Quantitative in vivo characterization of intracellular and extracellular pH profiles in heterogeneous tumors: a novel method enabling multiparametric pH analysis.

Acid production and transport are currently being studied to identify new targets for efficient cancer treatment, as subpopulations of tumor cells frequently escape conventional therapy owing to their particularly acidic tumor microenvironment. Heterogeneity in intracellular and extracellular tumor pH (pHi, pHe) has been reported, but none of the methods currently available for measuring tissue pH provides quantitative parameters characterizing pH distribution profiles in tissues. To this intent, we present here a multiparametric, noninvasive approach based on in vivo (31)P nuclear magnetic resonance (NMR) spectroscopy and its application to mouse tumor xenografts.

Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans.

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min(-1), CV(inter-subject) = 42%) as compared with PF (46 ± 20 mM min(-1), CV(inter-subject) = 44%) and tended to be higher in FF (43 ± 35 mM min(-1), CV(inter-subject) = 80%).

Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo.

Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation.

Combined MRI and ³¹P-MRS investigations of the ACTA1(H40Y) mouse model of nemaline myopathy show impaired muscle function and altered energy metabolism.

Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1) account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear.

Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia.

Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K⁺ channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K⁺ channel, is involved in the pathophysiology of brain ischemia.

Cine-ASL: a steady-pulsed arterial spin labeling method for myocardial perfusion mapping in mice. Part I. Experimental study.

Arterial spin labeling has been developed and used for the quantitative and completely noninvasive assessment of myocardial perfusion in vivo. Here we propose a novel arterial spin labeling method called cine-ASL, which is based on an electrocardiogram-gated steady-pulsed labeling approach combined with simultaneous readout over the cardiac cycle using cine-fast low-angle shot. This method led to shorter acquisition times than the previously used Look-Locker flow-sensitive alternating inversion recovery gradient-echo technique while preserving spatial resolution and robustness with respect to cardiac motion.

Cine-ASL: a steady-pulsed arterial spin labeling method for myocardial perfusion mapping in mice. Part II. Theoretical model and sensitivity optimization.

In small rodent myocardial perfusion studies, the most widely used method is based on Look-Locker measurements of the magnetization recovery after FAIR preparation, which bears limitations regarding acquisition efficiency due to the pulsed arterial spin labeling nature of the sequence. To improve efficiency, this two-article set proposes a new steady-pulsed arterial spin labeling scheme using a cine readout incorporating one tagging pulse per heart cycle. In this part, we derive a theoretical description of the magnetization time evolution in such a scheme.

Multimodal MR imaging (diffusion, perfusion, and spectroscopy): is it possible to distinguish oligodendroglial tumor grade and 1p/19q codeletion in the pretherapeutic diagnosis?

Background And Purpose: Pretherapeutic determination of tumor grade and genotype in grade II and III oligodendroglial tumors is clinically important but is still challenging. Tumor grade and 1p/19q status are currently the 2 most important factors in therapeutic decision making for patients with these tumors. Histopathology and cMRI studies are still limited in some cases.

In vivo short TE localized 1H MR spectroscopy of mouse cervical spinal cord at very high magnetic field (11.75 T).

MR spectroscopy allows a noninvasive assessment of metabolic information in healthy and pathological central nervous system. Whereas MR spectroscopy has been extensively applied in the brain, only few spectroscopic studies of the spinal cord (SC) have been performed so far. For mice, due to additional technical challenges, in vivo 1H SC MRS has not yet been reported.

Value of in vivo T2 measurement for myocardial fibrosis assessment in diabetic mice at 11.75 T.

Objective: The aim of the study was to assess the value of in vivo T2 measurements to noninvasively quantify myocardial fibrosis in diabetic mice at 11.75 T. Diabetic cardiomyopathy is characterized by extracellular matrix alteration and microcirculation impairment.

Epileptogenic brain lesions in children: the added-value of combined diffusion imaging and proton MR spectroscopy to the presurgical differential diagnosis.

Purpose: Focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumors (DNTs), and gangliogliomas (GGs) share many clinical features, and the presurgical differential diagnosis of these lesions using conventional magnetic resonance imaging (MRI) is challenging in some cases. The purpose of this work was thus to evaluate the capacity of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS) to distinguish each lesion from the others.

Methods: Seventeen children (mean age 9.

Pseudo-continuous arterial spin labeling at very high magnetic field (11.75 T) for high-resolution mouse brain perfusion imaging.

With the increasing number of transgenic mouse models of human brain diseases, there is a need for a sensitive method that allows assessing quantitative whole brain perfusion within a reasonable scan time. Arterial spin labeling (ASL), an MRI technique that permits the noninvasive quantification of cerebral blood flow, has been used to assess rodents brain perfusion. For mice, the reported experiments performed with continuous or pulsed ASL were challenged by poor multislice capability, limited sensitivity, or quantification issues.

Epicardial fat volume is associated with coronary microvascular response in healthy subjects: a pilot study.

