In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial.

The standardization and reproducibility of techniques required to acquire anatomically localized 31P MR spectra non-invasively while studying tumors in cancer patients in a multi-institutional group at 1.5 T are reported. This initial group of patients was studied from 1995 to 2000 to test the feasibility of acquiring in vivo localized 31P MRS in clinical MR spectrometers. The cancers tested were non-Hodgkin's lymphomas, sarcomas of soft tissue and bone, breast carcinomas and head and neck carcinomas. The best accrual and spectral quality were achieved with the non-Hodgkin's lymphomas. The initial analysis of the spectral values of the sum of phosphoethanolamine plus phosphocholine normalized by the content of nucleotide triphosphates in a homogeneous sample of 32 NHL patients studied by in vivo (31)P MRS showed good reproducibility among different institutions. No statistical differences were found between the institution with the largest number of cases accrued and the rest of the multi-institutional NHL data (2.28 +/- 0.64, mean +/- standard error; n = 17, vs 2.08 +/- 0.14, n = 15). The preliminary data reported demonstrate that the institutions involved in this trial are obtaining reproducible 31P MR spectroscopic data non-invasively from human tumors. This is a fundamental prerequisite for the international cooperative group to be able to demonstrate the clinical value of the normalized determination of phosphoethanolamine plus phosphocholine by 31P MRS as predictor for treatment response in cancer patients.

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Methodology for applied 4 MHz RF hyperthermia concomitant with 31P NMR spectroscopic monitoring of murine tumours.

It has been generally found that solid tumours in vivo are more susceptible to destruction by heat than normal tissues. Hyperthermia has, thus, been employed in the treatment of cancer either applied alone or in combination with other modalities such as chemotherapy and radiotherapy. However, the critical mechanism(s) by which heat sensitizes and kills cells in the solid tumour remains poorly defined. Magnetic resonance spectroscopic monitoring of tumour metabolism during application of hyperthermia may provide important insight into the response to hyperthermic challenge. The implementation of dual antenna-coil methodology that provides for NMR spectroscopic monitoring (31P at 121 MHz) concomitant with applied 4 MHz RF hyperthermia in murine tumours is described herein, in some detail. This technology, which does not require advanced (and expensive) magnetic resonance imaging systems, should be readily adaptable by other laboratories with an interest in murine tumour models.

Methodological standardization for a multi-institutional in vivo trial of localized 31P MR spectroscopy in human cancer research. In vitro and normal volunteer studies.

A multi-institutional group has been created to demonstrate the utility of in vivo 31P magnetic resonance spectroscopy (31P-MRS) to study human cancers in vivo. This review is concerned with the novel problems concerning quality control in this large multinational trial of 31P MRS. Our results show that the careful and systematic performance of the quality control tests depicted here (standardized dual 1H/31P tuned radiofrequency probe, quality control procedures, routine use of 1H irradiation while acquiring 31P MR signals) has ensured comparable results between the different institutions. In studies made in vitro, the root-mean-square error was 3.6 %, and in muscle of healthy volunteers in vivo the coefficients of variance for the ratios phosphocreatine/nucleotide-triphosphates, phosphocreatine/noise and nucleotide-triphosphate/noise were 12.2, 7.0 and 10.8 %, respectively. The standardization of the acquisition protocol for in vivo-localized 31P MR spectroscopy across the different institutions has resulted in comparable in vivo data, decreasing the possible problems related to a research study carried out under a multi-institutional setting.

Therapeutic efficacy as predicted by quantitative assessment of murine RIF-1 tumour pH and phosphorous metabolite response during hyperthermia: an in vivo 31P NMR study.

Described herein are the initial findings from an 'in-magnet' 31P NMR compatible hyperthermia system capable of concurrently heating and monitoring the metabolic response of murine tumours; the murine radiation induced fibrosarcoma (RIF-1) was employed for these studies. At thermal doses sufficient to raise tumour temperature to 41.5 and 43 degrees C for a period of 30 min, a marked and rapid decrease in nucleoside triphosphate concentration and in pH was observed during the heating period, while inorganic phosphate concentration increased significantly but more gradually. These 31P NMR determined metabolic indices remained depressed/elevated throughout a 1.5 h post-hyperthermia monitoring period. Importantly, these metabolic indices correlated significantly with specific growth delay. This suggests a possible role for NMR spectroscopy in early assessment, and perhaps control, of therapeutic response to hyperthermia.

pH and therapy of human cancers.

