In vivo study of halothane hepatotoxicity in the rat using magnetic resonance imaging and 31P spectroscopy

Using magnetic resonance imaging (MRI) and spectroscopy (MRS), in vivo halothane hepatotoxicity was assessed in male Wistar rats. With 1.5% halothane in 100 or 20% O2, an edematous region, characterized by increased intensity on T2 weighted images and an increase in regional tissue water content (rho water), was seen proximal to the hepatic portal vein in the liver. Both spin-lattice relaxation (T1) and spin-spin relaxation (T2) increased in this region, relative to distal regions of the liver. Similarly, a high signal intensity on proton density weighted images was observed in this area. As halothane anaesthesia progressed, a decrease in the adenosine triphosphate-inorganic phosphate ratio (ATP/Pi) and an increase in the phosphomonoester-phosphodiester (PME/PDE) ratio was detected in the liver. In addition, intracellular pH decreased and intracellular free magnesium concentration [Mg2+] increased with time of exposure. Excessive vacuolation, ribosomal disappearance from rough endoplasmic reticulum, mitochondrial swelling and fragmentation of smooth endoplasmic reticulum were observed by transmission electron microscopy (TEM) in samples from the edematous region of the liver.     

Brain regional distribution pattern of metabolite signal intensities in young adults by proton magnetic resonance spectroscopic imaging

Proton magnetic resonance spectroscopy (1H-MRS) is evolving from single-volume localized acquisitions to multiple-volume acquisitions using magnetic resonance spectroscopic imaging (1H-MRSI). The normal regional patterns of 1H-MRSI-detectable metabolite signal intensities have yet to be established. We studied 13 healthy young adults with a multiple-section 1H-MRSI technique. The metabolite signals measured were N-acetylaspartate (NA), choline-containing compounds (CHO), creatine-phosphocreatine (CRE), and lactate. Ten neuroanatomic regions (nine bilateral) were identified in gray matter, white matter, and basal nuclei. Analysis of the data led to the following conclusions: (1) NA and CHO signals from centrum semiovale (CSO) can be used as a normalizing factor to reduce intersubject variability due to external causes; (2) in normal human brain, there is no left versus right asymmetry in the regions studied; (3) statistically significant patterns of signal distribution of NA, CHO, and CRE can be identified in normal human brain; and (4) CSO-normalized metabolite signal intensities and metabolite ratios complement each other for the detection of significant regional differences.     

Alterations in heart and kidney membrane phospholipids in hypertension as observed by 31P nuclear magnetic resonance

Abnormalities of phospholipids in hypertension have previously been described in human erythrocyte, platelet, and plasma lipoproteins. Since the heart and kidney are adversely affected by hypertension, we investigated possible alterations in their membrane phospholipids, which could play a role in the derangement of intracellular ion balance widely observed in hypertension. The phospholipid compositions of heart and kidney from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were determined by using 31P nuclear magnetic resonance (NMR) spectroscopy. Absolute contents of all phospholipids in hypertensive hearts and kidneys were significantly higher than in normotensive hearts and kidneys. Expressed as a fraction of total phospholipid, cardiolipin (CL) and phosphatidylethanolamine plasmalogen (PEp) were significantly increased in SHR hearts compared to WKY hearts (CL and PEp were 7.95+/-0.22% and 13.16+/-0.35% in SHR vs. 7.01+/-0.20% and 11.19+/-0.42% in WKY rats, P< or =0.05), but phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were significantly decreased in SHR (PE and PC were 22.46+/-0.37% and 44.81+/-0.43% in SHR vs. 24.02+/-0.44% and 46.01+/-0.50% in WKY rats, P< or =0.05). In the phospholipids extracted from rat kidneys, the percentage of PE was significantly higher for SHR than for WKY rats (20.37+/-0.60% vs. 18.43+/-0.37%, P< or =0.05), while PEp and phosphatidylserine (PS) were significantly lower for SHR (PEp and PS were 10.22+/-0.36% and 8.42+/-0.28% in SHRs vs. 11.29+/-0.36% and 9.71+/-0.40% in WKY rats, P< or =0.05). The above alterations in phospholipid composition might contribute to the higher oxygen consumption in the hypertensive heart and abnormal intracellular ion concentrations and ion transport in the heart and the kidney in hypertension.     

