Intracellular bimodal nanoparticles based on quantum dots for high‐field MRI at 21.1 T

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high‐field MR applications—including biomedical imaging at 21.1 T, the highest magnetic field available for MRI—these nanoparticles capitalize on the improved performance of chelated Dy³⁺ with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell‐penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self‐transfecting high‐field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG‐micelles

Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)‐specific antibodies. The abdominal aortas of atherosclerotic apoE‐KO mice were imaged with T₁‐weighted high‐resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE‐KO) mice that were injected with MSR‐targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR‐targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE‐KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA. Magn Reson Med 58:1164–1170, 2007. © 2007 Wiley‐Liss, Inc.     

Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T(1) mapping.

There has been growing interest in using manganese-enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn(2+) produces a very wide range of T(1) change. In particular, in neuronal tract tracing experiments the site of Mn(2+) injection can have very short T(1) while distant regions have small T(1) reductions, primarily due to dilution of Mn(2+). Most MEMRI studies use T(1)-weighted sequences, which can only give optimal contrast for a narrow range of T(1) changes. To improve sensitivity to the full extent of Mn(2+) concentrations and to optimize detection of low concentrations of Mn(2+), a fast T(1) mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T(1) compared to more conventional T(1) measurements. Using center-out segmented EPI, whole-brain 3D T(1) maps with 200-microm isotropic resolution were obtained in 2 h from rat brain. Mn(2+) transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T(1). With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn(2+) used.     

Compressed sensing reconstruction for magnetic resonance parameter mapping

Compressed sensing (CS) holds considerable promise to accelerate the data acquisition in magnetic resonance imaging by exploiting signal sparsity. Prior knowledge about the signal can be exploited in some applications to choose an appropriate sparsifying transform. This work presents a CS reconstruction for magnetic resonance (MR) parameter mapping, which applies an overcomplete dictionary, learned from the data model to sparsify the signal. The approach is presented and evaluated in simulations and in in vivo T₁ and T₂ mapping experiments in the brain. Accurate T₁ and T₂ maps are obtained from highly reduced data. This model‐based reconstruction could also be applied to other MR parameter mapping applications like diffusion and perfusion imaging. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Effect of gender on in vivo cartilage magnetic resonance imaging T2 mapping

PURPOSE: To determine if gender is a significant variable for in vivo magnetic resonance imaging (MRI) T2-mapping of knee articular cartilage in young asymptomatic volunteers. MATERIALS AND METHODS: Cartilage MRI T2 mapping was performed in a young healthy population consisting of seven male and 10 female volunteers, 22 to 29 years of age. High-resolution in vivo T2 maps were obtained of patellar, tibial, and weight-bearing femoral articular cartilage. Spatial dependency of cartilage T2 between groups was evaluated through a comparison of cartilage T2 as a function of normalized distance from bone. RESULTS: Bulk cartilage T2 values were similar at all three anatomic sites, and between male and female volunteers. All volunteers demonstrated similar spatial variation in cartilage MRI T2 values, with a minimum located in the radial zone and increasing T2 values toward the articular surface. There was no difference in spatial dependency of cartilage T2 between males and females. CONCLUSION: In young, healthy volunteers, the magnitude and spatial dependency of cartilage T2 does not differ with gender.     

Gadolinium‐modulated 19F signals from perfluorocarbon nanoparticles as a new strategy for molecular imaging

Recent advances in the design of fluorinated nanoparticles for molecular magnetic resonance imaging (MRI) have enabled specific detection of ¹⁹F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total ¹⁹F in imaging voxels is often limited. By directly incorporating a relaxation agent, gadolinium (Gd), into the lipid monolayer that surrounds the perfluorocarbon (PFC), a marked augmentation of the ¹⁹F signal from 200‐nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the ¹⁹F nuclei fourfold at 1.5 T and effects a 125% increase in signal—an effect that is maintained when they are targeted to human plasma clots. By varying the surface concentration of Gd, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of ¹⁹F MRI/MRS and forms the basis for designing contrast agents capable of sensing their surface chemistry. Magn Reson Med 60:1066–1072, 2008. © 2008 Wiley‐Liss, Inc.     

In vivo 3.0‐tesla magnetic resonance T1ρ and T2 relaxation mapping in subjects with intervertebral disc degeneration and clinical symptoms

The purpose of this study is (1) to determine the correlation between T_1ρ and T₂ and degenerative grade in intervertebral discs using in vivo 3.0‐T MRI, and (2) to determine the association between T_1ρ and T₂ and clinical findings as quantified by the SF‐36 Questionnaire and Oswestry Disability Index. Sixteen subjects participated in this study, and each completed SF‐36 and Oswestry Disability Index questionnaires. MRI T_1ρ and T₂ mapping was performed to determine T_1ρ (77 discs) and T₂ (44 discs) in the nucleus of the intervertebral disc, and T₂‐weighted images were acquired for Pfirrmann grading of disc degeneration. Pfirrmann grade was correlated with both T_1ρ (r = ?0.84; P < 0.01) and T₂ (r = ?0.61; P < 0.01). Mixed‐effects models demonstrate that only T_1ρ was associated with clinical questionnaires (R²_SF‐36 = 0.55, R²_O.D.I. = 0.56; P < 0.05). Although the averaged values of T_1ρ and T₂ were significantly correlated, they presented differences in spatial distribution and dynamic range, thus suggesting different sensitivities to tissue composition. This study suggests that T_1ρ may be sensitive to early degenerative changes (corroborating previous studies) and clinical symptoms in intervertebral disc degeneration. Magn Reson Med 63:1193–1200, 2010. © 2010 Wiley‐Liss, Inc.     

Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Magnetoferritin nanoparticles have been developed as high‐relaxivity, functional contrast agents for MRI. Several previous techniques have relied on unloading native ferritin and re‐incorporation of iron into the core, often resulting in a polydisperse sample. Here, a simplified technique is developed using commercially available horse spleen apoferritin to create monodisperse magnetoferritin. Iron oxide atoms were incorporated into the protein core via a step‐wise Fe(II)Chloride addition to the protein solution under low O₂ conditions; subsequent filtration steps allow for separation of completely filled and superparamagnetic magnetoferritin from the partially filled ferritin. This method yields a monodisperse and homogenous solution of spherical particles with magnetic properties that can be used for molecular magnetic resonance imaging. With a transverse per‐iron and per‐particle relaxivity of 78 mM^?1 sec^?1 and 404,045 mM^?1 sec^?1, respectively, it is possible to detect ～10 nM nanoparticle concentrations in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.