Yaowen Chen

Behavioral deficits, abnormal corticosterone, and reduced prefrontal metabolites of adolescent rats subject to early life stress.

The present study investigated the effect of early life stress in adolescent rats on brain metabolites, serum corticosterone, and depressive-like behavior. A group of rats was subject to early life stress from postnatal day (PND) 1 to 14. A matched control group was studied. Behavioral tests, serum corticosterone and high-resolution proton magnetic resonance spectroscopy were conducted between PND 30 and 40. In this study, adolescent rats exposed to early life stress demonstrated depressive-like behavior and increased serum corticosterone during adolescence. They also showed reduced glutamate, glutamine, and N-acetylaspartate (NAA) levels in the prefrontal cortex. A reduced myo-inositol level, consistent with astroglial deficits, was observed but was not statistically significant. Together, these findings characterize the effect of early life stress on adolescent animals and underscore the long-lasting and detrimental effects of childhood adversities.

Human umbilical mesenchymal stem cell and its adipogenic differentiation: Profiling by nuclear magnetic resonance spectroscopy

AIM To study the metabolic profile of human umbilical mesenchymal stem cells (HUMSC) and adipogenic differentiation by nuclear magnetic resonance (NMR) spectroscopy. METHODS HUMSC isolated from human umbilical cord stroma were induced to adipocytes over 2 wk by adding dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin to the culture medium. Adipogenic differentiation was confirmed by Red O staining and transcription-polymerase chain reaction. Perchloric acid extracts of the HUMSCs and adipocytes (about 7 × 10(6)) were characterized for metabolites by using in vitro high resolution 9.4T NMR spectroscopy. RESULTS Several major metabolites, such as: choline, creatine, glutamate and myo-inositol, acetate, and some fatty acids/triglycerides, were observed in the MR spectroscopic pattern of HUMSCs and their adipogenic differentiation. HUMSCs are characterized by an unusually low number of NMR-detectable metabolites, high choline, acetate, glutamate and creatine content. However, the metabolic profiles of adipogenic differentiation demonstrated considerably higher methionine and fatty acids, and non-detectable creatine. CONCLUSION The biomarkers of HUMSCS and adipocytes were obtained and assigned. NMR spectroscopy will be a promising tool for monitoring stem cell differentiation.

Hippocampal Neurochemical Changes in Senescent Mice Induced with Chronic Injection of D-Galactose and NaNO2: An In Vitro High-Resolution NMR Spectroscopy Study at 9.4T

Proton magnetic resonance spectroscopy (1H-MRS) has been used to provide useful information about the neurochemical changes reflecting early pathological alterations in Alzheimers disease (AD) brain. In this study, we have longitudinally measured the hippocampal neurochemical profile in vitro in senescent mice induced with chronic injection of D-Galactose and NaNO2, at different time point from day 30 to day 70 with a 10-day interval. Pathological brain alterations induced by D-Galactose and NaNO2 were monitored through hematoxylin and eosin (HE) staining, Congo red staining and bielschowsky silver staining, and the cognition deficits were assessed via Morris Water Maze (MWM) test. This D-galactose and NaNO2 treated mouse model, characterized by an early-onset memory dysfunction, a robust neuronal loss, amyloid plaques and neurofibrillary tangles in hippocampal subdivision, well mimics a prodromal Alzheimers phenotype. Consistent with previously published in vivo 1H MRS findings in human AD patients and AD transgenic mice, our in vitro 1H MRS on the perchloric acid extractions of hippocampus in senescent mice observed significant decreases of N-acetylaspartate (NAA) and Glutamate (Glu) but an increase in Myo-inositol (mIns). Elevated mIns occurred prior to the reduction of NAA and Glu during the progression of aging. In addition, changes in mIns, NAA and Glu were found to precede pathological abnormalities. Overall, our in vitro findings in senescent mice validated the concept that hippocampal neurochemical alternations preceded the pathological changes of the brain, and could serve as potential markers of AD progression. Reductions of NAA and Glu can be interpreted in terms of neuronal degeneration and dysfunctions in glutamatergic activity that may contribute to the pathophysiological mechanisms underlying AD. Elevated mIns might be related to glial activation. Further experiments are needed to explore the potential value of mIns in the early diagnosis of AD, to verify whether glial cell proliferation occurs earlier than neuronal changes.

