Effect of hypothyroidism on phosphorus metabolism in muscle and liver: in vivo P-31 MR spectroscopy study.

Hypothyroidism is known to affect nearly every organ and organ system of the human body. The goal of the present study was to gain insight into the phosphorus metabolism and bioenergetic function of striated (calf) muscle and liver in patients with hypothyroidism before and after thyroid hormone treatment. With an ISIS (image-selected in vivo spectroscopy) magnetic resonance (MR) technique for volume selection, phosphorus-31 metabolism of the calf muscle in 10 patients and of the liver in seven patients with severe hypothyroidism was studied before and after treatment. In addition, spectra from the calf muscle and liver were obtained in 10 healthy volunteers. Relative to those from the healthy subjects, the P-31 MR spectra from patients with hypothyroidism showed a significantly diminished phosphocreatine/inorganic phosphate ratio (P less than .01). After thyroid hormone substitution therapy, this ratio returned to normal values within several weeks. No statistically significant changes in the spectra of liver tissue could be detected. The results support the theory that hypothyroidism induces a hormone-dependent, fully reversible impairment of the energy metabolism of striated muscle. Changes in liver metabolism observed with biochemical methods are apparently not detectable with state-of-the-art P-31 MR spectroscopy.     

Localized 31P MR spectroscopy of the transplanted human kidney in situ shows altered metabolism in rejection and acute tubular necrosis

The purpose of this study was to investigate the function of transplant kidneys in situ, and to detect pathologic changes, using volume-selective phosphorous NMR spectroscopy (³¹P MRS). Localized ³¹P MR spectra were obtained from 37 patients using a whole-body MR scanner with a combination of surface coils, adiabatic excitation pulses, and a modified image-selected in vivo spectroscopy (ISIS) sequence. Seventeen patients with pathologic changes after renal transplant were compared with a control group of 20 patients with no evidence of transplant dysfunction. The transplant kidneys with rejection reaction showed higher ratios of inorganic phosphate (P_i) to adenosine triphosphate-α (ATP-α) than the normal control group (.4 ± .16 compared with .22 ± .11, P = .01) and reduced pH. The spectra of transplant kidneys with tubular necrosis had lower phosphomonoester (PME)/phosphodiester (PDE) ratios than the control group (.65 ± .35 compared with .96 ± .5, P = .04). The pathologies of rejection and tubular necrosis could be differentiated from each other by pH (6.93 ± .1 in rejection versus 7.14 ± .19 in tubular necrosis, P = .04). Preliminary results indicate that localized image-guided ³¹P MR spectroscopy of transplant kidneys in situ can detect rejection reactions and acute tubular necrosis noninvasively, providing an incentive for further research.     

Cardiac metabolism in patients with dilated and hypertrophic cardiomyopathy: assessment with proton-decoupled P-31 MR spectroscopy.

Proton-decoupled phosphorus-31 heart spectroscopy was performed in healthy subjects (n = 9) and patients with dilated cardiomyopathy (DCM, n = 9) or hypertrophic cardiomyopathy (HCM, n = 8). The phosphocreatine (PCr)-to-adenosine triphosphate ratio (+/- one standard deviation) after correction for blood contribution and partial saturation was significantly lower in HCM patients relative to the control subjects (1.32 +/- 0.29 vs 1.65 +/- 0.26, P < .05) but not in DCM patients (1.52 +/- 0.58 vs 1.65 +/- 0.26). The inorganic phosphate (Pi) peak was resolved only in patients with the highest spectral quality. Myocardial pH was lower in HCM patients (n = 6) relative to control subjects (n = 4) (7.07 +/- 0.07 vs 7.15 +/- 0.03, P < .05). The Pi/PCr ratio was higher in DCM (n = 3) and HCM (n = 6) patients relative to control subjects (n = 4) (0.29 +/- 0.06 and 0.20 +/- 0.04, respectively, vs 0.14 +/- 0.06; P < .05). Elevated phosphodiester signal in DCM patients correlated with 2,3-diphosphoglycerate signal (r = .94), reflecting blood pool contamination. P-31 spectroscopy enabled detection of abnormalities in cardiac metabolism and determination of pH in patients with HCM and DCM.     

