Noninvasive study of high-energy phosphate metabolism in human heart by depth-resolved 31P NMR spectroscopy.

Phosphorus-31 nuclear magnetic resonance (NMR) spectra showing the relative concentrations of high-energy phosphate metabolites have been recorded noninvasively from the human heart in vivo. Spectral data were spatially localized by combining a pulsed magnetic field gradient with surface NMR excitation-detection coils. The location of the selected spectral region was determined by conventional proton NMR imaging immediately before examination by phosphorus-31 NMR spectroscopy.

Assessment of pharmacological treatment of myocardial infarction by phosphorus-31 NMR with surface coils.

Phosphorus-31 nuclear magnetic resonance (NMR) measurements with small surface coils have been used to observe phosphorus metabolism of perfused hearts within localized regions. The method allows for direct, noninvasive, sequential assessment of the altered regional metabolism resulting from myocardial infarction and its response to drug treatment, which cannot be observed by conventional techniques.

In vivo tumor discrimination in a rat by proton nuclear magnetic resonance imaging.

Transverse cross-sectional images which represent the spatial distribution of the proton nuclear magnetic resonance signal in a live Wistar rat have been produced by the multiple-sensitive-point method. The images form a chronological series demonstrating the detection and development of a D23 hepatoma in the abdomen. Discrimination of the tumor is by contrast with the surrounding tissue and is attributed to the elevated water content and relaxation times of the former.

Attenuated myocardial vasodilator response in patients with hypertensive hypertrophy revealed by oxygenation-dependent magnetic resonance imaging.

BACKGROUND: Oxygen (O(2)) homeostasis is central to myocardial tissue functioning, and increased O(2) demand is thought to be satisfied by a vasodilatory mechanism that results in increased blood and O(2) delivery. We applied blood oxygenation level-dependent (BOLD) MRI in conjunction with vasodilatory stress to index the ability to augment intramyocardial oxygenation in hypertensive hypertrophy, the primary cause of heart failure. METHODS AND RESULTS: Nine healthy controls and 10 hypertensive subjects with moderate-to-severe hypertrophy underwent imaging on a 1.5 T clinical scanner. The dipyridamole-induced change in the apparent transverse relaxation rate, R2*, which correlates with hemoglobin oxygenation, was -5.4+/-2.2 s(-1) (95% CI, -4.0 to -6.8 s(-1)) in controls compared with -1.7+/-1.4 s(-1) (95% CI, -0.8 to -2.6 s(-1)) in hypertensive patients (P=0.0003). CONCLUSIONS: Patients with hypertensive hypertrophy demonstrate an impaired ability to increase intramyocardial oxygenation during vasodilatory stress, as indexed by BOLD MRI. The capacity to image vascular function with BOLD MRI may advance the understanding of the development of ventricular dysfunction in hypertension.

An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.

OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Spatial localization in NMR spectroscopy in vivo.

Spatial localization techniques are necessary for in vivo NMR spectroscopy involving heterogeneous organisms. Localization by surface coil NMR detection alone is generally inadequate for deep-lying organs due to contaminating signals from intervening surface tissues. However, localization to preselected planar volumes can be accomplished using a single selective excitation pulse in the presence of a pulsed magnetic field gradient, yielding depth-resolved surface coil spectra (DRESS). Within selected planes, DRESS are spatially restricted by the surface coil sensitivity profiles to disk-shaped volumes whose radii increase with depth, notwithstanding variations in the NMR signal density distribution. Nevertheless, DRESS is a simple and versatile localization procedure that is readily adaptable to spectral relaxation time measurements by adding inversion or spin-echo refocusing pulses or to in vivo solvent-suppressed spectroscopy of proton (1H) metabolites using a combination of chemical-selective RF pulses. Also, the spatial information gathering efficiency of the technique can be improved to provide simultaneous acquisition of spectra from multiple volumes by interleaving excitation of adjacent planes within the normal relaxation recovery period. The spatial selectivity can be improved by adding additional selective excitation spin-echo refocusing pulses to achieve full, three-dimensional point resolved spectroscopy (PRESS) in a single excitation sequence. Alternatively, for samples with short spin-spin relaxation times, DRESS can be combined with other localization schemes, such as image-selected in vivo spectroscopy (ISIS), to provide complete gradient controlled three-dimensional localization with a reduced number of sequence cycles.

