Biomedical subjects

Paul A Bottomley

Publications and source records attributed to Paul A Bottomley.

16 recordsLinked to original sources

PubMed2006

Monitoring and correcting spatio-temporal variations of the MR scanner's static magnetic field.

The homogeneity and stability of the static magnetic field are of paramount importance to the accuracy of MR procedures that are sensitive to phase errors and magnetic field inhomogeneity. It is shown that intense gradient utilization in clinical horizontal-bore superconducting MR scanners of three different vendors results in main magnetic fields that vary on a long time scale both spatially and temporally by amounts of order 0.8-2.5 ppm. The observed spatial changes have linear and quadratic variations that are strongest along the z direction. It is shown that the effect of such variations is of sufficient magnitude to completely obfuscate thermal phase shifts measured by proton-resonance frequency-shift MR thermometry and certainly affect accuracy. In addition, field variations cause signal loss and line-broadening in MR spectroscopy, as exemplified by a fourfold line-broadening of metabolites over the course of a 45 min human brain study. The field variations are consistent with resistive heating of the magnet structures. It is concluded that correction strategies are required to compensate for these spatial and temporal field drifts for phase-sensitive MR protocols. It is demonstrated that serial field mapping and phased difference imaging correction protocols can substantially compensate for the drift effects observed in the MR thermometry and spectroscopy experiments.

Brain↗

PubMed2006

Altered creatine kinase adenosine triphosphate kinetics in failing hypertrophied human myocardium.

BACKGROUND: The progression of pressure-overload left ventricular hypertrophy (LVH) to chronic heart failure (CHF) may involve a relative deficit in energy supply and/or delivery. METHODS AND RESULTS: We measured myocardial creatine kinase (CK) metabolite concentrations and adenosine triphosphate (ATP) synthesis through CK, the primary energy reserve of the heart, to test the hypothesis that ATP flux through CK is impaired in patients with LVH and CHF. Myocardial ATP levels were normal, but creatine phosphate levels were 35% lower in LVH patients (n = 10) than in normal subjects (n = 14, P < 0.006). Left ventricular mass and CK metabolite levels in LVH were not different from those in patients with LVH and heart failure (LVH+CHF, n = 10); however, the myocardial CK pseudo first-order rate constant was normal in LVH (0.36 +/- 0.04 s(-1) in LVH versus 0.32 +/- 0.06 s(-1) in normal subjects) but halved in LVH+CHF (0.17 +/- 0.06 s(-1), P < 0.001). The net ATP flux through CK was significantly reduced by 30% in LVH (2.2 +/- 0.7 micromol x g(-1) x s(-1), P = 0.011) and by a dramatic 65% in LVH+CHF (1.1 +/- 0.4 micromol x g(-1) x s(-1), P < 0.001) compared with normal subjects (3.1 +/- 0.8 micromol x g(-1) x s(-1)). CONCLUSIONS: These first observations in human LVH demonstrate that it is not the relative or absolute CK metabolite pool sizes but rather the kinetics of ATP turnover through CK that distinguish failing from nonfailing hypertrophic hearts. Moreover, the deficit in ATP kinetics is similar in systolic and nonsystolic heart failure and is not related to the severity of hypertrophy but to the presence of CHF. Because CK temporally buffers ATP, these observations support the hypothesis that a deficit in myofibrillar energy delivery contributes to CHF pathophysiology in human LVH.

Adenosine Triphosphate↗

PubMed2006

Optimizing the intrinsic signal-to-noise ratio of MRI strip detectors.

