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。     

P-31 spectroscopy study of response of superficial human tumors to therapy

Studies were performed to characterize phosphorus-31 magnetic resonance (MR) spectra obtained from 10 superficial human tumors outside the brain and to determine whether P-31 MR spectroscopy could allow detection of a response to therapy before a change in tumor size was measured. The ratio of phosphomonoester to adenosine triphosphate peak intensities (PME/ATP) was unusually large in all tumors studied. The average PME/ATP in lymphomas (1.8 +/- 0.5) was greater than in nonlymphoma cancers (1.1 +/- 0.15). The average PME/ATP for all tumors studied (1.4 +/- 0.5) was much greater than that of underlying skeletal muscle (0.23 +/- .09). Eight of the tumors were studied before and after therapy. Responders were distinguished from nonresponders on the basis of changes in tumor size. PME/ATP decreased during therapy in three lymphomas that responded to therapy. In an adenocarcinoma and Ewing sarcoma that did not respond to therapy, PME/ATP increased. PME/ATP remained constant in two squamous cell carcinomas that responded to therapy and decreased in one squamous cell carcinoma that decreased in size by 40% but was classified as a nonresponder. Changes in PME/ATP did not always parallel changes in tumor size during therapy. In two patients, a decrease in PME/ATP preceded a decrease in tumor size. In four patients, PME/ATP increased transiently during periods when tumor size remained constant.     

MR image-guided P-31 MR spectroscopy in the evaluation of brain tumor treatment

Magnetic resonance (MR) image-guided phosphorus-31 MR spectra have been obtained from in situ brain tumors. The volumes of interest used for spectroscopy were defined from hydrogen-1 MR images. Direct comparisons were possible between normal and abnormal tissue, since P-31 spectra from different parts of the brain could be measured in a single examination. P-31 MR spectra of the tumors often showed abnormally high concentrations of phosphomonoesters and low concentrations of phosphocreatines. The effects of pharmacotherapy and radiation therapy were studied in three patients; in each of these cases changes were observed in the P-31 spectra of the tumor. The correlation between MR imaging and P-31 MR spectroscopy was essential for the interpretations of these results.     

P-31 MR spectroscopy of normal human brain and brain tumors

Image-guided phosphorus-31 magnetic resonance (MR)-localized image-selected in vivo spectroscopy was performed on normal human brain and brain tumors. Peak area ratios, absolute molar concentrations of metabolites, and pH were determined. T1 values in normal brain were measured. The most important finding was that the metabolite concentrations detectable with MR spectroscopy in brain tumors were reduced from 20% to 70%. Phosphomonoesters, phosphodiesters, and phosphocreatine (PCr) showed the greatest decreases, while inorganic phosphate (Pi) showed the least change. The PCr-Pi ratio was significantly reduced in tumors. The pH of brain tumors (7.12 +/- 0.03) was more alkaline than that of normal brain (6.99 +/- 0.01). The authors conclude that the metabolite concentrations and pH in human brain tumors differ significantly from those in normal brain. These differences may be ultimately useful in characterizing tumors in man.     

In vivo human testicular function assessed with P-31 MR spectroscopy

The clinical feasibility of assessing testicular metabolic integrity with phosphorus-31 magnetic resonance (MR) spectroscopy was investigated in six healthy volunteers and 23 patients with azoospermia. MR spectroscopic findings were compared with sperm count and motility in all patients and with findings at testicular biopsy in 23 patients. Significant differences (P less than .05) were found between the P-31 spectra of normal and azoospermic testicles in the following peak area ratios: phosphomonoester (PM)/beta-adenosine triphosphate, PM/phosphodiester, and inorganic phosphate/PM. In the patients with azoospermia, there were significant differences in these same peak area ratios between patients with primary testicular failure and those with chronic tubular obstruction. Although the differences between these two groups were statistically significant, there was a large overlap in numbers, and therefore a study with a larger patient population will be required. P-31 MR spectroscopy is a sensitive tool for assessment of testicular metabolic integrity and differentiation of normal testicles from those with markedly decreased spermatogenesis.     

Extremity bone tumors: evaluation by P-31 MR spectroscopy

High-resolution P-31 MR spectra were obtained in four patients with bone tumors of their distal extremities. In one case the tumor, a Ewing sarcoma of the tibia, was investigated during clinical remission after radiation therapy and chemotherapy. The other three cases - one low-grade chondrosarcoma of the tibial head, one malignant fibrous histiocytoma of the tibia, and one chondroblastoma of the medial femoral condyle - showed clinically active tumor growth, with corresponding increased metabolism as demonstrated by bone scintigraphy. The spectra of the three active tumors indicated a comparably high adenosine triphosphate content, similar to previously published spectra from animal tumors or human tumors implanted into animals. There were also high resonances of inorganic phosphate and low resonances of phosphocreatine; there were definite peaks in the phosphodiester and phosphomonoester regions, indicating the existence of these metabolites in the tumors. Slight but definite changes in the metabolite content were observed in one tumor after chemotherapy. The spectra of the unaffected leg did not show any well-resolved P-31 signals, which is typical for healthy bone. These are the first P-31 MR spectra of human bone tumors measured in patients to our knowledge.     

