Local perfusion and metabolic demand during exercise: a noninvasive MRI method of assessment.

A noninvasive magnetic resonance imaging (MRI) method to assess the distribution of perfusion and metabolic demand (Q/VO(2)) in exercising human skeletal muscle is described. This method combines two MRI techniques that can provide accurate multiple localized measurements of Q/VO(2) during steady-state plantar flexion exercise. The first technique, (31)P chemical shift imaging, permits the acquisition of comparable phosphorus spectra from multiple voxels simultaneously. Because phosphocreatine (PCr) depletion is directly proportional to ATP hydrolysis, its relative depletion can be used as an index of muscle O(2) uptake (VO(2)). The second MRI technique allows the measurement of both spatially and temporally resolved muscle perfusion in vivo by using arterial spin labeling. Promising validity and reliability data are presented for both MRI techniques. Initial results from the combined method provide evidence of a large variation in Q/VO(2), revealing areas of apparent under- and overperfusion for a given metabolic turnover. Analysis of these data in a similar fashion to that employed in the assessment of ventilation-to-perfusion matching in the lungs revealed a similar second moment of the perfusion distribution and PCr distribution on a log scale (log SD(Q) and log SD(PCr)) (0.47). Modeling the effect of variations in log SD(Q) and log SD(PCr) in terms of attainable VO(2), assuming no diffusion limits, indicates that the log SD(Q) and log SD(PCr) would allow only 92% of the target VO(2) to be achieved. This communication documents this novel, noninvasive method for assessing Q/VO(2), and initial data suggest that the mismatch in Q/VO(2) may play a significant role in determining O(2) transport and utilization during exercise.     

In Vivo NMR Studies of Neurodegenerative Diseases in Transgenic and Rodent Models

In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide unique quality to attain neurochemical, physiological, anatomical, and functional information noninvasively. These techniques have been increasingly applied to biomedical research and clinical usage in diagnosis and prognosis of diseases. The ability of MRS to detect early yet subtle changes of neurochemicals in vivo permits the use of this technology for the study of cerebral metabolism in physiological and pathological conditions. Recent advances in MR technology have further extended its use to assess the etiology and progression of neurodegeneration. This review focuses on the current technical advances and the applications of MRS and MRI in the study of neurodegenerative disease animal models including amyotrophic lateral sclerosis, Alzheimer's, Huntington's, and Parkinson's diseases. Enhanced MR measurable neurochemical parameters in vivo are described in regard to their importance in neurodegenerative disorders and their investigation into the metabolic alterations accompanying the pathogenesis of neurodegeneration.     

MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates

Transgenic mice are increasingly used to probe genetic aspects of cardiovascular pathophysiology. However, the small size and rapid rates of murine hearts make noninvasive, physiological in vivo studies of cardiac bioenergetics and contractility difficult. The aim of this report was to develop an integrated, noninvasive means of studying in vivo murine cardiac metabolism, morphology, and function under physiological conditions by adapting and modifying noninvasive cardiac magnetic resonance imaging (MRI) with image-guided (31)P magnetic resonance spectroscopy techniques used in humans to mice. Using spatially localized, noninvasive (31)P nuclear magnetic resonance spectroscopy and MRI at 4.7 T, we observe mean murine in vivo myocardial phosphocreatine-to-ATP ratios of 2.0 +/- 0.2 and left ventricular ejection fractions of 65 +/- 7% at physiological heart rates ( approximately 600 beats/min). These values in the smallest species studied to date are similar to those reported in normal humans. Although these observations do not confirm a degree of metabolic scaling with body size proposed by prior predictions, they do suggest that mice can serve, at least at this level, as a model for human cardiovascular physiology. Thus it is now possible to noninvasively study in vivo myocardial bioenergetics, morphology, and contractile function in mice under physiological conditions.     

Brain Magnetic Resonance in the Diagnostic Evaluation of Mitochondrial Encephalopathies

Brain MR imaging techniques are important ancillary tests in the diagnosis of a suspected mitochondrial encephalopathy since they provide details on brain structural and metabolic abnormalities. This is particularly true in children where non-specific neurologic symptoms are common, biochemical findings can be marginal and genetic defects may be not discovered. MR imaging modalities include conventional, or structural, imaging (MRI) and functional, or ultrastructural, imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI––ASL). Among them MRI and MRS are the main tools for diagnosis and work up of MD, and this review will focus mainly on them. The MRI findings of MD are very heterogeneous, as they depend on the metabolic brain defects, age of the patient, stage and severity of the disease. No correlation has been found between genetic defects and neuroimaging picture; however, some relationships between MR findings and clinical phenotypes may be identified. Different combinations of MRI signal abnormalities are often encountered but the most common findings may be summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii) leukodystrophic-like. Regarding the functional MR techniques, only proton MRS plays an important role in demonstrating an oxidative metabolism impairment in the brain since it can show the accumulation of lactate, present as a doublet peak at 1.33 ppm. Assessment of lactate should be always performed on brain tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS abnormalities can be of different types, and two distinct patterns can be recognized: non-specific and specific. The specific metabolic profiles, although not frequent to find, are highly pathognomonic of MD. The un-specific metabolic profiles add value to structural images in allowing to define the lesion load and to monitor the response to therapy trials.     

