Figure 3 The prevalence of HPR in normal subjects, on axial
T2-weighted images. The prevalence is given for each age group.
“n” refers to the number of subjects in each age group. No
significant difference in the prevalence of HPR was observed among
the age groups.
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Discussion
Our results suggest that HPR can be observed in normal
subjects with a prevalence of 38.5% on T2-weighted
images at 1.5 T. Compared to the report by Fujii et al.
[10], our results showed a lower prevalence of HPR. This
may be attributable to the difference in magnetic field
strength between the two studies. The study by Fujii
et al. was performed using 3 T, whereas this study was
performed using 1.5 T. Imaging at 3 T allows acquisition
of images with smaller pixel sizes without additional
time constraints, and these images allow visualization of
small or fine structures [15]. The voxel size of T2-
weighted images in the study by Fujii et al. was
0.66×0.41×5 mm, whereas that in this study was
1.02×0.47×5 mm. Improved contrast between HPR and
the nearby putamen can also be expected at 3 T. At 3 T,
the nearby putamen is usually hypointense due to age-
related ferritin and hemosiderin deposition. Hypointen-
sity of the nearby putamen allows improved visualization
of HPR. An improved contrast-to-noise ratio (CNR) may
also allow improved visualization of HPR. However, a
comparison of CNR between the two studies was not
possible due to the insufficient information about CNR
in the study by Fujii et al. It is not clear why Lee et al.
failed to observe HPR at 1.5 T [9], but the limited sam-
ple size and spatial resolution along the Y-axis (i.e.,
frequency-encoding direction) may have played a role
[9]. A difference in TE between 3 T and 1.5 T in their
Table 2 The characteristics of HPR (HPR classified as “present”) observed in normal patients
Variable PrevalenceP-value♠
Gender ratioMen 47.0% 0.33
Women53.0%
LateralityRight49.0%0.71
Left51.0%
Maximum anteroposterior dimensionAnterior edge ~ Anterior quarter3.0%
Anterior edge ~ Anterior half37.0%
Anterior edge ~ Anterior three quarters21.0%
Posterior edge ~ Posterior quarter0.0%
Posterior edge ~ Posterior half0.0%
Posterior edge ~ Posterior three quarters0.0%
Nearly full to full length39.0%
Maximum transverse dimension
>2 mm0.0%
<2 mm 100.0%
Discontinuity of HPR Present 21.0%
Absent 79.0%
Association with hypointensity of nearby putamenPresent (Mild hypointensity) 38.0% 0.77
Present (Moderate hypointensity)0.6%
Present (Intense hypointensity) 0.0%
Absent63.4%
♠Compared with those without HPR.
Figure 4 HPR observed in MSA patients. Representative
examples of HPR observed in (A) MSA-P (a 61-year-old woman;
disease duration=2 years) and (B) MSA-C (a 66-year-old
woman; disease duration=7 years) patients are shown. In (A),
HPR is located predominantly at the posterior part of the lateral
margin of the putamen. Moderate hypointensity of the posterior half
of the putamen is also seen. Putaminal atrophy is not observed in
this case. HPR observed in the MSA-C patient (B) is not easily
distinguishable from that of a normal subject (Figure 1C).
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study as well as between their study and ours may have
also been contributed.
Fujii et al. compared T2-weighted postmortem images
with the histological findings in four autopsy cases who
died of non-neurologic disorders, in order to explore the
aetiology of HPR [10]. According to their results, HPR
coincides with the myelin sparse zone at the lateral mar-
gin of the putamen. This zone is free of, or contains only
scant amounts of ferritin and hemosiderin deposition.
Taken together with the observation of HPR in subjects
between 30 and 70 years of age (i.e. the age at which
age-related iron deposition in the other parts of puta-
men occurs), they proposed that lack or scarcity of
ferritin and hemosiderin deposition leads to hyperinten-
sity of the zone relative to the other parts of putamen.