Breast tumors: evaluation with P-31 MR spectroscopy

Differences in the energetics of breast carcinomas and benign breast tumors were monitored by recording their high-energy phosphate concentrations using phosphorus-31 magnetic resonance (MR) spectroscopy. Analysis of the P-31 spectra of biopsy samples from five benign breast tumors and nine breast carcinomas showed that the concentrations of nucleoside triphosphates and phosphomonoesters are consistently higher in the carcinomas than in the benign tumors by an average factor of about three. In addition, the chemical shift differences between the alpha-adenosine triphosphate (alpha-ATP) and beta-ATP signals and between the gamma-ATP and beta-ATP signals were larger by about 0.2 ppm in the carcinomas. These differences result from the lower fraction of magnesium-bound ATP found in the carcinomas under our experimental conditions and reflect a decrease of about two in the concentration of free magnesium ions in the carcinomas relative to that in the benign tumors. Despite the limited number of tumors studied, the results suggest that in vivo P-31 MR spectroscopy may become a reliable method for the diagnosis of breast tumors.     

Human leg neuromuscular diseases: P-31 MR spectroscopy

Phosphorus-31 magnetic resonance (MR) spectra of leg muscles in patients with the neuromuscular diseases Duchenne dystrophy, myotonic dystrophy, postpoliomyelitis, Werdnig-Hoffmann disease, and pedal dystonia were recorded. Ratios of beta-adenosine triphosphate (ATP), inorganic phosphate (Pi), alpha-glycerophosphorylcholine (GPC), and phosphomonoesters to phosphocreatine (PCr) were calculated from peak integrals and compared with normal muscle ratios. In all diseases studied, beta-ATP/PCr and Pi/PCr values showed an increase from normal values. The extent of increase in beta-ATP/PCr was related to the clinical severity of the disease, suggesting that this could be a useful noninvasive means of monitoring effectiveness of therapy for neuromuscular disorders. In myotonic dystrophy and Werdnig-Hoffmann disease, GPC/PCr values increased greatly. The intracellular pH in Duchenne and postpoliomyelitis muscles was slightly elevated compared with that in normal muscles. Hydrogen-1 MR images of muscles showed fat infiltration in all patients, more in weaker muscles and less in stronger muscles.     

Assessment of testicular metabolic integrity with P-31 MR spectroscopy

To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.     

Characterization of tumor hypoxia by 31P MR spectroscopy.

Tumor hypoxia is of considerable importance to the oncologist in selecting and optimizing cancer therapy, because hypoxia can determine the effectiveness of various therapies. The relationship between tumor hypoxia and tumor bioenergetics, assessed by 31P MR spectroscopy, is examined to determine whether 31P MR spectroscopy can be clinically useful to measure or characterize tumor hypoxia. Work with experimental tumors has suggested that several different types of hypoxia may exist and that 31P MR spectroscopy cannot be used to characterize all types. Metabolic hypoxia is the level of hypoxia that results in mitochondrial impairment in cells, and it is associated with declining cellular bioenergetic status, which can be measured by enzymatic assay of adenosine triphosphate (ATP). Because 31P MR spectroscopy is sensitive to levels of ATP, it is potentially sensitive to metabolic hypoxia in vivo and may provide a rapid and noninvasive technique for characterizing metabolic hypoxia in tumors. Radiobiologic hypoxia is the level of hypoxia that results in attenuated cell death due to radiation, because radiotoxicity is directly related to tissue levels of oxygen. Radiobiologic hypoxia of tumors thus has more impact on choice of therapy, yet the relationship between metabolic hypoxia and radiobiologic hypoxia remains to be elucidated. An analysis of published data suggests that 31P MR spectroscopy is directly sensitive to metabolic hypoxia in tumors, but it is only indirectly sensitive to radiobiologic hypoxia in tumors. Therefore, 31P MR spectroscopy may be unable to quantify the cell fraction of a tumor that has radiobiologic hypoxia. However, preliminary data suggest that MR spectroscopy may prove useful for determining the effectiveness of therapeutic interventions designed to manipulate radiobiologic hypoxia in tumors or for monitoring the kinetics of tumor reoxygenation after treatment.     

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.     

Application of image-guided surface coil P-31 MR spectroscopy to human liver, heart, and kidney

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.     

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.     