Biochemical characterization of breast tumors by in vivo and in vitro magnetic resonance spectroscopy (MRS)

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have evolved as sensitive tools for anatomic and metabolic evaluation of breast cancer. In vivo MRS studies have documented the presence of choline containing compounds (tCho) as a reliable biochemical marker of malignancy and also useful for monitoring the tumor response to therapy. Recent studies on the absolute quantification of tCho are expected to provide cut-off values for discrimination of various breast pathologies. Addition of MRS investigation was also reported to increase the specificity of MRI. Further, ex vivo and in vitro MRS studies of intact tissues and tissue extracts provided several metabolites that were not be detected in vivo and provided insight into underlying biochemistry of the disease processes. In this review, we present briefly the role of various ¹H MRS methods used in breast cancer research and their potential in relation to diagnosis, monitoring of therapeutic response and metabolism.     

Quantification of ethanol methyl 1H magnetic resonance signal intensity following intravenous ethanol administration in primate brain

In vivo ¹H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl ¹H MRS signal intensity relates to tolerance to ethanol’s intoxicating effects. More recently, the ethanol ¹H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T₂ within these environments. The methods presented here extend ethanol MRS techniques to non-human primate subjects. Twelve monkeys were administered ethanol while sedated and positioned within a 3T MRI system. Chemical shift imaging (CSI) measurements were performed following intravenous infusion of 1 g/kg ethanol. Magnetic resonance imaging (MRI) data were also recorded for each monkey to provide volume fractions of GM, WM, and CSF for each CSI spectrum. To estimate co-variance of ethanol MRS intensity with GM, WM, and CSF volume fractions, the relative contribution of each tissue subtype was determined following corrections for radiofrequency pulse profile non-uniformity, chemical shift artifacts, and differences between the point spread function in the CSI data and the imaging data. The ethanol MRS intensity per unit blood ethanol concentration was found to differ between GM, WM, and CSF. Individual differences in MRS intensity were larger in GM than WM. This methodology demonstrates the feasibility of ethanol MRS experiments and analysis in non-human primate subjects, and suggests GM may be a site of significant variation in ethanol MRS intensity between individuals.     

Evaluation of exercise muscle energetics by NMR

Magnetic resonance imaging (MRI) is superior to ultrasonography and X-CT especially in density resolution in soft tissue. 31P NMR provides information on metabolism, which has not been obtained in vivo by conventional methods, such as phosphocreatine (PCr), inorganic phosphate (Pi), ATP, and intracellular pH. We used MRI and 31P NMR spectroscopy to study skeletal muscle metabolism of human and rat. These NMR results suggested that 1) estimation of muscle fiber composition, 2) evaluation of muscle ATP turnover and 3) imaging of local muscle fatigue are possible.     

Biofilm shows spatially stratified metabolic responses to contaminant exposure

Biofilms are core to a range of biological processes, including the bioremediation of environmental contaminants. Within a biofilm population, cells with diverse genotypes and phenotypes coexist, suggesting that distinct metabolic pathways may be expressed based on the local environmental conditions in a biofilm. However, metabolic responses to local environmental conditions in a metabolically active biofilm interacting with environmental contaminants have never been quantitatively elucidated. In this study, we monitored the spatiotemporal metabolic responses of metabolically active Shewanella oneidensis MR‐1 biofilms to U(VI) (uranyl, UO₂ ²⁺) and Cr(VI) (chromate, CrO₄ ^2?) using non‐invasive nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) approaches to obtain insights into adaptation in biofilms during biofilm‐contaminant interactions. While overall biomass distribution was not significantly altered upon exposure to U(VI) or Cr(VI), MRI and spatial mapping of the diffusion revealed localized changes in the water diffusion coefficients in the biofilms, suggesting significant contaminant‐induced changes in structural or hydrodynamic properties during bioremediation. Finally, we quantitatively demonstrated that the metabolic responses of biofilms to contaminant exposure are spatially stratified, implying that adaptation in biofilms is custom‐developed based on local microenvironments.     

