Publications by authors named "Xiao-Hong Zhu"

106 Publications

Machine Learning-Enabled High-Resolution Dynamic Deuterium MR Spectroscopic Imaging.

IEEE Trans Med Imaging 2021 Jul 28;PP. Epub 2021 Jul 28.

Deuterium magnetic resonance spectroscopic imaging (DMRSI) has recently been recognized as a potentially powerful tool for noninvasive imaging of brain energy metabolism and tumor. However, the low sensitivity of DMRSI has significantly limited its utility for both research and clinical applications. This work presents a novel machine learning-based method to address this limitation. The proposed method synergistically integrates physics-based subspace modeling and data-driven deep learning for effective denoising, making high-resolution dynamic DMRSI possible. Specifically, a novel subspace model was used to represent the dynamic DMRSI signals; deep neural networks were trained to capture the low-dimensional manifolds of the spectral and temporal distributions of practical dynamic DMRSI data. The learned subspace and manifold structures were integrated via a regularization formulation to remove measurement noise. Theoretical analysis, computer simulations, and in vivo experiments have been conducted to demonstrate the denoising efficacy of the proposed method which enabled high-resolution imaging capability. The translational potential was demonstrated in tumor-bearing rats, where the Warburg effect associated with cancer metabolism and tumor heterogeneity were successfully captured. The new method may not only provide an effective tool to enhance the sensitivity of DMRSI for basic research and clinical applications but also provide a framework for denoising other spatiospectral data.
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http://dx.doi.org/10.1109/TMI.2021.3101149DOI Listing
July 2021

Noninvasive assessment of myocardial energy metabolism and dynamics using in vivo deuterium MRS imaging.

Magn Reson Med 2021 Jul 6. Epub 2021 Jul 6.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.

Purpose: The assessment of cellular energy metabolism is crucial for understanding myocardial physiopathology. Here, we conducted a pilot study to develop an alternative imaging approach for the assessment of myocardial energy metabolism.

Methods: We developed a deuterium MRSI method to noninvasively monitor the accumulation of deuterated downstream metabolites and deuterated water in rat hearts infused with deuterated glucose or acetate substrate on a 16.4 Tesla animal scanner.

Results: We found that the deuterated water accumulation rate and isotopic turnover rate of deuterated glutamate/glutamine via the tricarboxylic acid cycle and exchange in rat hearts were much higher when infused with acetate compared to that with glucose, demonstrating the myocardium substrate preference for acetate over glucose.

Conclusion: We demonstrated the feasibility of deuterium MRSI for noninvasive imaging and assessment of myocardial energy metabolism in vivo. Although the strong signal and large dynamics of myocardial deuterated water may provide a sensitive imaging biomarker, quantifying the metabolic rates still poses a challenge due to the confounding effects of blood recirculation, perfusion, and multiple deuterated water production pathways. In contrast, the deuterated glutamate/glutamine signal and change should directly reflect the metabolic activity of the myocardial tricarboxylic acid cycle, which can be used to study the metabolic shift in substance preference between acetate and glucose in the diseased state. Deuterium MRSI is noninvasive and robust and may have the potential to assess myocardial energy metabolism in human patients.
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http://dx.doi.org/10.1002/mrm.28914DOI Listing
July 2021

The safety and tolerability of alkaloids from leaves in healthy Chinese volunteers: a single-centre, randomized, double-blind, placebo-controlled phase I clinical trial.

Pharm Biol 2021 Dec;59(1):484-493

Institute of Drug Clinical Trials, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Context: Capsule of alkaloids from the leaf of (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma.

Objective: To observe the clinical safety and tolerability of CALAS.

Materials And Methods: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects.

Results: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group ( > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%).

Discussion And Conclusions: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.
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http://dx.doi.org/10.1080/13880209.2021.1893349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086589PMC
December 2021

Novel Composite Gold-Aluminum Electrode with Application to Neural Recording and Stimulation in Ultrahigh Field Magnetic Resonance Imaging Scanners.

Ann Biomed Eng 2021 Apr 21. Epub 2021 Apr 21.

Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA.

Traditional electrodes used for neural recording and stimulation generate large regions of signal void (no functional MRI signal) when used in ultrahigh field (UHF) MRI scanners. This is a significant disadvantage when simultaneous neural recording/stimulation and fMRI signal acquisition is desired, for example in understanding the functional mechanisms of deep brain stimulation (DBS). In this work, a novel gold-aluminum microwire neural electrode is presented which overcomes this disadvantage. The gold-aluminum design greatly reduces the magnetic susceptibility difference between the electrode and brain tissue leading to significantly reduced regions of signal void. Gold-aluminum microwire samples are imaged at ultrahigh field 16.4 Tesla and compared with gold-only and aluminum-only microwire samples. First, B field mapping was used to quantify field distortions at 16.4T and compared with analytical computations in an agarose phantom. The gold-aluminum microwire samples generated substantially less field distortion and signal loss in comparison with gold-only and aluminum-only samples at 16.4T using gradient echo imaging and echo planar imaging sequences. Next, the proposed gold-aluminum electrode was used to successfully record local field potential signals from a rat cortex. The newly proposed gold-aluminum microwire electrode exhibits reduced field distortions and signal loss at 16.4T, a finding which translates to MRI scanners of lower magnetic field strengths as well. The design can be easily reproduced for widespread study of DBS using MRI in animal models. Additionally, the use of non-reactive gold and aluminum materials presents an avenue for translation to human implant applications in the future.
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http://dx.doi.org/10.1007/s10439-021-02779-yDOI Listing
April 2021

Quantitative Assessment of Occipital Metabolic and Energetic Changes in Parkinson's Patients, Using In Vivo P MRS-Based Metabolic Imaging at 7T.