Studies in model systems have demonstrated that tumour pH can be a determinant of treatment response. The potential that tumour pH differs from that of normal tissues may provide a basis for selective killing of tumour cells. Although the data are limited, pH measurements in humans indicate a difference between tumour and normal tissues. In general, electrode pH (generally considered to reflect primarily extracellular pH, pHe) is lower in tumour than normal tissue. However, pH measured by magnetic resonance spectroscopy (MRS) or positron emission tomography (PET; both are generally considered to reflect primarily intracellular pH, pHi) is equal to or slightly higher in tumours than normal tissues. Hence, not only may pHe and pHi differ between normal and malignant tissues, but the pH gradient (which determines the distribution of chemotherapeutic agents that are weak acids or bases) is also reduced or reversed in tumours. To date, the majority of treatment-related studies conducted have focused on hyperthermia (combined with radiotherapy) due to the recognized importance of acidic pH as a thermal sensitizer. However, the results have been somewhat surprising: patients with a better response to hyperthermia radiotherapy have higher pH (as measured by electrode or 31P MRS) prior to treatment.

Pulse waveform analysis of arterial compliance: relation to other techniques, age, and metabolic variables.

To assess the physiologic and clinical relevance of newer noninvasive measures of vascular compliance, computerized arterial pulse waveform analysis (CAPWA) of the radial pulse was used to calculate two components of compliance, C1 (capacitive) and C2 (oscillatory or reflective), in 87 normotensive (N1BP, n = 20), untreated hypertensive (HiBP, n = 21), and treated hypertensive (HiBP-Rx, n = 46) subjects. These values were compared with two other indices of compliance, the ratio of stroke volume to pulse pressure (SV/PP) and magnetic resonance imaging (MRI)-based aortic distensibility; and were also correlated with demographic and biochemical values. The HiBP subjects displayed lower C1 (1.34 +/- 0.09 v. 1.70 +/- 0.11 mL/mm Hg, significance [sig] = .05) and C2 (0.031 +/- 0.003 v 0.073 +/- 0.02 mL/mm Hg, sig = .005) than N1BP subjects. This was not true for C1 (1.64 +/- 0.08 mL/mm Hg) and C2 (0.052 +/- 0.005 mL/mm Hg) values in HiBP-Rx subjects. The C1 (r = 0.917, P < .0001) and C2 (r = 0.677, P < .0001) were both closely related to SV/PP, whereas C1 (r = 0.748, P = .002), but not C2, was significantly related to MRI-determined aortic distensibility. Among other factors measured, age exerted a strong negative influence on both C1 (r = -0.696, P < .0001) and C2 (r = -0.611, P < .0001) compliance components. Positive correlations were observed between C1 (r = 0.863, P = .006), aortic distensibility (r = 0.597, P = .19) and 24-h urinary sodium excretion, and between C1- and MR spectroscopy-determined in situ skeletal muscle intracellular free magnesium (r = 0.827, P = .006), whereas C2 was inversely related to MRI-determined abdominal visceral fat area (r = -0.512, P = .042) and fasting blood glucose (r = -0.846, P = .001). Altogether, the close correspondence between CAPWA, other compliance techniques, and known cardiovascular risk factors suggests the clinical relevance of CAPWA in the assessment of altered vascular function in hypertension.

Applications of magnetic resonance in model systems: cancer therapeutics.

The lack of information regarding the metabolism and pathophysiology of individual tumors limits, in part, both the development of new anti-cancer therapies and the optimal implementation of currently available treatments. Magnetic resonance [MR, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electron paramagnetic resonance (EPR)] provides a powerful tool to assess many aspects of tumor metabolism and pathophysiology. Moreover, since this information can be obtained nondestructively, pre-clinical results from cellular or animal models are often easily translated into the clinic. This review presents selected examples of how MR has been used to identify metabolic changes associated with apoptosis, detect therapeutic response prior to a change in tumor volume, optimize the combination of metabolic inhibitors with chemotherapy and/or radiation, characterize and exploit the influence of tumor pH on the effectiveness of chemotherapy, characterize tumor reoxygenation and the effects of modifiers of tumor oxygenation in individual tumors, image transgene expression and assess the efficacy of gene therapy. These examples provide an overview of several of the areas in which cellular and animal model studies using MR have contributed to our understanding of the effects of treatment on tumor metabolism and pathophysiology and the importance of tumor metabolism and pathophysiology as determinants of therapeutic response.

Magnetic resonance imaging to measure therapeutic response using an orthotopic model of human pancreatic cancer.

