兔Vx2肿瘤对表阿霉素骨水泥介入治疗反应的^31P磁共振频谱监测

目的：用３１Ｐ ＭＲＳ监测表阿霉素骨水泥介入兔Ｖｘ２ 肿瘤的治疗反应。　方法：对５ 个皮下Ｖｘ２ 实体瘤作表阿霉素骨水泥经皮介入治疗;对另５ 个肿瘤仅作单纯骨水泥注入以作对照。对二组肿瘤均作治疗前后３１Ｐ ＭＲＳ检查。　结果：表阿霉素骨水泥治疗早期出现ＰＯＥ和Ｐｉ峰值升高,ＰＭＥ和ＡＴＰ信号峰减低的改变,提示良好的治疗反应。　结论：表阿霉素骨水泥可从骨水泥中释放并具有抗肿瘤效应;３１ＰＭＲＳ具有早期监测肿瘤化疗反应的作用。     

Magnetic resonance spectroscopy of the heart. Overview of studies in animals and man

Magnetic resonance spectroscopy (MRS) has been used effectively in the evaluation of cardiac physiology. Studies have been done at various levels of complexity extending from isolated hearts to man. Correlation of high-energy phosphate compounds with contractile function is achieved by simultaneous or immediate sequential measurement of ventricular contractile function and the phosphorus-31 MR spectra. Studies in isolated hearts have monitored the response to ischemia of normal and hypertrophic hearts and the preservation of myocardial function and high- energy phosphate stores by drugs administered prior to the ischemic event. Regional myocardial ischemia has been evaluated by simultaneous monitoring of myocardial regional segment length by sonomicrometry and regional myocardial 31P MRS in the intact heart of larger animal models. Function and metabolism have been assessed in man by the combined application of cine MRI and 31P MRS acquired with a surface coil.     

Response of tumors to therapy studied by 31P magnetic resonance spectroscopy

Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.     

Accuracy of 1H and 31P MRS analyses of lactate in skeletal muscle.

As the end product of anaerobic metabolism and a source of H(+), lactic acid is important in metabolism and pH regulation. Several methods have been introduced to calculate changes in the lactate anion (Lac(-)) concentration in exercising skeletal muscle from information derived from the (31)P spectrum. Alternatively, Lac-may be observed directly with (1)H MRS. Both (1)H and (31)P spectroscopy have potential problems, which could prevent accurate determination of [Lac(-)]. It is demonstrated that quantitatively accurate (1)H MRS measurements of changes in [Lac(-)] due to exercise are possible in isolated muscle. In general, calculation by (31)P MRS overestimates Lac-production. An analysis is presented of possible sources of errors in the (1)H and (31)P MRS methods.     

脑放射损伤的影像学研究进展

脑放射损伤发病机制主要有三种学说即血管损伤、胶质损伤和免疫反应机制,最近多数学者的研究支持血管和胶质损伤机制,血管方面的改变在晚期放射效应中起主要作用。CT和MRI对局限性脑损伤和弥漫性脑白质损伤可明确诊断。MRI的T2加权成像(T2WI)显示水分变化敏感性高,又不受颅底线束硬化伪影的影响,MRI发现白质病变的敏感性是CT的2~3倍。如果是脑本身肿瘤放疗后,CT和MRI区别病灶复发或放射性坏死比较困难,PET和MRS(磁共振波谱成像)在两者鉴别诊断中则初步呈现出一定的优势。行PET检查时,如为肿瘤则代谢活跃,坏死则代谢低下,但敏感性和特异性欠理想。MRS测量感兴趣区内代谢产物的量或比率有助于两者的鉴别诊断。另外,PET功能成像和MRS还可预测放疗病人较早期无症状的可逆性放射损伤,以便及时应用激素等药物治疗,避免其进一步发展为临床症状明显的不可逆性损伤。     

Evaluation of BA1112 rhabdomyosarcoma oxygenation with microelectrodes, optical spectrophotometry, radiosensitivity, and magnetic resonance spectroscopy.