On neglecting chemical exchange effects when correcting in vivo (31)P MRS data for partial saturation.

Signal acquisition in most MRS experiments requires a correction for partial saturation that is commonly based on a single exponential model for T(1) that ignores effects of chemical exchange. We evaluated the errors in (31)P MRS measurements introduced by this approximation in two-, three-, and four-site chemical exchange models under a range of flip-angles and pulse sequence repetition times (T(R)) that provide near-optimum signal-to-noise ratio (SNR). In two-site exchange, such as the creatine-kinase reaction involving phosphocreatine (PCr) and gamma-ATP in human skeletal and cardiac muscle, errors in saturation factors were determined for the progressive saturation method and the dual-angle method of measuring T(1). The analysis shows that these errors are negligible for the progressive saturation method if the observed T(1) is derived from a three-parameter fit of the data. When T(1) is measured with the dual-angle method, errors in saturation factors are less than 5% for all conceivable values of the chemical exchange rate and flip-angles that deliver useful SNR per unit time over the range T(1)/5 < or = T(R) < or = 2T(1). Errors are also less than 5% for three- and four-site exchange when T(R) > or = T(1)(*)/2, the so-called "intrinsic" T(1)'s of the metabolites. The effect of changing metabolite concentrations and chemical exchange rates on observed T(1)'s and saturation corrections was also examined with a three-site chemical exchange model involving ATP, PCr, and inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion. Although the observed T(1)'s were dependent on metabolite concentrations, errors in saturation corrections for T(R) = 2 s could be kept within 5% for all exchanging metabolites using a simple interpolation of two dual-angle T(1) measurements performed at the start and end of the experiment. Thus, the single-exponential model appears to be reasonably accurate for correcting (31)P MRS data for partial saturation in the presence of chemical exchange. Even in systems where metabolite concentrations change, accurate saturation corrections are possible without much loss in SNR.

On neglecting chemical exchange when correcting in vivo (31)P MRS data for partial saturation: commentary on: "Pitfalls in the measurement of metabolite concentrations using the one-pulse experiment in in Vivo NMR".

This article replies to Spencer et al. (J. Magn. Reson. 149, 251--257, 2001) concerning the degree to which chemical exchange affects partial saturation corrections using saturation factors. Considering the important case of in vivo (31)P NMR, we employ differential analysis to demonstrate a broad range of experimental conditions over which chemical exchange minimally affects saturation factors, and near-optimum signal-to-noise ratio is preserved. The analysis contradicts Spencer et al.'s broad claim that chemical exchange results in a strong dependence of saturation factors upon M(0)'s and T(1) and exchange parameters. For Spencer et al.'s example of a dynamic (31)P NMR experiment in which phosphocreatine varies 20-fold, we show that our strategy of measuring saturation factors at the start and end of the study reduces errors in saturation corrections to 2% for the high-energy phosphates.

Orbital magnetic resonance imaging.

Magnetic resonance images of the eye and orbit performed with surface coils at 1.5 tesla showed anatomic details superior to those of conventional third- and fourth-generation computed tomography.

Power deposition in whole-body NMR imaging.

The surface radio frequency (rf) power absorption in human head and torso nuclear magnetic resonance (NMR) imaging experiments is estimated. The results are expressed as a function of the NMR frequency, the rf pulse length, and the pulse duty cycle, which are varied over six orders of magnitude for general applicability. The results are compared with average metabolic levels and the limits advised by the National Radiological Protection Broad of the United Kingdom. Heating due to time-dependent magnetic field gradients is discussed.

A signal-to-noise calibration procedure for NMR imaging systems.