Pancreatic cancer is one of the most incurable and lethal human cancers in the United States. To facilitate development of novel therapeutic agents, we previously established an orthotopic pancreatic tumor model that closely mimics the natural biological behavior of human pancreatic cancer. In this study, magnetic resonance imaging (MRI) techniques were developed to detect tumor formation noninvasively and monitor serially tumor growth kinetics in this orthotopic model used for experimental drug testing. By using an optimized T2-weighted imaging method, we were able to distinguish human pancreas cancer from normal mouse pancreas. Orthotopic tumor formation was detected as early as day 1 after tumor cell implantation with a tumor volume as small as 12 mm3. Mice with evidence of tumor were separated into four treatment groups: control, auristatin-PE, gemcitabine, and their combination. After treatment, the mice were imaged at least three times before termination of the experiment. Comparison between MRI tumor volume measurements and tumor weights made at biopsy resulted in a correlation coefficient of 0.98. The tumor growth curves constructed from serial magnetic resonance imaging (MRI) measurements clearly showed tumor growth inhibition in treated mice compared with the control group. As expected, the group treated with the combination had the highest response rate compared with either auristatin-PE or gemcitabine alone, and the data were statistically highly significant (p < 0.004). From these results, we conclude that noninvasive MRI can be used to monitor serially therapeutic response in this orthotopic human pancreatic tumor model and can be used in the future to evaluate novel antitumor agents before human studies.

MR imaging of tumor microcirculation: promise for the new millennium.

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is a method of imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE MRI can measure and predict tumor response to therapy. Recent advances in MR technology provide the enhanced spatial and temporal resolution that allow the application of this methodology in the management of cancer patients. The September issue of this journal provided a microcirculation section to update readers on this exciting and challenging topic. Evidence is mounting that DCE MRI-based measures correlate well with tumor angiogenesis. DCE MRI has already been shown in several types of tumors to correlate well with traditional outcome measures, such as histopathologic studies, and with survival. These new measures are sensitive to tumor physiology and to the pharmacokinetics of the contrast agent in individual tumors. Moreover, they can present anatomical images of tumor microcirculation at excellent spatial resolution. Several issues have emerged from recent international workshops that must be addressed to move this methodology into routine clinical practice. First, is complex modeling of DCE MRI really necessary to answer clinical questions reliably? Clinical research has shown that, for tumors such as bone sarcomas, reliable outcome measures of tumor response to chemotherapy can be extracted from DCE MRI by methods ranging from simple measures of enhancement to pharmacokinetic models. However, the use of similar methods to answer a different question-the differentiation of malignant from benign breast tumors-has yielded contradictory results. Thus, no simple, one-size-fits-all-tumors solution has yet been identified. Second, what is the most rational and reliable data collection procedure for the DCE MRI evaluation? Several groups have addressed population variations in some key variables, such as tumor T(1)0 (T(1) prior to contrast administration) and the arterial input function C(a)(t) for contrast agent, and how they influence the precision and accuracy of DCE MRI outcomes. However, despite these potential complications, clinical studies in this section show that some tumor types can be assessed by relatively simple dynamic measures and analyses. The clinical scenario and tumor type may well determine the required complexity of the DCE MRI exam procedure and its analysis. Finally, we suggest that a consensus on naming conventions (nomenclature) is needed to facilitate comparison and analysis of the results of studies conducted at different centers. J. Magn. Reson. Imaging 10:903-907, 1999.

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols.

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast-enhanced T(1)-weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K(trans) (min(-1)); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v(e) (0 < v(e) < 1); and c) the flux rate constant between EES and plasma k(ep) (min(-1)). The rate constant is the ratio of the transfer constant to the EES (k(ep) = K(trans)/v(e)). Under flow-limited conditions K(trans) equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K(trans) equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards.

Key factors in the acquisition of contrast kinetic data for oncology.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising method for both diagnosis and prognosis of cancer despite considerable variation in both the methods of data acquisition and analysis. Both to facilitate integration of results from multiple institutions and to ensure that the data reflect the underlying physiology as accurately as possible, several aspects of data acquisition should be taken into account when developing protocols for DCE-MRI regardless of how the data are analyzed. Among the relevant issues are the relationship between signal enhancement and contrast agent concentration, intra- or inter-patient variation in the blood contrast agent concentration as a function of time, requirements for spatial and temporal resolution, the impact of tumor heterogeneity, and the impact of patient motion during the study. This review considers these factors and, when possible, makes specific recommendations for addressing them experimentally.

Deuterium NMR tissue perfusion measurements using the tracer uptake approach: II. Comparison with microspheres in tumors.

