31P-nuclear magnetic resonance spectroscopy in vivo of four human melanoma xenograft lines: spin-lattice relaxation times.

Phosphorus spin-lattice relaxation times (T1s) were measured in vivo by 31P-nuclear magnetic resonance spectroscopy in tumors from four amelanotic human melanoma xenograft lines grown subcutaneously in BALB/c-nu/nu mice. The T1s were analyzed in relation to tumor volume, fractional tumor water content, and fraction of necrotic tumor tissue. The following resonances were studied: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr), and nucleoside triphosphates gamma, alpha, and beta (NTP gamma, alpha, and beta). Two different techniques were used to measure the T1s: superfast inversion recovery (SUFIR) and conventional inversion recovery (IR). The SUFIR and IR methods gave similar results. Tumors in the volume range 100-3000 mm3 were studied. The PME, Pi, PDE, and PCr resonances showed significantly longer T1s than the NTP gamma, alpha, and beta resonances at small tumor volumes. The T1s at small tumor volumes also differed significantly between the tumor lines. The T1s either decreased or remained unchanged with increasing tumor volume; the volume-dependence of the T1s differed significantly between the tumor lines but not between the resonances. Calculations based on the T1s measured here indicated that the errors in PCr/Pi and NTP beta/Pi resonance ratios due to partial saturation can vary with tumor volume but are usually < 20% at a repetition time of 2.0 s and < 15% at a repetition time of 3.0 s. There was no correlation between the T1s and fractional tumor water content.(ABSTRACT TRUNCATED AT 250 WORDS)

A 13 C NMR study of photosynthate transport and metabolism in the lichen Xanthoria calcicola Oxner.

13 C nuclear magnetic resonance (NMR) spectroscopy was applied to the lichen Xanthoria calcicola Oxner. The in vivo spectra were poorly resolved and although the line-broadening effect of variations in the bulk magnetic susceptibility could be eliminated by spinning the sample at the magic angle, the spectra were still relatively Uninformative in comparison with the spectra of methanol extracts of the tissue. The synthesis of ribitol by the algal symbiont and its subsequent metabolism to mannitol by the fungus was followed using pulse-chase experiments. The fine structure in the spectra provided support for the role of the pentose phosphate pathway in the conversion of ribitol to mannitol. Preliminary experiments, in which the conditions of the pulse-chase experiment were altered, showed that the incorporation of 13 C into mannitol was reduced at a lower temperature, and in thalli of low moisture content, and was abolished by darkness.

Computed tomography of experimental liver abscesses using a new liposomal contrast agent.

RATIONALE AND OBJECTIVES: Evaluation of computed tomographic enhancement characteristics of a new liposomal contrast agent (liposomal iodixanol [LI]) in a pyogenic liver abscess model in 17 rabbits. METHODS: Eight to 14 days after abscess induction (Escherichia coli), density-time curves were calculated for regions of interest in liver, abscess wall and center, spleen, portal vein, abdominal aorta, inferior vena cava, and kidney. Images were obtained every minute between 1 and 10 minutes, every 5 minutes between 15 and 60 minutes, and 75 minutes after 200 mg/kg LI application (group A: 7 rabbits) and after 600 mg/kg iopentol application (group B: 10 rabbits), and 90, 105, and 120 minutes after LI. RESULTS: The abscess wall-liver contrast after LI lasted from 10 to more than 120 minutes with a maximum of 30 delta Hounsfield Units (HU) at 45 minutes. For iopentol, the abscess wall-liver contrast lasted from 2 to 7 minutes with a maximum of 8 delta HU at 5 minutes. The abscess wall-center contrast after LI lasted from 1 to more than 120 minutes with a maximum of 112 delta HU at 40 minutes. For iopentol, the abscess wall-center contrast lasted from 1 to 75 minutes with a maximum of 79 delta HU at 1 minute. The liver-portal vein contrast after LI lasted from 1 to more than 120 minutes with a maximum of 100 delta HU at 20 minutes. For iopentol, the liver-portal vein contrast lasted from 1 to 8 minutes with a maximum of 38 delta HU at 2 minutes. An abscess wall was detected in a higher percentage of the LI images (86% LI, 56% iopentol), and images in the LI group correlated better with histopathology. CONCLUSIONS: The diagnostic value of LI exceeds that of iopentol in terms of overall abscess contrast and duration of the diagnostic interval. The higher hepatic vessel contrast allows better abscess localization.