However, in this study, HPR was observed at 1.5 T, and
susceptibility effects are less pronounced at this field
strength [15]. In addition, HPR was observed with equal
Table 3 The results of comparison of HPR (i.e., HPR classified as “present”) among MSA-P, MSA-C patients, and age-
matched normal subjects
VariablesMSA-P
(n=10)
MSA-C
(n=18)
Normal
(n=39)
P-value
Mean age ± standard deviation (age range) 57.9±4.7 years
(52–64 years)
59.1±4.2 years
(54–66 years)
57.0±3.8 years
(50–66 years)
0.1883
Gender ratioMen40.0% 38.9% 53.9%0.5614
Women60.0%61.1% 46.1%
Distribution of HPR Right 60.0%56.0% 51.0%0.8710
Left40.0% 44.0%49.0%
Maximum anteroposterior dimension of
HPR
Anterior edge ~ Anterior quarter0.0%5.5% 5.1%0.0003*
Anterior edge ~ Anterior half 0.0% 16.7% 28.2%
Anterior edge ~ Anterior three quarters0.0%0.0% 23.1%
Posterior edge ~ Posterior quarter0.0% 0.0% 0.0%
Posterior edge ~ Posterior half40.0%5.6% 0.0%
Posterior edge ~ Posterior three
quarters
0.0%0.0% 0.0%
Nearly full to full length60.0% 72.2%43.6%
Maximum transverse dimension of HPR
>2 mm10.0% 0.0% 0.0%0.0554
<2 mm90.0%100.0%100.0%
Discontinuity of HPRPresent 80.0%38.9% 28.2%0.0112*
Absent20.0% 61.1%71.8%
Hypointensity of nearby putamen Present 78.9%51.6% 49.2%0.0668
Absent 21.1%48.4% 50.8%
Putaminal atrophyPresent50.0% 11.1% 0.0%
<0.0001*
Absent50.0%88.9%100.0%
Note: “n” represents the number of putamina.
* represents statistical significance.
Table 4 The mean MD values of the putamen of the three groups
MD value (× 10−3s mm−2) P-value
Mean ± standard variationRange
Normal subjectswith HPR 0.75±0.030.66–0.85 0.07♠
without HPR0.76±0.02 0.71–0.82
MSA-Pwith HPR1.16±0.33 0.81–1.60
<0.0001 (F=15.76, df=37)* among groups#;
<0.0001* between MSA-P and normal
or MSA-C♣; 0.0003* between MSA-C
and normal♣
MSA-Cwith HPR0.89±0.140.78–1.23
Normal subjects
(age and gender-matched to the patients)
with HPR0.76±0.040.66–0.85
♠Two-sample t-test.
# One way ANOVA.
♣Post-hoc Bonferroni comparisons.
*represents statistical significance.
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prevalence between the younger and older age groups.
There was no association between HPR and the pres-
ence of hypointensity of the nearby putamen. Failure to
observe hypointensity of the putamen is consistent with
the findings of a previous study [16]. It is therefore pos-
sible that the scarcity of myelin itself contributes to the
appearance of HPR in normal subjects, at 1.5 T — by a
mechanism similar to that responsible for hyperintensity
in demyelinating and dysmyelinating lesions [17,18].
In this study, the length of HPR varied among normal
subjects. The etiology underlying this variation is not
known, but anatomical variation in the length of the myelin
sparse zone is a possible factor. Artifacts related to CSF-
flow within the third ventricle or Sylvian fissures might ac-
count for signal loss at the posterolateral aspect of puta-
men, but these effects are considered less likely as the
images selected for use in this study were free of obvious
artifacts. Although we could not determine the etiology
underlying the variation in length of HPR, its predominant
location can be a distinguishing feature between normal
subjects and those with MSA-P. Opposed to the predomin-
ant anterior location of HPR in normal subjects, HPR was
located predominantly posteriorly in MSA-P [4,19,20]. This
may be due to the pathological changes of MSA (such as
neuronal or axonal loss, demyelination, gliosis, tissue rar-
efaction, and dilatation of the perivascular spaces) which
are more pronounced at the posterolateral aspect of the pu-
tamen [21]. The failure to observe the predominant poster-
ior location of HPR in MSA-C may be due to the milder
pathological changes of the putamen in MSA-C [8].
In addition to the predominant location of HPR, this
study suggests some other MRI features which could
help in distinguishing between normal subjects and
MSA-P. In this study, discontinuity of HPR was more
frequently observed in MSA-P. Discontinuity of HPR
has been reported in MSA-P [11]. The reason is not
known, but susceptibility effects from the nearby puta-
men — which has intense iron deposition — may play a
role. Another feature of HPR in MSA-P is its more fre-
quent association with putaminal atrophy [4-7,11,22].
Although not statistically significant, our results also
revealed tendency toward a larger maximum transverse
dimension of HPR, and an association between HPR and
hypointensity of the nearby putamen, in MSA-P. The
latter has also been observed in the previous reports [1-
5,22]. According to these reports, hypointensity of the
nearby putamen is attributable to intense deposition of
iron compounds, i.e., a deposition more intense than
that in the normal aging process. The MRI characteris-
tics of HPR did not vary significantly between the MSA-
C patients and normal subjects. However, MSA-C may
be distinguished by abnormalities in the infratentorial
compartment, such as brainstem and cerebellar atrophy,
and the “hot cross bun” sign [1-8].
Quantitative analysis revealed significantly higher MD
values of the putamen in MSA-P and MSA-C patients. It
is considered that higher MD values are attributable to
pathological changes such as neuronal loss, which des-
troy the tissue architecture and remove restricting bar-
riers to water diffusion [23,24]. Alteration in MD values
Figure 5 The mean MD values of the putamen. Comparison of the MD values (A) between normal subjects with and without HPR, and
(B) among normal subjects, MSA-P and MSA-C patients with HPR. The MD values of the putamen varied significantly among the groups.
