Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
PLoS One ; 12(8): e0182086, 2017.
Article in English | MEDLINE | ID: mdl-28763477

ABSTRACT

OBJECTIVES: To assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients. METHODS: Spatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5-15.4 years) and 12 age-matched healthy controls (range: 5-14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets. RESULTS: PDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR. DISCUSSION AND CONCLUSION: The stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients.


Subject(s)
Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/metabolism , Phosphorus/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Muscular Atrophy/diagnosis , Phosphorus Isotopes/chemistry , Reproducibility of Results , Signal-To-Noise Ratio
2.
Chem Commun (Camb) ; 52(14): 3030-3, 2016 Feb 18.
Article in English | MEDLINE | ID: mdl-26792559

ABSTRACT

A hyperpolarization technique using carbonate precursors of biocompatible molecules was found to yield high concentrations of hyperpolarized (13)C bicarbonate in solution. This approach enabled large signal gains for low-toxicity hyperpolarized (13)C pH imaging in a phantom and in vivo in a murine model of prostate cancer.


Subject(s)
Biocompatible Materials , Carbon Isotopes/chemistry , Hydrogen-Ion Concentration , Carbon-13 Magnetic Resonance Spectroscopy
3.
J Musculoskelet Neuronal Interact ; 14(3): 255-66, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25198220

ABSTRACT

OBJECTIVES: Characterize bone loss in our newly developed severe contusion spinal cord injury (SCI) plus hindlimb immobilization (IMM) model and determine the influence of muscle contractility on skeletal integrity after SCI. METHODS: Female Sprague-Dawley rats were randomized to: (a) intact controls, (b) severe contusion SCI euthanized at Day 7 (SCI-7) or (c) Day 21 (SCI-21), (d) 14 days IMM-alone, (e) SCI+IMM, or (f) SCI+IMM plus 14 days body weight supported treadmill exercise (SCI+IMM+TM). RESULTS: SCI-7 and SCI-21 exhibited a >20% reduction in cancellous volumetric bone mineral density (vBMD) in the hindlimbs (p⋜0.01), characterized by reductions in cancellous bone volume (cBV/TV%), trabecular number (Tb.N), and trabecular thickness. IMM-alone induced no observable bone loss. SCI+IMM exacerbated cancellous vBMD deficits with values being >45% below Controls (p⋜0.01) resulting from reduced cBV/TV% and Tb.N. SCI+IMM also produced the greatest cortical bone loss with distal femoral cortical area and cortical thickness being 14-28% below Controls (p⋜0.01) and bone strength being 37% below Controls (p⋜0.01). SCI+IMM+TM partially alleviated bone deficits, but values remained below Controls. CONCLUSIONS: Residual and/or facilitated muscle contractility ameliorate bone decrements after severe SCI. Our novel SCI+IMM model represents a clinically-relevant means of assessing strategies to prevent SCI-induced skeletal deficits.


Subject(s)
Bone Resorption/pathology , Hindlimb Suspension/adverse effects , Spinal Cord Injuries/pathology , Animals , Biomechanical Phenomena , Bone Density , Bone and Bones/anatomy & histology , Casts, Surgical , Disease Models, Animal , Female , Physical Conditioning, Animal , Rats , Rats, Sprague-Dawley
4.
Gene Ther ; 21(4): 387-92, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24572791

ABSTRACT

In this study, we tested the feasibility of non-invasively measuring phosphoarginine (PArg) after gene delivery of arginine kinase (AK) using an adeno-associated virus (AAV) to murine hindlimbs. This was achieved by evaluating the time course, regional distribution and metabolic flux of PArg using (31)phosphorus magnetic resonance spectroscopy ((31)P-MRS). AK gene was injected into the gastrocnemius of the left hindlimb of C57Bl10 mice (age 5 weeks, male) using self-complementary AAV, type 2/8 with desmin promoter. Non-localized (31)P-MRS data were acquired over 9 months after injection using 11.1-T and 17.6-T Bruker Avance spectrometers. In addition, (31)P two-dimensional chemical shift imaging and saturation transfer experiments were performed to examine the spatial distribution and metabolic flux of PArg, respectively. PArg was evident in each injected mouse hindlimb after gene delivery, increased until 28 weeks, and remained elevated for at least 9 months (P<0.05). Furthermore, PArg was primarily localized to the injected posterior hindimb region and the metabolite was in exchange with ATP. Overall, the results show the viability of AAV gene transfer of AK gene to skeletal muscle, and provide support of PArg as a reporter that can be used to non-invasively monitor the transduction of genes for therapeutic interventions.