Quantification of choline concentration following liver cell apoptosis using 1H magnetic resonance spectroscopy

AIM To evaluate the feasibility of quantifying liver choline concentrations in both normal and apoptotic rabbit livers in vivo, using 1H magnetic resonance spectroscopy (1H-MRS). METHODS 1H-MRS was performed in 18 rabbits using a 1.5T GE MR system with an eight-channel head/neck receiving coil. Fifteen rabbits were injected with sodium selenite at a dose of 10 μmol/kg to induce the liver cell apoptosis. Point-resolved spectroscopy sequence-localized spectra were obtained from 10 livers once before and once 24 h after sodium selenite injection in vivo. T1 and T2 relaxation time of water and choline was measured separately in the livers of three healthy rabbits and three selenite-treated rabbits. Hematoxylin and eosin and dUTP-biotin nick end labeling (TUNEL) staining was used to detect and confirm apoptosis. Choline peak areas were measured relative to unsuppressed water using LCModel. Relaxation attenuation was corrected using the average of T1 and T2 relaxation time. The choline concentration was quantified using a formula, which was tested by a phantom with a known concentration. RESULTS Apoptosis of hepatic cells was confirmed by TUNEL assay. In phantom experiment, the choline concentration (3.01 mmol/L), measured by 1H-MRS, was in good agreement with the actual concentration (3 mmol/L). The average T1 and T2 relaxation time of choline was 612 ± 15 ms and 74 ± 4 ms in the control group and 670 ± 27 ms and 78 ± 5 ms in apoptotic livers in vivo, respectively. Choline was quantified in 10 rabbits, once before and once after the injection with sodium selenite. The choline concentration decreased from 14.5 ± 7.57 mmol/L before sodium selenite injection to 10.8 ± 6.58 mmol/L (mean ± SD, n = 10) after treatment (Z = -2.395, P < 0.05, two-sample paired Wilcoxon test). CONCLUSION 1H-MRS can be used to quantify liver choline in vivo using unsuppressed water as an internal reference. Decreased liver choline concentrations are found in sodium selenite-treated rabbits undergoing liver cell apoptosis.

Magnetic Resonance Spectroscopy Study of Amnestic Mild Cognitive Impairment and Vascular Cognitive Impairment With No Dementia

Amnestic mild cognitive impairment (aMCI) and vascular cognitive impairment with no dementia (VCIND) are highly predictive of Alzheimer’s disease and vascular dementia. In this study, a 2-dimensional magnetic resonance spectroscopy was performed in 25 patients with aMCI, 28 patients with VCIND, and 32 normal controls (NCs). The concentrations of N-acetyl aspartate (NAA), choline (Cho), myoinositol (MI), and creatine (Cr) were measured, and their ratios were calculated. The patients with aMCI displayed significantly lower NAA/MI bilaterally in the posterior cingulate gyrus (PCG) and white matter of occipital lobe (OLWM) than NC participants or patients with VCIND , whereas patients with VCIND displayed markedly lower NAA/Cho bilaterally in the white matter of frontal lobe (FLWM) and left OLWM, and right dorsal thalamus (DT) than patients with NC or aMCI. Compared with the controls, patients with aMCI displayed lower NAA and NAA/Cr in bilateral PCG, left precuneus, and DT, whereas patients with VCIND displayed lower NAA/Cr in bilateral DT and FLWM. In addition, increased MI in right PCG of patients with aMCI and increased Cho in left FLWM of patients with VCIND were also observed. The results might help guide a clinical differentiation between the 2 disorders.

Imaging pH phantoms using magnetization transfer technology at 1.5 Tesla

Magnetization transfer (MT) is an important source of contrast in magnetic resonance imaging (MRI), and is the basis of chemical exchange saturation transfer (CEST) imaging, which does not exist in our clinical MR scanner at 1.5 Tesla (T). Amide proton transfer (APT) imaging, a variant of CEST imaging, has been shown capable of detecting tissue acidosis during stroke at above 3.0 T. According to the theory of CEST and APT imaging developed by MT, our study is to make full use of MT technology in the clinic by modifying MT parameters to acquire clinical pH-weighted MT imaging. We modified the source codes of the MT sequence to enable the frequency offset to reach 121 Hz and 224 Hz for saturating the amine protons of creatine. The results showed that MT imaging at a frequency offset of 121 Hz could not be acquired clearly for free water saturation, and MT imaging at 224 Hz could reflect slightly different pH values. We analyzed MT imaging of the same and different pH phantoms, and gave reasonable explanation for the results. We conclude that MT imaging at clinical 1.5 T could differentiate pH phantoms by choosing appropriate parameters.

Preliminary Study of Mapping Brain ATP and Brain pH Using Multivoxel 31P MR Spectroscopy

