Free-breathing high isotropic resolution quantitative susceptibility mapping (QSM) of liver using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction.

PURPOSE: To enable free-breathing and high isotropic resolution liver quantitative susceptibility mapping (QSM) using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction. METHODS: Using 3D multi-echo UTE cones MRI, a respiratory motion was estimated from the k-space center of the imaging data. After sorting the k-space data with estimated motion, respiratory motion state-resolved reconstruction was performed for multi-echo data followed by nonlinear least-squares fitting for proton density fat fraction (PDFF), R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , and fat-corrected B0 field maps. PDFF and B0 field maps were subsequently used for QSM reconstruction. The proposed method was compared with motion-averaged (gridding) reconstruction and conventional 3D multi-echo Cartesian MRI in moving gadolinium phantom and in vivo studies. Region of interest (ROI)-based linear regression analysis was performed on these methods to investigate correlations between gadolinium concentration and QSM in the phantom study and between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM in in vivo study. RESULTS: Cones with motion-resolved reconstruction showed sharper image quality compared to motion-averaged reconstruction with a substantial reduction of motion artifacts in both moving phantom and in vivo studies. For ROI-based linear regression analysis of the phantom study, susceptibility values from cones with motion-resolved reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.31 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.05, R 2 $$ {R}^2 $$ = 0.999) and Cartesian without motion ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.32 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.04, R 2 $$ {R}^2 $$ = 1.000) showed linear relationships with gadolinium concentrations and showed good agreement with each other. For in vivo, motion-resolved reconstruction showed higher goodness of fit ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.00261 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.524, R 2 $$ {R}^2 $$ = 0.977) compared to motion-averaged reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.0021 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.572, R 2 $$ {R}^2 $$ = 0.723) in ROI-based linear regression analysis between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM. CONCLUSION: Feasibility of free-breathing liver QSM was demonstrated with motion-resolved 3D multi-echo UTE cones MRI, achieving high isotropic resolution currently unachievable in conventional Cartesian MRI.

MRI investigation of vascular remodeling for heterogeneous edema lesions in subacute ischemic stroke rat models: Correspondence between cerebral vessel structure and function.

The spatial heterogeneity in the temporal occurrence of pseudo-normalization of MR apparent diffusion coefficient values for ischemic lesions may be related to morphological and functional vascular remodeling. As the area of accelerated pseudo-normalization tends to expand faster and more extensively into the chronic stage, detailed vascular characterization of such areas is necessary. During the subacute stage of transient middle cerebral artery occlusion rat models, the morphological size of the macrovasculature, microvascular vessel size index (VSI), and microvessel density (MVD) were quantified along with functional perfusion measurements of the relative cerebral blood flow (rCBF) and mean transit time (rMTT) of the corresponding areas (33 cases for each parameter). When compared with typical pseudo-normalization lesions, early pseudo-normalization lesions exhibited larger VSI and rCBF (p < 0.001) at reperfusion days 4 and 7, along with reduced MVD and elongated rMTT (p < 0.001) at reperfusion days 1, 4, and 7. The group median VSI and rCBF exhibited a strong positive correlation (r = 0.92), and the corresponding MVD and rMTT showed a negative correlation (r = -0.48). Light sheet fluorescence microscopy images were used to quantitatively validate the corresponding MRI-derived microvascular size, density, and cerebral blood volume.

Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI.

Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases. Here, we established targeting ligand switchable nanoplatforms using lumazine synthase protein cage nanoparticles derived from Aquifex aeolicus (AaLS) by genetically introducing the SpyTag peptide (ST) to the C-terminus of the AaLS subunits to form an ST-displaying AaLS (AaLS-ST). Conversely, multiple targeting ligands were constructed by genetically fusing SpyCatcher protein (SC) to either HER2 or EGFR targeting affibody molecules (SC-HER2Afb or SC-EGFRAfb). Gd(III)-DOTA complexes were chemically attached to the AaLS-ST and the external surface of the Gd(III)-DOTA conjugated AaLS-ST (Gd(III)-DOTA-AaLS-ST) were successfully decorated with either the HER2Afb or the EGFRAfb. The resulting Gd(III)-DOTA-AaLS/HER2Afb and Gd(III)-DOTA-AaLS/EGFR2Afb exhibited high r1 relaxivity values of 57 and 25 mM-1 s-1 at 1.4 and 7 T, respectively, which were 10-fold or higher than those of the clinically used Dotarem. Their target-selective contrast enhancements were confirmed with in vitro cell-based MRI scans and the in vivo MR imaging of tumor-bearing mouse models at 7 T. A target-switchable AaLS-based nanoplatform that was developed in this study might serve as a promising T1 CA developing platform at a high magnetic field to detect various tumor sites in a target-specific manner in future clinical applications.