An MRI detector is formed from a conducting strip separated by a dielectric substrate from a ground plane, and tuned to a quarter-wavelength. By distributing discrete tuning elements along the strip, the geometric design may be adjusted to optimize the signal-to-noise ratio (SNR) for a given application. Here a numerical electromagnetic (EM) method of moments (MoM) is applied to determine the length, width, substrate thickness, dielectric constant, and number of tuning elements that yield the best intrinsic SNR (ISNR) of the strip detector at 1.5 Tesla. The central question of how strip performance compares with that of a conventional optimized loop coil is also addressed. The numerical method is validated against the known ISNR performance of loop coils, and its ability to predict the tuning capacitances and performance of seven experimental strip detectors of varying length, width, substrate thickness, and dielectric constant. We find that strip detectors with low-dielectric constant, moderately thin-substrate, and length about 1.3 (+/-0.2) times the depth of interest perform best. The ISNR of strips is comparable to that of loops (i.e., higher close to the detector but lower at depth). The SNR improves with two inherently-decoupled strips, whose sensitivity profile is well-suited to parallel MRI. The findings are summarized as design "rules of thumb."

Diagnostic Errors↗

PubMed2006

On restoring motion-induced signal loss in single-voxel magnetic resonance spectra.

Destructive interference from phase fluctuations caused by motion during (1)H magnetic resonance spectroscopy (MRS) stimulated-echo acquisition mode (STEAM) and point-resolved spectroscopy (PRESS) acquisitions can significantly diminish the traditional radicalN-gain in signal-to-noise ratio (SNR) afforded by averaging N signals, especially in the torso. The SNR loss is highly variable among individuals, even when identical acquisition protocols are used. This paper presents a theory for the SNR loss, assuming that the phase fluctuates randomly. It is shown that SNR in conventional averaging is reduced by the factor sinc(sigma(phi) radical3/pi), where sigma(phi) is the standard deviation (SD) of the phase. "Constructive averaging," whereby each individual acquisition is phase-corrected using the phase of a high-SNR peak before averaging, reverses the SNR loss from motion-induced dephasing, resulting in a {1/sinc(sigma(phi) radical3/pi)}-fold SNR improvement. It is also shown that basing phase corrections on an average of radicalN adjacent points both improves correction accuracy and effectively eliminates false signal artifacts when corrections are based on low-SNR peaks. The theory is validated over a sevenfold range of variation in signal loss due to motion observed in (1)H STEAM and PRESS data acquired from 17 human subjects (heart: N = 16; leg: N = 1). Constructive averaging should be incorporated as a routine tool for in vivo (1)H MRS.

Artifacts↗

PubMed2006

Deconvolution-interpolation gridding (DING): accurate reconstruction for arbitrary k-space trajectories.

A simple iterative algorithm, termed deconvolution-interpolation gridding (DING), is presented to address the problem of reconstructing images from arbitrarily-sampled k-space. The new algorithm solves a sparse system of linear equations that is equivalent to a deconvolution of the k-space with a small window. The deconvolution operation results in increased reconstruction accuracy without grid subsampling, at some cost to computational load. By avoiding grid oversampling, the new solution saves memory, which is critical for 3D trajectories. The DING algorithm does not require the calculation of a sampling density compensation function, which is often problematic. DING's sparse linear system is inverted efficiently using the conjugate gradient (CG) method. The reconstruction of the gridding system matrix is simple and fast, and no regularization is needed. This feature renders DING suitable for situations where the k-space trajectory is changed often or is not known a priori, such as when patient motion occurs during the scan. DING was compared with conventional gridding and an iterative reconstruction method in computer simulations and in vivo spiral MRI experiments. The results demonstrate a stable performance and reduced root mean square (RMS) error for DING in different k-space trajectories.

Algorithms↗

PubMed2005

Quantifying in vivo MR spectra with circles.

Accurate and robust quantification of in vivo magnetic resonance spectroscopy (MRS) data is essential to its application in research and medicine. The performance of existing analysis methods is problematic for in vivo studies where low signal-to-noise ratio, overlapping peaks and intense artefacts are endemic. Here, a new frequency-domain technique for MRS data analysis is introduced wherein the circular trajectories which result when spectral peaks are projected onto the complex plane, are fitted with active circle models. The use of active contour strategies naturally allows incorporation of prior knowledge as constraint energy terms. The problem of phasing spectra is eliminated, and baseline artefacts are dealt with using active contours-snakes. The stability and accuracy of the new technique, CFIT, is compared with a standard time-domain fitting tool, using simulated 31P data with varying amounts of noise and 98 real human chest and heart 31P MRS data sets. The real data were also analyzed by our standard frequency-domain absorption-mode technique. On the real data, CFIT demonstrated the least fitting failures of all methods and an accuracy similar to the latter method, with both these techniques outperforming the time-domain approach. Contrasting results from simulations argue that performance relative to Cramer-Rao Bounds may not be a suitable indicator of fitting performance with typical in vivo data such as these. We conclude that CFIT is a stable, accurate alternative to the best existing methods of fitting in vivo data.