In vivo assessment of nodularin-induced hepatotoxicity in the rat using magnetic resonance techniques (MRI, MRS and EPR oximetry)

Acute nodularin-induced hepatotoxicity was assessed in vivo, in rats using magnetic resonance (MR) techniques, including MR imaging (MRI), MR spectroscopy (MRS), and electron paramagnetic resonance (EPR) oximetry. Nodularin is a cyclic hepatotoxin isolated from the cyanobacterium Nodularia spumigena. Three hours following the intraperitoneal (i.p.) administration of nodularin (LD50), a region of 'damage', characterized by an increase in signal intensity, was observed proximal to the porta hepatis (PH) region in T2-weighted MR images of rat liver. Image analysis of these regions of apparent 'damage' indicated a statistically significant increase in signal intensity around the PH region following nodularin administration, in comparison with controls and regions peripheral to the PH region. An increase in signal intensity was also observed proximal to the PH region in water chemical shift selective images (CSSI) of nodularin-treated rat livers, indicating that the increased signal observed by MRI is an oedematous response to the toxin. Microscopic assessment (histology and electron microscopy) and serum liver enzyme function tests (aminotransferase (ALT) and aspartate ALT (AST)) confirmed the nodularin-induced tissue injury observed by MRI. In vivo and in vitro MRS was used to detect alterations in metabolites, such as lipids, Glu+Gln, and choline, during the hepatotoxic response (2-3 h post-exposure). Biochemical assessment of perchloric acid extracts of nodularin-treated rat livers were used to confirm the MRS results. In vivo EPR oximetry was used to monitor decreasing hepatic pO2 (approximately 2-fold from controls) 2-3 h following nodularin exposure. In vivo MR techniques (MRI, MRS and EPR oximetry) are able to highlight effects that may not have been evident in single end point studies, and are ideal methods to follow tissue injury progression in longitudinally, increasing the power of a study through repeated measures, and decreasing the number of animals to perform a similar study using histological or biochemical techniques.     

In vivo imaging of apoptosis in oncology: an update

In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data available are presented in order of occurrence in time of enzymatic and morphologic events occurring during apoptosis. Available studies suggest that various radiopharmaceutical probes bear great potential for apoptosis imaging by means of positron emission tomography and single-photon emission computed tomography (SPECT). However, for several of these probes, thorough toxicologic studies are required before they can be applied in clinical studies. Both preclinical and clinical studies support the notion that 99mTc-hydrazinonicotinamide-annexin A5 and SPECT allow for noninvasive, repetitive, quantitative apoptosis imaging and for assessing tumor response as early as 24 hours following treatment instigation. Bioluminescence imaging and near-infrared fluorescence imaging have shown great potential in small-animal imaging, but their usefulness for in vivo imaging in humans is limited to structures superficially located in the human body. Although preclinical tumor-based data using high-frequency-ultrasonography (US) are promising, whether or not US will become a routinely clinically useful tool in the assessment of therapy response in oncology remains to be proven. The potential of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for imaging late apoptotic processes is currently unclear. Neither 31P MRS nor 1H MRS signals seems to be a unique identifier for apoptosis. Although MRI-measured apparent diffusion coefficients are altered in response to therapies that induce apoptosis, they are also altered by nonapoptotic cell death, including necrosis and mitotic catastrophe. In the future, rapid progress in the field of apoptosis imaging in oncology is expected.     

Magnetic resonance spectroscopy and measurement of tau epitopes of autopsy proven sporadic Creutzfeldt-Jakob disease in a patient with non-specific initial EEG, MRI and negative 14-3-3 immunoblot

Limited potential of electroencephalogram (EEG), magnetic resonance images (MRI) and cerebrospinal fluid (CSF) test for 14-3-3 protein in the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) resulted in developments in diagnostic premortem tehniques. Recent studies provided evidence that magnetic resonance spectroscopy (MRS) and measurement of total-tau (T-tau) and phospho-tau (P-tau) may be useful to identify patients with CJD. We combined detected metabolic changes in the brain by MRS and measured T-tau and tau-pT181 by ELISA, and tau-pT231 by Westernblot in a patient with autopsy proven sCJD. Our results show that in contrast to negative CSF 14-3-3 protein, nonspecific EEG and MRI, MRS revealed metabolic alterations in regions of the brain that has appeared normal on MRI, and tau tests has shown measurable levels of phosphorylated and non-phosphorylated isoforms in CSF. We conclude that rapidly progressive dementia with negative 14-3-3 test and non-specific initial EEG and MRI must still be considered in the differential diagnosis of the sCJD. Combination of serial functional MRI along with MRS study and measurement of tau ratio could improve the early diagnosis of sCJD. The current case is the first attempt to study results of the use of MRS and tau tests in a case of sCJD with diagnostic dilemma.     