Note: “n” refers to the number of putamina.
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occurs earlier than the other MRI changes, and thus MD
can be considered a potential biomarker for the early
diagnosis of MSA [24,25]. Our results indicate that the
MD values of the putamen may be of use in distinguish-
ing among the three groups, in doubtful cases. Although
there have been a considerable number of reports on the
usefulness of MD values in distinguishing between
MSA-P and PD [23,25-27], reports on the usefulness of
MD values of the putamen in MSA-C are scarce. To our
knowledge, there have been only two reports on the MD
values of the putamen in MSA-C [27,28]. However, their
results were contradictory. Ito et al. observed an equiva-
lent degree of increase in MD values of the putamen be-
tween MSA-P and MSA-C [27], whereas Pellichia et al.
did not observe any appreciable change in MD values of
the putamen in MSA-C [28]. In this study, the MD
values of the putamen of MSA-C patients were between
those of normal subjects (The MD values of the puta-
men in normal subjects were comparable with those of
the previous studies [26-28]) and MSA-P patients. The
discrepancy may be at least partly related to the limited
number of patients enrolled in these studies and the var-
iations in disease duration or severity. Further studies
will be needed to explore this issue.
This study has a few limitations. First, we did not in-
clude normal subjects who were below 22 or above
67 years of age. Therefore, we were unable to examine
whether HPR appears in younger individuals or whether it
becomes indistinct in older individuals, as reported by
Fujii et al. [10]. Second, the number of MSA-P patients
was limited. This may have been attributable to the fact
that MSA-C is the predominant clinical phenotype in
Japan [29]. Third, the present study did not include
patients with PD, progressive supranuclear palsy, and cor-
ticobasal degeneration. Some studies have reported that
HPR can also be observed in these patients [4,14,22]. Be-
cause the present study did not include these patients, we
could not determine whether the HPR observed in normal
subjects was different from that observed in these diseases.
However, according to the findings of previous reports
which revealed HPR in these diseases, HPR may not be
distinguishable between these diseases and normal sub-
jects, and HPR may be a normal finding in these diseases.
Finally, in this study, a rough comparison of the preva-
lence of HPR among the studies was made. Ideally, identi-
cal scan parameters are desired. As variation in the scan
parameters can lead to variation in the conspicuity of
HPR, quantification of T2 values, rather than evaluation
of signal intensity on T2-weighted images, might be better
suited for future studies.
Conclusions
This study documented the appearance of HPR in nor-
mal subjects at 1.5 T. HPR may be observed in 38.5% of
normal subjects on T2-weighted images at 1.5 T. Thin
linear hyperintensity, which occupies the full length or
anterior half of the lateral margin of the putamen and
shows continuity throughout its length, is suggestive of
“normal.” In doubtful cases, measurement of MD values
of the nearby putamen may be valuable in distinguishing
among normal, MSA-P, and MSA-C patients. Radiolo-
gists and neurologists should be aware that HPR may be
observed in normal subjects at 1.5 T— so as to avoid
misinterpretation of normal HPR as a sign of patho-
logical state.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
KKT and ST are the guarantors of the integrity of the entire study. KKT
contributed to the study design, preparation for visual analysis, quantitative
analysis, statistical analysis, literature research, and writing of the manuscript.
ST contributed to the study design, visual analysis, and manuscript editing.
AT contributed in visual analysis and manuscript editing. RM contributed in
preparation for visual analysis and literature research. H. Soma, IY, and H.
Sasaki contributed in clinical studies and manuscript editing. YMI contributed
in statistical analysis and manuscript editing. H. Shirato contributed in overall
management and manuscript editing. All authors read and approved the
final manuscript.
Acknowledgements
This work was supported by (1) Creation of Innovation Centers for Advanced
Interdisciplinary Research Areas Program of Project for Developing
Innovation Systems of the Ministry of Education, Culture, Sports, Science and
Technology, the Japanese Government, and (2) the grant-in-aid for scientific
research from Japan Society for the Promotion in Science (2005).
Author details
1Department of Radiobiology and Medical Engineering, Hokkaido University
Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan.
2Department of Diagnostic Radiology, Hokkaido University Graduate School
of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan.3Department of
Neurology, Hokkaido University Graduate School of Medicine, N-15, W-7,
Kita-ku, Sapporo 060-8638, Japan.4Department of Clinical Trial Management,
Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku,
Sapporo 060-8638, Japan.
Received: 6 February 2012 Accepted: 31 May 2012
Published: 18 June 2012
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doi:10.1186/1471-2377-12-39
Cite this article as: Tha et al.: Hyperintense putaminal rim at 1.5 T:
prevalence in normal subjects and distinguishing features from multiple
system atrophy. BMC Neurology 2012 12:39.
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