Depth‐resolved surface coil MRS (DRESS)‐localized dynamic 31P‐MRS of the exercising human gastrocnemius muscle at 7 T

Dynamic ³¹P‐MRS with sufficiently high temporal resolution enables the non‐invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single‐voxel localized ³¹P‐MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single‐voxel localization scheme with adiabatic pulses limits the quantification of J‐coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth‐resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic ³¹P‐MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm /s versus 0.35 ± 0.18 mm /s) and maximum oxidative flux (0.41 ± 0.14 mm /s versus 0.54 ± 0.16 mm /s) were found between the non‐localized and DRESS‐localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non‐localized datasets, but in none of the DRESS‐localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle‐specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non‐echo‐based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle. Copyright © 2014 John Wiley & Sons, Ltd.     

Reproducibility of creatine kinase reaction kinetics in human heart: a 31P time‐dependent saturation transfer spectroscopy study

Creatine kinase (CK) is essential for the buffering and rapid regeneration of adenosine triphosphate (ATP) in heart tissue. Herein, we demonstrate a ³¹P MRS protocol to quantify CK reaction kinetics in human myocardium at 3 T. Furthermore, we sought to quantify the test–retest reliability of the measured metabolic parameters. The method localizes the ³¹P signal from the heart using modified one‐dimensional image‐selected in vivo spectroscopy (ISIS), and a time‐dependent saturation transfer (TDST) approach was used to measure CK reaction parameters. Fifteen healthy volunteers (22 measurements in total) were tested. The CK reaction rate constant (k_f) was 0.32 ± 0.05 s^?1 and the coefficient of variation (CV) was 15.62%. The intrinsic T₁ for phosphocreatine (PCr) was 7.36 ± 1.79 s with CV = 24.32%. These values are consistent with those reported previously. The PCr/ATP ratio was equal to 1.94 ± 0.15 with CV = 7.73%, which is within the range of healthy subjects. The reproducibility of the technique was tested in seven subjects and inferred parameters, such as k_f and T₁, exhibited good reliability [intraclass correlation coefficient (ICC) of 0.90 and 0.79 for k_f and T₁, respectively). The reproducibility data provided in this study will enable the calculation of the power and sample sizes required for clinical and research studies. The technique will allow for the examination of cardiac energy metabolism in clinical and research studies, providing insight into the relationship between energy deficit and functional deficiency in the heart. Copyright © 2014 John Wiley & Sons, Ltd.     

On the theoretical limits of detecting cyclic changes in cardiac high‐energy phosphates and creatine kinase reaction kinetics using in vivo 31P MRS

Adenosine triphosphate (ATP) is absolutely required to fuel normal cyclic contractions of the heart. The creatine kinase (CK) reaction is a major energy reserve reaction that rapidly converts creatine phosphate (PCr) to ATP during the cardiac cycle and at times of stress and ischemia, but is significantly impaired in conditions such as hypertrophy and heart failure. Because the magnitudes of possible in vivo cyclic changes in cardiac high‐energy phosphates (HEPs) during the cardiac cycle are not well known from previous work, this study uses mathematical modeling to assess whether, and to what extent, cyclic variations in HEPs and in the rate of ATP synthesis through CK (CK flux) could exist in the human heart, and whether they could be measured with current in vivo ³¹P MRS methods. Multi‐site exchange models incorporating enzymatic rate equations were used to study the cyclic dynamics of the CK reaction, and Bloch equations were used to simulate ³¹P MRS saturation transfer measurements of the CK reaction. The simulations show that short‐term buffering of ATP by CK requires temporal variations over the cardiac cycle in the CK reaction velocities modeled by enzymatic rate equations. The maximum variation in HEPs in the normal human heart beating at 60 min^–1 was approximately 0.4 m m and proportional to the velocity of ATP hydrolysis. Such HEP variations are at or below the current limits of detection by in vivo ³¹P MRS methods. Bloch equation simulations show that ³¹P MRS saturation transfer estimates the time‐averaged, pseudo‐first‐order forward rate constant, k_f,ap′, of the CK reaction, and that periodic short‐term fluctuations in k_f′ and CK flux are not likely to be detectable in human studies employing current in vivo ³¹P MRS methods. Copyright © 2015 John Wiley & Sons, Ltd.     

Interleaved 31P MRS imaging of human frontal and occipital lobes using dual RF coils in combination with single‐channel transmitter–receiver and dynamic B0 shimming

In vivo ³¹P magnetic resonance spectroscopy (MRS) provides a unique tool for the non‐invasive study of brain energy metabolism and mitochondrial function. The assessment of bioenergetic impairment in different brain regions is essential to understand the pathophysiology and progression of human brain diseases. This article presents a simple and effective approach which allows the interleaved measurement of ³¹P spectra and imaging from two distinct human brain regions of interest with dynamic B₀ shimming capability. A transistor–transistor logic controller was employed to actively switch the single‐channel X‐nuclear radiofrequency (RF) transmitter–receiver between two ³¹P RF surface coils, enabling the interleaved acquisition of two ³¹P free induction decays (FIDs) from human occipital and frontal lobes within the same repetition time. Linear gradients were incorporated into the RF pulse sequence to perform the first‐order dynamic shimming to further improve spectral resolution. The overall results demonstrate that the approach provides a cost‐effective and time‐efficient solution for reliable ³¹P MRS measurement of cerebral phosphate metabolites and adenosine triphosphate (ATP) metabolic fluxes from two human brain regions with high detection sensitivity and spectral quality at 7 T. The same design concept can be extended to acquire multiple spectra from more than two brain regions or can be employed for other magnetic resonance applications beyond the ³¹P spin.     

Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (³¹P) MRS, combined with saturation transfer (ST), provides non‐invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T₁^app measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four‐angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra‐high‐field MR system, to accelerate the measurement of both P_i‐to‐ATP and PCr‐to‐ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth‐resolved surface coil MRS (DRESS)‐localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, P_i‐to‐ATP and PCr‐to‐ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS‐localized FAST method. The repeatability of PCr‐to‐ATP and P_i‐to‐ATP exchange rate constants, determined by the slab‐selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr‐to‐ATP metabolic flux decreased (from F_CK = 8.21 ± 1.15 mM s^?1 to F_CK = 3.86 ± 1.38 mM s^?1) and the P_i‐to‐ATP flux increased (from F_ATP = 0.43 ± 0.14 mM s^?1 to F_ATP = 0.74 ± 0.13 mM s^?1). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS‐localized FAST method at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.