67 research outputs found
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Molecular characterization and quantification using state of the art solid-state adiabatic TOBSY NMR in burn trauma
We describe a novel solid-state nuclear magnetic resonance (NMR) method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS), relative conventional liquid-state NMR approaches, when applied to intact biopsies of skeletal muscle specimens collected from burn trauma patients. This novel method, termed optimized adiabatic TOtal through Bond correlation SpectroscopY (TOBSY) solid-state NMR pulse sequence for two-dimensional (2D)1H-1H homonuclear scalar-coupling longitudinal isotropic mixing, was demonstrated to provide a 40–60% improvement in signal-to-noise ratio (SNR) relative to its liquid-state analogue TOCSY (TOtal Correlation SpectroscopY). Using 1-and 2-dimensional HRMAS NMR experiments, we identified several metabolites in burned tissues. Quantification of metabolites in burned tissues showed increased levels of lipid compounds, intracellular metabolites (e.g., taurine and phosphocreatine) and substantially decreased water-soluble metabolites (e.g., glutathione, carnosine, glucose, glutamine/glutamate and alanine). These findings demonstrate that HRMAS NMR Spectroscopy using TOBSY is a feasible technique that reveals new insights into the pathophysiology of burn trauma. Moreover, this method has applications that facilitate the development of novel therapeutic strategies
Magnetization transfer contrast MRI in GFP-tagged live bacteria
Green fluorescent protein (GFP) is a widely utilized molecular reporter of gene expression. However, its use in in vivo imaging has been restricted to transparent tissue mainly due to the tissue penetrance limitation of optical imaging. Magnetization transfer contrast (MTC) is a magnetic resonance imaging (MRI) methodology currently utilized to detect macromolecule changes such as decrease in myelin and increase in collagen content. MTC MRI imaging was performed to detect GFP in both in vitro cells and in an in vivo mouse model to determine if MTC imaging could be used to detect infection from Pseudomonas aeruginosa in murine tissues. It was demonstrated that the approach produces values that are protein specific and concentration dependent. This method provides a valuable, non-invasive imaging tool to study the impact of novel antibacterial therapeutics on bacterial proliferation and perhaps viability within the host system, and could potentially suggest the modulation of bacterial gene expression within the host when exposed to such compounds
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Functional MRI using robotic MRI compatible devices for monitoring rehabilitation from chronic stroke in the molecular medicine era (Review)
The number of individuals suffering from stroke is increasing daily, and its consequences are a major contributor to invalidity in today’s society. Stroke rehabilitation is relatively new, having been hampered from the longstanding view that lost functions were not recoverable. Nowadays, robotic devices, which aid by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain which can be monitored by MRI. Multiparametric magnetic resonance imaging (MRI) of stroke patients participating in a training program with a novel Magnetic Resonance Compatible Hand-Induced Robotic Device (MR_CHIROD) could yield a promising biomarker that, ultimately, will enhance our ability to advance hand motor recovery following chronic stroke. Using state-of-the art MRI in conjunction with MR_CHIROD-assisted therapy can provide novel biomarkers for stroke patient rehabilitation extracted by a meta-analysis of data. Successful completion of such studies may provide a ground breaking method for the future evaluation of stroke rehabilitation therapies. Their results will attest to the effectiveness of using MR-compatible hand devices with MRI to provide accurate monitoring during rehabilitative therapy. Furthermore, such results may identify biomarkers of brain plasticity that can be monitored during stroke patient rehabilitation. The potential benefit for chronic stroke patients is that rehabilitation may become possible for a longer period of time after stroke than previously thought, unveiling motor skill improvements possible even after six months due to retained brain plasticity
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High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors
The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, MT and GBM biopsies (P≤0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification
Heterogeneous data fusion to type brain tumor biopsies
Abstract Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this paper, we use machine learning algorithms to create a novel framework to perform the heterogeneous data fusion on both metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) Magnetic Resonance Spectroscopy and gene transcriptome profiling, to intact brain tumor biopsies and to identify different profiles of brain tumors. Our experimental results show our novel framework outperforms any analysis using individual dataset
The role of ventral tegmental area in chronic stroke rehabilitation: an exploratory study
IntroductionThe acknowledged role of external rewards in chronic stroke rehabilitation, offering positive reinforcement and motivation, has significantly contributed to patient engagement and perseverance. However, the exploration of self-reward’s importance in this context remains limited. This study aims to investigate the functional connectivity of the ventral tegmental area (VTA), a key node in the brain’s reward circuitry, during motor task-based rehabilitation and its correlation with the recovery process.MethodsTwelve right-handed healthy volunteers (4 men, 8 women, aged 57.4 ± 11.3 years) and twelve chronic stroke patients (5 men, 7 women, aged 48.1 ± 11.1 years) with clinically significant right-sided motor impairment (mean FM-UE score of 27.6 ± 8.7) participated. The analysis employed the CONN toolbox to assess the association between motor tasks and VTA connectivity using psychophysiological interaction (PPI).ResultsPPI analysis revealed motor-dependent changes in VTA connectivity, particularly with regions within the motor circuitry, cerebellum, and