Whole-volume tumor perfusion measured using nuclear magnetic resonance (NMR) observation of deuterated water uptake after intravenous injection and a common arterial input function (AIF) derived from AIF estimates in a small set of animals was compared with perfusion measured by the commonly used microsphere method in rat 9L gliosarcomas. Tumor perfusion estimated with this optimized NMR technique using an appropriate common AIF (i.e., taking into account the duration of anesthesia) correlates highly (n = 13, P = 0. 001) with that measured by the microsphere method, yielding no significant differences (P = 0.5, paired Student's t-test). Thus, the optimized NMR method can be used for repeatable, non-invasive, and quantitative measurements of tumor perfusion. Magn Reson Med 42:240-247, 1999.

Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods.

This paper considers potential problems encountered when using the Kety approach to measure perfusion in small laboratory animals with nuclear magnetic resonance (NMR) tracer uptake methods: a) the need to measure the arterial input function (AIF) in each animal; b) sensitivity to perfusion heterogeneity; c) sensitivity to low signal-to-noise ratio (SNR); and d) influence of changes in the AIF. A method to estimate the AIF in rats is presented that derives an AIF from the time course of a tracer passing through a carotid chamber. The results of computer simulations indicate that a common AIF obtained in one set of animals can be used for perfusion estimations in another set of animals if the tracer is delivered as a dose and that optimal data analysis (fitting data vs. integration approach) is dictated by SNR and perfusion heterogeneity. Experimental strategies are suggested to minimize the effects of changes in the individual AIF that could distort perfusion estimates.

Direct magnetic resonance determination of aortic distensibility in essential hypertension: relation to age, abdominal visceral fat, and in situ intracellular free magnesium.

To investigate the contribution of vascular compliance to essential hypertension (EH), we developed magnetic resonance imaging (MRI) techniques to directly measure aortic distensibility (AD) in the ascending and descending thoracic and abdominal aorta of fasting normal (n= 10) and EH (n=20) subjects. These results were compared with concurrent MR-based measurements of left ventricular mass index (LVMI) and abdominal subcutaneous and visceral fat and with 31P-MR spectroscopic measurement of in situ intracellular free magnesium levels (Mgi) in brain and skeletal muscle. Aortic distensibility in EH was consistently and significantly reduced at all measured sites (2.5+/-0.4, 2.2+/-0.4, 2.3+/-0.4 versus 7.0+/-1.6, 5.1+/-0.3, 7.3+/-0.8 mm Hg(-1) x 10(-3), P<.05), as was Mgi in the brain (284+/-22 versus 383+/-34 micromol/L, P<.05) and skeletal muscle (397+/-10 versus 527+/-36 micromol/L, P<.05). For all subjects, systolic blood pressure (r=-.662, P<.0001) and LVMI (r=-.484, P<.01) were inversely related to AD. AD and brain Mgi were inversely related to age (AD, r=-.792, P<.0001; brain Mgi: r=-.673, P<.05). AD was inversely related to fasting blood glucose (r=-.413, P<.05) and to abdominal visceral fat (r=-.416, P<.05) but not to body mass index (BMI: r=-.328, P=NS) or subcutaneous fat (r=-.157, P=NS). AD was also significantly and positively related to in situ Mgi, both in the brain and skeletal muscle (brain: r=.712, P<.01; skeletal muscle: r=.632, P<.01). We conclude that (1) MR techniques can be used to coordinately and noninvasively assess cardiac, vascular, metabolic, and ionic aspects of hypertensive disease in humans; (2) increased systolic blood pressure and LVMI in EH may at least in part result from decreased AD; (3) decreased Mgi contributes to arterial stiffness in hypertension and may help to explain the characteristic age-related decreases in AD; and (4) decreased AD may be one mechanism by which abdominal visceral fat contributes to cardiovascular risk.

Musculoskeletal complications of neutron therapy for prostate cancer.