Magnetic resonance (MR) spectroscopy is a valuable method for the noninvasive investigation of metabolic processes. Although brain ATP studies can be found in multivoxel 31P MR spectroscopy, previous studies of intracellular brain pH was conducted in single-voxel 31P MR spectroscopy. The purpose of this study was to explore the feasibility of mapping brain ATP and brain pH by using multivoxel 31P MR spectroscopy. Phantom studies were carried out by using a GE 3T scanner firstly. Many available sequences were tested using phantom and the 2D PRESSCSI sequence was selected because of better signal to noise ratio. TR was 1000 msec and TE 144 msec with 128 scan averages. The acquisition matrix was 16 x 16 phase encodings over a 24-cm FOV. Slice thickness was 10 mm. Then a healthy volunteer from MR research team was studied. Data were processed offline using the SAGE/IDL software. Baseline and phase corrections were performed. Multivoxel spectra and brain ATP map were analyzed. Brain pH values were calculated from the difference in chemical shifts between inorganic phosphate (Pi) and phosphocreatine (PCr) resonances. Color scaling map was generated using MatLab software. Multivoxel 31P spectra were obtained for phantom and the healthy volunteer. PCr map was obtained in phantom. At this moment, peaks of PCr were not homogeneous in phantom studies. There was noise for multivoxel 31P spectra in volunteer study. Phosphomonoester (PME) peak, Pi peak, phosphodiester (PDE) peak, PCr peak, γATP peak, αATP peak, and βATP peak can be identified. Preliminary brain ATP map and brain pH map were generated in the volunteer. It is feasible to map brain ATP and brain pH using multivoxel 31P MR spectroscopy. However, endeavors should be made to improve quality of multivoxel 31P MR spectroscopy.

Investigating the stability of fast iterative shrinkage thresholding algorithm for MR imaging reconstruction using compressed sensing

Compressed sensing (CS) has been applied to the field of sub-sampled magnetic resonance imaging (MRI) reconstruction (CS-MRI). Fast iterative shrinkage-thresholding algorithm (FISTA) is an effective method for CS-MR images reconstruction. To investigate the accuracy and efficiency of the proposed algorithm, we applied it to the under-sampling MR images gained by different MRI scanning sequences. We found the peak signal to noise ratio (PSNR) of reconstructed MRI with varying sampling ratios diminished from Axial T1 weighted images (Ax T1) (45.13±12.97 dB), Axial T2 weighted images (Ax T2) (42.8 ± 14.95 dB), FLAIR (41.74 ± 14.15 dB), Diffusion Weighted Imaging (DWI) (40.23 ±17.40 dB) and Sagittal T2 weighted images (Sag T2) (36.28±12.32 dB), but there was no significant difference among the groups. In addition, the changes to the elapsed time of them was minor, Ax T1 (1.09±0.13 s), Ax T2 (1.30±0.13s), FLAIR (1.02±0.12s), DWI (1.07±0.13s) and Sag T2 (1.12±0.07s). Our results confirmed the stability of the proposed fast MRI reconstruction method for different scanning sequences. Further efforts are still needed to design the clinical sequence with sub-sampled acquisition strategy which may be a developing technique with clinical value.

Optimized nonlinear conjugate gradient algorithm for MR imaging reconstruction using compressed sensing

Compressed sensing (CS) is an innovative theory of signal acquisition and processing based on the areas of applied mathematics. CS-based MRI exploits the sparsity of an image in an appropriate transform domain to reconstruct images from incoherently under-sampled k-space data. However, it has proven that CS-MRI suffers sharply loss of low-contrast image features with increasing reduction factors. In this work, we explored an optimized nonlinear conjugate gradient (NLCG) procedure aiming to improve peak signal to noise ratio (PSNR) of sub-sampled MRI liver T2 map and shorten the scan time markedly. Data processing and analysis were being done by the software of Matlab. Our findings indicate that using the proposed algorithm, at least 60% of the k-space data measurements necessitates for recovery. This study demonstrated the feasibility of the proposed CS approach to accelerate MRI T2 map. Further studies are needed to design the clinical sequence with sparse acquisition strategy which may be a developing technique with clinical value.

Nuclear magnetic resonance spectroscopy is highly sensitive for lipid-soluble metabolites

Although the water-soluble metabolite profile of human mesenchymal stem cells is known, the lipid profile still needs further investigation. In this study, methanol-chloroform was used to extract pid-soluble metabolites and perchloric acid was used to extract water-soluble metabolites. Furthermore, a dual phase extraction method using methanol-chloroform and water was used to obtain both water and lipid fractions simultaneously. All metabolite extractions were analyzed on a 9.4T high-resolution nuclear magnetic resonance spectrometer. Metabolite resonance peaks were assigned in the acquired spectra according to the chemical shift, and the extraction efficiency of ferent methods was compared. Results showed that in the spectra of water-soluble extracts, major metabolites comprised low molecular weight metabolites, including lactate, acetic acid, fatty acids, threonine, glutamic acid, creatine, choline and its derivatives, while in the spectra of lipid-soluble extracts, most metabolites were assigned to fatty acids. Among the different extraction procedures, perchloric acid was more efficient in extracting water-soluble metabolites and methanol-chloroform was efficient in extracting organic components compared with the dual phase extraction method. Nuclear magnetic resonance spectroscopy showed that as low as 0.7 mg organic yield was enough to obtain clear resonance peaks, while about 6.0 mg water-soluble yield was needed to obtain relatively favorable spectral lines. These results show that the efficiency of extracting water and lipid fractions is higher using perchloric acid and methanol-chloroform compared with dual phase extraction and that nuclear magnetic resonance spectroscopy is highly sensitive for analyzing lipid-soluble extracts.