Metabolites 2021 Mar 1;11(3). Epub 2021 Mar 1.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA.

Abnormal energy metabolism associated with mitochondrial dysfunction is thought to be a major contributor to the progression of neurodegenerative diseases such as Parkinson's disease (PD). Recent advancements in the field of magnetic resonance (MR) based metabolic imaging provide state-of-the-art technologies for non-invasively probing cerebral energy metabolism under various brain conditions. In this proof-of-principle clinical study, we employed quantitative P MR spectroscopy (MRS) imaging techniques to determine a constellation of metabolic and bioenergetic parameters, including cerebral adenosine triphosphate (ATP) and other phosphorous metabolite concentrations, intracellular pH and nicotinamide adenine dinucleotide (NAD) redox ratio, and ATP production rates in the occipital lobe of cognitive-normal PD patients, and then we compared them with age-sex matched healthy controls. Small but statistically significant differences in intracellular pH, NAD and ATP contents and ATPase enzyme activity between the two groups were detected, suggesting that subtle defects in energy metabolism and mitochondrial function are quantifiable before regional neurological deficits or pathogenesis begin to occur in these patients. Pilot data aiming to evaluate the bioenergetic effect of mitochondrial-protective bile acid, ursodeoxycholic acid (UDCA) were also obtained. These results collectively demonstrated that in vivo P MRS-based neuroimaging can non-invasively and quantitatively assess key metabolic-energetic metrics in the human brain. This provides an exciting opportunity to better understand neurodegenerative diseases, their progression and response to treatment.
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http://dx.doi.org/10.3390/metabo11030145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000945PMC
March 2021

EGCG Enhanced the Anti-tumor Effect of Doxorubicine in Bladder Cancer via NF-κB/MDM2/p53 Pathway.

Front Cell Dev Biol 2020 23;8:606123. Epub 2020 Dec 23.

Key Laboratory of Medical Programming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Doxorubicin (DOX), the first-line chemotherapy for bladder cancer, usually induces side effects. We previously demonstrated that green tea polyphenol EGCG had potent anti-tumor effect in bladder cancer via down regulation of NF-κB. This study aimed to investigate the additive/synergistic effect EGCG and DOX against bladder cancer. Our results demonstrated that the combined use of DOX and EGCG inhibited T24 and SW780 cell proliferation. EGCG enhanced the apoptosis induction effect of DOX in both SW780 and T24 cells and resulted in significant differences. Besides, EGCG promoted the inhibitory effect of DOX against bladder cancer cell migration. In addition, the results demonstrated that DOX in combination with EGCG showed the most potent anti-tumor effects among DOX, EGCG and DOX+EGCG treatment groups. Further mechanistic studies determined that the combination of DOX and EGCG inhibited phosphorylated NF-κB and MDM2 expression, and up-regulated p53 expression in tumor, as assessed by western blot and immunohistochemistry. Western blot in SW780 cells also confirmed that the combined use of EGCG and DOX caused significant increase in p53, p21, and cleaved-PARP expression, and induced significant inhibition in phosphorylated NF-κB and MDM2. When NF-κB was inhibited, the expression of p53 and p-MDM2 were changed, and the combination of DOX and EGCG showed no obvious effect in transwell migration and cell viability. In conclusion, the novel application of chemotherapy DOX and EGCG demonstrated potent anti-tumor, anti-migration and anti-proliferation effects against bladder cancer. EGCG enhanced the anti-tumor effect of DOX in bladder cancer via NF-κB/MDM2/p53 pathway, suggesting the potential clinical application against bladder cancer patients.
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http://dx.doi.org/10.3389/fcell.2020.606123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793730PMC
December 2020

Quantitative and simultaneous measurement of oxygen consumption rates in rat brain and skeletal muscle using O MRS imaging at 16.4T.

Magn Reson Med 2021 04 26;85(4):2232-2246. Epub 2020 Oct 26.

High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Purpose: Oxygen-17 ( O) MRS imaging, successfully used in the brain, is extended by imaging the oxygen metabolic rate in the resting skeletal muscle and used to determine the total whole-body oxygen metabolic rate in the rat.

Methods: During and after inhalations of O gas, dynamic O MRSI was performed in rats (n = 8) ventilated with N O or N at 16.4 T. Time courses of the H O concentration from regions of interest located in brain and muscle tissue were examined and used to fit an animal-adapted 3-phase metabolic model of oxygen consumption. CBF was determined with an independent washout method. Finally, body oxygen metabolic rate was calculated using a global steady-state approach.

Results: Cerebral metabolic rate of oxygen consumption was 1.97 ± 0.19 μmol/g/min on average. The resting metabolic rate of oxygen consumption in skeletal muscle was 0.32 ± 0.12 μmol/g/min and >6 times lower than cerebral metabolic rate of oxygen consumption. Global oxygen consumed by the body was 24.2 ± 3.6 mL O /kg body weight/min. CBF was estimated to be 0.28 ± 0.02 mL/g/min and 0.34 ± 0.06 mL/g/min for the N and N O ventilation condition, respectively.

Conclusion: We have evaluated the feasibility of O MRSI for imaging and quantifying the oxygen consumption rate in low metabolizing organs such as the skeletal muscle at rest. Additionally, we have shown that CBF is slightly increased in the case of ventilation with N O. We expect this study to be beneficial to the application of O MRSI to a wider range of organs, although further validation is advised.
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http://dx.doi.org/10.1002/mrm.28552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775343PMC
April 2021

Adaptive virtual referencing for the extraction of extracellularly recorded action potentials in noisy environments.

J Neural Eng 2020 10 10;17(5):056011. Epub 2020 Oct 10.

Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, United States of America. Center for Magnetic Resonance Research (CMRR), Radiology Department, University of Minnesota, Minneapolis, MN, United States of America.