A nuclear magnetic resonance (NMR) imaging system signal-to-noise calibration technique based on an NMR projection of distilled water in a cylindrical bottle is proposed. This measurement can characterize any arrangement of rf coils in any magnetic field as signal to noise per ml times root Hz. Inductive losses in a typical patient must be included in the calibration, and such losses can be simulated in a particular system by an externally attached resistor(s) appropriate to that system. Alternatively, an rf inductive damping phantom consisting of a conducting loop of wire containing an appropriate resistor is suggested that can be inserted into any NMR imaging coil to simulate subject Q damping. The same resistor can be used, independent of the details of the coil construction. Furthermore, if the loop inductance is tuned out at each frequency with a series capacitor, then the same loop resistance will serve for all frequencies as a good approximation to human subject damping. This "projection method" signal-to-noise ratio is related to the conventional signal-to-noise ratio measured from a Lorentzian-shaped spectral line as psi P = psi L [2/T2]1/2, where psi stands for signal-to-noise ratio, subscripts P and L stand, respectively, for the projection and "Lorentzian" methods, and T2 is the transverse relaxation time of the spectral line used in the Lorentzian method.

A review of 1H nuclear magnetic resonance relaxation in pathology: are T1 and T2 diagnostic?

The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1-100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T1 data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T1 = AvB in the range 1-100 MHz with A and B empirically determined pathology-dependent constants. Pathological tissue T2 values are essentially independent of NMR frequency. Raw relaxation data, best-fit T1 parameters A and B, and the mean T2 values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T1 values and some breast, liver, and muscle tumor T2 values are significantly elevated (p greater than or equal to 0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T1 values of some brain, breast, and lung tumors, and most pathological tissue T2 values could not, however, be demonstrated in the presence of large statistical errors. Both T1 and T2 in uninvolved tissue from tumor-bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T1 and T2 indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement (p greater than or equal to 0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T1 and T2 data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components.(ABSTRACT TRUNCATED AT 400 WORDS)

A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1-100 MHz: dependence on tissue type, NMR frequency, temperature, species, excision, and age.

The longitudinal (T1) and transverse (T2) hydrogen (1H) nuclear magnetic resonance (NMR) relaxation times of normal human and animal tissue in the frequency range 1-100 MHz are compiled and reviewed as a function of tissue type, NMR frequency, temperature, species, in vivo versus in vitro status, time after excision, and age. The dominant observed factors affecting T1 are tissue type and NMR frequency (V). All tissue frequency dispersions can be fitted to the simple expression T1 = AVB in the range 1-100 MHz, with A and B tissue-dependent constants. This equation provides as good or better fit to the data as previous more complex formulas. T2 is found to be multicomponent, essentially independent of NMR frequency, and dependent mainly on tissue type. Mean and raw values of T1 and T2 for each tissue are tabulated and/or plotted versus frequency and the fitting parameters A, B and the standard deviations determined to establish the normal range of relaxation times applicable to NMR imaging. The mechanisms for tissue NMR relaxation are reviewed with reference to the fast exchange two state (FETS) model of water in biological systems, and an overview of the dynamic state of water and macromolecular hydrogen compatible with the frequency, temperature, and multicomponent data is postulated. This suggests that 1H tissue T1 is determined predominantly by intermolecular (possibly rotational) interactions between macromolecules and a single bound hydration layer, and the T2 is governed mainly by exchange diffusion of water between the bound layer and a free water phase. Deficiencies in measurement techniques are identified as major sources of data irreproducibility.

RF magnetic field penetration, phase shift and power dissipation in biological tissue: implications for NMR imaging.

The magnetic field penetration, phase shift and power deposition in planar and cylindrical models of biological tissue exposed to a sinusoidal time-dependent magnetic field have been investigated theoretically over the frequency range 1 to 100 MHz. The results are based on measurements of the relative permittivity and resistivity dispersions of a variety of freshly excised rat tissue at 37 and 25 degrees C, and are analysed in terms of their implications for human body nuclear magnetic resonance (NMR) imaging. The results indicate that at NMR operating frequencies much greater than about 30 MHz, magnetic field amplitude and phase variations experienced by the nuclei may cause serious distortions in an image of a human torso. The maximum power deposition envisaged during an NMR imaging experiment on a human torso is likely to be comparable to existing long-term safe exposure levels, and will depend ultimately on the imaging technique and NMR frequency employed.

A computer driven photoscanner for medical imaging.

