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.     

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.     

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.     

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.     

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.     

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.     

Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy

The ability of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy to permit accurate distinction between reperfused-viable and reperfused-infarcted myocardium was examined in a canine model of acute coronary occlusion. In vivo myocardial pH and phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were measured at baseline and for the first 90 minutes after reperfusion of a total coronary artery occlusion producing either predominantly viable (nine animals) or infarcted (nine animals) myocardium in the region of metabolic study. Myocardial viability was assessed in each animal by means of postmortem triphenyltetrazolium chloride staining. Tissue was characterized from the in vivo P-31 MR data by means of logistic regression analysis. The accuracy of using the P-31 MR data for distinguishing reperfused-viable from reperfused-infarcted myocardium was 100% (69 of 69 data points, 18 of 18 animals). Results of the logistic regression procedure indicated that phosphocreatine was the metabolic variable enabling most effective separation of reperfused-viable and reperfused-infarcted myocardium. Thus, metabolic data obtained with P-31 MR spectroscopy permit effective separation of reperfused-viable from reperfused-infarcted myocardium.     

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.     

Bone and soft-tissue lesions: diagnosis with combined H-1 MR imaging and P-31 MR spectroscopy

The feasibility of combined magnetic resonance (MR) imaging and surface coil phosphorus-31 MR spectroscopy at 1.5 T was examined in a clinical study of 34 patients before biopsy of bone or soft-tissue lesions of the extremity and trunk. The results confirmed the inability of MR imaging alone to distinguish most benign lesions from malignant ones. Malignant lesions were distinguished from benign lesions on the basis of significantly higher mean peak ratios of phosphomonoester (PME) to beta-nucleoside triphosphate (NTP) and of phosphodiester to NTP, a significantly lower mean peak area ratio of phosphocreatine to NTP, and a higher mean pH. The diagnostic performance of the PME/NTP peak area ratio is characterized by a sensitivity (true-positive fraction) of 1.00 and a specificity (true-negative fraction) of 0.93. This study provided preliminary evidence that P-31 MR spectroscopy may be used to improve diagnostic specificity in bone and soft-tissue lesions.     

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.     

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).     

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.     

Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease

Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment.     

Malignant hepatic tumors: P-31 MR spectroscopy with one-dimensional chemical shift imaging.

To determine the clinical feasibility and applicability of phosphorus-31 magnetic resonance (MR) spectroscopy and to assess its potential for characterization of human hepatic tissue, one-dimensional chemical shift imaging (CSI) was performed in 37 patients with various malignant hepatic neoplasms (30 metastases from a variety of primary tumors and seven hepatocellular carcinomas) and seven healthy volunteers. Tumors were grouped according to the percentage of the analyzed section that was occupied by tumor: less than 50% (group A) or more than 50% (group B). In group B, all phosphomonoester/beta-adenosine triphosphate ratios were significantly higher than normal (P less than .001). Hepatocellular carcinomas and metastases from various primary neoplasms could not be differentiated on the basis of spectral characteristics and metabolite ratios. Limitations of one-dimensional surface coil CSI prevented separation of spectra of small tumors and tumors deep within the liver parenchyma from spectra of normal liver parenchyma.     

Liver tumors: follow-up with P-31 MR spectroscopy after local chemotherapy and chemoembolization.

The authors examined and quantified the changes observed in the phosphorus-31 magnetic resonance (MR) spectra of liver tumors after chemotherapy and chemoembolization to investigate the suitability of P-31 MR spectroscopy for follow-up. A 1.5-T unit was used before and at specific times during therapy to obtain spectra of liver tumors in 10 patients with liver metastases from colorectal carcinoma and two patients with hepatocellular carcinoma. A marked increase in inorganic phosphate and a decrease in the alpha- and beta-nucleotide phosphate portions of the spectra were observed during the first few hours after local chemotherapy or chemoembolization. Later, the phosphomonoester signals increased markedly and the phosphodiester signals decreased slightly. The effects of successful chemoembolization or local chemotherapy become apparent in the P-31 MR spectrum during the first few hours after the start of therapy. The results demonstrate that P-31 MR spectroscopy is a suitable method for follow-up. However, long-term studies are needed to determine whether it also yields prognostic information.