Jean-Marie Escanye

Frequency dependence of water proton longitudinal nuclear magnetic relaxation times in mouse tissues at 20°C

We have measured the proton longitudinal relaxation times of tissue water of healthy and tumor-bearing mice as a function of the Larmor frequency in the range 6.7 to 90 MHz. These data can be rationalized according to T−11=A v−12+B, where A and B are constants specific to the tissue species. We present an interpretation of this frequency dependence within the Fast Exchange Two States model. It is shown that involving a distribution of correlation times for water proton-proton interaction does not yield consistent results, whereas a physically meaningful translational diffusion model pertinent to the dipolar interaction between water protons and macromolecules protons leads to the required frequency dependence. Essentially tissues would differ by the ‘bound’ versus ‘free’ proportion, or by structural properties of cells, rather than by the time-scales governing water motion.

Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: A phosphorus 31 nuclear magnetic resonance study

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.

Myocardial Effects of Experimental Acute Brain Death: Evaluation by Hemodynamic and Biological Studies

BACKGROUND Because of problems concerning the functional quality of heart transplants, more and more interest has been focused on the physiologic changes occurring during brain death, one of the major possible contributing factors to the myocardial alterations. METHODS The aim of this study was to describe the link between acute experimental brain death and myocardial metabolism. This was achieved by in vivo 3-hour hemodynamic and biological (myocardial lactate production) studies and then in vitro 6-hour phosphorus-31 nuclear magnetic resonance spectroscopy. Two groups of pigs were involved in the study: group I (n = 10) as control and group II (n = 10) as brain-dead animals. RESULTS Within the first hour, we observed a strong increase in myocardial activity associated with the onset of myocardial lactate production, lasting 2 hours and corresponding to a myocardial anaerobic metabolism period. Despite the apparent normalization before excision of the hearts, phosphorus-31 nuclear magnetic resonance spectroscopy revealed a significant decrease in adenosine triphosphate levels in group II when compared with group I. CONCLUSIONS We conclude that, in our study, acute experimental brain death is associated with an early and transient period of myocardial anaerobic metabolism and adenosine triphosphate consumption. These myocardial consequences of brain death could partially explain some observations of heart graft dysfunction.

Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock.

Background:Lactic acidosis is associated with cardiovascular failure. Buffering with sodium bicarbonate is proposed in severe lactic acidosis. Bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. The authors thus investigated the cardiovascular and metabolic effects of an adapted sodium bicarbonate therapy, including prevention of carbon dioxide increase with hyperventilation and ionized calcium decrease with calcium administration. Methods:Lactic acidosis was induced by hemorrhagic shock. Twenty animals were randomized into five groups: (1) standard resuscitation with blood retransfusion and norepinephrine (2) adapted sodium bicarbonate therapy (3) nonadapted sodium bicarbonate therapy (4) standard resuscitation plus calcium administration (5) hyperventilation. Evaluation was focused in vivo on extracellular pH, on intracellular pH estimated by P31 nuclear magnetic resonance and on myocardial contractility by conductance catheter. Aortic rings and mesenteric arteries were isolated and mounted in a myograph, after which arterial contractility was measured. Results:All animals in the hyperventilation group died prematurely and were not included in the statistical analysis. When compared with sham rats, shock induced extracellular (median, 7.13; interquartile range, [0.10] vs. 7.30 [0.01]; P = 0.0007) and intracellular acidosis (7.26 [0.18] vs. 7.05 [0.13]; P = 0.0001), hyperlactatemia (7.30 [0.01] vs. 7.13 [0.10]; P = 0.0008), depressed myocardial elastance (2.87 [1.31] vs. 0.5 [0.53] mmHg/&mgr;l; P = 0.0001), and vascular hyporesponsiveness to vasoconstrictors. Compared with nonadapted therapy, adapted bicarbonate therapy normalized extracellular pH (7.03 [0.12] vs. 7.36 [0.04]; P < 0.05), increased intracellular pH to supraphysiological values, improved myocardial elastance (1.68 [0.41] vs. 0.72 [0.44] mmHg/&mgr;l; P < 0.05), and improved aortic and mesenteric vasoreactivity. Conclusions:A therapeutic strategy based on alkalinization with sodium bicarbonate along with hyperventilation and calcium administration increases pH and improves cardiovascular function.

Nuclear magnetic relaxation studies of water in frozen biological tissues. Cross-relaxation effects between protein and bound water protons

Abstract Water proton longitudinal relaxation has been investigated in frozen mouse tissues including tumors. The nonfreezable water which gives rise to a relatively sharp NMR signal at this temperature (263 K) is identified as water bound to macromolecules. Measurements have been carried out by the nonselective inversion-recovery method at 90 and 6 MHz. Partially selective inversion has been achieved at 90 MHz by the DANTE sequence. The experimental data are analyzed by means of Solomon-type equations. This analysis provides the cross-relaxation term from which the dipolar contribution to water relaxation rate, arising from interactions with macromolecular protons, is calculated. This contribution seems to be dominant. The number of water protons interacting with a given macromolecular proton is found to be of the order of 10. The data at both frequencies can be consistently interpreted in terms of water diffusion, with a characteristic time of about 10 -9 sec. These conclusions are valid for all the tissues investigated here, their relaxation parameters exhibiting only slight differences.

