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Biomedical subjects

P A Bottomley

Publications and source records attributed to P A Bottomley.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adult↗
PubMed2001

Planar strip array (PSA) for MRI.

Parallel, spatial-encoded MRI requires a large number of independent detectors that simultaneously acquire signals. The loop structure and mutual coupling in conventional phased arrays limit the number of coils and therefore the potential reduction in minimum scan time achievable by parallel MRI tchniques. A new near-field MRI detector array, the planar strip array (PSA), is presented that eliminates the coupling problems and can be extended to a very large number of detectors and high MRI frequencies. Its basic structure is an array of parallel microstrips with a high permittivity substrate and overlay. The electromagnetic (EM) wavelength can be adjusted with the permittivity, and the strip lengths tuned to a preselected fraction of the wavelength of the MRI frequency. EM wave analysis and measurements on a prototype four-element PSA reveal that the coupling between the strips vanishes when the strip length is either an integer times a quarter wavelength for a standing-wave PSA, or a half wavelength for a travelling-wave PSA, independent of the spacing between the strips. The analysis, as well as phantom and human MRI experiments performed by conventional and parallel-encoded MRI with the PSA at 1.5 T, show that the decoupled strips produce a relatively high-quality factor and signal-to-noise ratio, provided that the strips are properly terminated, tuned, and matched or coupled to the preamplifiers. Magn Reson Med 45:673-683, 2001.

Humans↗
PubMed2001

Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI.

The transport of sodium and potassium between the intra- and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally-induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 +/- 14.3 mmol/kg wet wt, mean +/- SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 +/- 1.1, P < 0.001) and from normal controls (34.4 +/- 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 +/- 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.

Animals↗
PubMed2001

Superparamagnetic iron oxide MION as a contrast agent for sodium MRI in myocardial infarction.

An intravascular iron-based contrast agent was used as a sodium (23Na) MRI T2 relaxant in an effort to suppress the blood signal from the ventricular cavities in normal and infarcted canine myocardium in vivo. 23Na MRI signal decreases in blood were attributed to decreases in the fast (T2f) and slow (T2s) transverse relaxation components, which were quantified as a function of dose and MRI echo time (TE). In vivo 23Na MRI signal decreases up to 65% were noted in ventricular blood when imaging under dose and TE conditions of 10 mg/kg body weight and 5 ms, respectively. Contrast injection followed by subsequent 23Na MRI in canine myocardial infarction led to a clear delineation of the location of the injured tissue, as identified by postmortem triphenyltetrazolium chloride staining, and to an improvement in the contrast-to-noise ratio between the blood in the ventricular chamber and the infarcted tissue that was as high as 3.3-fold in the postcontrast images in comparison to the precontrast images.

Animals↗
PubMed2001

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.

Adenosine Triphosphate↗
PubMed2001

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.

Adenosine Triphosphate↗
PubMed2001

Noninvasive localized MR quantification of creatine kinase metabolites in normal and infarcted canine myocardium.

PURPOSE: To develop image-guided spatially localized magnetic resonance (MR) spectroscopy to provide a noninvasive quantitative probe of myocardial creatine kinase (CK) metabolism, and to use it to determine the extent of changes in CK energy metabolism in nonviable infarcted canine myocardium. MATERIALS AND METHODS: Water-referenced localized phosphorus and proton MR spectroscopy were combined in a single protocol to noninvasively measure phosphocreatine (PCr), adenosine triphosphate (ATP), and total of phosphorylated and unphosphorylated creatine (CR) concentrations and pH in the myocardium in six normal dogs and six dogs with surgically induced myocardial infarction. Unphosphorylated creatine and adenosine diphosphate (ADP) levels were calculated. The results were compared with biochemical measurements at postmortem biopsy. RESULTS: Significant reductions in PCr-to-ATP ratios (1.7 +/- 0.3 [SD] vs 1 +/- 0.4; P <.001), PCr (10.3 +/- 2.1 vs 4.3 +/- 2.0 micromol/g wet weight; P <.0001), ATP (6.4 +/- 1.4 vs 3.7 +/- 1.4 micromol/g wet weight; P <.001), and CR (24.7 +/- 6.1 vs 6.3 +/- 3.7; P <.0001) were measured noninvasively in infarcted, as compared with normal, tissue. Biopsy measurements confirmed infarct-related reductions observed at MR spectroscopy, although high-energy phosphate concentrations were lower at biopsy. ADP calculated from noninvasive MR spectroscopic measurements was 0.11 +/- 0.07 micromol/g wet weight in normal myocardium. CONCLUSION: This combined phosphorus and proton MR spectroscopic approach provides a near-complete picture of in vivo myocardial CK metabolism in normal and diseased heart and a tool for noninvasively measuring metabolite reductions associated with the loss of viability.

Adenosine Triphosphate↗
PubMed2000

A broadband phased-array system for direct phosphorus and sodium metabolic MRI on a clinical scanner.

