lei hu1, fei yun zha1, dong xing1, wei gong1, jiao wang1, yuan lin1, hui lin2, and xiao xu2
1Renmin Hospital of Wuhan University, wuhan, China, People's Republic of, 2GE healthcare, wuhan, China, People's Republic of
Synopsis
To
estimate the effect of diabetes on vertebral bone marrow, twelve young New
Zealand White rabbits including alloxan-induced diabetic rabbits (n=6) and the controls
(n=6) underwent sagittal magnetic resonance imaging (IDEAL-IQ, DCE-MRI) of
lumbar at each time point. At the week of 16, all rabbits were killed. L7
sampling, HE staining and immunoperoxidase CD31 labeling were performed.
According to statistical analysis, there were statistically significant
differences of the vertebral DCE-MRI parameters and fat fraction (FF) between
the diabetic groups and controls at each time point. The variety of vertebral microvascular
permeability was strongly associated with the increasing vertebral fat
deposition.Purpose
To
estimate the variation of the
vertebral microvascular permeability and vertebral fat
deposition in alloxan-induced diabetic rabbits
using
DCE-MRI
and IDEAL-IQ.
Methods
Twelve young New
Zealand White rabbits were randomly assigned to alloxan-induced diabetic
group (n=6)
and control group (n=6). The rabbits in
alloxan-induced diabetic group were injected with a total
amount of 100mg/kg of alloxan. All rabbits underwent
sagittal magnetic resonance imaging
(IDEAL-IQ, DCE-MRI)
of
lumbar on a 3.0T scanner (GE
Discovery 750 Plus) with an 8 channel knee coil at fixed
time points (0, 4, 8, 12, 16 week). Imaging parameters
for IDEAL- IQ were set as follows: FA = 6°; TE = 1.2, 3.2, 5.2, 7.2, 9.2 and 11.2
ms; TR = 19.6 ms; FOV = 16 x 12.8 cm
2; slice thickness = 3 mm; the
dynamic contrast-enhanced imaging was performed using a LAVA sequence with
following parameters: TE = 2.3 ms, TR = 4.9 ms, FA = 15°, FOV
= 16 x 12.8 mm
2. The contrast agent
with a concentration of 0.2 mmol/kg was injected after one
pre-contrast frame was acquired. L7 was chosen to measure vertebral
fat fraction and DCE-MRI parameters. Fat fraction(FF)
was measured on the fat fraction map produced by IDEAL-IQ to estimate the
variation of vertebral fat deposition. The DCE parameters were
measured using
GE Omni kinetics software. The Extended Tofts model was
used to estimate the quantitative parameters
including the transfer constant (
Ktrans) the
rate contrast (
kep),
fractional EES volume (
ve)
and fractional plasma volume (
vp)
1
in the ROI shown in Fig. 1a (right).
The Arterial Input Function (AIF) was determined from a circular
ROI in the center of abdominal aorta at the plane
of L7 (left in
Fig. 1a). Vertebral fat fraction
was measured
in fat fraction map in the ROI shown in
Fig1.
b. At the week 16, all
rabbits were sacrificed,
after which L7 sampling, HE staining and immunoperoxidase CD31
labeling . HE staining and immunoperoxidase CD31 labeling were performed as gold standards to estimate
the variation of bone marrow cell and vertebral microvascular
respectively. To count
microvessel density (MVD), a quantitative estimation was performed
using a light microscopy in a ×200 field. Repetitive measure analysis of
variance (ANOVA) was applied in analyzing FF and DCE-MRI
parameters at different time points. Pearson
correlations of DCE-MRI parameters with FF and with MVD were analyzed,
respectively. All of the thresholds of statistical significance
were set at
P < 0.05.
Results
HE
staining and immunohistochemistry showed that in
comparison to the control group, the amount of the fat cell in
diabetic group increased
while the bone
marrow cells and
microvessel reduced (
Fig. 2
and
3). The
FF,
Ktrans
and
kep increased while
ve and
vp
decreased in the diabetic group (
Fig.
4). Only the alloxan-induced diabetic group had statistically significant differences
in vertebral fat fraction and DCE parameters at each time point (FF:
F=50.387,
P<0.01;
Ktrans:
F=63.694,
P<0.05;
kep:
F=5.04,
P<0.05;
vp:
F=4.403,
P<0.05;
vp:
F=9.751,
P<0.05). As shown in
Fig.5, MVD showed negative correlation with
Ktrans and
kep
and
positive correlation with
ve
and
vp (
Ktrans:
r=-0.901,
P<0.05;
kep:
r=-0.731,
P<0.05;
ve:
r=0.741,
P<0.05;
vp:
r=0.593,
P<0.05) (
Fig. 5a-d) while FF showed positive
correlation with
Ktrans and
kep and negative
correlation with
ve and
vp (
Ktrans:
r=0.863,
P<0.05;
kep:
r=0.641,
P<0.05;
ve: r=-0.629,
P<0.05;
vp:
r=-0.665,
P<0.05) (
Fig. 5e-h).
Discussion and Conclusion:
The
results of this study demonstrated diabetes mellitus could cause the variation
of the vertebral microvascular permeability,
reduce the bone marrow cells and cause fat accumulation. In this study, MVD showed negative
correlation with
Ktrans
and
kep. It inferred that the increase of
Ktrans and
kep could indicate a destruction of sinusoids and capillaries. A consistent reduction of sinusoids
and arterioles can cause the decrease of
vp
which represent plasma volume. FF showed negative correlation with
ve and
vp.
The excess fat in vertebral bone marrow may replace hematological cells
2
and squeeze microvascular, which may be the explanation of decreased
interstitial volume (
ve). Compared
with previous study used marrow blood flow by Oikawa
3, our method achieved consistent results in
a noninvasive and simpler way. DCE-MRI and IDEAL-IQ can evaluate quantitatively
the variation trends of thevertebral microvascular permeability and vertebral
fat deposition in alloxan-induced diabetic rabbits. The variety of vertebral microvascular
permeability is strongly associated with the increasing vertebral fat
deposition.
Acknowledgements
No acknowledgement found.References
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fat in diabetic and healthy pigs: [(18)F]FDG-PET and MRI study. Bone, 2014. 61:
p. 33-8.
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