PHOSPHORUS MAGNETIC-RESONANCE SPECTROSCOPY - A NONINVASIVE TECHNIQUE FOR THE STUDY OF OCCLUSIVE ARTERIAL LEG DISEASE AND PERIPHERAL VASODILATOR THERAPY

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intra cellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index {[PCr] / ([PCr] + [Pi])} at rest was correlated with blood flow measured by plethys mography During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 ±3.04 J vs 58.89 ±8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 ±3.04 J vs 38.85 ±3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

Nonrigid registration improves MRI T2 quantification in heart transplant patient follow‐up

To evaluate the use of a nonrigid registration technique for detecting acute heart transplant rejection by MRI T2 quantification.

Diagnostic and prognostic value of MRI T2 quantification in heart transplant patients

This study was designed retrospectively to assess the value of myocardial T2 to detect or predict ongoing acute heart rejection, in heart transplant patients, with a 1.5‐T MRI magnet. One hundred and ninety‐six myocardial T2 quantifications were performed on sixty consecutive heart transplant patients during routine follow‐up. T2 values were assessed (i) with regard to the results of concomitant biopsies and (ii) with a Cox multivariate model for the prediction of subsequent rejections, defined by a ≥ grade 2 at biopsy or highly suspected in the absence of biopsy (>10% drop in ejection fraction with subsequent reversibility under treatment). T2 values were proposed as main covariate, after logit transformation and adjustment for other confounding parameters such as delay since graft surgery and delay before biopsy. T2 values were strongly linked (i) to the presence of rejection on concomitant biopsy (P < 0.0001) and (ii) to the risk of subsequent rejection on Cox multivariate model (P < 0.001). T2 values above 60 ms were associated with relative risk of rejection higher than 2.0 and rapidly increasing. In conclusion, myocardial T2 yields a high diagnostic and prognostic value for graft rejection in heart transplant patients.

Effect of physiological Heart Rate variability on quantitative T2 measurement with ECG-gated Fast Spin Echo (FSE) sequence and its retrospective correction

OBJECT Quantitative T2 measurement is applied in cardiac Magnetic Resonance Imaging (MRI) for the diagnosis and follow-up of myocardial pathologies. Standard Electrocardiogram (ECG)-gated fast spin echo pulse sequences can be used clinically for T2 assessment, with multiple breath-holds. However, heart rate is subject to physiological variability, which causes repetition time variations and affects the recovery of longitudinal magnetization between TR periods. MATERIALS AND METHODS The bias caused by heart rate variability on quantitative T2 measurements is evaluated for fast spin echo pulse sequence. Its retrospective correction based on an effective TR is proposed. Heart rate variations during breath-holds are provided by the ECG recordings from healthy volunteers. T2 measurements were performed on a phantom with known T2 values, by synchronizing the sequence with the recorded ECG. Cardiac T2 measurements were performed twice on six volunteers. The impact of T1 on T2 is also studied. RESULTS Maximum error in T2 is 26% for phantoms and 18% for myocardial measurement. It is reduced by the proposed compensation method to 20% for phantoms and 10% for in vivo measurements. Only approximate knowledge of T1 is needed for T2 correction. CONCLUSION Heart rate variability may cause a bias in T2 measurement with ECG-gated FSE. It needs to be taken into account to avoid a misleading diagnosis from the measurements.

Joint Reconstruction of Multiple Images and Motion in MRI: Application to Free-Breathing Myocardial

Exploiting redundancies between multiple images of an MRI examination can be formalized as the joint reconstruction of these images. The anatomy is preserved indeed so that specific constraints can be implemented (e.g. most of the features or spatial gradients should be in the same place in all these images) and only the contrast changes from one image to another need to be encoded. The application of this concept is particularly challenging in cardiovascular and body imaging due to the complex organ deformations, especially with the patient breathing. In this study a joint optimization framework is proposed for reconstructing multiple MR images together with a nonrigid motion model. The motion model takes into account both intra-image and inter-image motion and therefore can correct for most ghosting/blurring artifacts and misregistration between images. The framework was validated with free-breathing myocardial T2 mapping experiments from nine heart transplant patients at 1.5 T. Results showed improved image quality and excellent image alignment with the multi-image reconstruction compared to the independent reconstruction of each image. Segment-wise myocardial T2 values were in good agreement with the reference values obtained from multiple breath-holds (62.5 ± 11.1 ms against 62.2 ± 11.2 ms which was not significant with p=0.49).