Homogeneous tissue model estimates of RF power deposition in human NMR studies. Local elevations predicted in surface coil decoupling.
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Body Temperature↗
Biomedical subjects
P A Bottomley
Publications and source records attributed to P A Bottomley.
Proton Overhauser enhancements in human cardiac phosphorus NMR spectroscopy at 1.5 T.
Narrowband irradiation of water protons with a surface coil yields significant nuclear Overhauser enhancement (nOe) of phosphocreatine (PCr) and some adenosine triphosphate (ATP) moieties in localized and unlocalized phosphorus (31P) NMR spectra from chest and heart muscle. In seven normal subjects at 1.5 T the nOe values were 0.6 +/- 0.3, 0.6 +/- 0.3, 0 +/- 0.3, and 0.3 +/- 0.2 for myocardial PCr, gamma-ATP, alpha-ATP, and beta-ATP, respectively, not significantly different from those in chest muscle. Distortion of the measured PCr/ATP ratios due to differences in the nOe may require accurate correction to realize the full benefit of the effect in studies involving quantitative intergroup comparisons.
Adenosine Triphosphate↗
An NMR phased array for human cardiac 31P spectroscopy.
A four-coil phased-array 31P NMR receiver was designed and tested for human cardiac applications, to determine whether the combination of relatively high signal-to-noise ratio (SNR) and large field of view produced in 1H imaging is also realized for in vivo 31P spectroscopy. Spectra were acquired in parallel from an array of four overlapping 6.5-cm surface coils using one- and two-dimensional phase-encoding pulse sequences and were optimally combined to yield composite spectroscopic images. The phased array was found to generate useful 31P spectra from a 2.5-fold wider lateral region around the anterior myocardium than a single receiver of the same size as the array elements, with no increase in imaging time. In addition, the sensitive depth was increased by up to 2 cm over that of a single coil. Spectra could be acquired in roughly 15 min from a region extending to the middle of the heart, with voxel sizes of 2 x 2 x 4 cm3. For the average heart voxel, the SNR of the combined spectrum was higher than that of the best spectrum from any one coil in the array by 30%, with some voxels showing an increase as high as 60%.
Heart↗
Proton MR spectroscopy for diagnosing hepatic encephalopathy?
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Brain↗
Alzheimer dementia: quantification of energy metabolism and mobile phosphoesters with P-31 NMR spectroscopy.
To determine whether high-energy phosphate metabolism and mobile phosphoester indexes of membrane metabolism are altered in Alzheimer disease and to help resolve some inconsistencies in the literature, brain phosphate metabolite concentrations and ratios were measured in 11 patients with mild to severe dementia of the probable Alzheimer type and 14 healthy subjects. Fully relaxed, spatially localized, phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) MR imaging were performed. No significant differences were found in the concentrations and relative ratios of phosphocreatine, nucleoside triphosphate, inorganic phosphate, phosphomonoester, and phosphodiesters in whole axial sections through the lateral cerebral ventricles of the brain that could not be accounted for by atrophy. There was no correlation between P-31 NMR indexes and the severity of dementia as assessed with neuropsychologic testing. High-energy phosphate and membrane metabolism, as detected in vivo with P-31 NMR spectroscopy in whole-brain sections, do not appear to play a major role in the disease process, except as a direct consequence of atrophy quantified with H-1 MR imaging.
Aged↗
31P spectroscopic localization using pinwheel NMR excitation pulses.
Spectroscopic imaging with a one-dimensional phase-encoding gradient and surface-coil reception relies on the restricted range of sensitivity of the surface coil to provide localization in the dimensions transverse to the coil axis and consequently suffers from relatively poor localization in these dimensions. A two-dimensional (2D) cylindrically selective excitation pulse with a large spectral bandwidth is presented here to remedy this problem. The gradient waveforms are derived from multiple spirals in k space which form an overall pinwheel pattern, resulting in a pulse which is much shorter than the equivalent single-spiral trajectory. Nonuniform traversal of the spirals further reduces the pulse width under conditions of gradient slew-rate limitations, yielding overall gains in bandwidth of up to about 30 compared with the equivalent single-spiral trajectory traversed at constant angular rate. The accompanying rf waveform is obtained by weighted 2D Fourier transformation of the desired sensitivity profile. A new weighting factor is introduced into the rf waveform to compensate for nonuniform sampling of k space by the pinwheel near the origin. This factor is independent of the weighting used to account for the rate of traversal of the trajectory and is applicable to 2D pulse design in general. Pulse sequences employing pinwheel excitation in conjunction with either phase-encoding or slice-selective inversion are used to produce multiple-voxel and single-voxel localization in a human heart and a phantom. Pinwheel pulses may be used to advantage on moieties with long spin-lattice relaxation times and short transverse relaxation times and are therefore ideal for applications in phosphorus (31P) NMR.
Heart↗
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.
Adenosine Triphosphate↗
Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants.
To determine whether myocardial high-energy phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart).
Adenosine Triphosphate↗
The trouble with spectroscopy papers.