Subject(s)
Arginine Kinase/genetics , Arginine/analogs & derivatives , Dependovirus/genetics , Animals , Arginine/genetics , Arginine/metabolism , Arginine Kinase/therapeutic use , Genetic Therapy , Genetic Vectors , Hindlimb/metabolism , Mice , Muscle, Skeletal/metabolism , Organophosphorus Compounds/metabolism , Promoter Regions, Genetic , Transduction, Genetic
5.
Neuromuscul Disord ; 24(5): 393-401, 2014 May.
Article in English | MEDLINE | ID: mdl-24491484

ABSTRACT

Duchenne muscular dystrophy (DMD) is characterized by an increased muscle damage and progressive replacement of muscle by noncontractile tissue. Both of these pathological changes can lengthen the MRI transverse proton relaxation time (T2). The current study measured longitudinal changes in T2 and its distribution in the lower leg of 16 boys with DMD (5-13years, 15 ambulatory) and 15 healthy controls (5-13years). These muscles were chosen to allow extended longitudinal monitoring, due to their slow progression compared with proximal muscles in DMD. In the soleus muscle of boys with DMD, T2 and the percentage of pixels with an elevated T2 (⩾2SD above control mean T2) increased significantly over 1year and 2years, while the width of the T2 histogram increased over 2years. Changes in soleus T2 variables were significantly greater in 9-13years old compared with 5-8years old boys with DMD. Significant correlations between the change in all soleus T2 variables over 2years and the change in functional measures over 2years were found. MRI measurement of muscle T2 in boys with DMD is sensitive to disease progression and shows promise as a clinical outcome measure.


Subject(s)
Leg , Magnetic Resonance Imaging/methods , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/pathology , Adipose Tissue/pathology , Adolescent , Child , Disease Progression , Humans , Image Processing, Computer-Assisted , Leg/growth & development , Locomotion , Longitudinal Studies , Male , Muscle, Skeletal/growth & development , Muscular Dystrophy, Duchenne/physiopathology , Severity of Illness Index
6.
NMR Biomed ; 24(3): 281-90, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20862659

ABSTRACT

A totally noninvasive set-up was developed for comprehensive NMR evaluation of mouse skeletal muscle function in vivo. Dynamic pulsed arterial spin labeling-NMRI perfusion and blood oxygenation level-dependent (BOLD) signal measurements were interleaved with (31)P NMRS to measure both vascular response and oxidative capacities during stimulated exercise and subsequent recovery. Force output was recorded with a dedicated ergometer. Twelve exercise bouts were performed. The perfusion, BOLD signal, pH and force-time integral were obtained from mouse legs for each exercise. All reached a steady state after the second exercise, justifying the pointwise summation of the last 10 exercises to compensate for the limited (31)P signal. In this way, a high temporal resolution of 2.5 s was achieved to provide a time constant for phosphocreatine (PCr) recovery (τ(PCr)). The higher signal-to-noise ratio improved the precision of τ(PCr) measurement [coefficient of variation (CV) = 16.5% vs CV = 49.2% for a single exercise at a resolution of 30 s]. Inter-animal summation confirmed that τ(PCr) was stable at steady state, but shorter (89.3 ± 8.6 s) than after the first exercise (148 s, p < 0.05). This novel experimental approach provides an assessment of muscle vascular response simultaneously to energetic function in vivo. Its pertinence was illustrated by observing the establishment of a metabolic steady state. This comprehensive tool offers new perspectives for the study of muscle pathology in mice models.


Subject(s)
Energy Metabolism , Magnetic Resonance Spectroscopy/methods , Muscle, Skeletal/physiology , Animals , Electric Stimulation , Hindlimb/blood supply , Magnetic Resonance Spectroscopy/instrumentation , Male , Mice , Muscle, Skeletal/anatomy & histology , Perfusion , Phosphocreatine/metabolism , Physical Conditioning, Animal/physiology
7.
Gene Ther ; 17(3): 328-37, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20010628

ABSTRACT

Inhibiting myostatin (mstn) causes spectacular increase in muscle mass, spurring research for therapeutic approaches against neuromuscular disorders. Yet, possible functional deterioration and compromised force production have been reported in isolated muscle of null mstn(-/-) mice. We analyzed vascular and metabolic response to repeated electro-stimulated exercise in vivo in mstn(-/-) mice compared with FVB wild-type controls (WT), using interleaved multi-parametric functional nuclear magnetic resonance (NMR) imaging and spectroscopy. At steady-state exercise, specific force of plantar flexion, phosphocreatine consumption measured by phosphorus spectroscopy and maximum perfusion measured by arterial spin-labeled (ASL) NMR imaging were identical in both groups. After exercise, phosphorus spectroscopy revealed reduced oxidative mitochondrial capacity in mstn(-/-), whereas early recovery perfusion was identical and oxygen extraction, estimated from the blood oxygen level-dependent (BOLD) contrast, was decreased when compared with WT. Hyperemia was prolonged, indicating specific regulation of the perfusional response in mstn(-/-) mice. Histology showed an increased proportion of type IIb fibers in hypertrophied muscles, but the distribution of capillary contacts per fiber between oxidative and glycolytic fibers was unaltered in mstn(-/-) compared with WT. These integrated results formed coherent evidence of a congruous, non-pathologic shift toward a more glycolytic metabolism in this model of mstn(-/-).


