HoeSu Jung1, SeokHa Jin1, DongKyu Lee1, SoHyun Han1, and HyungJoon Cho1
1Ulsan National Institute of Science and Technology, Ulsan, Korea, Republic of
Synopsis
Transverse-relaxation-based ΔR2- and ΔR2*- micro MRAs are being investigated for
imaging cerebral vasculature in rodent brains with increased sensitivity for
intracortical arterioles and venules, in conjunction with exogenous blood pool
contrast agents. In this study, we simulated extravascular signal decay
behaviors of ΔR2, and ΔR2* values for
multiple cylindrical models with varying diameters to quantitatively assess
both sensitivity and size overestimation issues in micro MRA. The benefits of following
synergistic combination of ΔR2,
and ΔR2* angiograms
along with the UTE-derived positive angiogram were investigated, and
corresponding UTE-ΔR2-ΔR2* combined angiogram
was applied to normal and C6 glioma tumor model for the verifications.Purpose
The ability to visualize
whole-brain vasculature is important for quantitative in vivo investigation of
vascular malfunctions in cerebral small vessel diseases, including cancer,
stroke and neurodegeneration. Dual mode MRA acquisition with superparamagnetic
iron oxide nanoparticles (SPION) provides a unique opportunity to
systematically compare and synergistically combine both longitudinal (R
1) and transverse (ΔR
2 and ΔR
2*)
relaxation-based MRAs. Through Monte Carlo (MC)
simulation [1] and MRA experiments in normal and tumor-bearing animals with
intravascular SPION, we validate that the multiplied ΔR
2- and ΔR
2*-MRAs
simultaneously improve the sensitivity to intra-cortical penetrating vessels and reduces vessel size overestimation of ΔR
2*-MRA. Then direct benefits of the UTE-ΔR
2-ΔR
2* combined MRA were visualized and
quantified for normal and tumor-bearing rat brains.
Methods
Normal and tumor-bearing Sprague-Dawley
(SD) rats were used for the MRI experiments. MR images of the SD rat brain,
using UTE3D sequence (UTE MRA), RARE sequence (ΔR2
MRA) [2] and FLASH sequence
(ΔR2* MRA), before and after
injection of SPION were acquired on 7T MR scanner (Bruker, Germany). SPION was
administered at the dose of 120 μmol/kg for UTE MRA, 240 μmol/kg for ΔR2* MRA and 360
μmol/kg for ΔR2 MRA,
respectively. The ΔR2*
and ΔR2 values were
calculated using the following equation,
$$ \triangle R_2^*\ and\ \triangle R_2\ = \frac{1}{TE} ln \left(\frac{S_{pre}}{S_{post}}\right) $$
where TE is the echo time, and
Spre and
Spost are the pre- and post-contrast signal
intensities with gradient echo for ΔR2*
and spin echo for ΔR2.The processing equation for combining all MRAs is
described by:
$$ {{UTE}_{surface\ and\ inner\ area}}+\left[\triangle R_2^*\ \times\ \triangle R_2\right]_{inner\ area} $$
The resulting UTE-ΔR2-ΔR2*
combined MRA was used for visualizing the vascular structure with minimized
susceptibility artifacts and enhanced sensitivity.
Results & Discussion
Figure 1 describes the behaviors of ΔR2, ΔR2*, and ΔR2 × ΔR2* as the distance from vessel
surface using MC simulation. The red, blue, and purple lines
correspond to ΔR2, ΔR2*, and ΔR2 × ΔR2*, respectively. For ΔR2, the maximum amplitude decreases, while
the width of decay tends to slightly increase as the vessel size increases. For
ΔR2*, the maximum amplitude
remains at a constant level, but the width becomes significantly broader with
growing vessel size, as seen in Figure1A-1, B-1, C-1, and D-1. Standardized ΔR2, ΔR2*, and ΔR2 × ΔR2* values were superimposed
together in Figure 1A-2, B-2, C-2, and D-2 for multiple vessel sizes. The
maximum amplitudes of ΔR2 × ΔR2* were significantly higher
than those from individual ΔR2 and ΔR2* and the initial fast decay
of ΔR2 × ΔR2* followed that of ΔR2, indicating both improvement
in vessel sensitivity and minimization of vessel size overestimation from the
multiplicative process of ΔR2 × ΔR2*.
To directly compare each MRA, a line
profile analysis was applied to brain region in Figure 2. As shown in Figure 2A-2,
the overestimation of vessel size from the ΔR2*-MRA (blue) is clear compared
to that of ΔR2-MRA (red) for a relatively large
vessel. The combined MRA (yellow) increased the vessel/tissue contrast and
reduced the vessel size overestimation, in agreement with the simulation
results. Smaller cortical penetrating vessels were rarely detected in
UTE-(green) or ΔR2-MRA (red) in regions shown in Figure 2A-3,
but were visible for ΔR2*-MRA (blue) and combined MRA
(yellow), also in agreement with the simulation results for smaller vessels.
Figure 3 shows MRAs of SD rat
with C6 tumors.The enhanced contrast of tumor region was
represented well in ΔR2 image as indicated by white arrow. The
tumor region from the ΔR2 and ΔR2* MRAs (Figure 3A-1 and Figure
3A-2) in the cortex was broadly revealed, however, it was difficult to
distinguish the tumor boundary in the ΔR2*-MRA alone due to the lowered
ΔR2* pre image signal from the T2* effect. The relatively low
tumor contrast of the cortical tumor region UTE image is shown in Figure 3A-3. The
UTE-ΔR2-ΔR2* combined MRA showed
increased tumor contrast in cortical regions, as shown in Figure 6A-4.
As shown in
Figure 4, CNRs from both normal and tumor regions were measured for each rat (n
= 4) in order to compare the distinguishability of tumors from each MRA. The
highest CNR tumor region value was obtained from UTE-ΔR2-ΔR2* combined MRA. In addition,
the CNR difference was highest between the normal and tumor regions from UTE-ΔR2-ΔR2* combined MRA.
Acknowledgements
This
work was supported by the National Research Foundation of Korea Grants funded
by the Korean Government (No. 2010-0028684 and No. 2014 R1A1A1 008255).References
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