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T C Ng

Publications and source records attributed to T C Ng.

At least 55 records · Page 3Linked to original sources

Response of a non-Hodgkin lymphoma to 60Co therapy monitored by 31P MRS in situ.

High quality 31P MR spectra (signal to noise ratio (S/N) approximately 18, 15 min acquisition for each spectrum) were consistently obtained with surface coils over a period of 6-week RT. Both transient and steady state alterations in metabolites in response to RT were found in this case. The transient changes occurred during the first 3 hr immediately after the 3rd fractionated RT, these changes include the transient elevation of the PCr resonance, a decrease in PDE and an increase in intracellular pH. The monitoring showed that the metabolites approached steady state approximately 2 hr after the fractionated radiation intervention, suggesting that in vivo MRS can be useful for studying the dynamics of tumor response to RT such as repair of potential lethal damage, growth delay, and reoxygenation etc. The steady-state MR spectra showed the net response to each intervention and can clinically be useful for predicting and measuring the result of the fractionated RT. In this case study, the PDE peak which contains the phospholipid metabolites GPC and GPE, is the most sensitive resonance in response to RT. After the 3rd RT, prior to tumor size reduction, the PDE to ATP ratio decreased 33% and intracellular pH increased to 7.34 +/- 0.05 from 7.27 +/- 0.05. In the subsequent RT interventions, both the tumor size and PDE/ATP ratio continually decreased whereas the pH values remained alkaline and fluctuated around 7.34 to 7.65. The data suggest that the phospholipid metabolite PDE may signal important alterations in membrane metabolism that eventually lead to cell death.

Cobalt Radioisotopes↗

In vivo MR spectroscopy of human subjects with a 1.4-T whole-body MR imager.

A 1.4-T magnetic resonance (MR) imager was modified to perform MR spectroscopy measurements. The implementation involved only a few additions in hardware and practically no change in software. Procedures for acquiring the MR spectra are similar to those for MR images. Both sensitivity and homogeneity were found to be adequate over a region 12 cm in diameter. Typical scanning times are 4.5 minutes for human brain, 2.8 minutes for muscle, and 20-35 minutes for solid tumors. Preliminary spectral studies of the metabolism of human brains, tumors, and a muscle of the forearm during exercise obtained with the modified system are presented.

Adenosine Triphosphate↗

Shielded solenoidal probe for in vivo NMR studies of solid tumors.

A shielded solenoidal probe, suitable for in vivo NMR studies of subcutaneous solid tumors, is described. The 31P NMR spectra obtained from phantom samples and in vivo subcutaneous solid tumors in mice show that spurious signals from the body are totally eliminated if the proper shield is used.

Adenocarcinoma↗

Direct relationship between high-energy phosphate content and blood flow in thermally treated murine tumors.

In vivo 31P-nuclear magnetic resonance (NMR) spectroscopy and 133Xe clearance were used to monitor serially ATP content and blood flow, respectively, in C3H/HeJ mouse subcutaneous RIF-1 tumors treated with hyperthermia. There was a prompt decrease in ATP [measured spectroscopically and expressed as the ratio of ATP to Pi (ATP/Pi)]. The slope and magnitude of the change in ATP closely paralleled those of tumor blood flow. Close correlation between these two variables was seen when data were analyzed both by treatment group and by individual mouse. Ligated tumors showed qualitatively and quantitatively similar changes in ATP/Pi and blood flow. RIF-1 cells heated in vitro to a similar degree showed no decrease in ATP. The loss of ATP in subcutaneous RIF-1 tumors heated in vivo was primarily due to disruption of tumor blood flow. These data emphasize the importance of vascular factors to in vivo thermal effects. In vivo 31P-NMR spectroscopy can be used to monitor indirectly vascular effects from hyperthermia.

Adenosine Triphosphate↗

NMR study of in vivo RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances.

