A simulation study and application of UTE-ΔR2-ΔR2* combined MR whole brain angiogram using dual contrast superparamagnetic iron oxide nanoparticles.
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 (R1) and transverse (ΔR2 and ΔR2*) 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 ΔR2- and ΔR2*-MRAs simultaneously improve the sensitivity to intra-cortical penetrating vessels and reduces vessel size overestimation of ΔR2*-MRA. Then direct benefits of the UTE-ΔR2-ΔR2* 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

1. Pathak, A. P., Ward, B. D. & Schmainda, K. M. A novel technique for modeling susceptibility-based contrast mechanisms for arbitrary microvascular geometries: the finite perturber method. Neuroimage 2008;40:1130-1143.

2. Lin, C. Y., Lin, M. H., Cheung, W. M., et al. In vivo cerebromicrovasculatural visualization using 3D ΔR2-based microscopy of magnetic resonance angiography (3D ΔR2-mMRA). Neuroimage 2009:45:824-831.

Figures

Figure 1. The simulation results with different vessel diameters: Panels (A-1), (B-1), (C-1), and (D-1) plot the values of ΔR2 and ΔR2* with vessel diameters of 40, 60, 78, and 156 μm. Panels (A-2), (B-2), (C-2), and (D-2) show correspondingly standardized data from ΔR2, ΔR2* and ΔR2 × ΔR2*.

Figure 2. Comparison of line profiles from UTE- (green), ΔR2- (red), ΔR2*- (blue) and UTE-ΔR2-ΔR2* combined (yellow) MRAs in rat brain.

Figure 3. MR angiography of a C6 tumor rat in posterior-to-anterior views: panels (A-1), (A-2), (A-3) and (A-4) show posterior-to-anterior views of ΔR2-, ΔR2*-, UTE- and UTE-ΔR2-ΔR2* combined MRAs, respectively.

Figure 4. Comparison of CNRs between intra-cortical tumor and normal brain regions on the contralateral hemisphere for UTE- (A-1), ΔR2- (A-2), ΔR2*- (A-3)and UTE-ΔR2-ΔR2* combined (A-4) MRAs of C6 tumor rats: the CNR of the tumor region and CNR difference from UTE-ΔR2- ΔR2* combined MRA were the highest.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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