Artifacts↗

PubMed2005

ATP flux through creatine kinase in the normal, stressed, and failing human heart.

The heart consumes more energy per gram than any other organ, and the creatine kinase (CK) reaction serves as its prime energy reserve. Because chemical energy is required to fuel systolic and diastolic function, the question of whether the failing heart is "energy starved" has been debated for decades. Despite the central role of the CK reaction in cardiac energy metabolism, direct measures of CK flux in the beating human heart were not previously possible. Using an image-guided molecular assessment of endogenous ATP turnover, we directly measured ATP flux through CK in normal, stressed, and failing human hearts. We show that cardiac CK flux in healthy humans is faster than that estimated through oxidative phosphorylation and that CK flux does not increase during a doubling of the heart rate-blood pressure product by dobutamine. Furthermore, cardiac ATP flux through CK is reduced by 50% in mild-to-moderate human heart failure (1.6 +/- 0.6 vs. 3.2 +/- 0.9 micromol/g of wet weight per sec, P <0.0005). We conclude that magnetic resonance strategies can now directly assess human myocardial CK energy flux. The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of sufficient magnitude, even in the absence of a significant reduction in ATP stores, to contribute to the pathophysiology of human heart failure. These findings support the pursuit of new therapies that reduce energy demand and/or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.

Adenosine Triphosphate↗

PubMed2005

Measuring human cardiac tissue sodium concentrations using surface coils, adiabatic excitation, and twisted projection imaging with minimal T2 losses.

PURPOSE: To measure tissue sodium concentrations in the human heart with (23)Na MRI using a surface coil, thereby eliminating the effects of inhomogeneous excitation by surface coils and minimizing T(1) and T(2) relaxation. MATERIALS AND METHODS: We combined fully relaxed, very short-echo, (23)Na twisted projection imaging (TPI) with adiabatic half passage (AHP) excitation and external referencing on subjects and comparing with a concentration reference phantom scan to quantify TSC with surface coils. (23)Na signal losses during hard (square), composite, and tanh/tan amplitude/frequency-modulated AHP excitation pulses were analyzed over a wide range of RF field strengths and T(2short) values. RESULTS: AHP excitation yielded a homogeneous excitation flip angle and negligible losses compared to a 90 degrees hard pulse wherever the B1 field exceeded the adiabatic threshold, rendering this sequence suitable for applications that use surface coil excitation. An AHP (23)Na TPI sequence was used with a surface coil at 1.5 T to noninvasively quantify myocardial TSC in 10 normal volunteers. The mean TSC was 43 +/- 4, 53 +/- 12, and 17 +/- 4 micromol/g in the left ventricular (LV) free wall, septum, and adipose tissue, respectively, consistent with prior invasive measurements on biopsy and autopsy specimens. CONCLUSION: It is now possible to noninvasively quantify TSC in the human heart with surface coil (23)Na MRI.

Computer Simulation↗

PubMed2005

Effects of a pharmacologically-induced shift of hemoglobin-oxygen dissociation on myocardial energetics during ischemia in patients with coronary artery disease.

