Hyunsil Cha

Ligand-size and ligand-chain hydrophilicity effects on the relaxometric properties of ultrasmall Gd2O3 nanoparticles

The relaxometric properties of ultrasmall Gd2O3 nanoparticles coated with various ligands were investigated. These ligands include small diacids with hydrophobic chains, namely, succinic acid (Mw = 118.09 amu), glutaric acid (Mw = 132.12 amu), and terephthalic acid (Mw = 166.13 amu), and large polyethylenimines (PEIs) with hydrophilic chains, namely, PEI-1300 (M¯n=1300) and PEI-10000 (M¯n=10000). Ligand-size and ligand-chain hydrophilicity effects were observed. The longitudinal (r1) and transverse (r2) water proton relaxivities generally decreased with increasing ligand-size (the ligand-size effect). The ligand-size effect was weaker for PEI because its hydrophilic chains allow water molecules to access the nanoparticle (the ligand-chain hydrophilicity effect). This result was explained on the basis of the magnetic dipole interaction between the dipoles of the nanoparticle and water proton. In addition, all samples were found to be non-toxic in cellular cytotoxicity tests.

Altered power spectral density in the resting-state sensorimotor network in patients with myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disease that involves the brain with several neurological symptoms. Although there were few imaging studies on DM1, no studies have investigated functional alterations in the sensorimotor network at rest in patients with DM1. In the current study, a power spectral density (PSD) analysis of resting-state fMRI data was performed to assess possible alteration in spontaneous neural activity of the sensorimotor network in patients with DM1. Compared to healthy controls, patients with DM1 showed higher PSD responses in the orbitofrontal cortex, parahippocampus and basal ganglia (corrected P < 0.05). Patients with DM1 showed higher PSD responses in white matter structures associated with motor function (corrected P < 0.05). Furthermore, correlation analysis indicated that the brain regions showing PSD differences were correlated with measures of motor performance (P < 0.05). In gray matter, our findings suggest that motor disability in DM1 is not an isolated deterioration of the motor power but a multimodal dysfunction that also involves the visual system. In addition, the widespread PSD alteration in white matter structures suggest that motor deficits in DM1 involve motor movement structures as well as structures important for its coordination and regulation.

Magnetic resonance imaging, gadolinium neutron capture therapy, and tumor cell detection using ultrasmall Gd2O3 nanoparticles coated with polyacrylic acid-rhodamine B as a multifunctional tumor theragnostic agent

Monodisperse and ultrasmall gadolinium oxide (Gd2O3) nanoparticle colloids (davg = 1.5 nm) (nanoparticle colloid = nanoparticle coated with hydrophilic ligand) were synthesized and their performance as a multifunctional tumor theragnostic agent was investigated. The aqueous ultrasmall nanoparticle colloidal suspension was stable and non-toxic owing to hydrophilic polyacrylic acid (PAA) coating that was partly conjugated with rhodamine B (Rho) for an additional functionalization (mole ratio of PAA : Rho = 5 : 1). First, the ultrasmall nanoparticle colloids performed well as a powerful T1 magnetic resonance imaging (MRI) contrast agent: they exhibited a very high longitudinal water proton relaxivity (r1) of 22.6 s−1 mM−1 (r2/r1 = 1.3, r2 = transverse water proton relaxivity), which was ∼6 times higher than those of commercial Gd-chelates, and high positive contrast enhancements in T1 MR images in a nude mouse after intravenous administration. Second, the ultrasmall nanoparticle colloids were applied to gadolinium neutron capture therapy (GdNCT) in vitro and exhibited a significant U87MG tumor cell death (28.1% net value) after thermal neutron beam irradiation, which was 1.75 times higher than that obtained using commercial Gadovist. Third, the ultrasmall nanoparticle colloids exhibited stronger fluorescent intensities in tumor cells than in normal cells owing to conjugated Rho, proving their pH-sensitive fluorescent tumor cell detection ability. All these results together demonstrate that ultrasmall Gd2O3 nanoparticle colloids are the potential multifunctional tumor theragnostic agent.

Stable and non-toxic ultrasmall gadolinium oxide nanoparticle colloids (coating material = polyacrylic acid) as high-performance T1 magnetic resonance imaging contrast agents

For use as positive (T1) magnetic resonance imaging contrast agents (MRI-CAs), gadolinium oxide (Gd2O3) nanoparticle colloids (i.e. nanoparticles coated with hydrophilic ligands) should be stable, non-toxic, and ultrasmall in particle diameter for renal excretion. In addition, they should have a high longitudinal water proton relaxivity (r1) and r2/r1 ratio that is close to one (r2 = transverse water proton relaxivity) for high-performance. In this study, we report ultrasmall Gd2O3 nanoparticle colloids [coating material = polyacrylic acid, Mw = ∼5100 Da] satisfying these conditions. The particle diameter was monodisperse with an average value of 2.0 ± 0.1 nm. The colloidal suspension exhibited a high r1 value of 31.0 ± 0.1 s−1 mM−1 and r2/r1 ratio of 1.2, where r1 was ∼8 times higher than that of commercial Gd-chelates: the cooperative induction model was proposed to explain this. The effectiveness of the colloidal suspension as a high-performance T1 MRI-CA was confirmed by taking in vivo T1 MR images in a mouse after intravenous administration. Highly positive contrast enhancements were observed in various organs of the mouse such as the liver, kidneys, and bladder. The colloidal suspension was then excreted through the bladder.