Hyperpolarized MRI,functional MRI,MR spectroscopy and CEST to provide metabolic information in vivo

Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.     

High-Field Proton Magnetic Resonance Spectroscopy of a Swine Model for Axonal Injury

Abstract: A miniature swine model for diffuse brain injury has recently been developed that replicates the inertial loading conditions associated with rotational acceleration during automotive accidents. The swine model induces diffuse axonal pathology without macroscopic injury such as contusions and hematomas, thus affording a unique opportunity to study axonal injury with noninvasive techniques such as magnetic resonance imaging (MRI) and spectroscopy (MRS). In the present study, we evaluated this diffuse injury model with proton MRS, in vivo, using a high-field (4.0-T) MR scanner, since MRS has been demonstrated as a sensitive probe for detecting neurochemical abnormalities. Our study examined a region of the swine brain at timepoints before and after brain injury. Spectroscopic results indicate that N -acetylaspartate/creatine is diminished by at least 20% in regions of confirmed axonal pathology, whereas conventional MRI did not detect any abnormalities. These findings suggest that MRS has high sensitivity in diagnosing microscopic pathology following diffuse brain injury.     

Combined study of 1H-magnetic resonance imaging and depth-selected, EKG-gated 31P-magnetic resonance spectroscopy of the heart in vivo

NMR is useful for both 1H-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We undertook to combine these two merits of NMR for in vivo characterization of living rat heart in wide bore (9 cm) superconducting magnet under high magnetic field (6.4 Tesla). Spatial resolution of 1H-MRI attained 0.1 mm by spin warp method. Then, depth-selected, EKG-gated 31P-MRS was performed, adjusting the detection area to cover the heart that was identified by the preceding 1H-MRI. Three evidences that 31P-SMR signal chiefly originated from the heart without cross talk of adjacent organs indicated that combination of 1H-MRI and in vivo 31P-MRS under high magnetic field in whole animal is promising for more accurate evaluation of cardiac muscle metabolism.     

Advances in magnetic resonance imaging of lung physiology.

This review presents an overview of some recent magnetic resonance imaging (MRI) techniques for measuring aspects of local physiology in the lung. MRI is noninvasive, relatively high resolution, and does not expose subjects to ionizing radiation. Conventional MRI of the lung suffers from low signal intensity caused by the low proton density and the large degree of microscopic field inhomogeneity that degrades the magnetic resonance signal and interferes with image acquisition. However, in recent years, there have been rapid advances in both hardware and software design, allowing these difficulties to be minimized. This review focuses on some newer techniques that measure regional perfusion, ventilation, gas diffusion, ventilation-to-perfusion ratio, partial pressure of oxygen, and lung water. These techniques include contrast-enhanced and arterial spin-labeling techniques for measuring perfusion, hyperpolarized gas techniques for measuring regional ventilation, and apparent diffusion coefficient and multiecho and gradient echo techniques for measuring proton density and lung water. Some of the major advantages and disadvantages of each technique are discussed. In addition, some of the physiological issues associated with making measurements are discussed, along with strategies for understanding large and complex data sets.     

Application of Magnetic Resonance Spectroscopy in metabolic research

The etiology of metabolic disease in humans is far from understood, and even though potential pathways are identified in animal models and cell studies, it is often difficult to determine their relevance in humans, as the possibilities of tissue sampling are limited. The application of non-invasive imaging techniques can provide essential metabolic information and this mini review focuses on the opportunities of Magnetic Resonance Spectroscopy (MRS) to add to our understanding of the metabolic processes during health and disease. MRS is a volatile technique that can give us information about the concentrations of endogenous metabolites in a completely non-invasive way. In this mini review we discuss the opportunities that MRS is giving us by describing how the investigation of ectopic fat depots has gained a lot of attention and has really taken off after ¹H-MRS for quantification of lipid content became widely available. We furthermore discuss how other MRS techniques, such as ³¹P-MRS and ¹³C-MRS can add valuable information and especially highlight the strength of MRS to be applied dynamically and therefore monitor metabolic changes during physiological challenges such as exercise or meal tests.     