BACKGROUND: Conventional strategies to treat myocardial ischemia include interventions that reduce oxygen demand and/or increase myocardial blood flow. Animal experiments suggest that right-shifting the hemoglobin-oxygen dissociation curve may also attenuate the metabolic consequences of myocardial ischemia. We evaluated whether exercise-induced myocardial ischemia can be alleviated in subjects with coronary artery disease (CAD) by enhancing oxygen release with an allosteric modifier of hemoglobin's affinity for oxygen (RSR13). METHODS AND RESULTS: Seven subjects with CAD underwent a randomized, double-blind, cross-over study of the metabolic consequences of RSR13 administration on myocardial ischemia. Myocardial high-energy phosphates were quantified with 31P nuclear magnetic resonance (NMR) spectroscopy before, during, and after isometric handgrip-exercise. Subjects underwent NMR studies at baseline and on two separate occasions following the infusion of RSR13 (100 mg/kg) or placebo. RSR13 infusion significantly increased mean p50 by 8.1 +/- 2.7 mmHg at the end of the infusion, and it was still elevated by 4.9 +/- 3.3 mmHg after the completion of the treadmill tests while placebo had no effect. The myocardial creatine-phosphate (PCr) to adenosine-triphosphate (ATP) ratio decreased during handgrip-exercise in the baseline studies (from 1.39 +/- 0.23 before exercise to 0.95 +/- 0.21 during handgrip-exercise, p = 0.0001) and in the placebo studies (from 1.29 +/- 0.16 to 0.98 +/- 0.37, p = 0.06) but not during administration of RSR13 (from 1.28 +/- 0.18 to 1.02 +/- 0.24, p = 0.12). However, the mean values of cardiac PCr/ATP during handgrip-exercise did not differ significantly among the three measurements (baseline, placebo, RSR13). CONCLUSIONS: A single infusion of RSR13 to subjects with CAD increased mean p50 by 4.9-8.1 mmHg but did not significantly alter myocardial PCr/ATP during exercise. This is the largest right-shift in hemoglobin-oxygen binding affinity achieved in CAD subjects, and it did not provide clear evidence of protection from cardiac ischemia.

Adenosine Triphosphate↗

PubMed2004

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

PURPOSE: To investigate the diagnostic value of proton magnetic resonance spectroscopic imaging (MRSI) in patients with breast lesions. MATERIALS AND METHODS: Eighteen patients underwent breast MRSI and MRI at 1.5 T. Contrast-enhanced MR was used to identify the lesion, after which single-slice MRSI (TR/TE = 2000/272 msec, 10-mm slice thickness) was performed. Water, lipid, and choline (Cho) images were reconstructed from MRSI data. The area of the Cho was measured in the lesion and expressed relative to the background noise level (signal-to-noise ratio (SNR)), measured between 7.0 and 9.0 ppm. Cho SNRs were compared between benign and malignant lesions as determined by histopathology. RESULTS: Three cases were considered technical failures on MRSI. Of the remaining 15 cases, on histopathology, eight were classified as malignant carcinoma and seven were benign. The Cho SNR from malignant tissue was significantly elevated compared to benign tissue (6.2 +/- 2.1 vs. 2.4 +/- 0.7, P < 0.0008). CONCLUSIONS: MRSI measurements of Cho are feasible in the human breast, and the SNR for Cho was significantly different between benign and malignant lesions. The potential advantages of MRSI over SV spectroscopy include the ability to assess multiple lesions as well as tissue with normal MRI appearance, as well as to perhaps gauge lesion borders and infiltration into surrounding tissue.

Adult↗

PubMed2004

Lumped-element planar strip array (LPSA) for parallel MRI.

The recently introduced planar strip array (PSA) can significantly reduce scan times in parallel MRI by enabling the utilization of a large number of RF strip detectors that are inherently decoupled, and are tuned by adjusting the strip length to integer multiples of a quarter-wavelength (lambda/4) in the presence of a ground plane and dielectric substrate. In addition, the more explicit spatial information embedded in the phase of the signals from the strip array is advantageous (compared to loop arrays) for limiting aliasing artifacts in parallel MRI. However, losses in the detector as its natural resonance frequency approaches the Larmor frequency (where the wavelength is long at 1.5 T) may limit the signal-to-noise ratio (SNR) of the PSA. Moreover, the PSA's inherent lambda/4 structure severely limits our ability to adjust detector geometry to optimize the performance for a specific organ system, as is done with loop coils. In this study we replaced the dielectric substrate with discrete capacitors, which resulted in both SNR improvement and a tunable lumped-element PSA (LPSA) whose dimensions can be optimized within broad constraints, for a given region of interest (ROI) and MRI frequency. A detailed theoretical analysis of the LPSA is presented, including its equivalent circuit, electromagnetic fields, SNR, and g-factor maps for parallel MRI. Two different decoupling schemes for the LPSA are described. A four-element LPSA prototype was built to test the theory with quantitative measurements on images obtained with parallel and conventional acquisition schemes.