Objective: Removal of common mode noise and artifacts from extracellularly measured action potentials, herein referred to as spikes, recorded with multi-electrode arrays (MEAs) which included severe noise and artifacts generated by an ultrahigh field (UHF) 16.4 Tesla magnetic resonance imaging (MRI) scanner.

Approach: An adaptive virtual referencing (AVR) algorithm is used to remove artifacts and thus enable extraction of neural spike signals from extracellular recordings in anesthetized rat brains. A 16-channel MEA with 150-micron inter-site spacing is used, and a virtual reference is created by spatially averaging the 16 signal channels which results in a reference signal without extracellular spiking activity while preserving common mode noise and artifacts. This virtual reference signal is then used as the input to an adaptive FIR filter which optimally scales and time-shifts the reference to each specific electrode site to remove the artifacts and noise.

Main Results: By removing artifacts and reducing noise, the neural spikes at each electrode site can be well extracted, even from data originally recorded with a high noise floor due to electromagnetic interference and artifacts generated by a 16.4T MRI scanner. The AVR method enables many more spikes to be detected than would otherwise be possible. Further, the filtered spike waveforms can be well separated from each other using PCA feature extraction and semi-supervised k-means clustering. While data in a 16.4T MRI scanner contains significantly more noise and artifacts, the developed AVR method enables similar data quality to be extracted as recorded on benchtop experiments outside the MRI scanner.

Significance: AVR of extracellular spike signals recorded with MEAs has not been previously reported and fills a technical need by enabling low-noise extracellular spike extraction in noisy and challenging environments such as UHF MRI that will enable further study of neuro-vascular coupling at UHF.
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http://dx.doi.org/10.1088/1741-2552/abb73cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118086PMC
October 2020

Tunable Ultrahigh Dielectric Constant (tuHDC) Ceramic Technique to Largely Improve RF Coil Efficiency and MR Imaging Performance.

IEEE Trans Med Imaging 2020 10 20;39(10):3187-3197. Epub 2020 Apr 20.

This work introduces an innovative magnetic resonance (MR) imaging technology that incorporates radiofrequency (RF) coil(s) with permittivity-tunable ultrahigh dielectric constant (tuHDC) ceramics to significantly improve RF coil transmission and reception efficiencies, MR imaging sensitivity and signal-to-noise ratio (SNR). The tuHDC ceramics made of composite barium strontium titanate (BST) compounds (Ba Sr TiO) have low dielectric loss and very high permittivity tunability from 2,000 to 15000 by varying the ceramic temperature between 0°C and 40°C to achieve an optimal permittivity for MR imaging application. We demonstrated for the first time the proof of concept using the BST-based tuHDC-RF-coil technology to improve MR spectroscopic imaging performance of O nuclide at 10.5 Tesla (T) at a low ceramic temperature and Na nuclide at 7T at room temperature. We discovered a large and spatially independent noise reduction under an optimal ceramic temperature, which synergistically resulted in an unprecedented SNR improvement. Large improvements were also demonstrated for H MRI on a 1.5T clinical scanner using the same ceramics. The tuHDC-RF-coil technology is robust, flexible and cost-effective; it presents a technical breakthrough to significantly improve imaging sensitivity and resolution for broad MR imaging applications; which is critical for advancing biomedical and neuroscience research, and improving diagnostic imaging.
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http://dx.doi.org/10.1109/TMI.2020.2988834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529716PMC
October 2020

Pharmacokinetics, Safety, and Tolerability of Orally Administered Ursodeoxycholic Acid in Patients With Parkinson's Disease-A Pilot Study.

J Clin Pharmacol 2020 06 12;60(6):744-750. Epub 2020 Feb 12.

Center for Orphan Drug Research and Department of Experimental and Clinical Pharmacology, College of Pharmacy, Minneapolis, Minnesota, USA.

Mitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease. Preliminary data have shown lower brain adenosine triphosphate (ATP) levels in Parkinson's disease versus age-matched healthy controls. Ursodeoxycholic acid (UDCA) may improve impaired mitochondrial function. Our objective was to evaluate UDCA tolerability, pharmacokinetics, and its effect on brain bioenergetics in individuals with Parkinson's disease. An open-label, prospective, multiple-ascending-dose study of oral UDCA in 5 individuals with Parkinson's disease was completed. A blood safety panel, plasma concentrations of UDCA and UDCA conjugates, and brain ATP levels were measured before and after therapy (week 1: 15 mg/kg/day; week 2: 30 mg/kg/day; and weeks 3-6: 50 mg/kg/day). UDCA and conjugates were measured using liquid chromatography-mass spectrometry. ATP levels and ATPase activity were measured using 7-Tesla P magnetic resonance spectroscopy. Secondary measures included the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. UDCA was generally well tolerated. The most frequent adverse event was gastrointestinal discomfort, rated by subjects as mild to moderate. Noncompartmental pharmacokinetic analysis resulted in (mean ± standard deviation) a maximum concentration of 8749 ± 2840 ng/mL and half-life of 2.1 ± 0.71 hr. Magnetic resonance spectroscopy data were obtained in 3 individuals with Parkinson's disease and showed modest increases in ATP and decreases in ATPase activity. Changes in Unified Parkinson's Disease Rating Scale (parts I-IV) and Montreal Cognitive Assessment scores (mean ± standard deviation) were -4.6 ± 6.4 and 2 ± 1.7, respectively. This is the first report of UDCA use in individuals with Parkinson's disease. Its pharmacokinetics are variable, and at high doses it appears reasonably well tolerated. Our findings warrant additional studies of its effect on brain bioenergetics.
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http://dx.doi.org/10.1002/jcph.1575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245554PMC
June 2020

Computation of Magnetic Field Distortions and Impact on T*-weighted MRI with Application to Magnetic Susceptibility Parameter Estimation.