Three-dimensional display of cardiac structures using reconstructed magnetic resonance imaging

It is sometimes difficult to understand the three-dimensional (3D) relationship of cardiac and mediastinal structures despite advances in magnetic resonance (MR) imaging techniques. We present a low-cost system for 3D reconstruction of the major mediastinal structures by processing the MR imaging data on a NeXT workstation. MR images of multisection, multiphase, spin-echo techniques stored in a picture archiving and communication system (PACS) data base were used for the reconstruction. The computer program obtained the contours of the multiple components of the mediastinal structures by the combination of automatic and manual procedure. The bundled software of a 3D kit was used for surface rendering of hidden surface removal, shading of the visible parts of the surfaces, perspective transformation, and motion parallax by rotation of the surfaces. 3D reconstruction was performed in 15 patients with cardiac diseases, and the 3D-reconstructed images were compared with the plain chest x rays of the patients. The 3D presentation clearly showed the complex anatomy of cardiovascular diseases and helped elucidate the misconceptions in the interpretation of the plain chest x rays. Our 3D images are used for education and should be viewed by medical students and beginners in radiology at an individual pace with plain chest radiographs, MR images, and legends. Although applied to the heart and the great vessels in this report, this system is also applicable to other structures.     

Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: 31P and 1H magnetic resonance spectroscopic studies

Creatine (Cr) and cyclocreatine (cyCr) have been shown to inhibit the growth of a variety of human and murine tumours. The purpose of this study was to evaluate the anti-tumour effect of these molecules in relation to drug accumulation, energy metabolism, tumour water accumulation and toxicity. Nude mice carrying a human colon adenocarcinoma (LS174T) with a creatine kinase (CK) activity of 2.12 units mg(-1) protein were fed Cr (2.5% or 5%) or cyCr (0.025%, 0.1% or 0.5%) for 2 weeks and compared with controls fed standard diet. Cr concentrations of 2.5% and 5% significantly inhibited tumour growth, as did 0.1% and 0.5% cyCr. In vivo 31P magnetic resonance spectroscopy (MRS) after 2 weeks of treatment showed an increase in [phosphocreatine (PCr)+phosphocyclocreatine (PcyCr)]/nucleoside triphosphate (NTP) with increasing concentrations of dietary Cr and cyCr, without changes in absolute NTP contents. The antiproliferative effect of the substrates of CK was not related to energy deficiency but was associated with acidosis. Intratumoral substrate concentrations (measured by 1H-MRS) of 4.8 micromol g(-1) wet weight Cr (mice fed 2.5% Cr) and 6.2 micromol g(-1) cyCr (mice fed 0.1% cyCr) induced a similar decrease in growth rate, indicating that both substrates were equally potent in tumour growth inhibition. The best correlant of growth inhibition was the total Cr or (cyCr+Cr) concentrations in the tissue. In vivo, these agents did not induce excessive water accumulation and had no systemic effects on the mice (weight loss, hypoglycaemia) that may have caused growth inhibition.     

Three-dimensional echocardiographic measurement of right ventricular volume in children with congenital heart disease validated by magnetic resonance imaging

Measurement of right ventricular volume and function by two-dimensional echocardiography is unreliable because of the asymmetric shape of the right ventricle. The purpose of this study was to validate the accuracy of transthoracic three-dimensional echocardiography in assessing right ventricular volumes in children with congenital heart disease after surgical repair of the defects, by comparison with those measured by magnetic resonance imaging. We examined 13 children after repair of tetralogy of Fallot (10), hypoplastic left heart syndrome (2), or atrial septal defect (1). Each underwent magnetic resonance imaging followed by three-dimensional echocardiography done with a transthoracic 5 MHz, prototype internally rotating omniplane transducer. In both methods, endocardial borders were manually traced and volumetric slices were summated. Close correlation was observed between the two methods (R2 0.91 for end-systolic volumes, 0.90 for end-diastolic volumes, 0.64 for ejection fraction, and 0.92 for interobserver variability). A limits-of-agreement analysis showed no adverse trend between the two methods under values of 100 ml and low variation around the mean values. We conclude that three-dimensional echocardiography measurement of right ventricular volumes correlates closely with magnetic resonance imaging in children with operated congenital heart disease and may allow accurate serial evaluation in these patients.     

Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging

The relationship between brain structure and complex behavior is governed by large-scale neurocognitive networks. The availability of a noninvasive technique that can visualize the neuronal projections connecting the functional centers should therefore provide new keys to the understanding of brain function. By using high-resolution three-dimensional diffusion magnetic resonance imaging and a newly designed tracking approach, we show that neuronal pathways in the rat brain can be probed in situ. The results are validated through comparison with known anatomical locations of such fibers.     

Intracellular phosphates in inclusion body myositis--a 31P magnetic resonance spectroscopy study

Muscle phosphorus magnetic resonance spectroscopy was used to study oxidative metabolism at rest and during recovery from exercise in 7 patients with sporadic inclusion body myositis (s-IBM), compared with normal controls (n=8) and mitochondrial myopathies (n=20). At rest, 6/7 patients had elevated inorganic phosphates. Recovery parameters were not different from controls, in contrast with mitochondrial myopathies, who showed abnormal rest and recovery. The normal recovery suggests that mitochondrial oxidative capacity is not impaired in s-IBM.     

31P nuclear magnetic resonance study of phospholipids in ischemia/reperfusion injury in a rat fatty liver model

Obese Zucker rats are susceptible to increased hepatic ischemia/reperfusion (I/RP) injury. Increased lipid peroxidation occurs in this model with warm ischemia. We hypothesized that a severe depletion of phospholipids (PL) occurs with warm I/RP in fatty livers. Obese (Ob) and lean (Ln) Zucker rats were subjected to 90 min of in vivo partial hepatic warm I followed by RP. Total lipids extracted from one gm of liver (median lobe) taken at the end of 1, 2 and 6 hr of RP and sham (Sh) surgery (n=5 Ln & Ob) were analyzed by 202.3 MHz 31P NMR, which provided good resolution of individual PL. Obese (Sh) rats contained 22% more PL than Ln (P= < 0.01). Ischemia caused similar decreases in PL in both Ob (to 67% Sh) and Ln rats (62%). Following 2 hr RP, PL in Ob rats decreased further (46% Sh) and recovered only marginally at 6 hr (53%), in marked contrast to the rapid recovery in Ln to preischemic levels (110% Sh at both 2 and 6 hr; P=<0.001). Mole percents of individual PL did not change significantly except for lysophosphatidylcholine, which increased from 0.43 to 1.3% (Sh vs. 6 hr RP) in the Ob, but decreased from 0.98 to 0.52% in Ln animals (P = <0.001). Fatty livers thus are more vulnerable to phospholipid depletion in response to warm ischemia/reperfusion than normal livers.     

31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients

Most research with 31P-magnetic resonance spectroscopy (31P-MRS) in affective disorders has been done in the field of bipolar disturbances. Reduced frontal and temporal lobe phosphomonoester (PME) concentrations were measured in the euthymic state, whereas increased values were found in the depressed state. In bipolar-II patients reduced phosphocreatine (PCr) concentrations were reported in the euthymic, depressed, and manic state. The aim of the present study was to explore whether PME and PCr were also altered in the frontal lobe of major depressed, unipolar patients. Therefore, we used 31P-MRS to investigate the relative phospholipid and high-energy phosphate concentrations in the frontal lobe of 14 unipolar patients, mostly medicated, and 8 age-matched controls. We found increased PME and decreased ATP values. Other 31P-MRS parameters were not different in both groups. Phosphomonoester percentages correlated negatively with the degree of depression. Thus, the main alterations found in bipolar depressed patients could also be demonstrated in unipolar depressed patients. The results are discussed with regard to disturbed phospholipid and intracellular high-energy phosphate metabolism in depressed patients.     

