Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis.

BACKGROUND: Encephalitis is a common central nervous system inflammatory disease that seriously endangers human health owing to the lack of effective diagnostic methods, which leads to a high rate of misdiagnosis and mortality. Glutamate is implicated closely in microglial activation, and activated microglia are key players in encephalitis. Hence, using glutamate chemical exchange saturation transfer (GluCEST) imaging for the early diagnosis of encephalitis holds promise. METHODS: The sensitivity of GluCEST imaging with different concentrations of glutamate and other major metabolites in the brain was validated in phantoms. Twenty-seven Sprague-Dawley (SD) rats with encephalitis induced by Staphylococcus aureus infection were used for preclinical research of GluCEST imaging in a 7.0-Tesla scanner. For the clinical study, six patients with encephalitis, six patients with lacunar infarction, and six healthy volunteers underwent GluCEST imaging in a 3.0-Tesla scanner. RESULTS: The number of amine protons on glutamate that had a chemical shift of 3.0 ppm away from bulk water and the signal intensity of GluCEST were concentration-dependent. Under physiological conditions, glutamate is the main contributor to the GluCEST signal. Compared with normal tissue, in both rats and patients with encephalitis, the encephalitis areas demonstrated a hyper-intense GluCEST signal, while the lacunar infarction had a decreased GluCEST signal intensity. After intravenous immunoglobulin therapy, patients with encephalitis lesions showed a decrease in GluCEST signal, and the results were significantly different from the pre-treatment signal (1.34 ± 0.31 vs 5.0 ± 0.27%, respectively; p = 0.000). CONCLUSION: Glutamate plays a role in encephalitis, and the GluCEST imaging signal has potential as an in vivo imaging biomarker for the early diagnosis of encephalitis. GluCEST will provide new insight into encephalitis and help improve the differential diagnosis of brain disorders.

Nanomedicine Particles Associated With Chemical Exchange Saturation Transfer Contrast Agents in Biomedical Applications.

Theranostic agents are particles containing both diagnostic and medicinal agents in a single platform. Theranostic approaches often employ nanomedicine because loading both imaging probes and medicinal drugs onto nanomedicine particles is relatively straightforward, which can simultaneously provide diagnostic and medicinal capabilities within a single agent. Such systems have recently been described as nanotheranostic. Currently, nanotheranostic particles incorporating medicinal drugs are being widely explored with multiple imaging methods, including computed tomography, positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, and fluorescence imaging. However, most of these particles are metal-based multifunctional nanotheranostic agents, which pose potential toxicity or radiation risks. Hence, alternative non-metallic and biocompatible nanotheranostic agents are urgently needed. Recently, nanotheranostic agents that combine medicinal drugs and chemical exchange saturated transfer (CEST) contrast agents have shown good promise because CEST imaging technology can utilize the frequency-selective radiofrequency pulse from exchangeable protons to indirectly image without requiring metals or radioactive agents. In this review, we mainly describe the fundamental principles of CEST imaging, features of nanomedicine particles, potential applications of nanotheranostic agents, and the opportunities and challenges associated with clinical transformations.

2D-1H proton magnetic resonance spectroscopic imaging study on brain metabolite alterations in patients with diabetic hypertension.

The aim of the present study was to investigate the possible metabolic alterations in the frontal cortex and parietal white matter in patients with diabetic hypertension (DHT) using proton magnetic resonance (MR) spectroscopic imaging. A total of 33 DHT patients and 30 healthy control subjects aged between 45 and 75 were included in the present study. All subjects were right­handed. The spectroscopy data were collected using a GE Healthcare 1.5T MR scanner. The multi­voxels were located in the semioval center (repetition time/echo time=1,500 ms/35 ms). The area of interest was 8x10x2 cm in volume and contained the two sides of the frontal cortex and the parietal white matter. The spectra data were processed using SAGE software. The ratios of brain metabolite concentrations, particularly for N­acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr were calculated and analyzed. Statistical analyses were performed using SPSS 17.0. The NAA/Cr ratio of the bilateral prefrontal cortex of the DHT group was significantly lower than that of the control group (left t=­7.854, P=0.000 and right t=­5.787, P=0.000), The Cho/Cr ratio was also much lower than the control group (left t=2.422, P=0.024 and right t=2.920, P=0.007). NAA/Cr ratio of the left parietal white matter of the DHT group was extremely lower than that of the control group (t=­4.199, P=0.000). Therefore, DHT may result in metabolic disorders in the frontal cortex and parietal white matter but the metabolic alterations are different in various regions of the brain. The alteration in cerebral metabolism is associated with diabetes and hypertension. The ratios of NAA/Cr and Cho/Cr are potential metabolic markers for the brain damage induced by DHT.

Tracking of mesenchymal stem cells labeled with gadolinium diethylenetriamine pentaacetic acid by 7T magnetic resonance imaging in a model of cerebral ischemia.

Progress in the development of stem cell and gene therapy requires repeatable and non­invasive techniques to monitor the survival and integration of stem cells in vivo with a high temporal and spatial resolution. The purpose of the present study was to examine the feasibility of using the standard contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd­DTPA) to label rat mesenchymal stem cells (MSCs) for stem cell tracking. MSCs, obtained from the bilateral femora of rats, were cultured and propagated. The non­liposomal lipid transfection reagent effectene was then used to induce the intracellular uptake of Gd­DTPA. Electron microscopy was used to detect the distribution of Gd­DTPA particles in the MSCs. The labeling efficiency of the Gd­DTPA particles in the MSCs was determined using spectrophotometry, and MTT and trypan blue exclusion assays were used to evaluate the viability and proliferation of the labeled MSCs. T1­weighted magnetic resonance imaging (MRI) was used to observe the labeled cells in vitro and in the rat brain. Gd­DTPA particles were detected inside the MSCs using transmission electron microscopy and a high labeling efficiency was observed. No difference was observed in cell viability or proliferation between the labeled and unlabeled MSCs (P>0.05). In the in vitro T1­weighted MRI and in the rat brain, a high signal intensity was observed in the labeled MSCs. The T1­weighted imaging of the labeled cells revealed a significantly higher signal intensity compared with that of the unlabeled cells (P<0.05) and the T1 values were significantly lower. The function of the labeled MSCs demonstrated no change following Gd­DTPA labeling, with no evident adverse effect on cell viability or proliferation. Therefore, a change in MR signal intensity was detected in vitro and in vivo, suggesting Gd­DTPA can be used to label MSCs for MRI tracking.