The purpose of this study was to investigate the cause of hip complaints following conformal neutron therapy delivered by opposed lateral and oblique anterior ports to treat prostate cancer. Twenty-seven patients with hip complaints following neutron or mixed neutron and photon therapy for prostate cancer had 34 magnetic resonance imaging (MRI) studies 3-39 (mean 15.3) months following treatment; for comparison, 13 similarly treated patients without hip complaints were imaged 1-32 (mean 13.8) months post-treatment; 25/40 imaged patients received concurrent nonsteroidal hormone therapy. Coronal and axial images of the hips/pelvis were obtained utilizing T1 weighted spin echo and fat suppressed inversion recovery (STIR) sequences. Signal amplitude (SA) of involved muscles was measured on the STIR images and normalized to that of the psoas outside the treatment field. Hip complaints ranged from mild soreness or motion limitation to severe pain and limitation of ambulation; presence and severity of symptoms (sx) were significantly related to neutron dose (P = 0.020 and 0.0001) but not to hormone therapy (each P > 0.17). Normalized SA of the obturator muscles differed significantly with neutron dose (P = 0.013), the presence, and the severity, of sx (P = 0.0002 and 0.0007); estimated extent of abnormal muscle also differed significantly with neutron dose (P = 0.039), presence, and severity, of sx (P = 0.00004 and 0.0007); [hormone treatment had a profound effect on SA (P = 0.0001) and extent (P = 0.005) which was independent of sx (P = 0.10 and 0.14, respectively) and neutron dose (P = 0.33 and 0.32, respectively)]. Subcutaneous changes localized lateral to the greater trochanter were seen in all, and edema of the subjacent gluteus muscles in many, symptomatic hips; only 4/13 asymptomatic hips showed subcutaneous changes, 6 had mild gluteus edema. Avascular necrosis of the femoral head was seen in 5 symptomatic hips, with marked acetabular necrosis in 3 of these; small joint effusions were seen in 8 symptomatic hips; asymptomatic hips had no significant bone or joint abnormalities. Neutron therapy for prostate cancer designed to spare the rectum results in significant dose-dependent, musculoskeletal complications which are well demonstrated by MRI. SA abnormalities of irradiated muscle correlate significantly with neutron dose and both presence and severity of hip sx. Protocol modifications have been implemented to reduce these complications. MRI provides an objective means to assess both complications and the success of new protocols in ameliorating them. Concurrent hormone therapy has a profound effect on muscle changes on MRI which is independent of neutron dose and sx.

The NMR chemical shift pH measurement revisited: analysis of error and modeling of a pH dependent reference.

A standard differential calculus-based propagation of error treatment is applied to the traditional chemical-exchange Henderson-Hasselbalch NMR pH model in which the reference shift is pH independent. It is seen naturally from this analysis that (i) the error minimum in derived pH occurs in the region where pH and indicator pKa are equal and that (ii) the dynamic range, or difference between the limiting chemical shifts of acid and base forms of indicator species, determines the insensitivity of the technique to propagation of errors. To extend the useful pH range and utility of NMR pH determination methodology, a more general model is developed in which the internal reference species is also considered as having a pH-dependent chemical shift. Data from standard solution pH titrations are fitted to both models and parameters are estimated for the normally observed family of ionizable phosphorus metabolites (ATP, inorganic phosphate, phosphoethanolamine and phosphocholine) and the xenometabolite 2-deoxyglucose-6-phosphate with either phosphocreatine, the alpha-phosphate of ATP, or H2O taken as the 31P or 1H chemical shift internal reference species as well as with an external reference.

Tumor 31P NMR pH measurements in vivo: a comparison of inorganic phosphate and intracellular 2-deoxyglucose-6-phosphate as pHnmr indicators in murine radiation-induced fibrosarcoma-1.

Uncertainty regarding the intracellular/extracellular distribution of inorganic phosphate (P(i)) in tumors has raised concerns that pH calculated from the tumor P(i) chemical shift may not accurately represent the intracellular pH (pHin). This issue was addressed in subcutaneously transplanted murine radiation induced fibrosarcoma-1 by directly comparing pH measured via P(i) with pH measured via the in situ generated intracellular xenometabolite 2-deoxyglucose-6-phosphate (2DG6P). In 131 comparative measurements employing eight tumor-bearing mice under both control and hyperglycemic conditions (the latter to extend the range of tumor pH examined), the pH as derived from either 2DG6P or P(i) showed only a small, but statistically significant, difference (0.07 +/- 0.11 SD; P = 0.0001). Scatter in the comparative analysis over the pH range examined (ca. 5.5-7.5) was not uniform. Above pH 6.6, 2DG6P indicated a pH lower than that of P(i) by 0.088 +/- 0.105 SD (n = 107, P = 0.0001); below pH 6.6, 2DG6P indicated a pH essentially identical to and not statistically different from that of P(i) (mean difference 0.003 +/- 0.128 SD (n = 24, P = 0.92)). Evidence is presented in support of this differential arising from a systematic measurement error due to peak overlap between 2DG6P and endogenous phosphomonoester species. These results support the use of P(i) as a tumor 31P NMR pHin indicator, at least in RIF-1 tumors under control and hyperglycemic conditions.

Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study.

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic features observed in vivo with 1H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type. The institutions provided blinded, centralized MR spectroscopy data processing long with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data. Proton 1H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetylaspartate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensities were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these metabolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the 1H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero-geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstration that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients.