Synopsis
Microvascular function in the skeletal muscle can be
assessed through blood oxygenation level dependent (BOLD) MRI signal changes
after performing a brief exercise or following a period of induced ischemia. Such
BOLD related relaxation changes are mainly attributed to intravascular
mechanisms, such as changes in the hemoglobin content and oxygen saturation
levels. In this work, we developed and implemented a rapid echo-planar imaging
(EPI) method to map T2*
changes, following a single maximum voluntary contraction on a 3 T whole body
clinical scanner.Purpose
To develop and implement a rapid imaging method for estimating
T2* changes in the
muscles of the lower leg, following brief single maximum voluntary contractions
at 3 T.
Background
Muscle function impairment can result from reduced blood
supply and tissue oxygenation, as for example in patients with peripheral arterial
occlusive disease (PAOD).
1 Assessing the
microvascular function in such diseases may help to better understand the
factors responsible for their onset and progression. Microvascular function in
the skeletal muscle can be assessed through blood oxygenation level dependent
(BOLD) MRI signal changes after performing a brief exercise or following a
period of induced ischemia.
2 Multiple factors
influence BOLD signals, oxygenation and blood volume being the largest,
3 and it has been
shown that the muscle BOLD responses are different at long echo times (i.e. TE:
45 ms) compared to short echo times (TE: 6 ms).
4 Acquiring
multiple echoes for mapping effective relaxation time constant (
T2*) values better
reflects multiple components that influence small vessel function.
The time course of
T2*
changes has been reported previously in reactive hyperemia paradigms.
5,6
However, mild to moderate pain during cuff protocols has been reported, particularly
by PAOD patients.
7,8 It would therefore be useful
to establish a method to measure exercise induced
T2* changes that can be more easily tolerated
by these patient populations. In this work, we developed and implemented a
rapid echo-planar imaging (EPI) method to map
T2* changes, following a single maximum
voluntary contraction on a 3 T whole body clinical scanner.
Methods
We recruited 7 healthy subjects (three men and four
women, age: 33.5 ± 6.3 years, BMI 22.8 ± 4.1 kg/m
2, mean ± standard
deviation). We performed MRI measurements on a 3 T MRI whole body scanner (MAGNETOM
Prisma, Siemens Healthcare, Erlangen, Germany) using a 15-channel
transmit/receive knee coil (QED, Quality Electrodynamics LLC, Cleveland, OH). The subject’s right foot
was secured in a boot attached to a pedal of a custom-built foot device. The
footplate angle was fixed at 120
o for an isometric exercise. We
acquired images for 10 min, during which time subjects performed a 1-s duration
maximal voluntary plantar flexion every 90 s. We mapped
T2* dynamically, using a modified single-shot
echo-planar imaging sequence that continuously excited and acquired one slice for
a given TR with varied TE after each excitation. The data acquisition
parameters are, TR 100 ms, 10 EPI images with varied TE from 7.2 ms to 52.2 ms per
s, bandwidth-per-pixel 2242 Hz, iPat = 3, 25 cm field-of-view, 1 cm slice
thickness, 64×64 acquisition matrix, 21
o flip angle. We
acquired anatomical images to identify the largest cross-section area of the posterior
muscles of the lower leg that we also used to identify large blood vessels and
exclude them from
T2*
fitting in the BOLD experiment. We calculated
T2* values in the BOLD images pixel-wise
using custom written MATLAB code, and calculated four parameters in regions of
interest in the soleus muscle. These parameters are: 1) Pre-exercise
T2*, 2) Peak post-contraction
T2*, 3) Peak
T2* percent change,
4) time to peak (TTP).
Results
Sample images are shown in Figures 1.A and B. A time
course of
T2* in the soleus muscle during
a 10-min acquisition is shown in Figure 1.C. We did not perform
T2*
fitting on the set of EPI images during the contraction. After contraction,
T2* increased
rapidly with an average TTP of 13.8 ± 4.1 s (mean ± SD) across subjects.
T2* at rest was
25.4 ± 1.5 ms and increased by 3.8 ± 1.8%. The results across seven subjects are
summarized in Table 1.
Discussion
We developed and implemented a rapid (1-s temporal resolution) EPI
sequence for mapping
T2*
changes following single brief contractions. Exercise
induced BOLD is more physiologically relevant in disease conditions like PAOD, since
the control of blood flow from the terminal arterioles is greatly important
during the initial stages of exercise. Therefore initial responses to exercise
reflect the function of the microvasculature, which is captured with single
contraction protocols.
9,10
A limitation of our method is that it only allowed moderate
in plane resolution (3.9 x 3.9 mm
2). Higher in plane resolution may improve
our ability to exclude voxels containing big vessels.
Conclusion
We developed and implemented a rapid (1-s temporal
resolution) EPI sequence for mapping
T2*
changes following single brief contractions at 3 T. This development will allow
us to study microvascular function in patients with PAOD, who cannot tolerate
cuff protocols.
Acknowledgements
This study was supported by NIH grant RO1 DK106292,
and was performed under the rubric of the Center of Advanced Imaging Innovation
and Research (CAI2R), a NIBIB Biomedical Technology Resource Center
(NIH P41 EB017183).References
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