Biomed Phys Eng Express 2018 Jul 14;4(4). Epub 2018 Jun 14.

Department of Mechanical Engineering, University of Minnesota, 111 Church St. SE, Minneapolis, MN.

A two-step numerical computation of T* signal weighting maps in gradient echo magnetic resonance imaging in the presence of an object with varied susceptibility property is presented. In the first step, the magnetic scalar potential is computed for an arbitrary 2D magnetic susceptibility distribution using an algebraic solver. The corresponding magnetic field disturbance is computed from the magnetic scalar potential. In the second step, nonlinear operations are used to compute T* from the magnetic field disturbance and then to generate a map of T* signal weighting. The linearity of the first step of the solution process is used to implement a superposition of basis solutions approach that increases computational efficiency. Superposition of basis solutions, computed from a system composed of a single node of differing magnetic susceptibility from the surround, herein referred to as the base system, is found to provide an accurate estimation of the scalar potential for arbitrary susceptibility distributions. Afterwards, nonlinear computation of the T* signal weighting maps can be performed. The properties of the algebraic magnetic scalar potential solver are discussed in this work. Finally, the linearity of the magnetic scalar potential solver is used to estimate the magnetic susceptibility of various objects from MR-imaging data acquired at 9.4T.
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http://dx.doi.org/10.1088/2057-1976/aaca02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549516PMC
July 2018

[Clinical effect of fluticasone propionate, montelukast sodium and ketotifen in treatment of cough variant asthma in children].

Zhongguo Dang Dai Er Ke Za Zhi 2019 Apr;21(4):393-398

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/ China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

Objective: To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA).

Methods: A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence.

Results: After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P<0.05). After 2 and 3 months of treatment, the Ket group had a significantly higher cough symptom score and significantly lower FEV1% and PEF% than the other groups (P<0.05). After 3 months of treatment, there were no significant differences in cough symptom score, FEV1% and PEF% among the other groups (P>0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P<0.001), while there was no significant difference in this rate among the other groups (P>0.0024).

Conclusions: For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389222PMC
April 2019

Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway.

World J Gastroenterol 2019 Mar;25(12):1492-1501

Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.

Background: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid (UDCA) play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein (SREBP) 1c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism.

Aim: To investigate the functional mechanism of UDCA in an oleic acid (OA)-induced cellular model of NAFLD.

Methods: The cellular model of NAFLD was established using OA and treated with UDCA. First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and aspartate aminotransferase (AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.

Results: In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations (especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA.

Conclusion: Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.
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http://dx.doi.org/10.3748/wjg.v25.i12.1492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441910PMC
March 2019

Quantitative analysis of spatial averaging effect on chemical shift imaging SNR and noise coherence with k-space sampling schemes.

Magn Reson Imaging 2019 07 31;60:85-92. Epub 2019 Mar 31.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, MN, USA. Electronic address:

Spatial averaging of multiple voxels from high-resolution chemical shift imaging (hrCSI) is a common strategy for in vivo metabolic studies to achieve a better signal-to-noise ratio (SNR) for a region-of-interest. However, the mechanism about how the spatial averaging approach influences the respective spectral signal and noise and its relevance to the k-space sampling schemes remains unclear. Using three-dimension O CSI technique with the weighted k-space sampling method of Fourier series window, we performed quantitative SNR comparisons between a single low-resolution CSI (lrCSI) voxel (being 27 times larger than the hrCSI voxel size) and the spatially averaged hrCSI voxels with matched sampling volume and location. We demonstrated that the averaged hrCSI voxel spectrum had a large SNR loss (> 4 times) compared to the lrCSI voxel, which was resulted from unmatched increases in signal (~1.9 fold) and noise (~9.3 fold). The signal increase was caused by the spatial overlapping between the adjacent hrCSI voxels. The substantial noise increase was mainly attributed to the strong noise coherence among hrCSI voxels acquired with the weighted k-space sampling. This study presents a quantitative relation between the k-space sampling schemes to an apparent SNR penalty of the spatial averaging approach. The information could be useful for designing CSI acquisition method and determination of optimal spatial resolution for in vivo metabolic imaging studies.
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http://dx.doi.org/10.1016/j.mri.2019.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535123PMC
July 2019

X-Nuclear MRS Imaging Methods for Quantitative Assessment of Neuroenergetic Biomarkers in Studying Brain Function and Aging.

Front Aging Neurosci 2018 27;10:394. Epub 2018 Nov 27.

Center for Magnetic Resonance Research (CMRR), Department of Radiology, School of Medicine, University of Minnesota, Minneapolis, MN, United States.

Brain relies on glucose and oxygen metabolisms to generate biochemical energy in the form of adenosine triphosphate (ATP) for supporting electrophysiological activities and neural signaling under resting or working state. Aging is associated with declined mitochondrial functionality and decreased cerebral energy metabolism, and thus, is a major risk factor in developing neurodegenerative diseases including Alzheimer's disease (AD). However, there is an unmet need in the development of novel neuroimaging tools and sensitive biomarkers for detecting abnormal energy metabolism and impaired mitochondrial function, especially in an early stage of the neurodegenerative diseases. Recent advancements in developing multimodal high-field X-nuclear (e.g., H, O and P) MRS imaging techniques have shown promise for quantitative and noninvasive measurement of fundamental cerebral metabolic rates of glucose and oxygen consumption, ATP production as well as nicotinamide adenine dinucleotide (NAD) redox state in preclinical animal and human brains. These metabolic neuroimaging measurements could provide new insights and quantitative bioenergetic markers associated with aging processing and neurodegeneration and can therefore be employed to monitor disease progression and/or determine effectiveness of therapeutic intervention.
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http://dx.doi.org/10.3389/fnagi.2018.00394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277487PMC
November 2018

High-resolution imaging of distinct human corpus callosum microstructure and topography of structural connectivity to cortices at high field.