Evaluation of cardiac 31P magnetic resonance spectroscopy: reviewing NMR principles

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.     

Effect of anaemia correction on skeletal muscle metabolism in patients with end-stage renal disease: 31P magnetic resonance spectroscopy assessment

Skeletal muscle metabolism during exercise was compared in 5 patients with end-stage renal disease (ESRD) and 8 healthy controls, using a noninvasive technique, 31P magnetic resonance spectroscopy (MRS). After 3 months of anaemia correction with recombinant human erythropoietin (rHuEPO) these patients were re-evaluated. Maximal power achieved by the ESRD patients during a dynamic wrist flexion exercise test was 33% lower (p < 0.05) than the controls. Similarly in the ESRD group, the power at the onset of metabolic acidosis (the intracellular threshold) was 29% less than controls. The metabolic differences observed in the patients indicated a lower aerobic capacity. Three months of rHuEPO treatment resulted in a 55% increase in mean haematocrit but conferred no significant improvement in metabolic parameters at rest or during exercise. The lack of any significant changes in muscle metabolism following the correction of anaemia suggests that oxygen availability is not the exclusive limiting factor for aerobic metabolism in ESRD patients.     

Exercise metabolism in Duchenne muscular dystrophy: a biochemical and [31P]-nuclear magnetic resonance study of mdx mice

Intracellular pH, ratios of phosphocreatine (PCr) to ATP and PCr to inorganic phosphate (Pi) as well as isometric tension were measured during 1 Hz sciatic nerve stimulation and during recovery in the calf muscles of mdx (a model of Duchenne muscular dystrophy) and control mice. Tension did not decline significantly in either strain. The ratio of PCr/(PCr + Pi) was significantly reduced in mdx as against control muscle during exercise and recovery, but the ratio of PCr/ATP and the half-time for PCr recovery were similar in both strains. A reduction in the maximal activities of succinate dehydrogenase and succinate-cytochrome c reductase suggests that mitochondrial metabolism may be impaired. The similarity in PCr recovery times suggests that the muscle has adapted, making any impairment of oxidative metabolism negligible in the intact system. The rate of pH recovery is prolonged in mdx muscle and provides strong evidence for a decline in the capacity of dystrophic muscle to extrude proton equivalents. These data are compared with a previous study which used 10 Hz stimulation and also observed a slow pH recovery. The slow pH recovery could be explained by an elevation in intracellular sodium.     

A metabolism study of human masseter muscle by 31P magnetic resonance spectroscopy during long periods of exercise and recovery

The metabolism of the human masseter muscle was investigated using phosphorus (31p) magnetic resonance spectroscopy (MRS) during long periods of exercise and recovery. Eleven subjects aged 19 to 28 yr were examined by 31p MRS during four consecutive periods of 13 min each: rest, exercise, recovery 1 and 2. For each subject, a biting force equal to 20% of maximum voluntary biting force was applied and controlled during the exercise period to produce maximum fatigue. 31p MR spectra were localized from a 24 cm3 volume of interest using an image selected in vivo spectroscopy (ISIS) sequence and a 6 cm diameter surface coil placed on the left masseter. Compared to the resting level, the phosphocreatine (PCr) content decreased by 26% during exercise, while the inorganic phosphate (Pi) concentration increased by 65%. During the two recovery periods, the Pi content remained decreased compared with the resting level by 36% and 30%, respectively. The Pi/PCr ratio was increased from 0.30+/-0.04 at rest to 0.63+/-0.13 during exercise while the adenosine triphosphate (ATP)/Pi ratio was decreased. The pH decreased from 7.02+/-0.03 to 6.93+/-0.04 during exercise and returned to control level (7.09+/-0.08) only during the second recovery period. These results suggest that the masseter muscle is characterized by high ATP turnover and, therefore, high oxidative phosphorylative activity in agreement with its constitution of predominantly fatigue resistant type I fibers.     

Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images

Magnetic resonance spectroscopic imaging (MRSI) is capable of determining the spatial distribution in vivo of cerebral metabolites, including N-acetylaspartate (NAA), a compound found only in neurons. We used this technique in 10 patients with temporal lobe epilepsy (TLE) to determine the location of maximal neuronal/axonal loss or damage and to evaluate the potential of MRSI for presurgical lateralization. Asymmetry of the relative resonance intensity of NAA to creatine was determined for mid and posterior regions of the temporal lobes defined anatomically and also for "metabolic lesions" defined as the regions of maximal abnormality on MRSI. MRSI revealed decreased relative signal intensity in at least one temporal lobe of all patients. Two patients had a widespread reduction in NAA in both temporal lobes. The region of maximal abnormality was usually in the posterior temporal lobe but sometimes in the mid temporal lobe. The side of lowest NAA was ipsilateral to the clinical electroencephalographic lateralization in all patients. Lateralization based on NAA to creatine correlated with the atrophy of amygdala and hippocampus in 8 patients who showed this on magnetic resonance imaging volumetric measurements. MRSI can demonstrate regional neuronal loss or damage that correlates with clinical electroencephalographic and structural lateralization in temporal lobe epilepsy. The ability to identify a region of maximal metabolic abnormality on spectroscopic images may confer greater sensitivity than that available from single voxel methods. The maximal metabolic abnormality may not be located in a voxel defined a priori, and based on anatomical considerations, without knowledge of the distribution of the metabolic abnormality.     

Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination

The spatial distribution of metabolite signal intensities can be measured within entire sections of the brain by proton magnetic resonance spectroscopic imaging (1H-MRSI). A group of six patients (4 unrelated girls and 2 brothers from 5 families) with childhood ataxia with diffuse CNS hypomyelination (CACH) underwent long-echo-time, single-slice 1H-MRSI. Relative to controls, there was a decrease in the signal intensity of N-acetylaspartate, choline, and creatine throughout the white matter in all six patients. We identified lactate signals in white matter in three of them with advanced disease. The degree of white matter involvement was not homogeneous over the entire patient group, but did correlate with clinical presentation. Deep and posterior white matter tended to be more involved. There were no 1H-MRSI abnormalities in the gray matter. 1H-MRSI findings suggest that this syndrome is secondary to a metabolic defect causing hypomyelination, axonal degeneration, and, in the most compromised cases, accumulation of lactate. This study shows that CACH is not limited to girls.     

Phosphorus metabolism during growth of lymphoma in mouse liver: a comparison of 31P magnetic resonance spectroscopy in vivo and in vitro

Large phosphomonoester (PME) signals are detected in the phosphorus magnetic resonance spectra (31P MRS) of many neoplastic and rapidly dividing tissues. In addition, alterations in phosphodiester (PDE) signals are sometimes seen. The present study of a murine lymphoma growing in liver showed a positive correlation between the hepatic PME/PDE ratio measured in vivo by 31P MRS at 4.7 T and the degree of lymphomatous infiltration in the liver, quantified by histology. High-resolution 31P MRS of liver extracts at 9.7 T showed that the PME peak consists largely of phosphoethanolamine (PE) and to a lesser extent of phosphocholine (PC). The concentration of both PE and PC increased positively with lymphomatous infiltration of the liver. In vivo, the PDE peak contains signals from phospholipids (mostly phosphatidylethanolamine and phosphatidylcholine) and the phospholipid breakdown products glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC). Low levels of GPE and GPC were detected in the aqueous extracts of the control and infiltrated livers; their concentrations remained unchanged as the infiltration increased. The total concentration of phospholipids measured by 31P MRS of organic extracts decreased about 3-fold as the infiltration increased to 70%. Thus, our data showed that the increased PME/PDE ratio in vivo is due to both an increase in the PME metabolites and a decrease in the PDE metabolites. We propose that this ratio can be used as a non-invasive measure of the degree of lymphomatous infiltration in vivo.     