Despite their proven gains in signal-to-noise ratio and field-of-view for routine clinical MRI, phased-array detection systems are currently unavailable for nuclei other than protons (1H). A broadband phased-array system was designed and built to convert the 1H transmitter signal to the non-1H frequency for excitation and to convert non-1H phased-array MRI signals to the 1H frequency for presentation to the narrowband 1H receivers of a clinical whole-body 1.5 T MRI system. With this system, the scanner operates at the 1H frequency, whereas phased-array MRI occurs at the frequency of the other nucleus. Pulse sequences were developed for direct phased-array sodium (23Na) and phosphorus (31P) MRI of high-energy phosphates using chemical selective imaging, thereby avoiding the complex processing and reconstruction required for phased-array magnetic resonance spectroscopy data. Flexible 4-channel 31P and 23Na phased-arrays were built and the entire system tested in phantom and human studies. The array produced a signal-to-noise ratio improvement of 20% relative to the best-positioned single coil, but gains of 300-400% were realized in many voxels located outside the effective field-of-view of the single coil. Cardiac phosphorus and sodium MRI were obtained in 6-13 min with 16 and 0.5 mL resolution, respectively. Lower resolution human cardiac 23Na MRI were obtained in as little as 4 sec. The system provides a practical approach to realizing the advantages of phased-arrays for nuclei other than 1H, and imaging metabolites directly.

Amplifiers, Electronic↗
PubMed2000

An analytical SMASH procedure (ASP) for sensitivity-encoded MRI.

The simultaneous acquisition of spatial harmonics (SMASH) method of imaging with detector arrays can reduce the number of phase-encoding steps, and MRI scan time several-fold. The original approach utilized numerical gradient-descent fitting with the coil sensitivity profiles to create a set of composite spatial harmonics to replace the phase-encoding steps. Here, an analytical approach for generating the harmonics is presented. A transform is derived to project the harmonics onto a set of sensitivity profiles. A sequence of Fourier, Hilbert, and inverse Fourier transform is then applied to analytically eliminate spatially dependent phase errors from the different coils while fully preserving the spatial-encoding. By combining the transform and phase correction, the original numerical image reconstruction method can be replaced by an analytical SMASH procedure (ASP). The approach also allows simulation of SMASH imaging, revealing a criterion for the ratio of the detector sensitivity profile width to the detector spacing that produces optimal harmonic generation. When detector geometry is suboptimal, a group of quasi-harmonics arises, which can be corrected and restored to pure harmonics. The simulation also reveals high-order harmonic modulation effects, and a demodulation procedure is presented that enables application of ASP to a large numbers of detectors. The method is demonstrated on a phantom and humans using a standard 4-channel phased-array MRI system.

Fourier Analysis↗
PubMed2000

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.

Algorithms↗
PubMed2000

Human skeletal muscle: sodium MR imaging and quantification-potential applications in exercise and disease.

PURPOSE: To use sodium 23 magnetic resonance (MR) imaging to quantify noninvasively total sodium in human muscle and to apply the technique in exercise and musculoskeletal disease. MATERIALS AND METHODS: Total [Na] sodium was determined from the ratio of the relaxation-corrected (23)Na signal intensities measured from short echo-time (0.4 msec) (23)Na images to those from an external saline solution reference. The method was validated with the blinded use of saline solutions of varying sodium concentrations. [Na] was measured in the calf muscles in 10 healthy volunteers. (23)Na MR imaging also was performed in two healthy subjects after exercise, two patients with myotonic dystrophy, and two patients with osteoarthritis. RESULTS: (23)Na MR imaging yielded a total [Na] value of 28.4 mmol/kg of wet weight +/- 3.6 (SD) in normal muscle, consistent with prior biopsy data. Spatial resolution was 0.22 mL, with signal-to-noise ratio of 10-15. Mean signal intensity elevations were 16% and 22% after exercise and 47% and 70% in dystrophic muscles compared with those at normal resting levels. In osteoarthritis, mean signal intensity reductions were 36% and 15% compared with those in unaffected knee joints. CONCLUSION: (23)Na MR imaging can be used to quantify total [Na] in human muscle. The technique may facilitate understanding of the role of the sodium-potassium pump and perfusion in normal and diseased muscle.

Adult↗
PubMed1998

Mitral regurgitation: impaired systolic function, eccentric hypertrophy, and increased severity are linked to lower phosphocreatine/ATP ratios in humans.