P-31 MR spectroscopy in assessing testicular torsion: rat model

To develop phosphorus-31 magnetic resonance (MR) spectroscopy as an indicator of testicular viability, unilateral 720 degrees torsion of the spermatic cord was performed in 11 Copenhagen rats. In six of 11 rats, detorsion was done 1 hour later. The authors used special surface coils to obtain P-31 MR spectra (at 2 T) from both tests, then correlated MR findings with those from gross morphologic and histologic examination. In the normal testis, P-31 MR spectra had prominent phosphomonoester (PME) and adenosinetriphosphate (ATP) peaks. Testicular torsion dramatically reduced ATP to almost undetectable levels and significantly decreased the PME/Pi at 1 hour (1.18 +/- 0.22) in nine rats. In two rats, however, no spectral changes were present. Of the six rats in which detorsion was performed, three showed immediate regeneration of ATP and a normal PME/Pi (2.87 +/- 0.06) 3 hours later; testicles in the other three rats did not recover (PME/Pi = 0.72 +/- 0.01). Because gross morphologic observations and histologic findings prior to detorsion were unable to differentiate viable from nonviable tests, these preliminary data suggest P-31 MR spectroscopy may help clinicians diagnose testicular torsion and assess testicular viability.     

Evaluation of the effects of photoradiation therapy on brain tumors with in vivo P-31 MR spectroscopy

In vivo phosphorus-31 magnetic resonance (MR) spectra were obtained by a surface coil method from rat glioma tissue inoculated subcutaneously in CD Fisher rats, and the effects of photoradiation therapy on tumors were evaluated by sequentially observing spectral changes. In the control group, the nucleoside triphosphate (NTP) and phosphomonoester peaks were large, the phosphocreatine peak was small, and the inorganic phosphate (Pi) peak was intermediate. In all eight cases in the group in which a dose of 10 mg/kg of hematoporphyrin derivatives (HpD) was given before photoirradiation, NTP peaks decreased, and the Pi peak increased remarkably within 1 hour after the 60-minute white-light irradiation. Spectral changes were observed before histologic changes were apparent. Histologic examinations 3 days after irradiation showed extensive necrosis in the tumor tissue. With preinjection of 5 mg/kg HpD, three of the eight cases showed spectrum changes after the irradiation. No spectrum changes were observed in the group with preinjection of 2.5 mg/kg. In vivo P-31 MR spectra measurements are useful not only to investigate the energy metabolism of tumor tissue in vivo but also to evaluate the effects of photoradiation therapy on tumors.     

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.     

Abnormal testicular function: potential of P-31 MR spectroscopy in diagnosis

Phosphorus-31 MR spectroscopy of the human testis was performed on healthy volunteers (n = 17) and oligospermic (n = 7) and azoospermic patients (n = 4). All patients in the latter group had the Sertoli-cell-only syndrome. Determination of the ratios of phosphomonoesters (PMs) to adenosine triphosphate (ATP), phosphodiesters (PDs) to ATP, and inorganic phosphate (Pi) to ATP made it possible to discriminate among these three groups. The testicular PM/ATP ratio was 1.71 +/- 0.03 (mean +/- standard deviation) in the healthy volunteers and dropped to 1.41 +/- 0.06 (P less than .001 in comparison with healthy volunteers) in the oligospermic patients and to 1.22 +/- 0.07 (P less than .001) in the azoospermic patients. The testicular PD/ATP ratio did show a slight increase from 0.52 +/- 0.10 in healthy volunteers to 0.68 +/- 0.09 (not significant) for oligospermic patients and to 0.83 +/- 0.10 (P less than .01) for azoospermic patients. The Pi/ATP ratio did not show significant differences between healthy volunteers (0.12 +/- 0.07) and oligospermic patients (0.23 +/- 0.08) but was elevated in the azoospermic patients (0.79 +/- 0.12) (P less than .001).     

Soft-tissue sarcomas: detection of metabolic heterogeneity with P-31 MR spectroscopy

Regional variations in metabolic parameters derived with multivoxel, localized phosphorus-31 magnetic resonance (MR) spectroscopy in spontaneous human-soft-tissue sarcomas were compared with variations in the same parameters in normal human legs. In addition, multivoxel P-31 MR spectroscopy of transplanted rodent sarcomas and microelectrode measurement of pH and PO2 in several locations within them were performed, and, when appropriate, results were compared with the clinical data. Striking voxel-voxel variability in parameters derived with P-31 spectroscopy was found in tumors, with less marked variability seen in normal legs. In the rodent tumors, spatial variations also were found in pH and PO2 measured by means of microelectrodes. These data are consistent with the results of regional measurements in tumors by means of other methods and suggest that clinical MR spectroscopic studies of tumors may need to consider the variability within malignant lesions.