Equipment Design↗

PubMed2004

Large field-of-view real-time MRI with a 32-channel system.

The emergence of parallel MRI techniques and new applications for real-time interactive MRI underscores the need to evaluate performance gained by increasing the capability of MRI phased-array systems beyond the standard four to eight high-bandwidth channels. Therefore, to explore the advantages of highly parallel MRI a 32-channel 1.5 T MRI system and 32-element torso phased arrays were designed and constructed for real-time interactive MRI. The system was assembled from multiple synchronized scanner-receiver subsystems. Software was developed to coordinate across subsystems the real-time acquisition, reconstruction, and display of 32-channel images. Real-time, large field-of-view (FOV) body-survey imaging was performed using interleaved echo-planar and single-shot fast-spin-echo pulse sequences. A new method is demonstrated for augmenting parallel image acquisition by independently offsetting the frequency of different array elements (FASSET) to variably shift their FOV. When combined with conventional parallel imaging techniques, image acceleration factors of up to 4 were investigated. The use of a large number of coils allowed the FOV to be doubled in two dimensions during rapid imaging, with no degradation of imaging time or spatial resolution. The system provides a platform for evaluating the applications of many-channel real-time MRI, and for understanding the factors that optimize the choice of array size.

Abdomen↗

PubMed2004

Multiparametric and multinuclear magnetic resonance imaging of human breast cancer: current applications.

The exploration of novel imaging methods that have the potential to improve specificity for the identification of malignancy is still critically needed in breast imaging. Changes in physiologic alterations of soft tissue water associated with breast cancer can be visualized by magnetic resonance (MR) imaging. However, it is unlikely that a single MR parameter can characterize the complexity of breast tissue. Techniques such as multiparametric MR imaging, proton magnetic resonance spectroscopic (MRSI) imaging, and 23Na sodium MR imaging when used in combination provide a comprehensive data set with potentially more power to diagnose breast disease than any single measure alone. A combination of MR, MRSI, and 23Na sodium MR parameters may be examined in a single MR imaging examination, potentially resulting in improved specificity for radiologic evaluation of malignancy.

Adolescent↗

PubMed2003

Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging.

PURPOSE: To use combined proton (1H) and sodium 23 (23Na) magnetic resonance (MR) imaging to noninvasively quantify total tissue sodium concentration and to determine if concentration is altered in malignant human brain tumors. MATERIALS AND METHODS: Absolute tissue sodium concentration in malignant gliomas was measured on quantitative three-dimensional 23Na MR images with tissue identification from registered 1H MR images. Concentration was determined in gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and vitreous humor in 20 patients with pathologically proven malignant brain tumors (astrocytoma, n = 17; oligodendroglioma, n = 3) and in nine healthy volunteers. Sodium concentration in tumors and edema was determined from 23Na image signal intensities in regions that were contrast material enhanced on T1-weighted 1H images (tumors) or regions that were only hyperintense on fluid-attenuated inversion recovery (FLAIR) 1H images (edema). Sodium concentrations were measured noninvasively from 23Na images obtained with short echo times (0.4 msec) by using external saline solution phantoms for reference. Differences in mean sodium concentration of all healthy tissue and lesions in patients were tested with a paired t test. Concentration in uninvolved tissues in patients was compared with that in the same tissue types in the volunteers with an independent samples two-tailed t test. RESULTS: Mean concentration (in millimoles per kilogram wet weight) was 61 +/- 8 (SD) for GM, 69 +/- 10 for WM, 135 +/- 10 for CSF, 113 +/- 14 for vitreous humor, 103 +/- 36 for tumor, 68 +/- 11 for unaffected contralateral tissue, and 98 +/- 12 for FLAIR hyperintense regions surrounding tumors. Significant differences (P <.002) in sodium concentration were demonstrated by using a t test for both tumors and surrounding FLAIR hyperintense tissues versus GM, WM, CSF, and contralateral brain tissue. CONCLUSION: 23Na MR imaging with short echo times can be used to quantify absolute tissue sodium concentration in patients with brain tumors and shows increased sodium concentration in tumors relative to that in normal brain structures.