We studied tumor tissue oxygenation in the BA1112 rhabdomyosarcoma using micro-electrode pO2 measurements, optical spectrophotometry, analyses of cell survival after irradiation, and 31P magnetic resonance spectroscopy (MRS). Studies were carried out in WAG/Rij/Y rats breathing normoxic, hypoxic, and hyperoxic gas mixtures with and without iv administration of perfluorochemical. Significant changes in tissue oxygenation and metabolic status were found when pO2 values, optical measurements of hemoglobin saturation and cytochrome a, a3 reduction-oxidation, radiation cell survival determinations, and MRS measurements of phosphometabolite ratios were obtained in rats breathing different gas mixtures. Inhalation of 100% O2 caused increases in tumor pO2, hemoglobin saturation, cytochrome a, a3 oxidation, tumor radiosensitivity, and PCr/Pi, NTP/Pi, and PDE/Pi ratios. Such changes were augmented by pretreatment with iv perfluorochemicals. Inhalation of hypoxic gas mixtures resulted in reductions in the above parameters. These results indicate that tissue oxygenation can be manipulated reproducibly in the BA1112 rhabdomyosarcoma and suggest that 31P MRS can be used to monitor changes in tumor oxygenation in this model system.     

Phosphorus-31 MRS of the kidney

Phosphorus-31 (31P) magnetic resonance spectroscopy of the kidneys promises to provide metabolic information leading to better assessment of renal physiology. However, the problems of studying the metabolism of the heterogeneous renal architecture by precisely localizing the origin of the signal obtained from small voxels and eliminating motion artifacts have not been solved as yet. The normal 31P MRS spectra show a characteristic fingerprint of six peaks including phosphomonoesters, phosphodiesters, inorganic phosphorus, and gamma, alpha, beta adenosine triphosphate (ATP). Renal failure, regardless of its etiology and mechanism of inducement (hypoxia, ischemia, acidosis, or obstruction) produces a loss of ATP with a progressive increase of inorganic phosphorus and a decline in intracellular pH. The severity of renal failure correlates with the severity of the metabolic disturbance. The potential use of 31P MRS in the assessment of renal viability has been applied to the study of renal preservation methods and prediction of renal function following transplantation.     

Tumor characterization using unconventional MR modalities

This article reviews many of the promising new magnetic resonance (MR) modalities for the characterization of tumor structure and metabolism, excluding 31P magnetic resonance spectroscopy (MRS). The report focuses on recent work with localized proton MRS, MR imaging of diffusion and perfusion, and work on imaging bound pools of sodium ions. The technical problems associated with these methods are discussed, along with the unique information each provides. Many of these techniques have already been used in studies of human disease, or are of sufficient importance that clinical applications are imminent.     

常规MRI结合31P MR波谱在骨及软组织肿瘤中的临床应用进展

磁共振波谱分析 (MRS)是目前对人体唯一无创伤的研究活体组织器官代谢、生化变化及化合物定且分析的方法 ,能显示肿瘤和正常组织之间代谢的不同 ,能在分子水平上反映病理情况。磷是肌肉代谢中的重要要素 ,因而磷谱在肌肉骨酪系统影像中的意义较大。本文综述了常规MRIU结合3 1PMR波谱在骨及软组织肿瘤中的应用进展。     

Ifosfamide pharmacokinetics and hepatobiliary uptake in vivo investigated using single- and double-resonance 31P MRS.

MRS has considerable potential for the measurement of drug pharmacokinetics in vivo. In this study single- and double-resonance (31)P MRS was used to investigate the biodistribution, pharmacokinetics, and metabolism of ifosfamide following administration of 500 mg/kg ifosfamide in guinea pigs. (1)H-decoupling was found to nearly double the signal of detected peaks. However, in contrast to studies of ifosfamide in solution, the polarization transfer sequence gave no further signal enhancements. This was attributed to significantly reduced relaxation times in vivo. Chemical shift imaging (CSI) measurements showed that significant proportions of ifosfamide-related (31)P MRS signals arose from the liver, as expected, but also from the gall bladder, which was not predicted from the current literature. Signals were observed within 5 min of the end of administration. The halflife in liver was approximately 74 min, whereas in gall bladder there was no measurable signal decay during the 2.5-hr studies. High-resolution (31)P MRS of bile showed that the "ifosfamide" peak in vivo consists of at least two compounds. The lower-concentration peak is ifosfamide, and an investigation is under way to identify the higher-concentration peak. Other peaks observed in bile are tentatively assigned to carboxy-ifosfamide and dechloroethyl-ifosfamide. Overall, (1)H-decoupled (31)P MRS has proved to be a useful tool for investigating the metabolism of ifosfamide in vivo.     