Correlation of MR changes with Doppler US measurements of blood flow in exercising normal muscle.

Muscle data from phosphorus-31 magnetic resonance (MR) spectroscopy and hydrogen-1 MR imaging and popliteal artery data from duplex Doppler ultrasound were compared during an exercise test of the anterior compartment of the leg, in nine healthy volunteers. Significant variations (mean +/- standard deviation) were observed at the end of exercise versus rest in intracellular pH (pHi) (6.32 +/- 0.02 vs 7.02 +/- 0.04, P < .001), T2 (38.2 msec +/- 2.3 vs 29.5 msec +/- 1.1, P < .001), and popliteal output (652 mL/min +/- 232 vs 149 mL/min +/- 65, P < .001). These variables showed the following significant correlations at the end of exercise: T2 and pHi (r = -.784, P < .01), T2 and popliteal output (r = .737, P < .03), and pHi and popliteal output (r = -.902, P < .001). However, during recovery, the T2 curve was significantly different from those of pHi and popliteal output. This suggests that even if circulatory conditions play a role in the maximum T2 variation during exercise, they do not directly explain T2 changes. Furthermore, the correlations involving pHi suggest the role of the metabolism of exercising muscle in transcapillary fluid movement.     

Peripheral arterial occlusive disease: P-31 MR spectroscopy of calf muscle

The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion.     

3T动态磁共振磷谱对正常人骨骼肌线粒体功能的在体研究

目的：运用3T高场强磁共振动态磷谱技术（^31P-MRS）在体评价骨骼肌线粒体能量代谢情况。方法：对20名正常人受试者骨骼肌进行动态31P-MRS采集,后期利用Matlab软件对无机磷（Pi）、磷酸肌酸（PCr）、三磷酸腺苷（ATP）等化合物的峰下面积进行定量分析,分别计算在静止期,运动末期及数个恢复期骨骼肌内高能磷酸化合物的含量,同时计算二磷酸腺苷（ADP）和细胞内PH值,评价磁共振动态磷谱技术对研究骨骼肌线粒体功能的价值。结果：肌肉运动时PCr含量明显降低,Pi、Pi/PCr和ADP升高,恢复期各含磷化合物含量逐渐恢复至静息水平。结论：3T高场强动态磷谱技术可以无创性定量评价骨骼肌线粒体功能,为肌肉的功能影像学提供客观证据,为以后客观研究肌肉相关疾病提供了理想的方法。     

Measurement of skeletal muscle motion in vivo with phase-contrast MR imaging

The ability to measure skeletal muscle motion with phase-contrast magnetic resonance (MR) imaging was tested with a motion phantom that simulated muscle activity. Quantitative analytic data on unidimensional, bidirectional skeletal muscle motion measured in vivo was obtained in four healthy volunteers. MR images of the subjectss' forearms were obtained during flexion and extension of the fingers and of the anterior and posterior muscle compartments of the lower leg with various resistances to ankle dorsiflexion and plantar flexion. It was necessary to correct the data for the effects of eddy currents. In vitro evaluation of the technique was done by studying through-plane sinusoidal motion of solid objects. The largest error was underestimation of the peak excursion of 11.5 mm by 0.09 mm (the root mean square error for the cycle was 0.04 mm) In vivo experiments demonstrated the contraction of muscles in relation to each other. Data acquisition and analysis techniques must be refined, but measuring skeletal muscle motion with phase-contrast MR imaging should enhance the understanding of bioengineering fundamentals and muscular changes in disease and adaptation.     

