Yongmin Chang

Paramagnetic Ultrasmall Gadolinium Oxide Nanoparticles as Advanced T1 MRI Contrast Agent: Account for Large Longitudinal Relaxivity, Optimal Particle Diameter, and In Vivo T1 MR Images

Paramagnetic ultrasmall gadolinium oxide (Gd(2)O(3)) nanoparticles with particle diameters (d) of approximately 1 nm were synthesized by using three kinds of Gd(III) ion precursors and by refluxing each of them in tripropylene glycol under an O(2) flow. A large longitudinal relaxivity (r(1)) of water proton of 9.9 s(-1) mM(-1) was estimated. As a result, high contrast in vivo T(1) MR images of the brain tumor of a rat were observed. This large r(1) is discussed in terms of the huge surface to volume ratio (S/V) of the ultrasmall gadolinium oxide nanoparticles coupled with the cooperative induction of surface Gd(III) ions for the longitudinal relaxation of a water proton. It is found from the d dependence of r(1) that the optimal range of d for the maximal r(1), which may be used as an advanced T(1) MRI contrast agent, is 1-2.5 nm.

Manganese exposure and cognitive deficits: A growing concern for manganese neurotoxicity

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on childrens cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

A Facile Synthesis, In vitro and In vivo MR Studies of d-Glucuronic Acid-Coated Ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho, and Er) Nanoparticles as a New Potential MRI Contrast Agent

A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles is presented. Their water proton relaxivities were studied to address their possibility as a new potential MRI contrast agent. We focused on the d-glucuronic acid-coated ultrasmall Dy(2)O(3) nanoparticle because it showed the highest r(2) relaxivity among studied nanoparticles. Its performance as a T(2) MRI contrast agent was for the first time proved in vivo through its 3 T T(2) MR images of a mouse, showing that it can be further exploited for the rational design of a new T(2) MRI contrast agent at high MR fields.

Paramagnetic nanoparticle T1 and T2 MRI contrast agents.

There is no doubt that magnetic resonance imaging contrast agents (MRI CAs) can play a vital role in diagnosing diseases. Therefore, demand for new MRI CAs with an enhanced sensitivity and advanced functionalities is very high. Here, paramagnetic nanoparticles (NPs) are reviewed as new potential candidates for either T(1) or T(2) MRI CAs or both. These include surface coated lanthanide (Ln) oxide NPs (Ln = Gd, Dy, and Ho) and manganese oxide NPs. Surface coating materials should be biocompatible and hydrophilic. Compared to conventional large NPs, these surface coated paramagnetic NPs can be made ultrasmall with core particle diameter ranging from 1 to 3 nm, but their magnetic properties are still sufficient for MRI CAs. At this particle diameter, they can be easily excreted from the body through the renal system, which is prerequisite for in vivo applications. Mixed lanthanide oxide NPs into which a fluorescent Ln material is incorporated will be valuable as multiple imaging agents for both MRI-fluorescent imaging (FI) and MRI-cellular imaging (CL). These paramagnetic NPs can be further functionalized towards target-specific imaging, multiplex imaging, and drug delivery.

Water-Soluble MnO Nanocolloid for a Molecular T1 MR Imaging: A Facile One-Pot Synthesis, In vivo T1 MR Images, and Account for Relaxivities

A facile one-pot synthesis of a water-soluble MnO nanocolloid (i.e., D-glucuronic acid-coated MnO nanoparticle) is presented. The MnO nanoparticle in the MnO nanocolloid was coated with a biocompatible and hydrophilic D-glucuronic acid, and its particle diameter was nearly monodisperse and ranged from 2 to 3 nm. The average hydrodynamic diameter of the MnO nanocolloid was estimated to be 5 nm. The MnO nanoparticle was nearly paramagnetic down to T=3 K. The MnO nanocolloid showed a high longitudinal water proton relaxivity of r1=7.02 s(-1) mM(-1) with the r2/r1 ratio of 6.83 due to five unpaired S-state electrons of Mn(II) ion (S=5/2) as well as a high surface to volume ratio of the MnO nanoparticle. High contrast in vivo T1 MR images were obtained for various organs, showing the capability of the MnO nanocolloid as a sensitive T1 MRI contrast agent. The suggested three key-parameters which control the r1 and r2 relaxivities of nanocolloids (i.e., the S value of a metal ion, the spin structure, and the surface to volume ratio of a nanoparticle) successfully accounted for the observed r1 and r2 relaxivities of the MnO nanocolloid.

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders

OBJECTIVES The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. METHODS A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. RESULTS Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. CONCLUSIONS The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.

Gold nanoparticles functionalised by Gd-complex of DTPA-bis(amide) conjugate of glutathione as an MRI contrast agent.

The work is directed toward the synthesis of gold nanoparticles (Au NPs) coated with paramagnetic Gd-complex of DTPA-bis(amide) conjugate of glutathione (GdL) for use as a highly efficient MRI contrast agent. Well-dispersed spherical Au NPs coated with gadolinium complexes, abbreviated as Au@GdL, have been obtained; the mean size of Au@GdL is 5-7 nm, and the numbers of GdL are 1.36x10(4) per Au NP. Au@GdL exhibits high longitudinal (r1) and transverse (r2) relaxivities of 1.87x10(5) and 3.02x10(5) mM(-1) s(-1), respectively.

Gold nanoparticles functionalized by gadolinium-DTPA conjugate of cysteine as a multimodal bioimaging agent.

The synthesis and characterization of gold nanoparticles coated with Gd-chelate (Au@GdL), where L is a conjugate of DTPA and cysteine, is described. These particles are obtained by the replacement of citrate from the gold nanoparticle surfaces with gadolinium chelate (GdL). The average size of Au@GdL is 14 nm with a loading of GdL reaching up to 2.9x10(3) per particles, and they demonstrate very high R1 relaxivity (approximately 10(5) mM(-1) s(-1)) as well as X-ray attenuation. The R1 relaxivity per [Gd] is 17.9 mM(-1) s(-1). The present system also exhibits macrophage-specific property, as demonstrated by histological and TEM images as well as CT and MR, rendering itself as a new class of T1 multimodal CT/MR contrast agent.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26–38 s−1mM−1 and r2/r1 = 1.4–1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Alteration of functional connectivity in tinnitus brain revealed by resting-state fMRI?: A pilot study

Abstract Objective: We report a case study on possible alterations in resting-state functional connectivity between the auditory network and non-auditory brain regions in tinnitus patients. Design: Independent component analyses were performed to evaluate coherent spontaneous activity in distributed brain networks. The resting-state functional connectivity scores between the right and left auditory networks were measured. Direct comparison of resting-state connectivity between tinnitus patients and controls was made using a two-sample t-test. Study sample: Four patients (three male, one female; mean age 45 ± 3.92 years) with chronic tinnitus lateralized to the left ear, and six age-matched controls (four male, two female; mean age 45 ± 2.76 years) participated in this case study. Results: The average resting-state functional connectivity (FC) score between the left and right auditory cortical regions was significantly lower in tinnitus patients than in controls (P < 0.05). Direct comparison between patients and controls showed that increased functional connectivity caused by tinnitus occurred predominantly in the left amygdala and in the dorsomedial prefrontal cortex. Conclusions: Our pilot study suggested that resting state functional magnetic resonance imaging (fMRI) could be useful to investigate possible alterations in resting-state neuronal activity between the auditory and non-auditory networks in tinnitus patients.