Use of in vivo magnetic resonance spectroscopy for studying metabolic diseases

Owing to the worldwide obesity epidemic and the sedentary lifestyle in industrialized countries, the number of people with metabolic diseases is explosively increasing. Magnetic resonance spectroscopy (MRS), which is fundamentally similar to magnetic resonance imaging, can detect metabolic changes in vivo noninvasively. With its noninvasive nature, 1H, 13C and 31P MRS are being actively utilized in clinical and biomedical metabolic studies to detect lipids and important metabolites without ionizing radiation. 1H MRS can quantify lipid content in liver and muscle and can detect other metabolites, such as 2-hydroxyglutarate, in vivo. Of interest, many studies have indicated that hepatic and intramyocellular lipid content is inversely correlated with insulin sensitivity in humans. Thus, lipid content can be utilized as an in vivo biomarker for detecting early insulin resistance. Employing 13C MRS, hepatic glycogen synthesis and breakdown can be directly detected, whereas 31P MRS provides in vivo adenosine triphosphate (ATP) synthesis rates by saturation transfer methods in addition to ATP content. These in vivo data can be very difficult to assess by other methods and offer a critical piece of metabolic information. To aid the reader in understanding these new methods, fundamentals of MRS are described in this review in addition to promising future applications of MRS and its limitations.

Biochemical metabolic changes detected by phosphorus-31 MR spectroscopy in liver of fasting rabbits / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the biochemical metabolic changes detected by phosphorus-31 MR spectroscopy ((31)P MRS) with pathologic changes in the liver of fasting rabbits.</p><p><b>METHODS</b>A total of 22 rabbits were under the starvation up to death to establish animal models. Hepatic (31)P MRS was performed in different period of 10 rabbits including normal condition, over-starvation, agonal condition and death after 30 min. Other 9 rabbits were divided into three type including over-starvation, agonal condition and death group with 3 rabbits in each group, and 3 healthy rabbits served as controls. All the 12 rabbits were sacrificed for the hepatic pathological examination. The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured.</p><p><b>RESULTS</b>All the relative quantification of phosphorus metabolites were changed significantly from starvation to death (X(2)=23.13-35.41, P<0.01). The relative quantifications of ATP of normal condition, over-starvation, agonal condition and death were 2.54 +/-0.53, 1.73 +/-0.14, 0.88 +/-0.23 and 0.05 +/-0.08, respectively (rs=1.0, P<0.01). The relative quantifications of PDE from normal to death were 1.25 +/-0.54, 2.76 +/-0.23, 3.33 +/-0.49 and 3.87 +/-0.43, respectively, and those of Pi were 0.42 +/-0.02, 0.65 +/-0.05, 0.89 +/-0.15 and 0.99 +/-0.08, respectively (rs=1.0, P <0.01). The relative quantifications of PME were also significantly changed (rs=0.4, P=0.6). The pathologic changes of normal condition, over-starvation, agonal condition and death: decreased size of hepatocytes, loss of cell number, cellular swelling, degeneration and cell necrosis or hepatic hemorrhage became more and more pronounced.</p><p><b>CONCLUSION</b>(31)P MRS can monitor dynamic changes of relative quantification of phosphorus metabolites, which are correlated with the pathological severity of acute hepatic injury by fasting.</p>

Evaluation of biochemical metabolites by 31P MR spectroscopy in leukemic infiltration of liver / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the changes of phosphorus metabolites in leukemic infiltration of liver (LIL) with two-dimensional chemical shift imaging(2D CSI)(31)phosphorus MR spectroscopy ((31)P MRS).</p><p><b>METHODS</b>Fifteen patients with LIL and 12 healthy subjects (control group) were scanned with liver 2D CSI(31)P MRS by a 1.5T MR Scanner(Sonata, Siemens Corporation). Relative quantification of phosphorus metabolites including phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE) and beta-adenosine- triphosphate (beta-ATP) were detected and after calibrated with model factor, the ratios of PME/PDE, PME/(PME+PDE), PME/ATP, PDE/ATP and Pi/ATP were analyzed.</p><p><b>RESULTS</b>Compared with control group, the PME value, PME/PDE ratio, PME/(PME+PDE) ratio and PME/ATP ratio were increased in LIL group (1.992 +/-0.876 Compared with 1.167 +/-0.427, P <0.05), (0.551 +/-0.339 Compared with 0.254 +/-0.059,P <0.01), (0.326 +/-0.13 Compared with 0.199 +/-0.049, P <0.01)and (1.402 +/-0.654 Compared with 0.792 +/-0.232, P <0.01) respectively.</p><p><b>CONCLUSION</b>(31)P MRS examination can be used as a non-invasive procedure to evaluate the changes of phosphorus metabolites of leukemic infiltration of liver. The increase of PME value and its ratios to PDE, ATP and PME+PDE may indicate leukemic infiltration of liver.</p>