Perchloric acid extracts of radiation-induced fibrosarcoma (RIF-1) tumors grown in mice have been analyzed by multinuclear NMR spectroscopy and by various chromatographic methods. This analysis has permitted the unambiguous assignment of the 31P resonances observed in vivo to specific phosphorus-containing metabolites. The region of the in vivo spectra generally assigned to sugar phosphates has been found in RIF-1 tumors to contain primarily phosphorylethanolamine and phosphorylcholine rather than glycolytic intermediates. Phosphocreatine was observed in extracts of these tumor cells grown in culture as well as in the in vivo spectra, indicating that at least some of the phosphocreatine observed in vivo arises from the tumor itself and not from normal tissues. In the 31P-NMR spectra of the perchloric acid extract, resonances originating from purine and pyrimidine nucleoside di- and triphosphate were resolved. HPLC analyses of the nucleotide pool indicate that adenine derivatives were the most abundant components, but other nucleotides were present in significant amounts. The 1H and 13C resonance assignments of the majority of metabolites present in RIF-1 extracts have also been made. Of particular importance is the ability to observe lactate, the levels of which may provide a noninvasive measure of glycolysis in these cells in both the in vitro states. In addition, the aminosulfonic acid, taurine, was found in high levels in the tumor extracts.

Animals↗

Structural studies of apolipoprotein A-I/phosphatidylcholine recombinants by high-field proton NMR, nondenaturing gradient gel electrophoresis, and electron microscopy.

Complexes formed between apolipoprotein A-I (apo A-I) and dimyristoylphosphatidylcholine (DMPC) or egg phosphatidylcholine have been studied by high-field 1H NMR, nondenaturing gradient gel electrophoresis, electron microscopy, and gel filtration chromatography. Emphasis has been placed on an analysis of the particle size distribution within the micellar complexes produced at lipid/protein molar ratios of 40-700. As determined by electron microscopy and gel filtration of DMPC/apo A-I complexes, the size of the discoidal micelles produced appears to increase uniformly with an increasing lipid/protein ratio. By electron microscopy, the diameters of isolated DMPC/apo A-I discoidal micelles range from approximately 89 A at a 40 molar ratio to 205 A at a 700 molar ratio. Analysis of the micellar complexes by 1H NMR shows that concomitant with the increase in size is the progressive downfield shift of the choline N-methyl proton resonance of the complex which is observed from 3.245 to 3.267 ppm over the above molar ratio range. The relationship between chemical shift and micelle size is most simply interpreted as arising from a weighted averaging of two lipid environments--lipid-lipid and lipid-protein. In contrast to the above interpretation of the gel filtration experiments on DMPC/apo A-I complexes, nondenaturing gradient gel electrophoresis analysis of particle size distribution leads to an unexpected observation: as the DMPC/apo A-I ratio increases, discrete complexes of increasing size are formed in an apparently quantized manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

Depth pulse sequences for surface coils: spatial localization and T1 measurements.

The depth pulse sequences theta;[2 theta(+/- x, +/- y)]2 and 2 theta;theta(+/- x);[2 theta(+/- x, +/- y)]2 have been implemented with a 20 mm diameter two-turn surface coil operating at 31P resonance (89.96 MHz). In these sequences theta refers to the pi/2 rf pulse at the center of the sensitive region of the coil, +/- x and +/- y denote the four orthogonal phases of the rf pulses, and ";" represents an optional brief delay (e.g., 4 microseconds) between pulses to facilitate switching between different phases. Localization of the sensitive region was demonstrated with phantom samples by in vivo monitoring of rat livers and detection of necrotic regions of subcutaneously implanted tumors. The inversion-recovery pulse sequence, 2 theta-tau-theta(+/- x);[2 theta(+/- x, +/- y)]2, where tau is a variable delay, was employed to measure the spin-lattice relaxation time of a selected region, which could be varied by changing the pulse width and the size of the surface coil.

Animals↗

Application of in vivo NMR spectroscopy to cancer.

A critical review is presented of NMR spectroscopic studies of isolated tumor cells, excised tumors, and in vivo tumors. Although the majority of the studies examined deal with 31P NMR spectroscopy, the potential utility of multinuclear NMR investigations is emphasized. A major theme of this review is the evaluation of the potential applications of in vivo NMR spectroscopy to experimental tumor biology and to the clinical diagnosis and management of cancer. Data are presented demonstrating that this method may prove useful in distinguishing between relatively well vascularized aerobic tumors and poorly vascularized hypoxic tumors. This could provide a basis for identifying tumors responsive to X radiation or hyperthermia. Preliminary experiments point to the possibility that in vivo NMR spectroscopy will be capable of detecting tumor response to chemotherapy, X radiation, and hyperthermia and may also detect drug-induced toxicity to tissues vital to the survival of the host.