Brain Struct Funct 2019 Mar 3;224(2):949-960. Epub 2018 Dec 3.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, 2021 Sixth Street SE, Minneapolis, MN, 55455, USA.

Characterization of the microstructural properties and topography of the human corpus callosum (CC) is key to understanding interhemispheric neural communication and brain function. In this work, we tested the hypothesis that high-resolution T relaxometry at high field has adequate sensitivity and specificity for characterizing microstructural properties of the human CC, and elucidating the structural connectivity of the callosal fibers to the cortices of origin. The high-resolution parametric T images acquired from healthy subjects (N = 16) at 7 T clearly showed a consistent T distribution among individuals with substantial variation along the human CC axis, which is highly similar to the spatial patterns of myelin density and myelinated axon size based on the histology study. Compared to the anterior part of the CC, the posterior midbody and splenium had significantly higher T values. In conjunction with T-based classification method, the splenial T values were decoded more reliably compared to a conventional partitioning method, showing a much higher T value in the inferior splenium than in the middle/superior splenium. Moreover, the T profile of the callosal subdivision represented the topology of the fiber connectivity to the projected cortical regions: the fibers in the posterior midbody and inferior splenium with a higher T (inferring a larger axon size) were mainly connected to motor-sensory and visual cortical areas, respectively; in contrast, the fibers in the anterior/posterior CC with a lower T (inferring a smaller axon size) were primarily connected to the frontal/parietal-temporal areas. These findings indicate that high-resolution T relaxometry imaging could provide a complementary and robust neuroimaging tool, useful for exploring the complex tissue properties and topographic organization of the human corpus callosum.
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http://dx.doi.org/10.1007/s00429-018-1804-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420868PMC
March 2019

MiR-135b is a novel oncogenic factor in cutaneous melanoma by targeting LATS2.

Melanoma Res 2019 04;29(2):119-125

Department of Dermatology, Wuxi No. 2 People's Hospital, Wuxi, China.

Melanoma develops from pigment-producing melanocytes in the epidermis, and is the most common type of skin cancer. Because of the lack of effective therapies, the median survival of patients developing metastatic melanoma is less the 1 year. In this paper, we studied the oncogenic role of miR-135b in melanoma cells. We compared the miR-135b levels in 20 melanoma tissues in reference to their corresponding nontumor regions. Next, we studied the impact of miR-135b or its inhibitor on cell proliferation, migration, or apoptosis in either primary melanocytes or the melanoma cell line, respectively. Finally, we validated large tumor suppressor kinase 2 (LATS2) as the downstream target of miR-135b in a luciferase reporter assay, western blotting analysis, and knockdown study in primary melanocytes. MiR-135b expression was significantly upregulated in melanoma tissue. Overexpressing miR-135b in primary melanocytes promoted cell proliferation and migration. In contrast, inhibition of miR-135b expression suppressed the growth and metastasis of A-375 cells and enhanced cell apoptosis. LATS2 was confirmed as the target of miR-135b. Knockdown of LATS2 in melanocytes also promoted cell growth, but not cell invasion potential. Our findings showed miR-135b as a novel oncogene in melanoma tumorigenesis. The oncogenic mechanism may involve the downregulation of LATS2.
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http://dx.doi.org/10.1097/CMR.0000000000000524DOI Listing
April 2019

[Pharmacokinetics Study of Phentolamine Mesylate Injection in Healthy Volunteers].

Sichuan Da Xue Xue Bao Yi Xue Ban 2018 Nov;49(6):929-933

Phase Ⅰ Clinical Research Unit, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers.

Methods: A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate (16 time points). Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters.

Results: Time to peak concerntration () ranged from 12 to 13 min. Half-time of elimination () ranged from 3.84 to 4.07 h, with a clearance () of 190 L/h. Peak concentration (), area under concentration-time curves from 0 to t hour and from 0 to infinite time ( and ) increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments.

Conclusions: Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.
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November 2018

Multi-Band Texture Image Fusion Based on the Embedded Multi-Scale Decomposition and Possibility Theory.

Guang Pu Xue Yu Guang Pu Fen Xi 2016 Jul;36(7):2337-43

The combination of multi-scale transform and the rules which are “high-frequency coefficients combined by selecting the maximum gray value or energy” and “low-pass ones combined by weighting average” is an effective method in dual-band image fusion. However, when these methods are used to fuse multi-band images, sequential weighted average often leads the weakening of the inherent different information of original images, which affects the subsequent target recognition and scene understanding. The problem is more obvious when fusing multi-band images with texture features. In order to describe the scene in a more comprehensive and precise way, a new multi-band texture image fusion method based on embedded multi-scale decomposition and possibility theory is proposed. The method consists of three parts. The original multi-band images are decomposed into their high- and low-frequency components through a multi-scale transform. The high-frequency components are fused per-pixel by extracting the maximum gray value, whereas the last layer of low-frequency components of original multi-band images with the largest standard deviation is blocked through the another multi-scale transform. Based on the specific sizes and positions of these blocks, the remaining two original images are divided. All the blocks from three bands are traversely fused according to the possibility theory, and the low-frequency image is formed by mosaicing these fused blocks. Then, this image is inversely transformed with its high-frequency counterparts to get the final fusion image. This method not only integrates the pixel-level with feature-level fusion methods, but also integrates the space domain with transform domain technologies together, and solves the problem of sawtooth effect on the edge of the target through the different fusion rules with the different sizes of blocks. The validity of the method proposed is proved.
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July 2016

Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear H, O and P MRS at ultra-high field.