Alcoholic liver disease: quantitative image-guided P-31 MR spectroscopy

Phosphorus-31 magnetic resonance (MR) spectroscopy was performed on the liver of patients with alcoholic hepatitis (n = 10), alcoholic cirrhosis (n = 9), and viral hepatitis B (n = 3) and on healthy control subjects (n = 21). A hydrogen-1 MR image-guided localization technique (ISIS) was used to acquire P-31 spectra selectively from a volume of interest within the liver. Spectra were analyzed to yield absolute molar concentrations of hepatic phosphomonoesters, phosphodiesters, inorganic phosphate, and adenosine triphosphate. It was found that (a) hepatic metabolite ratios in alcoholic liver disease were not significantly different from those in healthy subjects, (b) absolute hepatic metabolite concentrations were decreased by 25%-46% in alcoholic hepatitis and 13%-50% in alcoholic cirrhosis compared with those in healthy subjects, and (c) hepatic intracellular pH was 7.4 in healthy subjects, more acidic in alcoholic cirrhosis, and more alkaline in alcoholic hepatitis. The findings indicate that hepatic metabolite ratios are not a sensitive measure of alcoholic liver disease, that quantitative P-31 MR spectroscopy is able to noninvasively show metabolic changes associated with alcoholic liver disease, and that alcoholic hepatitis and cirrhosis may be distinguished by means of hepatic intracellular pH measured with MR spectroscopy.     

MR imaging of muscle and tender points in fibromyalgia

Fibromyalgia is a syndrome manifested by chronic, diffuse muscu-loskeletal aching and soreness, palpable muscle tender points, and other symptoms. Standardized clinical diagnostic criteria have recently been developed. Skeletal muscle has been postulated as the end organ in this disease. Biochemical, histologic, electromyographic, and conventional radiographic studies have demonstrated no definitive abnormality. This study sought to establish whether magnetic resonance (MR) imaging could demonstrate any abnormality in these patients. Eighteen patients were entered in the study, 14 of whom were able to complete their examinations. T1 -weighted, T2-weighted, gradient-echo, and STIR (short-tau inversion-recovery) sequences were performed in all patients, with selected patients examined with T1weighted, gadopentetate dimeglu-mine-enhanced sequences. The trapezius and suboccipital regions were imaged in patients who, clinically, had active fibro-myalgia. No abnormalities could be detected. The authors conclude that the conventional MR imaging used in this study was unable to depict any primary skeletal muscle abnormality in fibromyalgia.     

Phosphorus nuclear magnetic resonance spectroscopy: In vivo magnesium measurements in the skeletal muscle of normal subjects

³¹P nuclear magnetic resonance spectroscopy was used to study the skeletal muscle of 33 normal males and 32 females. Free intracellular magnesium levels and the ratios of the phosphorus metabolites were determined. Males had significantly lower free magnesium levels (499.8 μM ± 26.3 μM vs. 530.7 μM ± 36.0 μM, P = 0.001, d.f. = 63, analysis of variance). The free magnesium level (r_s = −0.5431, P = 0.001) and the phosphocreatine/inorganic phosphate ratio in males (r_s = −0.4102, P = 0.018), and the phosphocreatine/inorganic phosphate ratio in females (r_s = −0.4759, P = 0.009) fell with the increasing Minnesota Heart Health Program Questionnaire score.     

Phosphorus-31 brain MR spectroscopy in women during and after pregnancy compared with nonpregnant control subjects

BACKGROUND AND PURPOSE: A reversible decrease in brain size has been demonstrated during normal pregnancy that is maximal at term and returns to normal after many months. The purpose of this longitudinal study was to use phosphorus-31 MR spectroscopy to determine if metabolic changes explain this physiologic event. METHODS: Pregnant women (n = 12) were examined at term and up to 6 months after delivery. Nonpregnant control subjects (n = 7) were imaged twice (a month apart) to exclude hormone effects. Brain (31)P MR spectra were acquired at 1.5 T, and intracellular pH was calculated from the chemical shift between phosphocreatine and inorganic phosphate resonances. Statistical analysis was performed by using an analysis of variance. RESULTS: We found no statistically significant differences in the relative levels of metabolite associated with cerebral bioenergetics and cell membrane metabolism between pregnant women and nonpregnant women. However, a significant increase in cerebral pH was observed in pregnant women at 6 weeks after delivery compared with control subjects (7.074 +/- 0.063 vs 7.017 +/- 0.041; P < .05). pH returned to normal by 6 months after delivery (7.014 +/- 0.010). CONCLUSION: Changes in brain size associated with pregnancy appear to be associated with an increase in intracellular pH after delivery. The observed alkalosis may reflect altered cellular metabolism. These persistent brain perturbations associated with pregnancy indicate that, when postpartum physiologic and pharmacologic changes are measured, long-term effects may be expected in central nervous system processing.     

Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.     

Phosphorus‐31 magnetic resonance spectroscopy of skeletal muscle in maternally inherited diabetes and deafness A3243G mitochondrial mutation carriers

Purpose

To investigate high‐energy phosphate metabolism in striated skeletal muscle of patients with Maternally Inherited Diabetes and Deafness (MIDD) syndrome.

Materials and Methods

In 11 patients with the MIDD mutation (six with diabetes mellitus [DM] and five non‐DM) and eight healthy subjects, phosphocreatine (PCr) and inorganic phosphate (Pi) in the vastus medialis muscle was measured immediately after exercise using ³¹P‐magnetic resonance spectroscopy (MRS). The half‐time of recovery (t1/2) of monoexponentially fitted (PCr+Pi)/PCr was calculated from spectra obtained every 4 seconds after cessation of exercise. A multiple linear regression model was used for statistical analysis.

Results

Patients with the MIDD mutation showed a significantly prolonged t1/2 (PCr+Pi)/PCr after exercise as compared to controls (13.6±3.0 vs. 8.7±1.3 sec, P = 0.01). No association between the presence of DM and t1/2 (PCr + Pi)/PCr was found (P = 0.382).

Conclusion

MIDD patients showed impaired mitochondrial oxidative phosphorylation in skeletal muscle shortly after exercise, irrespective of the presence of DM. J. Magn. Reson. Imaging 2009;29:127–131. © 2008 Wiley‐Liss, Inc.     

Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis.

To determine the cause of reduced urea synthesis in cirrhosis, absolute concentrations of phosphorus metabolites in the human liver have been measured in vivo with magnetic resonance (MR) spectroscopy. One-dimensional chemical shift imaging was used to obtain phosphorus-31 spectra from five healthy volunteers and five patients with alcoholic cirrhosis. A reference standard included in all studies enabled the calculation of absolute concentrations. In contrast to hepatic metabolite ratios, absolute concentrations reveal that in the cirrhotic patients, concentrations of adenosine triphosphate (ATP) were significantly reduced and concentrations of phosphomonoesters slightly reduced. Intracellular pH was unchanged. Histologic evidence suggests that the amount of ATP per cell was unchanged and could not account for the reduced urea production. Instead, urea synthesis depends on the functional liver cell mass, which was reduced by 31% in alcoholic cirrhosis. Quantitative in vivo P-31 MR spectroscopy of liver has potential clinical applications and can supplement the more generally used P-31 metabolite ratios.     

Magnetic resonance imaging of muscle injury

To further evaluate the role of magnetic resonance (MR) imaging in diagnosing and managing muscle injuries, eight patients with muscle pain or palpable masses were imaged. MR findings were correlated with clinical follow-up data. Increased signal was noted on T2-weighted images in torn and overused muscles. One extensively scarred muscle required surgical biopsy to exclude a fibrous tumor. Three partial muscle tears were treated conservatively. One complete musculotendinous junction tear required tendon transfer. MR studies noninvasively identified and staged various muscle injuries, thereby influencing management.     

Phosphorus-31 MR spectroscopy in pediatric liver transplant recipients: a noninvasive assessment of graft status with correlation with liver function tests and liver biopsy

