Dataset Information

Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.

ABSTRACT: Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of [Formula: see text] and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.4 T after injection of USPIO. Focal areas with increased magnetic susceptibility and [Formula: see text] values were discernible across several brain regions in 12-month-old arcAβ compared to 6-month-old arcAβ mice and to non-transgenic littermates, indicating accumulation of particles after USPIO injection. This was concomitant with higher [Formula: see text] and increased magnetic susceptibility differences relative to cerebrospinal fluid measured in USPIO-injected compared to non-USPIO-injected 12-month-old arcAβ mice. No differences in [Formula: see text] and magnetic susceptibility were detected in USPIO-injected compared to non-injected 12-month-old non-transgenic littermates. Histological analysis confirmed focal uptake of USPIO particles in perivascular macrophages adjacent to small caliber cerebral vessels with radii of 2-8 µm that showed no cerebral amyloid angiopathy. USPIO-enhanced [Formula: see text] and quantitative susceptibility mapping constitute quantitative tools to monitor such functional microvasculopathies.

SUBMITTER: Klohs J

PROVIDER: S-EPMC5010097 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.

Klohs Jan J Deistung Andreas A Ielacqua Giovanna D GD Seuwen Aline A Kindler Diana D Schweser Ferdinand F Vaas Markus M Kipar Anja A Reichenbach Jürgen R JR Rudin Markus M

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20151201 9

Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of [Formula: see text] and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.4 T after injection of USPIO. ...[more]

PMID: 26661253

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Project description:There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 × 0.44 × 1 mm3 at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration = 4 mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 μm-100 μm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 μm should be visible with the maximum dose of 4 mg/kg.

Project description:PurposeTo develop a method to reconstruct quantitative susceptibility mapping (QSM) from multi-echo, multi-flip angle data collected using strategically acquired gradient echo (STAGE) imaging.MethodsThe proposed QSM reconstruction algorithm, referred to as "structurally constrained Susceptibility Weighted Imaging and Mapping" scSWIM, performs an ℓ 1 and ℓ 2 regularization-based reconstruction in a single step. The unique contrast of the T1 weighted enhanced (T1WE) image derived from STAGE imaging was used to extract reliable geometry constraints to protect the basal ganglia from over-smoothing. The multi-echo multi-flip angle data were used for improving the contrast-to-noise ratio in QSM through a weighted averaging scheme. The measured susceptibility values from scSWIM for both simulated and in vivo data were compared to the: original susceptibility model (for simulated data only), the multi orientation COSMOS (for in vivo data only), truncated k-space division (TKD), iterative susceptibility weighted imaging and mapping (iSWIM), and morphology enabled dipole inversion (MEDI) algorithms. Goodness of fit was quantified by measuring the root mean squared error (RMSE) and structural similarity index (SSIM). Additionally, scSWIM was assessed in ten healthy subjects.ResultsThe unique contrast and tissue boundaries from T1WE and iSWIM enable the accurate definition of edges of high susceptibility regions. For the simulated brain model without the addition of microbleeds and calcium, the RMSE was best at 5.21ppb for scSWIM and 8.74ppb for MEDI thanks to the reduced streaking artifacts. However, by adding the microbleeds and calcium, MEDI's performance dropped to 47.53ppb while scSWIM performance remained the same. The SSIM was highest for scSWIM (0.90) and then MEDI (0.80). The deviation from the expected susceptibility in deep gray matter structures for simulated data relative to the model (and for the in vivo data relative to COSMOS) as measured by the slope was lowest for scSWIM + 1%(-1%); MEDI + 2%(-11%) and then iSWIM -5%(-10%). Finally, scSWIM measurements in the basal ganglia of healthy subjects were in agreement with literature.ConclusionThis study shows that using a data fidelity term and structural constraints results in reduced noise and streaking artifacts while preserving structural details. Furthermore, the use of STAGE imaging with multi-echo and multi-flip data helps to improve the signal-to-noise ratio in QSM data and yields less artifacts.

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Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.

Publications

Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.

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