J Magn Reson 2018 07;292:155-170

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, School of Medicine, Minneapolis, MN 55455, USA. Electronic address:

Brain energy metabolism relies predominantly on glucose and oxygen utilization to generate biochemical energy in the form of adenosine triphosphate (ATP). ATP is essential for maintaining basal electrophysiological activities in a resting brain and supporting evoked neuronal activity under an activated state. Studying complex neuroenergetic processes in the brain requires sophisticated neuroimaging techniques enabling noninvasive and quantitative assessment of cerebral energy metabolisms and quantification of metabolic rates. Recent state-of-the-art in vivo X-nuclear MRS techniques, including H, O and P MRS have shown promise, especially at ultra-high fields, in the quest for understanding neuroenergetics and brain function using preclinical models and in human subjects under healthy and diseased conditions.
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http://dx.doi.org/10.1016/j.jmr.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996770PMC
July 2018

[Pharmacokinetics of Phosphate Retagliptin Tabletin in Patients with Renal Dysfunction].

Sichuan Da Xue Xue Bao Yi Xue Ban 2018 Jan;49(1):74-80

Phase I Clinical Research Unit,West China Hospital,Sichuan University,Chengdu 610041, China; 2.

Objective: To compared the differences in pharmacokinetics of phosphate retagliptin tablets in patients with varying degrees of renal dysfunction.

Methods: A total of 32 patients were categorized into five groups according to their renal function: normal,mild dysfunction, moderate dysfunction,severe dysfunction,and end stage renal dysfunction (ESRD). All of the patients took a single dose of 50 mg phosphate retagliptin tablet. Their plasma and urinary concentrations of phosphate retagliptin (SP2086) and phosphate retagliptin acid (SP2086 acid) were determined using LC-MS/MS methods. The plasma pharmacokinetic parameters were calculated using WinNolin 6.1 software.

Results: Peak concentrations () of SP2086 reached at (1.07±0.35) h in the patients with mild renal dysfunction,(1.50±0.89) h in the patients with moderate renal dysfunction,(1.67±2.16) h in the patients with severe renal dysfunction,(2.42±2.15) h in the patients with ESRD,and (1.75±1.21) h in the normal participants,with a clearance () of (23.50±6.01) ,(12.90±4.34) ,(6.70±1.55) ,(3.10±0.48) ,and (30.50±10.70) L/h,respectively. With the increasing damages in renal function presented an incease in ,time to reach (),and area under curve (), a decrease in , of SP2086 and SP2086 acid. The 0-96 hurine cumulative excretion percentage (Ae%) of SP2086 ranged from 0.441% to 4.530%. The Ae% of SP2086 acid reached (71.7±14.3) % in the patients with mild renal dysfunction, (59.5±22.7) % in the patients with moderate renal dysfunction, (63.3±13.9) % in the patients with severe renal dysfunction, (34.1±20.0) % in the patient with ESRD,and (74.2±14.6) % in the normal participants, with a renal clearance (CL/R) of (220.0±51.2),(105.0±64.5),(54.5±7.6),(13.5±7.8),and (289.0±73.7) mL/min,respectively. Compared with the participants with normal renal function,the s of SP2086 and SP2086 acid were 1.44 times and 2.32 times higher in the patients with moderate renal dysfunction,2.20 times and 4.39 times higher in the patients with severe renal dysfunction, and 2.83 times and 9.28 times higher in the patients with ESRD.

Conclusion: The dosage of phosphate retagliptin tablet is recommended at 100 mg/d for patients with normal renal function and those with mild renal dysfunction,at 50 mg/d for patients with moderate renal dysfunction,and at 25 mg/d for patients with severe renal dysfunction. No phosphate retagliptin tablet is recommended for patients with ESRD.
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January 2018

Functional energetic responses and individual variance of the human brain revealed by quantitative imaging of adenosine triphosphate production rates.

J Cereb Blood Flow Metab 2018 06 10;38(6):959-972. Epub 2018 Apr 10.

Center for Magnetic Resonance Research (CMRR), Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.

Cellular ATP energy metabolism and regulation are essential for brain function and health. Given the high ATP expenditure at resting-state, it is not yet clear how the human brain at working-state can effectively regulate ATP production to meet higher energy requirement. Through quantitative measurement of regional cerebral ATP production rates and associated neurophysiological parameters in human visual cortex at rest and during visual stimulation, we found significant stimulus-induced and highly correlated neuroenergetic changes, indicating distinctive and complementary roles of the ATP synthesis reactions in supporting evoked neuronal activity and maintaining ATP homeostasis. We also uncovered large individual variances in the neuroenergetic responses and significant reductions in intracellular [H] and free [Mg] during the stimulation. These results provide new insights into the mechanism underlying the brain ATP energy regulation and present a sensitive and much-needed neuroimaging tool for quantitatively assessing neuroenergetic state in healthy and diseased human brain.
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http://dx.doi.org/10.1177/0271678X18769039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998995PMC
June 2018

Comparative Effectiveness of Prophylactic Strategies for Perinatal Transmission of Hepatitis B Virus: A Network Meta-analysis of Randomized Controlled Trials.

Open Forum Infect Dis 2017 17;4(4):ofx225. Epub 2017 Oct 17.

Center for Liver Diseases.

Background: Perinatal transmission is the main route of hepatitis B virus (HBV) transmission. While several measures have been attempted as means of preventing perinatal HBV transmission, the optimal strategy remains inconclusive.

Methods: We conducted a comprehensive search, through December 2016, for randomized controlled trials (RCTs) that compared the following measures among pregnant women with HBV infection: placebo/none, active immunoprophylaxis (hepatitis B vaccine series starting at birth [HBVac]), passive-active immunoprophylaxis (hepatitis B immunoglobulin and vaccine [HBIG+HBVac]), prenatal HBIG administration (HBIG/HBIG+HBVac), and prenatal antiviral therapy (AVT/HBIG+HBVac). Direct, indirect, and network meta-analyses were performed for all treatment comparisons.