Magnetic resonance spectroscopy. Evaluation of ischemic heart disease

Magnetic resonance spectroscopy (MRS) is a valuable tool for the study of myocardial ischemia. Phosphorus (31P) MRS can detect changes in high-energy phosphates resulting from ischemia and has been used to determine the sensitivity of metabolic changes to ischemia as well as to investigate the metabolic factors important for myocardial dysfunction. The mechanisms mediating postischemic dysfunction have been investigated using 31P MRS, as have interventions to limit metabolic and functional damage from ischemia. These investigations have laid the groundwork for human cardiac studies. While abnormalities following myocardial infarction have been shown in man, further work must be performed to reliably acquire localized spectra under conditions of ischemia.     

Influence of drugs on diseased states of the heart. A 31P NMR and [Ca]i study

Phosphorus 31 magnetic resonance spectroscopy (MRS) can be used to monitor the direct effect of drugs on energy metabolites of the heart. Using the isolated perfused heart of the cardiomyopathic hamster (late heart failure), drugs that exacerbate the diastolic level of calcium [Ca]i (e.g., dobutamine and digoxin) augment intracellular phosphomonoester sugars, while drugs which increase cyclic adenosine mono-phosphate [cAMP]i (e.g. isoprel, dibutyryl cAMP, and amrinone) lower phosphomonoester sugars. The phosphomonoester sugars are inversely related to developed pressure and oxygen consumption. Accumulation of sugar phosphates indicates inhibition of glycolysis and limited delivery of pyruvate to the mitochondria, thereby decreasing oxygen consumption. The phosphorylation potential obtained from standardized 31P MRS values showed a direct relationship to the rate pressure product in hamsters with heart failure; however, the two parameters were inversely related in control hamsters.     

Multinuclear MR investigation of the metabolic response of the murine RIF-1 tumor to 5-fluorouracil chemotherapy

The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy.     

Clinical utility of muscle MR spectroscopy

31Phosphorus (31P) magnetic resonance spectroscopy (MRS) is well suited for gathering data on skeletal muscle energetics in vivo. The technique has evolved to the point where it has become an important tool in the study of the pathophysiology both of rare primary disorders of muscle such as the mitochondrial myopathies and of more common systemic diseases such as renal failure, which also influence muscle metabolism. 31P-MRS is used for providing information about the biochemical composition of tissue without invasive sampling, and it has the unique ability to measure intracellular pH. In some conditions it can be used as an aid to diagnosis. Because MRS is well tolerated and examinations are easily repeated, the technique can also be employed in longitudinal studies of disease progression or the effects of treatment. Magnetic resonance spectroscopy is being increasingly used in conjunction with other noninvasive technologies to investigate effects of gene function on metabolism.     

人肝脏活体31P MRS谱图后处理的应用研究

目的探讨肝脏31P MRS谱图后处理的最佳途径.方法用1.5T超导MR扫描仪,Heart/Liver频谱表面线圈,俯卧位加呼吸门控(Resp/Trigger)采集数据,对象是15～58岁正常志愿者或肝硬化、肝肿瘤等肝病患者,数据采集后利用各种后处理方法è分别处理,加以比较.结果正常志愿者肝脏31P MR谱图20例,31P MRS谱图的后处理可简单地归结为在J-coupling型峰类型下,进行Filter、Zero-filling、Curve fitting处理,所有被检查者均可获得肝脏良好的31P MRS谱图、各种物质浓度及其相互间的比率.结论波谱后处理方法简便易行,充分利用Edit的编辑技巧,能得到符合要求的曲线和精确的数据.     

Clinical magnetic resonance spectroscopy: a critical evaluation

The present status of magnetic resonance spectroscopy (MRS) in the clinical radiology setting is discussed critically. The number of groups reporting clinical MRS results has increased, indicating the feasibility of performing localized MRS studies on current 1.5 T whole body MR imagers. However the lack of high quality radiofrequency (RF) coils for MRS and proven user-independent methods for the analysis of spectral data is still hampering further development. At present there is no consensus as to the optimal localization scheme which should be employed for phosphorus (31P) MRS. For proton MRS the stimulated echo sequence is gaining wide acceptance. The minimum voxel sizes achievable for proton and 31P MRS in the brain are calculated to be 2 and 30 cm3, respectively. The recent results obtained with proton decoupling for 31P clearly demonstrate that there is a great deal of improvement possible in the quality of localized 31P spectra at 1.5 T. Both the instrument manufacturers and researchers in the field face important challenges in translating methods which have proven feasibility in the research environment into routine clinical protocols.     

