Localized In Vivo 1 H Magnetic Resonance Spectroscopy and In Vitro Analyses of Heterogeneous Brain Tumors

1995 ◽  
Vol 5 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Linda Chang ◽  
Duncan McBride ◽  
Bruce L. Miller ◽  
Marsha Cornford ◽  
Ruth A. Booth ◽  
...  
2013 ◽  
Vol 72 (2) ◽  
pp. 316-323 ◽  
Author(s):  
Changho Choi ◽  
Sandeep K. Ganji ◽  
Akshay Madan ◽  
Keith M. Hulsey ◽  
Zhongxu An ◽  
...  

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Georgios Batsios ◽  
Meryssa Tran ◽  
Céline Taglang ◽  
Anne Marie Gillespie ◽  
Sabrina Ronen ◽  
...  

Abstract Metabolic reprogramming is a fundamental hallmark of cancer, which can be exploited for non-invasive tumor imaging. Deuterium magnetic resonance spectroscopy (2H-MRS) recently emerged as a novel, translational method of interrogating flux from 2H-labeled substrates to metabolic products. However, to date, preclinical studies have been performed in vivo, an endeavor which suffers from low-throughput and potential wastage of animal life, especially when considering studies of treatment response. Developing in vitro assays for monitoring metabolism of 2H-labeled substrates will enhance throughput, lead to the rapid evaluation of new 2H-based probes and enable identification of treatment response biomarkers, thereby allowing the best 2H-based probes to be translated for further in vivo assessment. The goal of this study was to develop a preclinical cell-based platform for quantifying metabolism of 2H-labeled probes in brain tumor models. Since the Warburg effect, which is characterized by elevated glycolytic production of lactate, is a metabolic phenotype of cancer, including brain tumors, we examined metabolism of 2H-glucose or 2H-pyruvate in patient-derived glioblastoma (GBM6) and oligodendroglioma (BT88) cells and compared to normal human astrocytes (NHACONTROL). Following incubation in media containing [6,6’-2H]glucose or [U-2H]pyruvate, 2H-MR spectra obtained from live cell suspensions showed elevated 2H-lactate production in GBM6 and BT88 cells relative to NHACONTROL. Importantly, 2H-lactate production from [6,6’-2H]glucose or from [U-2H]pyruvate was reduced in GBM6 or BT88 cells subjected to irradiation and temozolomide, which is standard of care for glioma patients, pointing to the utility of this method for detecting response to therapy. Collectively, we have, for the first time, demonstrated the ability to quantify metabolism of 2H-MRS probes in live cell suspensions and validated the utility of our assay for differentiating tumor from normal cells and assessing response to therapy. Our studies will expedite the identification of novel 2H-MRS probes for imaging brain tumors and potentially other types of cancer.


Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 735-743 ◽  
Author(s):  
S D Taylor-Robinson ◽  
J Sargentoni ◽  
J D Bell ◽  
E L Thomas ◽  
C D Marcus ◽  
...  

Background—In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS) provides non-invasive information about phospholipid metabolism.Aims—To delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR) and to characterise spectral changes by in vitro MRS and electron microscopy.Patients and methods—Sixteen liver transplant recipients (four with CDR; 12 with good graft function) and 29 controls (23 healthy volunteers; six patients with biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide triphosphates (NTP) were measured. In vitro MRS and electron microscopy were performed on biopsy specimens from five patients with CDR, freeze clamped at retransplantation. Phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) concentrations were measured.Results—The 12 patients with good graft function displayed no spectral abnormalities in vivo; the four patients with CDR showed significantly elevated PME:NTP (p<0.01) and PDE:NTP ratios (p<0.005). Patients with biliary strictures had significant differences in PME:NTP (p<0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR patients showed elevated PE and PC, mirroring the in vivo changes in PME, but reduced GPE and GPC concentrations were observed, at variance with the in vivo PDE findings. On electron microscopy, there was no proliferation in hepatocyte endoplasmic reticulum.Conclusions—The increase in PME:NTP reflects altered phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may represent a significant contribution from bile phospholipid.


1990 ◽  
Vol 72 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Leslie N. Sutton ◽  
Robert E. Lenkinski ◽  
Bruce H. Cohen ◽  
Roger J. Packer ◽  
Robert A. Zimmerman

✓ Fourteen children aged 1 week to 16 years, with a variety of large or superficial brain tumors, underwent localized in vivo 31P magnetic resonance spectroscopy of their tumor. Quantitative spectral analysis was performed by measuring the area under individual peaks using a computer algorithm. In eight patients with histologically benign tumors the spectra were considered to be qualitatively indistinguishable from normal brain. The phosphocreatine/inorganic phosphate ratio (PCr/Pi) averaged 2.0. Five patients had histologically malignant tumors; qualitatively, four of these were considered to have abnormal spectra, showing a decrease in the PCr peak. The PCr/Pi ratio for this group averaged 0.85, which was significantly lower than that seen in the benign tumor group (p < 0.05). No difference between the two groups was seen in adenosine triphosphate or phosphomonoesters. It is concluded that a specific metabolic “fingerprint” for childhood brain tumors may not exist, but that some malignant tumors show a pattern suggestive of ischemia.


1999 ◽  
Vol 34 (3) ◽  
pp. 230-235 ◽  
Author(s):  
JEAN SABATIER ◽  
VERONIQUE GILARD ◽  
MYRIAM MALET-MARTINO ◽  
JEAN-PHILIPPE RANJEVA ◽  
CORINNE TERRAL ◽  
...  

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