OBJECTIVE: Noninvasive in vivo hepatic phosphorus-31 MR spectroscopy has recently been shown to provide information about hepatic functional status. We sought to show the correlation of phosphorus-31 MR spectroscopy with blood biochemistry and liver biopsy results in pediatric patients after liver transplantation. MATERIALS AND METHODS: Eleven pediatric transplant recipients (eight with good graft function, two with chronic hepatitis, and one with acute rejection) and four healthy control subjects were studied with in vivo 31P MR spectroscopy. Ratios of phosphomonoesters (PME) to total phosphorus (TP), phosphodiester (PDE) to TP, nucleotide triphosphates (NTP), inorganic phosphate (Pi), and intracellular acid-base status (pH) were measured. Liver function test (n = 11) and biopsy (n = 3) results were obtained for correlation with spectroscopic findings. RESULTS: The eight patients with good graft function displayed spectral profiles similar to those of the healthy subjects, and no significant difference in the metabolic ratios of these patients compared with the control subjects was detected. Three patients with abnormal liver function and biopsy-proven hepatic complications showed elevated PME/TP ratios when compared with those of both the control subjects and the group with good graft function. CONCLUSION: Phosphorus-31 MR spectroscopy is a feasible technique for the noninvasive assessment of host-related complications in pediatric patients after liver transplantation. Our preliminary data suggest that the technique may be integrated with MRI for the investigation of impaired liver function in transplant recipients when neither a biliary complication nor a vascular complication is identified.     

Prediction of treatment response of head and neck cancers with P-31 MR spectroscopy from pretreatment relative phosphomonoester levels

RATIONALE AND OBJECTIVES: Combinations of chemotherapy and fractionated radiation therapy are the currently preferred nonsurgical treatment methods for squamous cell carcinoma of the head and neck, but to the authors' knowledge there is no reliable marker for predicting therapeutic response. Early identification of nonresponders would allow prompt replacement of ineffective, toxic therapy by alternative, potentially more effective procedures. Frequent regional node involvement facilitates surface coil investigation with phosphorus-31 magnetic resonance spectroscopy. MATERIALS AND METHODS: P-31 magnetic resonance spectra were acquired from 12 patients before radiation therapy or chemotherapy. In vivo three-dimensional localized P-31 nuclear magnetic resonance chemical shift imaging was performed with a 1.5-T clinical imager and a dual-tuned H-1/P-31 surface coil. Proton decoupling and nuclear Overhauser enhancement were used to improve sensitivity and resolve overlapping signals in the phosphomonoester region of the spectrum. RESULTS: The average pretreatment ratio of phosphomonoester to beta-nucleoside triphosphate was significantly smaller in complete responders (n = 4) than in incomplete responders (partial responders plus nonresponders, n = 8) (0.0 +/- 0.0 vs 1.22 +/- 0.17 [P = .004]). CONCLUSION: Results of this preliminary study suggest that H-1-decoupled P-31 magnetic resonance spectroscopy may prove to be a useful predictor of therapeutic response in head and neck cancers.     

An MR‐compatible bicycle ergometer for in‐magnet whole‐body human exercise testing

An MR‐compatible ergometer was developed for in‐magnet whole‐body human exercise testing. Designed on the basis of conventional mechanically braked bicycle ergometers and constructed from nonferrous materials, the ergometer was implemented on a 1.5‐T whole‐body MR scanner. A spectrometer interface was constructed using standard scanner hardware, complemented with custom‐built parts and software to enable gated data acquisition during exercise. High‐quality ³¹P NMR spectra were reproducibly obtained from the medial head of the quadriceps muscle of the right leg of eight healthy subjects during two‐legged high‐frequency pedaling (80 revolutions per minute) at three incremental workloads, including maximal. Muscle phosphocreatine content dropped 82%, from 32.2 ± 1.0 mM at rest to 5.7 ± 1.1 mM at maximal workload (mean ± standard error; n = 8), indicating that the majority of quadriceps motor units were recruited. The cardiovascular load of the exercise was likewise significant, as evidenced by heart rates of 150 (±10%) beats per minute, measured immediately afterward. As such, the newly developed MR bicycling exercise equipment offers a powerful new tool for clinical musculoskeletal and cardiovascular MR investigation. The basic design of the ergometer is highly generic and adaptable for application on a wide selection of whole‐body MR scanners. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans

The value of ³¹P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). ³¹P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm³ each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ATP) ratio of volunteers (SD 1.72 ± 0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47 ± 0.38 (non-significant vs volunteers; p > 0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92 ± 0.73 vs 6.68 ± 0.80; patients vs volunteers; p <0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction. Received: 9 September 1999; Revised: 30 November 1999; Accepted: 24 December 1999     

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.