Magnetic resonance imaging and magnetic resonance spectroscopy in a patient with amyotrophic lateral sclerosis and frontotemporal dementia

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have been investigated in a single neurodegenerative disease manifesting as either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) alone, but have not been examined in combined disorders such as ALS with FTD (ALS-FTD). To our knowledge, this study is the first attempt to demonstrate relationship between MRI abnormalities and MR spectroscopic metabolite changes of the motor cortex, frontal white matter and corticospinal tract in a patient with the diagnosis of ALS with probable upper motor neuron signs (ALS-PUMNS) and FTD. Patient presented underwent MRI of the brain and MRS. The ratio of N-acetylaspartate (NAA) to creatine (Cr), choline to Cr, myo-inositol (ml) to Cr and glutamate-glutamine (Glx) to Cr were derived from peak area measurement. Spectra from the right motor cortex, frontal white matter and corticospinal tract were obtained. MR images were evaluated for sulcus centralis enlargement, corticospinal tract hyperintensity and frontal lobes atrophy. Spectra showed reduced NAA/Cr and Glx/Cr ratio, yet the ratio of Cho/Cr exhibited significant elevation. MR images revealed sulcus centralis enlargement, high signal intensity of corticospinal tract and atrophy of both frontal lobes. Proton spectroscopic metabolic changes in a current patient fully correlate with previously reported MRS metabolic changes in ALS alone. Surprisingly, normal ml (glial marker) values have been found in almost all measured voxels of interest except in the frontal white matter. These findings differ from the previous findings in ALS or FTD alone. In conclusion, these findings support the concept that ALS, FTD and ALS-FTD may represent different manifestations of a single pathological continuum.     

Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of Fatty Liver in Diabetic Patients in Clinical Practice?

Objective

To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification.

Methods

Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54±9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman''s correlation coefficients.

Results

The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis.

Conclusions

Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.     

Neuroimaging of mitochondrial disease

Mitochondrial disease represents a heterogeneous group of genetic disorders that require a variety of diagnostic tests for proper determination. Neuroimaging may play a significant role in diagnosis. The various modalities of nuclear magnetic resonance imaging (MRI) allow for multiple independent detection procedures that can give important anatomical and metabolic clues for diagnosis. The non-invasive nature of neuroimaging also allows for longitudinal studies. To date, no pathonmonic correlation between specific genetic defect and neuroimaging findings have been described. However, certain neuroimaging results can give important clues that a patient may have a mitochondrial disease. Conventional MRI may show deep gray structural abnormalities or stroke-like lesions that do not respect vascular territories. Chemical techniques such as proton magnetic resonance spectroscopy (MRS) may demonstrate high levels of lactate or succinate. When found, these results are suggestive of a mitochondrial disease. MRI and MRS studies may also show non-specific findings such as delayed myelination or non-specific leukodystrophy picture. However, in the context of other biochemical, structural, and clinical findings, even non-specific findings may support further diagnostic testing for potential mitochondrial disease. Once a diagnosis has been established, these non-invasive tools can also aid in following disease progression and evaluate the effects of therapeutic interventions.     

New concepts in characterization of ischemically injured myocardium by MRI

New concepts regarding the assessment of ischemic myocardial injuries have been addressed in this Minireview using magnetic resonance imaging (MRI). MRI, with its different techniques, brings not only anatomic, but also physiologic, information on ischemic heart disease. It has the ability to measure identical parameters in preclinical and clinical studies. MRI techniques provide the ideal package for repeated and noninvasive assessment of myocardial anatomy, viability, perfusion, and function. MR contrast agents can be applied in a variety of ways to improve MRI sensitivity for detecting and assessing ischemically injured myocardium. With MR contrast agents protocol, it becomes possible to identify ischemic, acutely infarcted, and peri-infarcted myocardium in occlusive and reperfused infarctions. Necrosis specific and nonspecific extracellular contrast-enhanced MRI has been used to assess myocardial viability. Contrast-enhanced perfusion MRI can explore the disturbances in large (angiography) and small coronary arteries (myocardial perfusion) as the underlying cause of myocardial dysfunction. Perfusion MRI has been used to measure myocardial perfusion (ml/min/g) and to demonstrate the difference in transmural myocardial blood flow. Information on no-reflow phenomenon is derived from dynamic changes in regional signal intensity after bolus injection of MR contrast agents. Another development is the near future availability of blood pool MR contrast agents. These agents are able to assess microvascular permeability and integrity and are advantageous in MR angiography (MRA) due to their persistence in the blood. Noncontrast-enhanced MRI such as cine MRI at rest/stress, sodium MRI, and MR spectroscopy also have the potential to noninvasively assess myocardial viability in patients. Futuristic applications for MRI in the heart will focus on identifying coronary artery disease at an early stage and the beneficial effects of new therapeutic agents such as intra-arterial gene therapy. MR techniques will have great future in the drug discovery process and in testing the effects of drugs on myocardial biochemistry, physiology, and morphology. Molecular imaging is going to bloom in this decade.