Results: Fifteen RCTs involving 2706 infants of HBV carrier mothers were eligible for analysis. Network meta-analysis demonstrated similar results as direct and indirect comparisons. HBVac alone significantly reduced the risk of hepatitis B infection in infants of HBV carrier mothers (relative risk [RR], 0.32; 95% confidence interval [CI], 0.21-0.50). The combination of immunoglobulin with vaccine is superior to vaccine alone (RR, 0.37; 95% CI, 0.20-0.67). Prenatal HBIG administration and antiviral therapy offer further advantages over current passive-active immunoprophylaxis for infants of highly viremic (HBV DNA level higher than 2 × 10 IU/mL) mothers (RR, 0.47; 95% CI, 0.29-0.75; and RR, 0.31; 95% CI, 0.10-0.99, respectively). There was no significant publication bias.

Conclusions: Based on the universal infantile vaccination program, HBIG for infants born to HBV carrier mothers further reduces transmission. For highly viremic mothers whose children are still at risk for transmission under current immunoprophylaxis, prenatal HBIG administration or antiviral therapy in late pregnancy may be considered if more long-term evidence supports its efficacy and safety.
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http://dx.doi.org/10.1093/ofid/ofx225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695632PMC
October 2017

Interleaved P MRS imaging of human frontal and occipital lobes using dual RF coils in combination with single-channel transmitter-receiver and dynamic B shimming.

NMR Biomed 2018 Jan 26;31(1). Epub 2017 Oct 26.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.

In vivo P magnetic resonance spectroscopy (MRS) provides a unique tool for the non-invasive study of brain energy metabolism and mitochondrial function. The assessment of bioenergetic impairment in different brain regions is essential to understand the pathophysiology and progression of human brain diseases. This article presents a simple and effective approach which allows the interleaved measurement of P spectra and imaging from two distinct human brain regions of interest with dynamic B shimming capability. A transistor-transistor logic controller was employed to actively switch the single-channel X-nuclear radiofrequency (RF) transmitter-receiver between two P RF surface coils, enabling the interleaved acquisition of two P free induction decays (FIDs) from human occipital and frontal lobes within the same repetition time. Linear gradients were incorporated into the RF pulse sequence to perform the first-order dynamic shimming to further improve spectral resolution. The overall results demonstrate that the approach provides a cost-effective and time-efficient solution for reliable P MRS measurement of cerebral phosphate metabolites and adenosine triphosphate (ATP) metabolic fluxes from two human brain regions with high detection sensitivity and spectral quality at 7 T. The same design concept can be extended to acquire multiple spectra from more than two brain regions or can be employed for other magnetic resonance applications beyond the P spin.
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http://dx.doi.org/10.1002/nbm.3842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736151PMC
January 2018

Changes in [F]Fluorodeoxyglucose Activities in a Shockwave-Induced Traumatic Brain Injury Model Using Lithotripsy.

J Neurotrauma 2018 01 16;35(1):187-194. Epub 2017 Oct 16.

11 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical School , Baltimore, Maryland.

We present a longitudinal study of cerebral metabolism using [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a rat model of shockwave-induced traumatic brain injury (SW-TBI). Anesthetized rats received 5 or 10 SW pulses to the right anterior lateral or dorsal frontal regions using SW lithotripsy. Animals were scanned for FDG uptake at baseline, 3 h post-injury, and 3 days post-injury, using a small animal PET/computed tomography (CT) scanner. FDG uptake at all time-points was quantified as the ratio of brain activity relative to peripheral activity in the left ventricle (LV) in the heart (A/A) for the entire brain, each hemisphere, and four cortices (motor, cingulate, somatosensory, and retrosplenial). The mixed-designed models analysis of variance (ANOVA) for the hemispheric and global FDG uptake ratio showed a significant effect of the time-of-scan (p = 0.038) and measured region (p = 6.12e-09). We also observed a significant effect of the time-of-scan (p = 0.046) and measured region (p = 2.28e-09) for the FDG uptake ratio in four cortical regions. None of the measurements (global or local) showed a significant effect for the number of SW pulses (5 or 10) or SW location (lateral or dorsal frontal regions). Our data suggest that SW-TBI causes hypermetabolism on the impact side of the rat brain at 3 h post-injury compared with the baseline measurements. However, the increase in FDG uptake by day 3 post-injury was not significant. Further studies on post-TBI metabolic changes are needed to understand better the pathophysiology of the injury.
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http://dx.doi.org/10.1089/neu.2017.5208DOI Listing
January 2018

Large improvement of RF transmission efficiency and reception sensitivity for human in vivoP MRS imaging using ultrahigh dielectric constant materials at 7T.

Magn Reson Imaging 2017 10 21;42:158-163. Epub 2017 Jul 21.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, MN, USA. Electronic address:

In vivoP MRS provides a unique and important imaging tool for studying high-energy phosphate metabolism and bioenergetics noninvasively. However, compared to H MRS, P MRS with a relatively low gyromagnetic ratio (γ) has a lower and limited sensitivity even at ultrahigh field. The proof of concept has been recently demonstrated that the use of high dielectric constant (HDC) materials between RF coil and object sample could increase MRI signal and reduce required RF transmission power for reaching the same RF pulse flip angle in the region of interest. For low-γ MRS applications operated at relatively lower frequency, however, it demands the dielectric materials with a much higher permittivity for achieving optimal performance. We conducted a P MRS imaging study using ultra-HDC (uHDC; with a relative permittivity of ~1200) material blocks incorporated with an RF volume coil at ultrahigh field of 7.0T. The experimental results from phantom and human calf muscle demonstrate that the uHDC technique significantly enhanced RF magnetic transmit field (B) and reception field (B) and the gain could reach up to two folds in the tissue near the uHDC blocks. The overall results indicate that the incorporation of the uHDC materials having an appropriate permittivity value with a RF coil can significantly increase detection sensitivity and reduces RF transmission power for X-nuclei MRS applications at ultrahigh field. The uHDC technology could provide an efficient, cost-effective engineering solution for achieving high detection sensitivity and concurrently minimizing tissue heating concern for human MRS and MRI applications.
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http://dx.doi.org/10.1016/j.mri.2017.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961500PMC
October 2017

Functional MRI BOLD response in sickle mice with hyperalgesia.