prefrontal cortex. Notably, stronger connectivity between the ipsilesional VTA and cerebellum was observed in healthy controls compared to chronic stroke patients, highlighting the importance of VTA-cerebellum interactions in motor function. Stroke patients’ motor performance was associated with VTA modulation in areas related to both motor tasks and reward processing, emphasizing the role of self-reward processes in rehabilitation. Changes in VTA influence on motor circuitry were linked to improvements in motor performance resulting from rehabilitation.DiscussionOur findings underscore the potential of neuroimaging techniques in quantifying and predicting rehabilitation outcomes by examining self-reward processes. The observed associations between VTA connectivity and motor performance in both healthy and stroke-affected individuals emphasize the role of psychological factors, particularly self-reward, in the rehabilitation process. This study contributes valuable insights into the intricate interplay between reward circuits and motor function, highlighting the importance of addressing psychological dimensions in neurorehabilitation strategies
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In vivo high-resolution magic angle spinning magnetic resonance spectroscopy of Drosophila melanogaster at 14.1 T shows trauma in aging and in innate immune-deficiency is linked to reduced insulin signaling
In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live Drosophila at 14.1 T. We demonstrated, for the first time, the feasibility of using HRMAS MRS for molecular characterization of Drosophila with a conventional MR spectrometer equipped with an HRMAS probe. We showed that the metabolic HRMAS MRS profiles of injured, aged wild-type (wt) flies and of immune deficient (imd) flies were more similar to chico flies mutated at the chico gene in the insulin signaling pathway, which is analogous to insulin receptor substrate 1–4 (IRS1–4) in mammals and less to those of adipokinetic hormone receptor (akhr) mutant flies, which have an obese phenotype. We thus provide evidence for the hypothesis that trauma in aging and in innate immune-deficiency is linked to insulin signaling. This link may explain the mitochondrial dysfunction that accompanies insulin resistance and muscle wasting that occurs in trauma, aging and immune system deficiencies, leading to higher susceptibility to infection. Our approach advances the development of novel in vivo non-destructive research approaches in Drosophila, suggests biomarkers for investigation of biomedical paradigms, and thus may contribute to novel therapeutic development
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fMRI-compatible rehabilitation hand device
BACKGROUND: Functional magnetic resonance imaging (fMRI) has been widely used in studying human brain functions and neurorehabilitation. In order to develop complex and well-controlled fMRI paradigms, interfaces that can precisely control and measure output force and kinematics of the movements in human subjects are needed. Optimized state-of-the-art fMRI methods, combined with magnetic resonance (MR) compatible robotic devices for rehabilitation, can assist therapists to quantify, monitor, and improve physical rehabilitation. To achieve this goal, robotic or mechatronic devices with actuators and sensors need to be introduced into an MR environment. The common standard mechanical parts can not be used in MR environment and MR compatibility has been a tough hurdle for device developers. METHODS: This paper presents the design, fabrication and preliminary testing of a novel, one degree of freedom, MR compatible, computer controlled, variable resistance hand device that may be used in brain MR imaging during hand grip rehabilitation. We named the device MR_CHIROD (Magnetic Resonance Compatible Smart Hand Interfaced Rehabilitation Device). A novel feature of the device is the use of Electro-Rheological Fluids (ERFs) to achieve tunable and controllable resistive force generation. ERFs are fluids that experience dramatic changes in rheological properties, such as viscosity or yield stress, in the presence of an electric field. The device consists of four major subsystems: a) an ERF based resistive element; b) a gearbox; c) two handles and d) two sensors, one optical encoder and one force sensor, to measure the patient induced motion and force. The smart hand device is designed to resist up to 50% of the maximum level of gripping force of a human hand and be controlled in real time. RESULTS: Laboratory tests of the device indicate that it was able to meet its design objective to resist up to approximately 50% of the maximum handgrip force. The detailed compatibility tests demonstrated that there is neither an effect from the MR environment on the ERF properties and performance of the sensors, nor significant degradation on MR images by the introduction of the MR_CHIROD in the MR scanner. CONCLUSION: The MR compatible hand device was built to aid in the study of brain function during generation of controllable and tunable force during handgrip exercising. The device was shown to be MR compatible. To the best of our knowledge, this is the first system that utilizes ERF in MR environment
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Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke
Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post-stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state-of-the-art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand-induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (p<0.001). New corticospinal tract (CST) fibers projecting progressively closer to the motor cortex appeared during training. Volumetric data analysis showed a statistically significant increase in the cortical thickness of the ventral postcentral gyrus areas of patients after training relative to pre-training cortical thickness (p<0.001). We suggest that rehabilitation is possible for a longer period of time after stroke than previously thought, showing that structural plasticity is possible even after 6 months due to retained neuroplasticity. Our study is an example of personalized medicine using advanced neuroimaging methods in conjunction with robotics in the molecular medicine era
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