Diffusion tensor imaging and voxel-based morphometry reveal corticospinal tract involvement in the motor dysfunction of adult-onset myotonic dystrophy type 1

Magnetic resonance imaging (MRI) studies have demonstrated that patients with myotonic dystrophy type 1 (DM1) exhibit gray and white matter abnormalities that are correlated with various genetic and neuropsychological measures. However, few MRI studies have focused on the correlations between brain abnormalities and overall motor function including gait performance. Here, we investigated the correlations between brain abnormalities, as assessed with MRI including diffusion tensor imaging (DTI), and motor performance, as assessed with the Medical Research Council sum score (MRCSS), 6-minute walk test (6MWT), and hand grip power, in patients with DM1. Eighteen patients with DM1 and twenty healthy controls participated in this study. The MRCSS and 6MWT reflect patients’ general motor performance, particularly gait, while hand grip reflects the presence of myotonia. We found significant relationships between DTI parameters in the corticospinal tract (CST) and genetic factors and motor performance in patients with DM1. These findings suggest that CST involvement reflecting deterioration of the motor tracts may play a significant role in clinical myotonia. Further, a direct relationship between the cortical gray matter volume and DTI measures in the CST suggests that white matter abnormalities in the CST are strongly associated with volume reductions in the sensorimotor cortex of patients with DM1.

Neural processing of lower- and upper-case text in second language learners of English: an fMRI study

ABSTRACT Upper-case text is considered detrimental to the reading comprehension of second language learners of English. Little is known about the neurocognitive mechanisms underlying the processing of upper-case text. To investigate this issue, Korean students (n = 23) performed 40 reading trials, and their reading comprehension of text written in either upper- or lower-case letters was recorded while their brain activities were scanned with functional magnetic resonance imaging. Compared to lower-case text, upper-case text elicited greater activation of the primary visual areas in both hemispheres associated with orthographic processing. In contrast, lower-case text increased neural activity in brain regions associated with higher-order reading comprehension processes (e.g. the integration of text information) and the premotor cortex. Collectively, based on automacity theory, these results suggested that upper-case text interferes with reading comprehension because it requires increased orthographic processing, which in turn leaves fewer neural resources for phonological processing and higher-order reading comprehension processes.

Relaxometric, Optical and Cell Viability Properties of D-Glucuronic Acid Coated Cr2O3 Nanoparticles

D-glucuronic acid-coated ultrasmall chromium oxide (Cr2O3) nanoparticles were synthesized by a one-pot polyol method and their relaxometric and optical properties were investigated. The as-synthesized D-glucuronic acid-coated nanoparticles were amorphous owing to ultrasmall particle diameters (davg = 2.0 nm), whereas orthorhombic Cr2O3 nanoparticles with two size groups (davg = 3.6 and 5.7 nm) were observed after thermogravimetric analysis (900 °C) as a result of particle growth. The nanoparticles exhibited size-dependent UV-visible absorption maxima at 238, 274, and 372 nm with increasing particle diameter, corresponding to band gaps of 5.13, 4.45, and 3.28 eV, respectively. D-glucuronic acid-coated ultrasmall Cr2O3 nanoparticles revealed low water proton relaxivities of r1 = 0.05 s-1mM-1 and r2 = 0.20 s-1mM-1, consistent with the antiferromagnetic property of Cr2O3. They showed good biocompatibility up to 500 μM of Cr.

Longitudinal Water Proton Relaxivity and In Vivo T1 MR Images of Mixed Zn(II)/Gd(III) Oxide Nanoparticles

Mixed Zn(II)/Gd(III) oxide nanoparticles (~8 mole%Zn) with d(avg) of 2.1 nm were synthesized. The D-glucuronic acid coated Zn(II)/Gd(III) oxide nanoparticles showed a longitudinal water proton relaxivity (r₁) of 12.3 s⁻¹mM⁻¹ with r₂/r₁ = 1.1, corresponding to an ideal condition for T₁ MRI contrast agent. We attribute this to reduced magnetization of the mixed nanoparticles owing to non-magnetic Zn in the nanoparticles. Their effectiveness as a T₁ MRI contrast agent was confirmed by acquiring In Vivo T₁ MR images of a mouse after intravenous injection.