Showing papers by "Jeffrey L. Evelhoch published in 1996"
TL;DR: Each type and grade of tumor is a metabolically hetero-geneous group and the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients is hypotheses.
Abstract: 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.
360 citations
TL;DR: A dose-dependent, reversible increase in tumour ADC was observed after cyclophosphamide treatment, which is consistent with an increase in the fraction of interstitial water due to treatment-induced cell death and could provide a novel means for early detection of response to anti-cancer therapy.
Abstract: Nuclear magnetic resonance (NMR) non-invasively measures the apparent diffusion coefficient (ADC) of water, which is sensitive to the biophysical characteristics of tissue. Because anti-cancer treatment alters tumour pathophysiology, tumour ADC may be altered by treatment. In order to test this hypothesis, ADC was measured in s.c. implanted murine RIF-1 tumours before and up to 9 days after treatment with cyclophosphamide. A dose-dependent, reversible increase in tumour ADC was observed after cyclophosphamide treatment, which is consistent with an increase in the fraction of interstitial water due to treatment-induced cell death. Because tumour water ADC is increased substantially at a time when there is no change in tumour volume for a dose which produces minimal cell kill, its measurement could provide a novel means for early detection of response to anti-cancer therapy. If the changes in ADC observed in the present study are evident for commonly used anti-cancer therapies in different tumour types and specific to a therapeutic response, the approach could be broadly applicable as a response predictor since magnetic resonance imaging can be used to measure ADC in human tumours.
188 citations
TL;DR: 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.
Abstract: 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 pK a 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 α-phosphate of ATP, or H 2 O taken as the 31 P or 1 H chemical shift internal reference species as well as with an external reference.
46 citations
TL;DR: Evidence is presented in support of the use of Pi as a tumor 31P NMR pHin indicator, at least in RIF‐1 tumors under control and hyperglycemic conditions.
Abstract: 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.
26 citations