Writing a critique and guide for authors of clinical spectroscopy research papers is a likely way of ensuring that one never sees another of one's own papers published in this field. Nevertheless, it is disappointing, though perhaps predictable, that despite its historical foundations in quantitative spectroscopy, the field has its fair share of findings that are not so obviously reconciled. Here is the view of one author, one referee, and one spectroscopy protagonist about what might be expected of a clinical spectroscopy paper. In addition to novelty, the fundamental criteria for acceptance should be that the conclusions are supported by properly and objectively quantified results, and that sufficient experimental detail is provided so that one skilled in the art could reproduce the study and its findings.
Humans↗
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.
Adenosine Triphosphate↗
Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance.
Cardiac-gated phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopic imaging with surface coils resolves in three dimensions the spatial distribution of high energy phosphate metabolites in the human heart noninvasively. 31P spectra derive from 6- to 14-cm3 volumes of myocardium in the anterior left ventricle, septum, and apex, at depths of up to about 8 cm from the chest, as identified by proton (1H) NMR anatomical images acquired without moving the subject. Spectroscopic images are acquired in 9 to 21 min at 1.5 T. Metabolite concentrations are quantified with reference to a standard located outside the chest, yielding normal in vivo concentrations of phosphocreatine and adenosine triphosphate of about 11.0 +/- 2.7 (SD) and 6.9 +/- 1.6 mumol/g of wet heart tissue, respectively. High energy phosphate contents did not vary significantly with location in the normal myocardium, but 2,3-diphosphoglycerate signals from blood varied with subject and location.
Adenosine Triphosphate↗
AIDS dementia complex: brain high-energy phosphate metabolite deficits.
To test whether compromised high-energy phosphate metabolism is implicated in the neurologic impairment of acquired immunodeficiency syndrome dementia complex (ADC), brain phosphate metabolite concentrations and ratios were measured noninvasively in 12 patients with mild to moderate ADC and 29 healthy volunteers by use of localized phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) magnetic resonance (MR) imaging. In patients, brain phosphocreatine (PCr) and nucleoside triphosphate (NTP) concentrations in sections through the centrum semiovale that were seen with NMR spectroscopy were reduced significantly from normal values of 4.92 mmol/kg wet weight +/- .13 (standard error of the mean) and 2.79 mmol/kg +/- .11, respectively, to 3.33 mmol/kg +/- .26 and 1.99 mmol/kg +/- .13 (P less than .0001). The ratios of metabolites detectable with P-31 NMR spectroscopy did not differ significantly from those of control subjects. The magnitude of the PCr and NTP deficits in ADC was not explicable by focal abnormalities or cerebral atrophy quantified in images of the same regions. These results are consistent with the hypothesis of a generalized virus-associated toxic process affecting brain cell function in ADC. Noninvasive measurement of metabolite concentrations with NMR spectroscopy provides new functional information that may help quantify disease progression and response to therapy.
AIDS Dementia Complex↗
Proton-decoupled, Overhauser-enhanced, spatially localized carbon-13 spectroscopy in humans.
Spatially localized, natural abundance, carbon (13C) NMR spectroscopy has been combined with proton (1H) decoupling and nuclear Overhauser enhancement to improve 13C sensitivity up to five-fold in the human leg, liver, and heart. Broadhand-decoupled 13C spectra were acquired in 1 s to 17 min with a conventional 1.5-T imaging/spectroscopy system, an auxiliary 1H decoupler, an air-cooled dual-coil coplanar surface probe, and both depth-resolved surface coil spectroscopy (DRESS) and one-dimensional phase-encoding gradient NMR pulse sequences. The surface coil probe comprised circular and figure-eight-shaped coils to eliminate problems with mutual coupling of coils at high decoupling power levels applied during 13C reception. Peak decoupler RF power deposition in tissue was computed numerically from electromagnetic theory assuming a semi-infinite plane of uniform biological conductor. Peak values at the surface were calculated at 4 to 6 W/kg in any gram of tissue for each watt of decoupler power input excluding all coil and cable losses, warning of potential local RF heating problems in these and related experiments. The average power deposition was about 9 mW/kg per watt input, which should present no systemic hazard. At 3 W input, human 13C spectra were decoupled to a depth of about 5 cm while some Overhauser enhancement was sustained up to about 3 cm depth, without ill effect. The observation of glycogen in localized natural abundance 13C spectra of heart and muscle suggests that metabolites in the citric acid cycle should be observable noninvasively using 13C-labeled substrates.
Carbon Isotopes↗
Problems and expediencies in human 31P spectroscopy. The definition of localized volumes, dealing with saturation and the technique-dependence of quantification.