Subject(s)
Muscle, Skeletal/physiology , Myostatin/deficiency , Animals , Exercise Test , Glycolysis/genetics , Hyperemia/metabolism , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Knockout , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Myostatin/genetics , Phosphocreatine/metabolism
8.
Gene Ther ; 16(6): 734-45, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19282845

ABSTRACT

1H-NMR (nuclear magnetic resonance) imaging is regularly proposed to non-invasively monitor cell therapy protocols. Prior to transplantation, cells must be loaded with an NMR contrast agent (CA). Most studies performed so far make use of superparamagnetic iron oxide particles (SPIOs), mainly for favorable detection sensitivity. However, in the case of labeled cell death, SPIO recapture by inflammatory cells might introduce severe bias. We investigated whether NMR signal changes induced by preloading with SPIOs or the low molecular weight gadolinium (Gd)-DTPA accurately monitored the outcome of transplanted cells in a murine model of acute immunologic rejection. CA-loaded human myoblasts were grafted in the tibialis anterior of C57BL/6 mice. NMR imaging was repeated regularly until 3 months post-transplantation. Label outcome was evaluated by the size of the labeled area and its relative contrast to surrounding tissue. In parallel, immunohistochemistry assessed the presence of human cells. Data analysis revealed that CA-induced signal changes did not strictly reflect the graft status. Gd-DTPA label disappeared rapidly yet with a 2-week delay compared with immunohistochemical evaluation. More problematically, SPIO label was still visible after 3 months, grossly overestimating cell survival (<1 week). SPIOs should be used with extreme caution to evaluate the presence of grafted cells in vivo and could hardly be recommended for the long-term monitoring of cell transplantation protocols.


Subject(s)
Contrast Media/pharmacokinetics , Ferrosoferric Oxide/pharmacokinetics , Gadolinium DTPA/pharmacokinetics , Magnetic Resonance Spectroscopy , Myoblasts/transplantation , Transplantation Immunology , Animals , Cell Death , Cell Survival , Cell Transplantation/methods , Cells, Cultured , Contrast Media/toxicity , Disease Models, Animal , Ferrosoferric Oxide/toxicity , Flow Cytometry , Gadolinium DTPA/toxicity , Half-Life , Hindlimb , Humans , Macrophages , Mice , Mice, Inbred C57BL , Myoblasts/cytology , Myoblasts/drug effects , Nanoparticles , Phagocytosis , Prussian Blue Reaction , Time Factors , Transplantation, Heterologous/methods
9.
NMR Biomed ; 19(7): 954-67, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17075963

ABSTRACT

Tissue perfusion and oxygenation in many organs can be evaluated by various NMR techniques. This review focuses on the specificities, limitations and adaptations of the NMR tools available to investigate perfusion and oxygenation in the skeletal muscle of humans and animal models. A description of how they may be used simultaneously is provided as well. 1H NMR spectroscopy of myoglobin (Mb) monitors intramyocytic oxygenation. It measures the level of deoxy-Mb, from which Mb concentration, Mb desaturation/resaturation rates, muscle oxygenation changes and intracellular partial oxygen pressure (pO2) can be calculated. Positive and negative blood oxygen level-dependent (BOLD) contrasts exist in skeletal muscle. BOLD contrasts primarily reflect changes in capillary-venous oxygenation, but are also directly or indirectly dependent on muscle blood volume, perfusion, vascular network architecture and angulation, relative to the main magnetic field. Arterial spin labelling (ASL) techniques, having high spatial and temporal resolution, are the methods of choice to quantify and map skeletal muscle perfusion non-invasively. Limitations of ASL are poor contrast-to-noise ratio and sensitivity to movement; however, with the introduction of specific adaptations, it has been proven possible to measure skeletal muscle perfusion at both rest and during exercise. The possibility of combining these NMR measurements with others into a single dynamic protocol is most interesting. The 'multiparametric functional (mpf) NMR' concept can be extended to include the evaluation of muscle energy metabolism simultaneously with 31P NMR or with lactate double quantum filtered 1H NMR spectroscopy, an approach which would make NMR an exceptional tool for non-invasive investigations of integrative physiology and biochemistry in skeletal muscle in vivo.


Subject(s)
Blood Flow Velocity/physiology , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiology , Oxygen Consumption/physiology , Oxygen/metabolism , Animals , Humans , Image Interpretation, Computer-Assisted/methods , Rheology/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...