Quantitative 31P magnetic resonance spectroscopy of the human breast at 7 T

This study presents quantified levels of phosphorylated metabolites in glandular tissue of human breast using (31)P magnetic resonance spectroscopy at 7 T. We used a homebuilt (1)H/(31)P radiofrequency coil to obtain artifact-free (31)P MR spectra of glandular tissue of healthy females by deploying whole breast free induction decay (FID) detection with adiabatic excitation and outer volume suppression. Using progressive saturation, the estimated apparent T(1) relaxation time of (31)P spins of phosphocholine and phosphoethanolamine was 4.4 and 5.7 s, respectively. Quantitative measures for phosphocholine and phosphoethanolamine levels in glandular tissue were established based on MR imaging. We used a 3D (1)H image of the breast to segment the glandular tissue; this was matched to a 3D (31)P image of the B1- field of the (31)P coil to correct for differences in glandular tissue volume and B(1) inhomogeneity of the (31)P coil. The (31)P MR spectra were calibrated using a phantom with known concentration. Average levels of phosphocholine and phosphoethanolamine in 11 volunteers were 0.84 ± 0.21 mM and 1.18 ± 0.41 mM, respectively. In addition, data of three patients with breast cancer showed higher levels of phosphocholine and phosphoethanolamine compared with healthy volunteers. This may indicate a potential role for the use of (31)P magnetic resonance spectroscopy for characterization, prognosis, and treatment monitoring in breast cancer.     

Semi‐LASER localized dynamic 31P magnetic resonance spectroscopy in exercising muscle at ultra‐high magnetic field

Magnetic resonance spectroscopy (MRS) can benefit from increased signal‐to‐noise ratio (SNR) of high magnetic fields. In this work, the SNR gain of dynamic ³¹P MRS at 7 T was invested in temporal and spatial resolution. Using conventional slice selective excitation combined with localization by adiabatic selective refocusing (semi‐LASER) with short echo time (TE = 23 ms), phosphocreatine quantification in a 38 mL voxel inside a single exercising muscle becomes possible from single acquisitions, with SNR = 42 ± 4 in resting human medial gastrocnemius. The method was used to quantify the phosphocreatine time course during 5 min of plantar flexion exercise and recovery with a temporal resolution of 6 s (the chosen repetition time for moderate T₁ saturation). Quantification of inorganic phosphate and pH required accumulation of consecutively acquired spectra when (resting) Pi concentrations were low. The localization performance was excellent while keeping the chemical shift displacement acceptably small. The SNR and spectral line widths with and without localization were compared between 3 T and 7 T systems in phantoms and in vivo. The results demonstrate that increased sensitivity of ultra‐high field can be used to dynamically acquire metabolic information from a clearly defined region in a single exercising muscle while reaching a temporal resolution previously available with MRS in non‐localizing studies only. The method may improve the interpretation of dynamic muscle MRS data. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Comparing localized and nonlocalized dynamic 31P magnetic resonance spectroscopy in exercising muscle at 7T

By improving spatial and anatomical specificity, localized spectroscopy can enhance the power and accuracy of the quantitative analysis of cellular metabolism and bioenergetics. Localized and nonlocalized dynamic ³¹P magnetic resonance spectroscopy using a surface coil was compared during aerobic exercise and recovery of human calf muscle. For localization, a short echo time single‐voxel magnetic resonance spectroscopy sequence with adiabatic refocusing (semi‐LASER) was applied, enabling the quantification of phosphocreatine, inorganic phosphate, and pH value in a single muscle (medial gastrocnemius) in single shots (T_R = 6 s). All measurements were performed in a 7 T whole body scanner with a nonmagnetic ergometer. From a series of equal exercise bouts we conclude that: (a) with localization, measured phosphocreatine declines in exercise to a lower value (79 ± 7% cf. 53 ± 10%, P = 0.002), (b) phosphocreatine recovery shows shorter half time (t_1/2 = 34 ± 7 s cf. t_1/2 = 42 ± 7 s, nonsignificant) and initial postexercise phosphocreatine resynthesis rate is significantly higher (32 ± 5 mM/min cf. 17 ± 4 mM/min, P = 0.001) and (c) in contrast to nonlocalized ³¹P magnetic resonance spectroscopy, no splitting of the inorganic phosphate peak is observed during exercise or recovery, just an increase in line width during exercise. This confirms the absence of contaminating signals originating from weaker‐exercising muscle, while an observed inorganic phosphate line broadening most probably reflects variations across fibers in a single muscle. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

In vivo 31P magnetic resonance spectroscopy of human brain at 7 T: an initial experience.