MRI Visualization of Whole Brain Macro- and Microvascular Remodeling in a Rat Model of Ischemic Stroke: A Pilot Study.

Using superparamagnetic iron oxide nanoparticles (SPION) as a single contrast agent, we investigated dual contrast cerebrovascular magnetic resonance imaging (MRI) for simultaneously monitoring macro- and microvasculature and their association with ischemic edema status (via apparent diffusion coefficient [ADC]) in transient middle cerebral artery occlusion (tMCAO) rat models. High-resolution T1-contrast based ultra-short echo time MR angiography (UTE-MRA) visualized size remodeling of pial arteries and veins whose mutual association with cortical ischemic edema status is rarely reported. ΔR2-ΔR2*-MRI-derived vessel size index (VSI) and density indices (Q and MVD) mapped morphological changes of microvessels occurring in subcortical ischemic edema lesions. In cortical ischemic edema lesions, significantly dilated pial veins (p = 0.0051) and thinned pial arteries (p = 0.0096) of ipsilateral brains compared to those of contralateral brains were observed from UTE-MRAs. In subcortical regions, ischemic edema lesions had a significantly decreased Q and MVD values (p < 0.001), as well as increased VSI values (p < 0.001) than normal subcortical tissues in contralateral brains. This pilot study suggests that MR-based morphological vessel changes, including but not limited to venous blood vessels, are directly related to corresponding tissue edema status in ischemic stroke rat models.

Pattern recognition analysis of directional intravoxel incoherent motion MRI in ischemic rodent brains.

This study aimed to demonstrate a reliable automatic segmentation method for independently separating reduced diffusion and decreased perfusion areas in ischemic stroke brains using constrained nonnegative matrix factorization (cNMF) pattern recognition in directional intravoxel incoherent motion MRI (IVIM-MRI). First, the feasibility of cNMF-based segmentation of IVIM signals was investigated in both simulations and in vivo experiments. The cNMF analysis was independently performed for S0 -normalized and scaled (by the difference between the maximum and minimum) IVIM signals, respectively. Segmentations of reduced diffusion (from S0 -normalized IVIM signals) and decreased perfusion (from scaled IVIM signals) areas were performed using the corresponding cNMF pattern weight maps. Second, Monte Carlo simulations were performed for directional IVIM signals to investigate the relationship between the degree of vessel alignment and the direction of the diffusion gradient. Third, directional IVIM-MRI experiments (x, y and z diffusion-gradient directions, 20 b values at 7 T) were performed for normal (n = 4), sacrificed (n = 1, no flow) and ischemic stroke models (n = 4, locally reduced flow). The results showed that automatic segmentation of the hypoperfused lesion using cNMF analysis was more accurate than segmentation using the conventional double-exponential fitting. Consistent with the simulation, the double-exponential pattern of the IVIM signals was particularly strong in white matter and ventricle regions when the directional flows were aligned with the applied diffusion-gradient directions. cNMF analysis of directional IVIM signals allowed robust automated segmentation of white matter, ventricle, vascular and hypoperfused regions in the ischemic brain. In conclusion, directional IVIM signals were simultaneously sensitive to diffusion and aligned flow and were particularly useful for automatically segmenting ischemic lesions via cNMF-based pattern recognition.

Cerebral blood perfusion deficits using dynamic susceptibility contrast MRI with gadolinium chelates in rats with post-ischemic reperfusion without significant dynamic contrast-enhanced MRI-derived vessel permeabilities: A cautionary note.

In this study, we quantified perfusion deficits using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with an extravasating contrast agent (CA). We also investigated the efficacy of leakage compensation from CA pre-load in brains from post-ischemic rat models without significant dynamic contrast-enhanced MRI (DCE-MRI)-derived vessel wall permeability. DSC measurements were obtained using fast (0.3 s) echo-planar imaging in both normal rats and rats with transient middle carotid artery occlusion (MCAO) (1-h MCAO, 24-h reperfusion) after successive administrations of gadoterate meglumine (Dotarem) and intravascular superparamagnetic iron oxide nanoparticles (SPION). The relative cerebral blood volume (CBV) and cerebral blood flow (CBF) values acquired using Dotarem were significantly underestimated (~20%) when compared to those acquired using SPION in ipsilesional post-ischemic brain regions. A slight overestimation of relative mean transit time was observed. Areas with underestimated CBV and CBF values from the corresponding error maps encompassed the area of infarcted tissue (apparent diffusion coefficient < 500 µm2/s) and mostly coincided with the area wherein conspicuous longitudinal relaxation time differences were observed pre- vs. post-injection of Dotarem. The DSC measurements with significant pre-load (0.3 mmol·kg-1) of Dotarem displayed minimal perfusion deficits when compared to those determined using the reference intravascular SPION.