Animals↗

Loss of high-energy phosphate following hyperthermia demonstrated by in vivo 31P-nuclear magnetic resonance spectroscopy.

We have used in vivo 31P-nuclear magnetic resonance spectroscopy to study the changes in high-energy phosphates following hyperthermia. Immediately after heating, there is a fall in adenosine triphosphate and apparent intracellular pH and an increase in inorganic phosphate. Following sublethal heating (40 degrees for 15 min), these changes were partial, and they resolved over the subsequent 45 hr. With tumors given severe hyperthermia (47 degrees for 15 min), there was complete disappearance of adenosine triphosphate, with no recovery by 24 hr posttreatment. Qualitatively similar effects were seen after heating of normal leg muscle. The degree of fall of the adenosine triphosphate/inorganic phosphate concentration ratio was directly proportional to the heat dose and to thermal cell kill. 31P-Nuclear magnetic resonance spectroscopy may be useful in thermal dosimetry and treatment evaluation following hyperthermia.

Animals↗

Detection of antineoplastic agent induced cardiotoxicity by 31P NMR of perfused rat hearts.

Development of dose dependent chronic irreversible cardiotoxicity is a key problem encountered in chemotherapy with adriamycin. Here it has been demonstrated that infusion of this agent produced distinct and largely irreversible changes in levels of phosphate metabolites and substantial acidosis that are detected by 31P NMR of the Langendorf perfused heart. Administration of the antioxidant, butylated hydroxytoluene minimizes these spectral changes but does not substantially diminish the antineoplastic activity of adriamycin. Bisantrene (CL 216,942), a noncardiotoxic anthracene with antineoplastic activity, produces only minor perturbations of the 31P spectrum of the perfused rat heart. These studies demonstrate the potential utility of employing 31P NMR to monitor acute or chronic cardiotoxicity in the perfused rat heart and for developing noninvasive in vivo NMR techniques for monitoring cardiotoxicity in experimental animals and humans.

Animals↗

In vivo 31P NMR study of the metabolism of murine mammary 16/C adenocarcinoma and its response to chemotherapy, x-radiation, and hyperthermia.

(31)P NMR spectroscopy with surface coils has been used to monitor, in vivo, the phosphate metabolism of subcutaneously implanted mammary 16/C adenocarcinoma in C3H/He mice. This model tumor was studied during untreated tumor growth and after treatment with adriamycin, hyperthermia, and x-radiation. The mammary 16/C tumor exhibited a Gompertzian growth pattern. Levels of high-energy phosphate metabolites-phosphocreatine and ATP-decreased with increases in tumor mass. There was a concomitant increase in the level of P(i) and a decrease in the apparent pH of the tumor. These spectral changes appear to reflect changes in tumor vascularization that accompany tumor growth, the tumor becoming progressively more hypoxic. Partial response of this tumor to chemotherapy with adriamycin was reflected in a small but measurable increase in the phosphocreatine resonance, a decrease in P(i), and a return of the intra-tumor pH to neutral. Hyperthermia resulted in progressive conversion of the (31)P NMR spectrum to that of a dead tumor (high levels of P(i), small levels of residual sugar phosphates and pyridine dinucleotides, and acidic pH). X-irradiation (14.0 Gy) led to disappearance of the phosphocreatine peak within 15 min of treatment. Subsequently, this resonance grew back beyond its pretreatment level. As the tumor receded, its spectrum reflected the characteristics of aerobically metabolizing tissue (high levels of phosphocreatine and ATP and low levels of P(i) and sugar phosphates).

Adenocarcinoma↗

In vivo measurement of 31P nuclear magnetic resonance spectrum of aging mouse brain.

31P nuclear magnetic resonance spectra of the brains of young, mature and old C57BL/6 mice were measured in vivo. Under normal conditions, no significant changes with age were observed in the spectra and there were no statistically significant age-related differences in the ratio of phosphocreatine to adenosine triphosphate (ATP). When the animals were stressed by subjecting them to oxygen restriction, the young and mature mice showed no change in the ratio, whereas it increased in the old mice. These results are consistent with the view that energy metabolism is unimpaired in the brains of unstressed old animals but that ATP synthesis may be decreased with age in a stressed animal.

Adenine Nucleotides↗