In vivo (31)P spectra were acquired from the human primary visual cortex at 7 T. The relaxation times of the cerebral metabolites, intracellular pH, rate constant (k(f)) of the creatine kinase (CK) reaction, and nuclear Overhauser enhancement (NOE) on the detected phosphorus moieties from irradiation of the water spins were measured from normal subjects. With a 5-cm-diameter surface coil, 3D (31)P chemical shift imaging was performed with a spatial resolution of 7.5 ml and an acquisition resolution of 8 min, resulting in a signal-to-noise ratio (SNR) for phosphocreatine (PCr) resonance of 32. The apparent T(1) and T(2) of PCr measured at 7 T were 3.37 +/- 0.29 s and 132.0 +/- 12.8 ms, respectively, which were considerably longer than those of adenosine triphosphate (ATP) (T(1): 1.02-1.27 s; T(2): 25-26 ms). The NOE measured in this study was 24.3% +/- 1.6% for PCr, and 10% for ATP. The k(f) measured in the human primary visual cortex was 0.24 +/- 0.03 s(-1). The results from this study suggest that ultra-high-field strength is advantageous for performing in vivo (31)P magnetic resonance spectroscopy (MRS) in the human brain.     

Comparisons of ATP turnover in human muscle during ischemic and aerobic exercise using 31P magnetic resonance spectroscopy

To investigate human muscle bioenergetics quantitatively in vivo, we used ³¹P magnetic resonance spectroscopy to study the flexor digitorum superficialis of four adult males during dynamic ischemic and aerobic exercise at 0.50–1.00 W and during recovery from aerobic exercise. During exercise, changes in pH and [PCr] were larger at higher power, but in aerobic exercise neither end-exercise [ADP] nor the initial postexercise PCr resynthesis rate altered with power. In ischemic exercise we estimated total ATP synthesis from the rates of PCr depletion and glycogenolysis (inferred using an analysis of proton buffering); this was linear with power output. In aerobic exercise, again we estimated ATP synthesis rates due to phosphocreatine hydrolysis and glycogenolysis (incorporating a correction for proton efflux) and also estimated oxidative ATP synthesis by difference, using the total ATP turnover rate established during ischemic exercise. We conclude that in early exercise oxidative ATP synthesis was small, increasing by the end of exercise to a value close (as predicted) to the initial postexercise rate of PCr resynthesis. Furthermore, a plausible estimate of proton efflux during aerobic exercise can be inferred from the pH-dependence of proton efflux in recovery.     

ATP production and mechanical work in exercising skeletal muscle: A theoretical analysis applied to 31P magnetic resonance spectroscopic studies of dialyzed uremic patients

³¹P magnetic resonance spectroscopy (³¹P MRS) can yield much information about bioenergetics in skeletal muscle. During mixed aerobic/glycolytic exercise, changes in phos-phocreatine (PCr) concentration and pH may be abnormal because of reduced muscle mass or reduced efficiency (which the authors combine here as “effective muscle mass”) or because of reduced oxidative capacity. The authors show how these can be distinguished by calculating the nonoxidative and oxidative costs of mechanical work, and also of work per unit of effective muscle mass (measured using the initial rate of ATP turnover). These quantities are substantially time-independent during incremental exercise, and so can be used to compare exercise studies of differing duration. The authors illustrate this analysis by showing that in dialyzed patients with chronic renal failure, the substantial exercise abnormalities seen by ³¹P MRS are due mainly to a decrease in effective muscle mass, which outweighs the oxidative defect implied by the abnormal PCr recovery kinetics.     

Optimized detection of changes in glucose-6-phosphate levels in human skeletal muscle by 31P MR spectroscopy.

As glucose-6-phosphate (G6P) plays a central role in muscle energy metabolism, the possibility to observe changes in the tissue level of this compound in vivo is very relevant. G6P can be detected noninvasively by (31)P MR spectroscopy, but its visibility in vivo is severely hampered due to low tissue levels and spectral overlap with other, stronger phosphomonoester signals. To optimize the observation of changes in G6P levels in human calf muscle by (31)P MR spectroscopy at 1.5 T, we implemented an approach involving a new RF probe and a postacquisition correction method. An anatomically shaped circularly polarized (31)P coil was designed for high intrinsic sensitivity. Together with an additional (1)H coil and (1)H blocking circuits this allowed the application of NOE and (1)H decoupling to further enhance sensitivity. A hyperglycemic hyperinsulinemic clamp was used to increase G6P levels. The spectra were corrected for frequency and phase drift due to scanner instability and leg movements using an automated phase and frequency correction method. Difference (31)P spectroscopy was applied to detect changes of the G6P signal. The result, in five healthy subjects, demonstrated that the combination of sensitivity optimization with automated drift correction enabled a robust detection of G6P changes in time series experiments down to a resolution of 10 min.     

