Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance

Bottomley, Paul A.; Hardy, Christopher J.; Roemer, Peter B.

doi:10.1002/mrm.1910140302

Cited by 133 publications

(88 citation statements)

References 25 publications

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“…At rest, the flux in the patient is lower (e). In each study, four such 31 P data sets are acquired with saturation and two different flip angles (20); then a 31 P and a 1 H data set are acquired without saturation to measure concentrations (10,11,22). The spectral scale is chemical shift in ppm.…”

Section: Resultsmentioning

confidence: 99%

“…PCr and ATP concentrations were determined by both the water-and phosphate-reference methods (10,11,22), except for the normal dobutamine studies, when only the phosphate-reference method was used (10,22). Comparison of measurements using both methods showed no significant difference.…”

Section: Methodsmentioning

confidence: 99%

“…Comparison of measurements using both methods showed no significant difference. Metabolite measurements were saturation-corrected and ATP concentration was corrected for blood contamination (10,11,14,22).…”

Section: Methodsmentioning

confidence: 99%

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

Weiss

Gerstenblith

Bottomley

2005

Proc. Natl. Acad. Sci. U.S.A.

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300

348

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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 mol͞g 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 and͞or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.heart failure ͉ magnetic resonance spectroscopy ͉ metabolism A TP provides the chemical energy that fuels myocardial contractile function. Relatively large rates of ATP synthesis are required to sustain normal systolic and diastolic function. The ''energy starvation'' hypothesis of heart failure suggests that inadequate ATP supply underlies the contractile dysfunction present in heart failure (1, 2). Large-scale clinical trials demonstrating that pharmacologic agents such as beta-blockers and angiotensin-converting enzyme inhibitors that reduce metabolic demand improve outcomes in heart failure, whereas those such as positive inotropic agents that increase energetic demand worsen outcomes (3) are consistent with the energy-starvation hypothesis. However, the ability to test the energy-starvation hypothesis has been limited, in part, by an inability to directly measure ATP synthesis in the human heart.Creatine kinase (CK) is central to mammalian energy metabolism and serves as the prime energy reserve of the heart. CK reversibly converts ADP and creatine phosphate (PCr) to ATP and creatine (Cr). This reaction allows tight control of ADP and ATP concentrations in cardiac and skeletal muscle as well as in brain, providing a rapid source of ATP during ischemia and burst activity in skeletal muscle (4-6). It is also hypothesized that the CK reaction serves as an intracellular spatial energy shuttle, facilitating the transfer of high-energy phosphates from the mitochondria (where AT...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

Weiss

Gerstenblith

Bottomley

2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

300

348

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“…In addition to operating as a Tx-only coil (detuned during receive), the Tx-coil was designed to function as a Txreceive coil to facilitate amplitude of radiofrequency Txfield mapping on a per-subject basis. During array reception the Tx-elements are detuned by series pin diodes, as shown in Bottomley et al (22) and Hardy et al (23), to prevent electromagnetic coupling with the receive-elements (Fig. 4).…”

Section: Coilsmentioning

confidence: 99%

Design and evaluation of a 32‐channel phased‐array coil for lung imaging with hyperpolarized 3‐helium

Meise

Rivoire

Terekhov

et al. 2010

Magnetic Resonance in Med

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Imaging with hyperpolarized 3-helium is becoming an increasingly important technique for MRI diagnostics of the lung but is hampered by long breath holds (>20 sec), which are not always applicable in patients with severe lung disease like chronic obstructive pulmonary disease (COPD) or a-1-anti-trypsin deficiency. Additionally, oxygen-induced depolarization decay during the long breath holds complicates interpretation of functional data such as apparent diffusion coefficients. To address these issues, we describe and validate a 1.5-T, 32-channel array coil for accelerated 3 He lung imaging and demonstrate its ability to speed up imaging 3 He. A signal-to-noise ratio increase of up to a factor of 17 was observed compared to a conventional double-resonant birdcage for unaccelerated imaging, potentially allowing increased image resolution or decreased gas production requirements. Accelerated imaging of the whole lung with one-dimensional and two-dimensional acceleration factors of 4 and 4 3 2, respectively, was achieved while still retaining excellent image quality. Key words: MRI; parallel imaging; helium; lung; phased array coil Lung imaging using hyperpolarized 3 He has received increased attention in the last several years for studying lung diseases (1-12). So far, functional imaging, e.g., the apparent diffusion coefficient (ADC) or methods to observe the microstructure of the lung (12,13), requires long breath holds (up to 30 sec), which are the main barrier to applying this technology to patients with severe lung disease. Improvements in array coil methodology are a promising approach for increasing signal-to-noise ratio (SNR) and allowing significant acceleration of the image-encoding process. Lee et al. (14,15) presented a 24-channel array and later a 128-channel array for 3 He imaging, which demonstrated the feasibility of this approach. The acceleration afforded by parallel imaging is particularly important for hyperpolarized gas imaging since the nonequilibrium state of the magnetization allows faster imaging, often without incurring the standard SNR penalty proportional to the square root of imaging time (16). To analyze the improvements of these techniques in more detail, a 32-channel phased array was designed and built. For comparison, imaging protocols such as used in the European Community Framework V project ''Polarized Helium Imaging of the Lung'' were applied, as well as newly developed protocols, which utilize the extra sensitivity of the array. The sensitivity improvements were compared to a single-channel volume coil and the benefits of parallel imaging for lung diagnostics were analyzed by theoretical geometry-factor (g-factor) maps for the array and demonstrated in accelerated imaging. MATERIALS AND METHODS CoilsThe phased-array coil (Fig. 1) consists of 32 loops mounted on a clamshell former, which was presented by Schmitt et al. (17) for cardiac imaging. The 32 receive elements were milled from 35-lm copper-plated 1.5mm-thick FR4 circuit board material and arranged in two groups of 16 ele...

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“…First, excitation/sensitivity maps can be created by imaging a uniform phantom or by computation. The reciprocal of the map is multiplied with the 23 Na signal in each pixel to compensate for the fading sensitivity with depth (33). Alternatively, a low-resolution proton ( 1 H) image of water can be acquired with the same ( 23 Na) coil and used as a spatially-dependent concentration reference once the tissue water content is known or is determined.…”

Section: Quantificationmentioning

confidence: 99%

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

Constantinides

Kraitchman

O'Brien

et al. 2001

Magnetic Resonance in Med

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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 ( 23 Na) 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 23 Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23 Na 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 23 Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P ‫؍‬ NS). Sodium content measured by 23 Na 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 23 Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.

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Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance

Cited by 133 publications

References 25 publications

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

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

Design and evaluation of a 32‐channel phased‐array coil for lung imaging with hyperpolarized 3‐helium

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

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Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance

Cited by 133 publications

References 25 publications

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

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

Design and evaluation of a 32‐channel phased‐array coil for lung imaging with hyperpolarized 3‐helium

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

Contact Info

Product

Resources

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