Adolescent↗

PubMed2003

The effect of orientation on quantification of muscle creatine by 1H MR spectroscopy.

Creatine is a central energy metabolite whose N-CH3 group can be detected with 1H MR spectroscopy (1H MRS) with relatively high sensitivity. Prior studies suggest that muscle fiber orientation can influence the appearance of other resonances attributed to total creatine (CR). Our purpose was to determine whether muscle fiber orientation affects muscle CR concentration quantification by 1H MRS with the commonly used N-CH3 resonance at 3.0 ppm. Skeletal muscle CR was quantified with water-referenced 1H MRS in normal subjects with different forearm muscle orientations relative to the static magnetic field at 1.5T. There were no significant differences in mean total [CR] in two different series of experiments separately including two orthogonal orientations and four orientations (0 degrees, 30 degrees, 60 degrees, 90 degrees) of the forearm relative to the static field using either short (TE = 15 ms) or long (TE = 100 ms) echo times for voxels containing or centered on the same tissues. Subtle differences in CR line-width and T2 correction factors were observed with orientation. These observations are consistent with the primary hypothesis that careful water-referenced [CR] quantification, accounting for T2 effects and using the N-CH3 peak at 3.0ppm, is not affected by muscle orientation.

Creatine↗

PubMed2002

Four-angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo.

A new fast method of measuring kinetic reaction rates for two-site chemical exchange is described. The method employs saturation transfer magnetic resonance spectroscopy (MRS) and acquisition of only four spectra under partially saturated, high signal-to-noise ratio (SNR) conditions. In two acquisitions one of the exchanging species is saturated; the other two employ a control saturation. Each pair of acquisitions is applied with two different flip angles, and the equilibrium magnetization, relaxation times, and reaction rates are calculated therefrom. This four-angle saturation transfer (FAST) method is validated theoretically using the Bloch equations modified for two-state chemical exchange. Potential errors in the rate measurements due to the effects of exchange are evaluated for creatine kinase (CK) metabolism modeled for skeletal and heart muscle, and are found to be < 5% for forward CK flux rates of 0.05 < or = k(f) < or = 1.0 s(-1), and up to a 90% depletion of phosphocreatine (PCr). The effect of too much or too little saturating irradiation on FAST appears to be comparable to that of the conventional saturation transfer method, although the relative performance deteriorates when spillover irradiation cuts the PCr signal by 50% or more. "FASTer" and " FASTest" protocols are introduced for dynamic CK studies wherein [PCr] and/or k(f) changes. These protocols permit the omission of one or two of the four acquisitions in repeat experiments, and the missing information is recreated from initial data via a new iterative algorithm. The FAST method is validated empirically in phosphorus ((31)P) MRS studies of human calf muscle at 1.5 T. FAST measurements of 10 normal volunteers yielded the same CK reaction rates measured by the conventional method (0.29 +/- 0.06 s(-1)) in the same subjects, but an average of seven times faster. Application of the FASTer algorithm to these data correctly restored missing information within seven iterations. Finally, the FAST method was combined with 1D spatially localized (31)P MRS in a study of six volunteers, yielding the same k(f) values independent of depth, in total acquisition times of 17-39 min. These timesaving FAST methods are enabling because they permit localized measurements of metabolic flux, which were previously impractical due to intolerably long scan times.

Algorithms↗