~(31)P磁共振波谱回顾及其在肝脏等脏器中的临床应用

常规方法检测肝脏ATP需要大量组织标本 ,在同一批动物或人体的重复检测是不可能的 ,并且不能监测早期或可逆性细胞损伤中的轻微新陈代谢变化。3 1PMRS是活体检测高能磷酸盐的唯一手段。无机磷 (Pi)与磷酸单酯 (PME)比率 (细胞生存和代谢的标志 )以及各种ATP可以重复定量检测。在细胞死亡和随后的器官病变之前 ,利用3 1PMRS ,可检测到早期轻微能量变化引起的β ATP明显减少 ,Pi/ β ATP比率减少以及PME/ β ATP比率的显著升高[1] 。在正常肝脏的波谱中 ,含磷总量的PME波峰为 4 .77% (可信区间CI:4 .11～ 5 .4 2 ) ,在轻度肝硬化 [5 .80 % (95 %CI:5 .4 6～ 6 .14 ) ,P =0 0 0 5 1,对正常肝 ]和重度肝硬化 [9.6 4 % (95 %CI:8.71～ 10 .5 7) ,P =0 .0 0 0 2 ,对正常肝和P =0 .0 0 1,对轻度肝硬化 ]明显升高[2 ] 。在对所有原发或继发肿瘤患者的研究中 ,PME/PDE比率是增加的 ,作者认为3 1PMRS是检测肝脏疾病进展和治疗效果的有效方法[3 ] 。     

Magnetization exchange observed in human skeletal muscle by non‐water‐suppressed proton magnetic resonance spectroscopy

Many metabolites in the proton magnetic resonance spectrum undergo magnetization exchange with water, such as those in the downfield region (6.0–8.5 ppm) and the upfield peaks of creatine, which can be measured to reveal additional information about the molecular environment. In addition, these resonances are attenuated by conventional water suppression techniques complicating detection and quantification. To characterize these metabolites in human skeletal muscle in vivo at 3 T, metabolite cycled non‐water‐suppressed spectroscopy was used to conduct a water inversion transfer experiment in both the soleus and tibialis anterior muscles. Resulting median exchange‐independent T₁ times for the creatine methylene resonances were 1.26 and 1.15 s, and for the methyl resonances were 1.57 and 1.74 s, for soleus and tibialis anterior muscles, respectively. Magnetization transfer rates from water to the creatine methylene resonances were 0.56 and 0.28 s^?1, and for the methyl resonances were 0.39 and 0.30 s^?1, with the soleus exhibiting faster transfer rates for both resonances, allowing speculation about possible influences of either muscle fibre orientation or muscle composition on the magnetization transfer process. These water magnetization transfer rates observed without water suppression are in good agreement with earlier reports that used either postexcitation water suppression in rats, or short CHESS sequences in human brain and skeletal muscle. Magn Reson Med, 70:916–924, 2013. © 2012 Wiley Periodicals, Inc.     

Direct noninvasive quantification of lactate and high energy phosphates simultaneously in exercising human skeletal muscle by localized magnetic resonance spectroscopy.

A novel method based on interleaved localized 31P- and 1H MRS is presented, by which lactate accumulation and the accompanying changes in high energy phosphates in human skeletal muscle can be monitored simultaneously during exercise and recovery. Lactate is quantified using a localized double quantum filter suppressing the abundant lipid signals while taking into account orientation dependent signal modulations. Lactate concentration after ischemic exercise directly quantified by DQF 1H spectroscopy was 24 +/- 3 mmol/L cell water, while 22 +/- 3 mmol/L was expected on the basis of 31P MRS acquired simultaneously. Lactate concentration in a sample of porcine meat was estimated to be 40 +/- 7 mmol/L by means of DQF quantitation, versus 39 +/- 5 mmol/L by biochemical methods. Excellent agreement is shown between lactate concentrations measured noninvasively by 1H MRS, measured biochemically ex vivo, and inferred indirectly in vivo from changes in pH, P(i), and PCr as obtained from 31P MRS data.     

Phosphocreatine resynthesis during recovery in different muscles of the exercising leg by 31P‐MRS

To investigate the high‐energy phosphate metabolism by ³¹P‐nuclear magnetic resonance spectroscopy during off‐transition of exercise in different muscle groups, such as calf muscles and biceps femoris muscles, seven male long‐distance runners (LDR) and nine untrained males (UT) performed both submaximal constant and incremental exercises. The relative exercise intensity was set at 60% of the maximal work rate (60%Wmax) during both knee flexion and plantar flexion submaximal constant load exercises. The relative areas under the inorganic phosphate (P_i) and phosphocreatine (PCr) peaks were determined. During the 5‐min recovery following the 60%Wmax, the time constant for the PCr off‐kinetics was significantly faster in the plantar flexion (LDR: 17.3 ± 3.6 s, UT: 26.7 ± 6.7 s) than in the knee flexion (LDR: 29.7 ± 4.7 s, UT: 42.7 ± 2.8 s, P < 0.05). In addition, a significantly faster PCr off‐kinetics was observed in LDR than in UT for both exercises. The ratio of P_i to PCr (P_i/PCr) during exercise was significantly lower during the plantar flexion than during the knee flexion (P < 0.01). These findings indicated that the calf muscles had relatively higher potential for oxidative capacity than that of biceps femoris muscles with an association of training status.