A novel and versatile instrument for producing high quality monochrome and colour hard-copy of medical images from an array of digital information is described. Images are produced on standard photographic print paper mounted on the bed of a conventional X-Y plotter by scanning a time-modulated light source over the paper using a computer driven raster. A matrix board gives control of both greyscale and colour attribution. Examples of NMR images produced by the system are presented. A refinement of the technique which allows two variables to be displayed on one image is also described.

Cerebral energy metabolism in rats studied by phosphorus nuclear magnetic resonance using surface coils.

Phosphorus nuclear magnetic resonance with surface coils was used to investigate the regional metabolism of the rat brain in vivo under conditions of normoxia, severe hypoxemia, partial necrosis, and partial ischemia. The results show an increase in sugar phosphate and/or inorganic phosphate with injury in accordance with in vivo assays. The technique provides a powerful means of monitoring the metabolism of stroke and its response to therapy in vivo.

Restoration of low resolution metabolic images with a priori anatomic information: 23Na MRI in myocardial infarction.

A new iterative extrapolation image reconstruction algorithm is presented, which enhances low resolution metabolic magnetic resonance images (MRI) with information about the bounds of signal sources obtained from a priori anatomic proton ((1)H) MRI. The algorithm ameliorates partial volume and ringing artefacts, leaving unchanged local metabolic heterogeneity that is present in the original dataset but not evident at (1)H MRI. Therefore, it is ideally suited to metabolic studies of ischemia, infarction and other diseases where the extent of the abnormality at (1)H MRI is uncertain. The performance of the algorithm is assessed by simulations, MRI of phantoms, and by surface coil 23Na MRI studies of canine myocardial infarction on a clinical scanner where the injury was not evident at (1)H MRI. The algorithm includes corrections for transverse field inhomogeneity, and for the leakage of intense signals into regions of interest such as 23Na MRI signals from ventricular blood ringing into the myocardium. The simulations showed that the algorithm reduced ringing artefacts by 15%, was stable at low SNR ( approximately 7), but is sensitive to the positioning of the (1)H MRI boundaries. The 23Na MRI showed hyperenhancement of regions identified as infarcted at post-mortem histological staining. The areas of hyperenhancement were measured by five independent observers in four 23Na images of infarction reconstructed with and without the algorithm. The infarct areas were correlated with areas determined by post-mortem histological staining with coefficient 0.85 for the enhanced images, compared to 0.58 with the conventional images. The scatter in the amplitude and in the area measurements of ischemia-associated hyper-enhancement in 23Na MRI was reduced by the algorithm by 1.6-fold and by at least 3-fold, respectively, demonstrating its ability to substantially improve quantification of the extent and intensity of metabolic changes in injured tissue that is not evident by (1)H MRI.

Head and body imaging by hydrogen nuclear magnetic resonance.

A hydrogen (1H) nuclear magnetic resonance (NMR) imaging study of the normal head, thorax, and limbs is reported. The images are 10 to 15 mm thick transverse slices obtained in 2 to 4 min using a two-dimensional Fourier transform technique. Spatial resolution in the imaging plane is about 2 mm, enabling the optic nerve and many small blood vessels to be observed. Thorax scans show details of the cardiac chambers, aorta wall, and lungs without artefacts arising from physiological motion.

Display of cross sectional anatomy by nuclear magnetic resonance imaging. 1978.

High definition cross-sectional images produced by a new nuclear magnetic resonance (NMR) technique are shown. The images are a series of thin section scans in the coronal plane of the head of a rabbit. The NMR images are derived from the distribution of the density of mobile hydrogen atoms. Various tissue types can be distinguished and a clear registration of gross anatomy is demonstrated. No known hazards are associated with the technique.

Display of cross sectional anatomy by nuclear magnetic resonance imaging.

High definition cross-sectional images produced by a new nuclear magnetic resonance (NMR) technique are shown. The images are a series of thin section scans in the coronal plane of the head of a rabbit. The NMR images are derived from the distribution of the density of mobile hydrogen atoms. Various tissue types can be distinguished and a clear registration of gross anatomy is demonstrated. No known hazards are associated with the technique.