BACKGROUND: A number of phosphorus (31P) magnetic resonance spectroscopy (MRS) studies link alterations of high-energy phosphate metabolism in valvular disease and cardiomyopathy to the clinical severity of heart failure. However, correlations between MRS and indexes of ventricular dysfunction are inconclusive to date. We examined whether changes in 31P MRS are associated with the impaired contractility, which predisposes to chronic congestive heart failure in patients with mitral regurgitation. METHODS AND RESULTS: Thirteen normal control subjects and 22 patients with echocardiographically characterized chronic mitral regurgitation were studied by 31P MRS. The apical phosphocreatine-to-ATP ratio (PCr/ATP) was lower in severe disease (P<.02) and those on therapy (n=13, 1.29+/-0.29, P<.01) in contrast to control subjects (n=13, 1.61+/-0.3). Compared to those with mild mitral regurgitation, patients with more severe incompetence had lower mean myocardial PCr/ATP ratios (mild, n=6, 1.73 [0.17], P<.05 and P<.01; moderate, n=5, 1.49 [0.18], P<.05; and severe, n=1, 1.29 [0.32], P<.01). PCr/ATP in those referred for mitral valve replacement was lower (n=8, 1.17+/-0.23) although not significantly decreased compared with the ratio among subjects on medical therapy alone (n=5, 1.48+/-0.29). PCr/ATP correlated with the end-systolic diameter (r2=.7, P<.001), end-diastolic diameter (r2=.32, P<.05), left ventricular wall thickness (r2=.38, P<.01), left atrial dimension (r2=.36, P<.05), and derived measurements such as the percent fractional shortening (2=.5, P<.01), and left ventricular mass/body surface area (r2=.5, P<.001) but not with wall stress. CONCLUSIONS: These results demonstrate that abnormalities of PCr/ATP in mitral regurgitation are related to disease severity as measured by dimensional indexes of left ventricular dilatation. They suggest that impaired high-energy phosphate metabolism is a marker of hypertrophy and heart failure.

Adenosine Triphosphate↗
PubMed1998

Non-invasive magnetic-resonance detection of creatine depletion in non-viable infarcted myocardium.

BACKGROUND: Preserved energy metabolism is essential for myocardial viability and the creatine kinase reaction is central to energy production and reserve. Although the appearance of myocardial creatine kinase enzyme in the blood is widely used to diagnose cardiac necrosis, there are no non-invasive ways to measure local creatine concentrations in the healthy and diseased human heart. METHODS: We measured total myocardial creatine by spatially-localised, water-suppressed hydrogen magnetic-resonance spectroscopy (1H-MRS) on a clinical (1.5 T) magnetic-resonance-imaging system in ten healthy volunteers (controls) and ten patients with a history of myocardial infarction. We validated this technique by comparison of 1H-MRS values of creatine with biopsy assays in an animal model of infarction. FINDINGS: Total creatine was measured in the posterior and anterior left ventricle and septum, and was significantly lower in regions of infarction (10 [9] SD micromol/g wet weight) than in non-infarcted regions (26 [11] micromol/g, p=0.001) of myocardium in patients or in the myocardium of healthy controls (28 [6] micromol/g, p<0.0001). INTERPRETATION: Spatially localised 1H-MRS can be used to measure total creatine non-invasively throughout the human heart. The detection of regional creatine depletion may provide a metabolic means to distinguish healthy from infarcted non-viable myocardium.

Adult↗
PubMed1997

What is the optimum phased array coil design for cardiac and torso magnetic resonance?

To determine the optimum configuration of a phased array MR coil system for human cardiac applications, the sensitivity of 10 flexible array designs operating under ideal conditions was calculated at 13 points circling the myocardium of a model torso whose geometry was determined from healthy volunteers. The array geometries that were evaluated included continuous strips of 2, 4, 6, and 10 circular coils of diameter equal to half the torso thickness wrapped laterally around the torso, 2 pairs of coils located on the left side of the chest and back, clusters of 3 coils in 2 orientations, clusters of 4 and 6 coils, and a hybrid cross of 6 coils. The 4-, 6-, and 10-coil strip arrays out-performed the other designs for a given number of coils, yielding average theoretical sensitivity improvements of 45%, 53%, and 55% relative to a single flexible coil positioned at the point closest to the anterior myocardium, compared with about 30% for 4- and 6-coil clusters and the 2-pair geometry (P < 0.02). A flexible 4-coil strip array was constructed for a clinical 1.5 T scanner with 15-cm diameter circular surface coils on flexible circuit board. The signal-to-noise ratio (SNR) of this coil at the 13 cardiac locations was measured in 15 normal volunteers and compared with the SNR measured in images acquired with standard commercial MR coils: a body coil, a flexible torso array, a general purpose flexible coil, and, in 4 subjects, a dual array coil. In the prone orientation, the average myocardial SNR improvement of the 4-coil strip array was 650% relative to the whole body coil, compared with 310-340% for the other commercial coils (P < 0.00005). The twofold advantage over the commercial coils persisted in supine studies (P < 0.00005, n = 5). Thus, flexible circumferential phased arrays of strips of surface coils of diameter comparable with the depth of the heart generally out-perform many other standard geometries for a given number of coils, and can yield dramatically improved SNR over coils available for general use in the torso.

Adult↗
PubMed1997

The rise of human in vivo NMR spectroscopy.

NMR spectroscopy and NMR imaging with magnetic field gradients make strange bedfellows, the requirements for one seemingly ruling out the other for human applications. Nevertheless, their stories are intertwined; the advent of high field imaging systems arose because of the desire for human spectroscopy. Localized spectroscopy is possible because of NMR imaging. Both have links to physics at Nottingham, at least in the personalized account that follows. Today, virtually all NMR spectroscopy experiments can be conceived with a localized in vivo spectroscopy counterpart.

Animals↗