Blood Cells Mol Dis 2017 06 18;65:81-85. Epub 2017 Mar 18.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address:

Patients with sickle cell anemia (SCA) have abnormal hemoglobin (sickle hemoglobin S) leading to the crystallization of hemoglobin chains in red blood cells (RBCs), which assume sickle shape and display reduced flexibility. Sickle RBCs (sRBCs) adhere to vessel walls and block blood flow, thus preventing oxygen delivery to the tissues leading to vaso-occlusive crises (VOC), acute pain and organ damage. SCA patients often have chronic pain that can be attributed to inflammation, vasculopathy, neuropathy, ischemia-reperfusion injury and organ damage. Blood oxygenation level-dependent (BOLD) based functional magnetic resonance imaging (fMRI) technique that is commonly used for noninvasively mapping spontaneous or evoked brain activation in human or animal models has been applied in this study to assess abnormal oxygenation change in the brains of mice with SCA in response to hypoxia. We found that hyperalgesic HbSS-BERK sickle mice with chronic pain display reduced BOLD response to a hypoxia challenge compared to their control HbAA-BERK mice. Hypoxia/reoxygenation (H/R) treated sickle mice under acute pain episode exhibit even smaller BOLD signal changes than sickle mice without H/R, suggestive of correlations between cerebral BOLD signal changes and nociception.
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http://dx.doi.org/10.1016/j.bcmd.2017.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521217PMC
June 2017

A proof-of-concept study for developing integrated two-photon microscopic and magnetic resonance imaging modality at ultrahigh field of 16.4 tesla.

Sci Rep 2017 06 2;7(1):2733. Epub 2017 Jun 2.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, United States.

Functional magnetic resonance imaging (fMRI) based on the blood oxygen level dependent (BOLD) contrast has gained a prominent position in neuroscience for imaging neuronal activity and studying effective brain connectivity under working state and functional connectivity at resting state. However, the fundamental questions in regards to fMRI technology: how the BOLD signal inferences the underlying microscopic neuronal activity and physiological changes and what is the ultimate specificity of fMRI for functional mapping of microcircuits, remain unanswered. The capability of simultaneous fMRI measurement and functional microscopic imaging in a live brain thus holds the key to link the microscopic and mesoscopic neural dynamics to the macroscopic brain activity at the central nervous system level. Here we report the first demonstration to integrate high-resolution two-photon fluorescence microscopy (TPM) with a 16.4 tesla MRI system, which proves the concept and feasibility for performing simultaneous high-resolution fMRI and TPM imaging at ultrahigh magnetic field.
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http://dx.doi.org/10.1038/s41598-017-02864-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457450PMC
June 2017

Late Neolithic phytolith and charcoal records of human activities and vegetation change in Shijiahe culture, Tanjialing site, China.

PLoS One 2017 19;12(5):e0177287. Epub 2017 May 19.

Hubei Provincial Institute of Cultural Relic and Archaeology, Wuhan, China.

There is significant archaeological evidence marking the collapse of the Shijiahe culture in the middle reaches of the Yangtze River in China during the late Neolithic Period. However, the causes for this cultural collapse remain unclear. Our sedimentary records from a 3.3 m long profile and 76 phytolith and charcoal samples from the Tanjialing archaeological sites provide records of interactions between an ancient culture and vegetation change. During the early Shijiahe culture (c, 4850-4400 cal BP), the climate was warm and humid. Fire was intensively used to clear the vegetation. In the mid-period of the Shijiahe culture (c, 4400-4200 cal BP), the climate became slightly dry-cold and this was accompanied by decreasing water, leading to settlements. From c, 4200 cal BP, severe drought eroded the economic foundation of rice-cultivation. These conditions forced people to abandon the Shijiahe ancient city to find water in other regions, leading to the collapse of the Shijiahe culture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438134PMC
September 2017

Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy.

J Cereb Blood Flow Metab 2017 Nov 15;37(11):3518-3530. Epub 2017 May 15.

1 Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, MN, USA.

Quantitative assessment of cerebral glucose consumption rate (CMR) and tricarboxylic acid cycle flux (V) is crucial for understanding neuroenergetics under physiopathological conditions. In this study, we report a novel in vivo Deuterium (H) MRS (DMRS) approach for simultaneously measuring and quantifying CMR and V in rat brains at 16.4 Tesla. Following a brief infusion of deuterated glucose, dynamic changes of isotope-labeled glucose, glutamate/glutamine (Glx) and water contents in the brain can be robustly monitored from their well-resolved H resonances. Dynamic DMRS glucose and Glx data were employed to determine CMR and V concurrently. To test the sensitivity of this method in response to altered glucose metabolism, two brain conditions with different anesthetics were investigated. Increased CMR (0.46 vs. 0.28 µmol/g/min) and V (0.96 vs. 0.6 µmol/g/min) were found in rats under morphine as compared to deeper anesthesia using 2% isoflurane. This study demonstrates the feasibility and new utility of the in vivo DMRS approach to assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an alternative MRS tool for in vivo study of metabolic coupling relationship between aerobic and anaerobic glucose metabolisms in brain under physiopathological states.
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http://dx.doi.org/10.1177/0271678X17706444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669347PMC
November 2017
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