Epicardial fat (EF) is an active ectopic fat depot, which has been associated with coronary atherosclerosis, and which could early influence endothelial function. We thus investigated the relationship between EF and endothelium-dependent vasoreactivity of the coronary microcirculation, in highly selected healthy volunteers. Myocardial blood flow (MBF) was determined by measuring coronary sinus flow with velocity-encoded cine magnetic resonance imaging (MRI) at 3T.

Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus.

Background: Gender-specific differences in cardiovascular risk are well known, and current evidence supports an existing role of endothelium in these differences. The purpose of this study was to assess non invasively coronary endothelial function in male and female young volunteers by myocardial blood flow (MBF) measurement using coronary sinus (CS) flow quantification by velocity encoded cine cardiovascular magnetic resonance (CMR) at rest and during cold pressor test (CPT).

Methods: Twenty-four healthy volunteers (12 men, 12 women) underwent CMR in a 3 Tesla MR imager.

Is high-frequency neuromuscular electrical stimulation a suitable tool for muscle performance improvement in both healthy humans and athletes?

We aimed at providing an overview of the currently acknowledged benefits and limitations of neuromuscular electrical stimulation (NMES) training programs in both healthy individuals and in recreational and competitive athletes regarding muscle performance. Typical NMES resistance exercises are performed under isometric conditions and involve the application of electrical stimuli delivered as intermittent high frequencies trains (>40-50 Hz) through surface electrodes. NMES has been acknowledged as an efficient modality leading to significant improvements in isometric maximal voluntary strength.

Spinal cord - MR of rodent models.

Different MR techniques, such as relaxation times, diffusion, perfusion, and spectroscopy have been employed to study rodent spinal cord. In this chapter, a description of these methods is given, along with examples of normal metrics that can be derived from the MR acquisitions, as well as examples of applications to pathology.

Cerebral perfusion MRI in mice.

Perfusion MRI is a tool to assess the spatial distribution of microvascular blood flow. Arterial spin labeling (ASL) is shown here to be advantageous for quantification of cerebral microvascular blood flow (CBF) in rodents. This technique is today ready for assessment of a variety of murine models of human pathology including those associated with diffuse microvascular dysfunction.

Is brain maturation comparable in fetuses and premature neonates at term equivalent age?

Background And Purpose: Improved knowledge of brain maturation in fetuses and premature neonates is crucial for the early detection of pathologies and would help determine whether MR data from the premature brain might be used to evaluate fetal maturation. Using diffusion-weighted MR imaging and (1)H-MR spectroscopy, we compared cerebral microstructure and metabolism in normal in utero fetuses imaged near term and premature neonates imaged at term equivalent.

Materials And Methods: Forty-eight subjects were investigated: 24 in utero fetuses (mean gestational age, 37 ± 1 weeks) and 24 premature neonates (mean postconceptional age, 37 ± 1 weeks).

Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks.

Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal, as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a temporally coherent activity thought to reflect functionally relevant networks. Antero-mesial temporal structures are the site of early pathological changes in Alzheimer's disease and have been shown to be critical for declarative memory. Our study aimed at exploring the functional impact of basal connectivity of an anterior temporal network (ATN) on declarative memory.

Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.

Citrulline malate (CM; CAS 54940-97-5, Stimol®) is known to limit the deleterious effect of asthenic state on muscle function, but its effect under healthy condition remains poorly documented. The aim of this longitudinal double-blind study was to investigate the effect of oral ingestion of CM on muscle mechanical performance and bioenergetics in normal rat. Gastrocnemius muscle function was investigated strictly non-invasively using nuclear magnetic resonance techniques.

Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE).

Metabolic profiling in multiple sclerosis and other disorders by quantitative analysis of cerebrospinal fluid using nuclear magnetic resonance spectroscopy.

Cerebrospinal fluid (CSF) is being analyzed for the diagnosis of a variety of neurological diseases. Among the methods employed, metabolomics and proteomics are increasingly gaining popularity. At present, sensitivity and, in particular, specificity are limited in CSF metabolomics by nuclear magnetic resonance (NMR) spectroscopy.

In vivo quantification of brain injury in adult Niemann-Pick Disease Type C.

Development of surrogate markers is necessary to assess the potential efficacy of new therapeutics in Niemann-Pick Disease Type C (NP-C). In the present study, magnetization transfer ratio (MTR) imaging, a quantitative MRI imaging technique sensitive to subtle brain microstructural changes, was applied in two patients suffering from adult NP-C. Statistical mapping analysis was performed to compare each patient's MTR maps with those of a group of 34 healthy controls to quantify and localize the extent of brain injury of each patient.

Effects of a single bout of isometric neuromuscular electrical stimulation on rat gastrocnemius muscle: a combined functional, biochemical and MRI investigation.

While muscle damage resulting from electrically-induced muscle isometric contractions has been reported in humans, animal studies have failed to illustrate similar deleterious effects and it remains to be determined whether these conflicting results are related to differences regarding experimental procedures or to species. We have investigated in vivo, in rat gastrocnemius muscles, using experimental conditions as close as possible to those used in humans (i.e.