Induction of apoptosis in two mammalian cell lines results in increased levels of fructose-1,6-Bisphosphate and CDP-choline as determined by 31P MRS

Programmed cell death or apoptosis was induced in human promyelocytic leukemia (HL-60) and Chinese hamster ovary (CHO-K1) cells using several cytotoxic drugs that have different modes of action, including camptothecin, ceramide, chelerythrine, etoposide, farnesol, geranyl geraniol, and hexadecylphosphocholine. The consequent changes in cellular metabolism were monitored using ³¹P MRS measurements on intact cells and cell extracts. Cells undergoing programmed cell death exhibited characteristic changes in the levels of glycolytic and phospholipid metabolites. The most significant changes were increases in the concentration of the glycolytic intermediate, fructose-l,6-bisphosphate and in the concentration of CDP-choline, which is an intermediate in phosphatidylcholine biosynthesis. In HL-60 cells, the increase in fructose-l,6-bisphosphate levels could be explained by depletion of cellular NAD(H) levels. All of the agents used to induce apoptosis caused the accumulation of CDP-choline. Since the resonances of this compound occur in a relatively well resolved region of tissue spectra, it could provide a marker for apoptosis that would allow the noninvasive detection of the process in vivo using ³¹P MRS measurements.     

Complementarity of magnetic resonance spectroscopy, positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission.

The three techniques allowing the noninvasive study of cardiac metabolism, namely magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPET), all use external detection with stable or radioactive isotopes. These techniques yield different information. PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism (oxygen consumption, glucose and fatty acid utilization) to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high (hydrogen 1, phosphorus 31, fluorine 19...) or low (carbon 13, Deuterium) natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques (measurement of the volume, measurement of the quantity of each molecule, resolution, partial volume effect, improvement of the signal-to-noise ratio, movement of the organ). The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by 31P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and 13C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with 18F-fluorodeoxyglucose (18FDG) can determine the glucose consumption and 1H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with 11C for PET or 13C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyopathies, but some initial results using 31P-MRS are being obtained.     

Implementation and evaluation of CSI-localized J cross-polarization for detection of 31P magnetic resonance spectra in vivo.

Double resonance techniques such as INEPT (insensitive nuclei enhanced by polarization transfer) and JCP (J cross-polarization) have previously been applied in vitro to enhance the SNR of low-sensitivity nuclei and detect altered metabolism, for example, with 13C magnetic resonance spectroscopy (MRS), where the 1H-13C scalar couplings are of the order of 130 Hz. The aim of the present study was to investigate the potential advantage of using JCP for the detection of phosphomonoesters (PME) and phosphodiesters (PDE) with 31P MRS in vivo. These metabolites are involved in membrane metabolism and their concentration is altered in tumors and other pathologies. JCP has been implemented and compared with INEPT and pulse-and-acquire in vivo both in unlocalized and in localized spectra in order to select the optimum method for in vivo applications for PME and PDE detection. The results suggest that JCP can give up to 20% more signal in the PME region and up to 70% more signal in the PDE region, with 20 to 70% lower power deposition than INEPT. Such enhancement could be used to reduce the measurement times for equivalent signal-to-noise ratios. The JCP sequence is, however, slightly more sensitive than INEPT to RF field inhomogeneities, as predicted from theory.     

Hepatic cancers and their response to chemoembolization therapy. Quantitative image-guided 31P magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES. Hepatic embolization combined with intra-arterial administration of cytostatic drugs (chemoembolization) is frequently used to treat primary and metastatic cancers to the liver. Quantitative phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to assess the metabolic state of hepatic cancers and their metabolic response to chemoembolization. METHODS. Fifteen localized 31P MRS studies were performed on five patients with liver tumors. Thirteen healthy volunteers served as controls. Metabolite ratios and molar metabolite concentrations were calculated. RESULTS. Untreated hepatic tumors, relative to normal controls, showed elevated phosphomonoester/adenosine triphosphate (PME/ATP) ratios, reduced concentrations of ATP and inorganic phosphate (Pi), and normal phosphodiester (PDE) concentrations. As an acute response to chemoembolization, ATP, PME, and/or PDE concentrations diminished, whereas Pi concentrations increased or stayed relatively constant. Long-term follow-up after chemoembolization showed decreased PME/ATP and increased ATP concentrations in the absence of changes on standard magnetic resonance and computed tomographic images. CONCLUSIONS. These preliminary spectroscopic data suggest that quantitative 31P MRS can be successfully used to monitor directly metabolic response to hepatic chemoembolization.