Paul A. Bottomley

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.

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.

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)

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.

Regional Myocardial Metabolism of High-Energy Phosphates during Isometric Exercise in Patients with Coronary Artery Disease

BACKGROUND The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment.

Fluorine (19F) MRS and MRI in biomedicine

Shortly after the introduction of 1H MRI, fluorinated molecules were tested as MR‐detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine (19F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, 19F MRI of ‘hotspots’ of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants. Copyright

Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy.

Myocardial high-energy phosphate metabolism in patients with dilated cardiomyopathy (DCM) of ischemic or idiopathic etiology was assessed at rest by one-dimensional phase-encoded 31P-nuclear magnetic resonance (NMR) spectroscopy studies performed in conjunction with 1H imaging in 20 patients with DCM and in 12 normal volunteers. The measured values of anterior myocardial phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP), corrected for partial saturation and contamination of the spectra by blood metabolites, averaged 1.80 +/- 0.06 (mean +/- SE) in normal volunteers and 1.46 +/- 0.07 in the patients overall, a highly significant (p less than 0.001) decrease. In patients with DCM accompanied by coronary artery disease (n = 9), the PCr/beta-ATP ratio averaged 1.53 +/- 0.07, while in those with DCM alone it was 1.41 +/- 0.12 (n = 11), a value that was not significantly different. There was no significant correlation (r = 0.34) between myocardial PCr/ATP ratio and left ventricular ejection fraction in patients. These studies demonstrate that myocardial PCr/ATP ratios are reduced at rest in human ischemic and idiopathic dilated cardiomyopathy.

Signal, noise, and contrast in nuclear magnetic resonance (NMR) imaging

Calculations of the sensitivity of the saturation recovery and inversion recovery pulse sequences used in nuclear magnetic resonance imaging show the former to be superior in discriminating between tissues with the same proton density but different T1‘s. Two other pulse sequences, which are combinations of the above, have also been analyzed. These have lower T1 discrimination sensitivity, but other considerations, such as self-normalization, may still make them attractive. The calculations are only valid for selective excitation pulse sequences in which the selected slice profiles are approximately rectangular, and thus a sin(bt)/t radio frequency excitation is desirable. In order to ensure that the saturation recovery sequence gives valid results for pulse repetition times comparable to or shorter than T2 it is necessary to destroy the coherence between pulse applications. For this purpose we use a series of “spoiler” gradient pulses between pulse trains. The saturation recovery pulse sequence also has the advantage that, by the correct choice of interpulse spacing, sensitivity close to the optimum T1 discrimination can be achieved over a wide range of T1 values. This has the potential advantage to the clinician of simplifying his choice of parameters for imaging.

Radiographic thin-section image of the human wrist by nuclear magnetic resonance

WE present here a detailed image showing the distribution of mobile protons in a thin section through a human wrist. The image was produced by nuclear magnetic resonance (NMR) techniques. The image consists of 128 by 128 independent picture elements and has a resolution of about 0.4 mm. For the first time images produced by NMR can be compared in quality to those produced by X-ray tomography.

Proton magnetic resonance spectroscopic imaging of human breast cancer: A preliminary study

To investigate the diagnostic value of proton magnetic resonance spectroscopic imaging (MRSI) in patients with breast lesions.