Changes of 3-tesla 31P-MR spectroscopy of bone and soft tissue tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the characteristic changes of 31P-MR spectroscopy of bone and soft tissue tumors.</p><p><b>METHODS</b>41 patients were examined by phosphorus surface coil of 3 tesla MR machine, including 18 benign tumor foci and 28 malignant foci, and adjacent normal muscles. The areas under the peaks of various metabolites in the spectra were measured, including phosphomonoester (PME), inorganic phosphours (Pi), phosphodiester (PDE), phosphocreatine (Pcr), adenosine triphosphate (ATP) gamma, alpha, beta. The ratios of the metabolites to beta-ATP, NTP and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr.</p><p><b>RESULTS</b>The ratios of Pcr/PME and PME/NTP in benign and malignant tumor groups were significantly different from those of the normal group (P<0.05). Between benign and malignant tumor groups, the ratios of PME/beta-ATP and PME/NTP were significantly different (P<0.05).</p><p><b>CONCLUSION</b>Pcr/PME and PME/NTP are potential diagnostic indexes of bone and soft tissue tumors. PME/beta-ATP and PME/NTP are potential indexes of differential diagnosis of bone and soft tissue tumors.</p>

Non-invasive assessment of oxidative capacity in young Indian men and women: a 31P magnetic resonance spectroscopy study.

It is generally assumed that men display greater strength and muscle capacity than women. However, previous biochemical and histological studies have shown that men have greater capacity for anaerobic metabolism and women have higher or similar oxidative metabolism. Therefore, in the present study, we estimated oxidative capacity of gastrocnemius muscle and compared in Indian men and women using non-invasive in vivo 31P magnetic resonance spectroscopy (MRS). Healthy subjects (8 young males and 9 females, age-matched) performed plantar flexion exercise within a magnet and MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), ADP, and pH of the calf muscles were carried out using a 1.5 T whole-body MRI system. PCr values during recovery were fitted to an exponential curve, and oxidative capacity was calculated using rate constant (k(PCr)), as an index of oxidative phosphorylation. When men and women were compared for different metabolic ratios, ADP, pH, k(PCr) and oxidative capacity, all parameters turned out to be statistically insignificant. The results showed no gender effect on skeletal muscle oxidative metabolism. The study demonstrated the usefulness of such non-invasive method to indirectly measure the oxidative capacity of the muscle based on PCr recovery.

Tackling radioresistance of hypoxic cells by metabolic modulation of bioenergetics--a 31P MRS study on perfused Ehrlich ascites tumor cells.

In an attempt to overcome resistance of hypoxic cells to radiotherapy, the combination of a hematoporphyrin derivative (Hpd) and 2-deoxy-D-glucose (2-DG), a promising radiomodifier, was evaluated by assessing the alterations in phosphorylated metabolites and bioenergetics induced in perfused Ehrlich ascites tumor (EAT) cells, using Phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS). By reducing flow rate of perfusion, a relatively hypoxic condition of tumor was simulated. Changes in bioenergetics levels induced by the combined treatment of Photosan, a Hpd, and 2-DG, under reduced perfusion conditions were more pronounced. Significantly higher uptake of 2-DG and irreversibility of the reduction in cellular bioenergetics induced by the combined treatment, observed under simulated hypoxic conditions, might have considerable implications in optimizing tumor radiotherapy using 2-DG as an adjuvant. These result also suggest the usefulness of this technique to easily simulate hypoxic conditions of tumors in vitro that could be used for rapid in vitro pharmacological evaluation of promising therapeutic strategies.

Uso de fósforo 31 ressonância nuclear magnética para avaliaçäo da proteçäo do miocárdio utilizando cardioplegia sanguínea contínua e normotérmica / Use of phosphorus 31 nuclear magnetic ressonance for evaluation of the myocardial protection using blood continuous and normothermic cardioplegia

Um modelo isolado de coraçao de porco perfundido com sangue foi adaptado para o uso de fósforo 31 ressonância nuclear magnética (31 pRNM) em estudos de espectroscopia do metabolismo cardíaco durante cardioplegia sangüínea contínua e normotérmica (CSCN). O experimento foi dividido em dois grupos: Grupo I (n=5): os coraçoes foram submetidos a l hora de CSCN. Grupo II (n=5): um período de 20 minutos de isquemia normotérmica durante o período de 1 hora de CSCN 17. A funçao do ventrículo esquerdo (VE) foi avaliada, com o coraçao batendo, utilizando um balao intraventricular, antes do período de parada cardioplégica e a seguir, quando o coraçao foi novamente perfundido com sangue normokalêmico. Durante todo o protocolo, análise espectroscópica do metabolismo cardíaco foi obtida utilizando-se 4.7 T/3Ocm Bruker TM Biospec 31 p RNM com uma resoluçao de 2 minutos para cada resultado. Ao final dos experimentos biopsias miocárdicas foram obtidas para anáiise de ATP e fosfocreatina (PCr) utilizando cromatografia liqüída de alta "performance" (HPLC). Nao houve perda significante de ATP e PCr durante o período de parada cardioplégica com CSCN (Grupo I). Contudo, no Grupo II, a análise espectroscópica demonstrou perda completa de PCr após 14 ñ 2 minutos durante a isquemia normotérmica acompanhada de aumento de fosfato inorgânico (Pi) e diminuiçao do pH intracelular. Quando reperfundido com CSCN, PCr, pH e Pi retomaram aos valores normais em 3 minutos. A funçao do VE avaliada através da elastância sistólica final foi mantida em l00 ñ 10 por cento dos valores obtidos antes da parada cardioplégica no Grupo I. No Grupo II, a funçao do VE foi de 88 ñ 7 por cento (p