Lateralization of human temporal lobe epilepsy by 31P NMR spectroscopic imaging at 4.1 T

OBJECTIVE: To compare the phosphorous metabolite ratios in the mesial temporal lobe of healthy volunteers (n = 20) with the corresponding ratios in patients with temporal lobe epilepsy (n = 30) using 31P NMR spectroscopic imaging and to lateralize the seizure focus in temporal lobe epilepsy patients using various phosphorous metabolite ratios-phosphocreatine to inorganic phosphate (PCr/Pi), PCr to adenosine triphosphate (PCr/gamma-ATP), and (gamma-ATP/Pi)--and to compare with clinical lateralization results. METHODS: All 31P NMR spectroscopic imaging studies were performed on a high-field, 4.1 T, whole-body NMR spectroscopic imaging system using a 31P/1H double-tuned volume coil. RESULTS: We found an average reduction of 15% in the PCr/Pi and gamma-ATP/Pi ratios compared with the corresponding ratios in healthy volunteers in the entire mesial temporal lobe, and more than a 30% reduction in these two ratios in the anterior region of the epileptogenic mesial temporal lobe. These ratios were also reduced significantly in the ipsilateral lobe when compared with their corresponding values in the contralateral lobe. In patients we lateralized the seizure focus, based on these 31P NMR data, and compared the results with the clinical lateralization. The lateralization based on either the PCr/Pi or the gamma-ATP/Pi ratio yielded a correspondence of 70 to 73% with the final clinical lateralization. In the subgroup of patients (n = 9) that needed intracranial EEG for the presurgical lateralization because of inconclusive results from the noninvasive methods, a 78% correspondence was found with the 31P NMR-based lateralization, whereas MRI provided a correspondence of only 33%, and scalp EEG provided a correspondence of only 56%. CONCLUSIONS: These results suggest the utility of adding the 31P NMR method to the group of noninvasive modalities used for presurgical decision making in temporal lobe epilepsy patients.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

Functional and metabolic evaluation of the athlete's heart by magnetic resonance imaging and dobutamine stress magnetic resonance spectroscopy

BACKGROUND: The question of whether training-induced left ventricular hypertrophy in athletes is a physiological rather than a pathophysiological phenomenon remains unresolved. The purpose of the present study was to detect any abnormalities in cardiac function in hypertrophic hearts of elite cyclists and to examine the response of myocardial high-energy phosphate metabolism to high workloads induced by atropine-dobutamine stress. METHODS AND RESULTS: We studied 21 elite cyclists and 12 healthy control subjects. Left ventricular mass, volume, and function were determined by cine MRI. Myocardial high-energy phosphates were examined by 31P magnetic resonance spectroscopy. There were no significant differences between cyclists and control subjects for left ventricular ejection fraction (59+/-5% versus 61+/-4%), left ventricular cardiac index (3.4+/-0.4 versus 3.4+/-0.4 L x min(-1) x m[-2]), peak early filling rate (562+/-93 versus 535+/-81 mL/s), peak atrial filling rate (315+/-93 versus 333+/-65 mL/s), ratio of early and atrial filling volumes (3.0+/-1.0 versus 2.6+/-0.6), mean acceleration gradient of early filling (5.2+/-1.4 versus 5.8+/-1.9 L/s2), mean deceleration gradient of early filling(-3.1 +/- 0.9 versus -3.2 +/- 0.7 L/s2), mean acceleration gradient of atrial filling (3.6+/-1.8 versus 4.5+/-1.7 L/s2), and atrial filling fraction (0.23+/-0.06 versus 0.26+/-0.04, respectively). Cyclists and control subjects showed similar decreases in the ratio of myocardial phosphocreatine to ATP measured with 31P magnetic resonance spectroscopy during atropine-dobutamine stress (1.41+/-0.20 versus 1.41+/-0.18 at rest to 1.21+/-0.20 versus 1.16+/-0.13 during stress, both P=NS). CONCLUSIONS: Left ventricular hypertrophy in cyclists is not associated with significant abnormalities of cardiac function or metabolism as assessed by MRI and spectroscopy. These observations suggest that training-induced left ventricular hypertrophy in cyclists is predominantly a physiological phenomenon.