Several technological problems in in vivo localized spectroscopy of metabolism are discussed in the context of comparing data obtained by different means. Deficiencies in spectroscopy localization methods can produce spectra that are dominated by artefactual signals derived from outside of selected volumes. Such artefacts are not usually correctly accounted for by representations of the profiles of the transverse magnetization alone. Selected sensitive volumes should be defined in terms of the size of tissue contributing the major fraction of signal to an observed spectrum, which is the integrated response from the sample including any phase cancellation effects. Phase cancellation in one-dimensional localization techniques employing excitation by an RF field with uniform phase distribution and surface coil detection such as depth resolved surface coil spectroscopy, chemical shift imaging (CSI) and rotating frame zeugmatography (RFZ) can significantly alter the effective radius of the sensitive volumes depending on the sample distribution and the extent of the homogeneous region of the magnet. Also, discrete spatial sampling in RFZ and CSI can radiate signal artefacts of around 25% into adjacent elements depending on the location and distribution of signal sources. Acquisition delays between excitation and detection and partial saturation are other major sources of systematic error. Saturation factors for metabolites are not easily obtainable on localized volumes during clinical exams on an individual basis, but may be expediently obtained as larger-volume tissue-averages. Better documentation of saturation effects, acquisition delays and localized volume sizes is needed to compare and validate clinical results and performance.
Brain↗
Human in vivo NMR spectroscopy in diagnostic medicine: clinical tool or research probe?
In this critical review of human in vivo nuclear magnetic resonance (NMR) spectroscopy, the questions of which chemical species can be detected and with what sensitivity, their biochemical significance, and their potential clinical value are addressed. The current in vivo detectability limit is about 10(-6) of that of tissue water protons, necessitating a 1-10 cm3-volume of tissue and approximately 10-minute averaging time. This permits access to fats, membrane lipid metabolism, high-energy phosphate metabolism, glycogen, some neurotransmitters and metabolites in the citric acid cycle, and artificially introduced fluorocompounds. While hydrogen-31, phosphorus-31, carbon-13, sodium-23, and fluorine-19 in vivo results are discussed, the majority of patient studies use P-31 NMR spectroscopy. Here results from metabolic and ischemic disorders substantiate a case for spectroscopy as a diagnostic modality. The use of a broad range of spatial localization strategies is justifiable on the basis of the location and size of the pathologic condition and of NMR sensitivity. Abnormalities in spectra from many other disorders, most notably cancer, and improvements are often observed early in the course of successful therapy. Yet the potential impact of these results on clinical diagnosis and therapeutic monitoring is not always well understood, and many questions remain. Neurotransmitters and citric acid cycle metabolites exhibit high H-1 NMR sensitivities and represent major untapped potential for human clinical spectroscopy research. Studies evaluating spectroscopy in the context of existing modalities are needed. The unique ability of spectroscopy to provide noninvasive information about tissue chemistry in patients bodes well for its impact on clinical research and disease diagnosis.
Amino Acids↗
Rapid, reliable in vivo assays of human phosphate metabolites by nuclear magnetic resonance.
This accurate, reliable, and fast method of assaying absolute concentrations of phosphate metabolites noninvasively in living tissue, including that of humans, combines 31P nuclear magnetic resonance (NMR) spectroscopy and 1H NMR imaging. The images are used to measure the areas of metabolite-bearing tissue in selected sections through the subject, and 31P spectra are acquired from the same section, together with a concentration reference located on the periphery. Metabolite concentrations are calculated from the ratios of areas and integrated signal intensities. Apparatus and protocol are designed to eliminate corrections due to magnetic field nonuniformities and NMR relaxation times. Mean (and SD) concentrations of adenosine triphosphate (ATP), phosphocreatine, and inorganic phosphate (Pi) measured in the brains of 15 normal adult human volunteers with a 1.5-T NMR system were 3.03 (0.49), 5.18 (0.89), and 1.5 (0.7) mmol per liter of wet tissue, respectively. Acquisition times of only a few minutes should facilitate metabolic studies of patients with disorders in limbs and brain, particularly those affecting entire organs.
Adenosine Triphosphate↗
Human in vivo phosphate metabolite imaging with 31P NMR.
Phosphorus (31P) spectroscopic images showing the distribution of high-energy phosphate metabolites in the human brain have been obtained at 1.5 T in scan times of 8.5 to 34 min at 27 and 64 cm3 spatial resolution using pulsed phase-encoding gradient magnetic fields and three-dimensional Fourier transform (3DFT) techniques. Data were acquired as free induction decays with a quadrature volume NMR detection coil of a truncated geometry designed to optimize the signal-to-noise ratio on the coil axis on the assumption that the sample noise represents the dominant noise source, and self-shielded magnetic field gradient coils to minimize eddy-current effects. The images permit comparison of metabolic data acquired simultaneously from different locations in the brain, as well as metabolite quantification by inclusion of a vial containing a standard of known 31P concentration in the image array. Values for the NMR visible adenosine triphosphate in three individuals were about 3 mM of tissue. The ratio of NMR detectable phosphocreatine to ATP in brain was 1.15 +/- 0.17 SD in these experiments. Potential sources of random and systematic error in these and other 31P measurements are identified.
Adenosine Triphosphate↗
Rapid 31P spectroscopy on a 4-T whole-body system.
Initial 31P spectroscopy results from a 4-T whole-body system are reported. Localized spectra from the human head, liver, and calf were obtained using DRESS, slice-interleaved DRESS, and volume 3DFT spectroscopic imaging techniques. Substantial reductions in data acquisition times to 10 s-4 min were achieved relative to previous similar experiments at 1.5 T. Some gain in spectral resolution (as measured in ppm) was also realized in the head.
Head↗