A magnetization transfer preparation scheme for snapshot FLASH imaging.

A rapid method of generating images whose contrast is dependent on the exchange of magnetization between the free and restricted proton pools is presented. The contrast obtained is similar to that obtained from T2-weighted spin-echo images. The rapid nature of the sequence means that the RF power deposition problems encountered when using magnetization transfer in conjunction with conventional imaging sequences are avoided.

Effect of temperature on cold-hardiness and tissue ice formation in the adult chrysomelid beetle Melasoma collaris L.

The freeze-tolerant chrysomelid beetle Melasoma collaris overwinters in plant litter on windswept ridges or covered with snow for 8-9 months in the Norwegian alpine region. Lower lethal temperature, supercooling and melting point depression were correlated to accumulation of glycerol. The lower limit of freeze tolerance was associated with the freezing of 73-75% body water. About 23-15.5% of the body water was osmotically inactive, and the highest percentage was revealed in individuals depleted of glycerol at 21 degrees C. A shift in cooling rate from 1 degrees Cmin(-1) to 1 degrees C every 13.5min lowered nucleating temperature markedly. The alteration in nucleating activity probably arises from the structure of the haemolymph nucleating agent that functions to slow embryo growth at the slow cooling rate. An enhanced supercooling is particularly beneficial in autumn before M. collaris has accumulated glycerol, since supercooled individuals accumulate glycerol in higher concentrations than frozen ones. Freezing at higher temperatures is probably a better survival strategy during brief intervals with pronounced decrease in air temperature.

The effects of organic and inorganic pollutants on intracellular phosphate compounds in blue mussels (Mytilus edulis).

1. The effects of sublethal concentrations of organic and inorganic pollutants on intracellular energy-rich phosphates in blue mussels, Mytilus edulis, were investigated by in vivo 31P-NMR. 2. Formaldehyde (30 and 10 mg/l), phenol, pyridine, mercury and cadmium gave marked reductions in phosphoarginine and, in some cases, the ATP amounts. The reduction in high-energy phosphate was accompanied by an increase in inorganic phosphate in all groups. 3. A "phosphorus index", the product of the ratios between phosphoarginine and inorganic phosphate, and ATP and inorganic phosphate, is suggested, which might serve as an early warning ("alarm") parameter in environmental monitoring. 4. Diversity in the responses to different pollutants make phosphorus compounds in M. edulis also an interesting element in a finger print parameter system designed to distinguish between pollutants in the marine environment.

Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration.

PURPOSE: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. MATERIAL AND METHODS: Formulations of either 14C-MnDPDP or 54MnDPDP were injected intravenously at near clinical doses in rats and dogs. RESULTS: The manganese (Mn) moiety is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moiety is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. CONCLUSION: The ligand does not appear to facilitate the transport of Mn into any organ except the kidney for subsequent excretion, and it reduces distribution to the heart. The Mn is taken up by those organs indicated for MR imaging, primarily liver and pancreas.

The NMDA antagonist MK-801 improved metabolic recovery after 10 minutes global cerebral ischaemia in rats measured with 31 phosphorous magnetic resonance spectroscopy.

The blockade of postsynaptic receptors for excitatory amino acids is a promising new field for the possible treatment of cerebral ischaemia. The most important receptor seems to be the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and MK-801 is a potent non-competitive antagonist to the NMDA receptor. 31P NMR Spectroscopy was used to measure the recovery of intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP after ten minutes of temporary global cerebral ischaemia in the rat. Cerebral ischaemia was obtained by combining bilateral carotid ligation and systemic hypotension (2 vessel occlusion model). Two intervention groups with intravenous injection of MK-801 in doses of 0.25 mg/kg and 0.5 mg/kg 15 minutes before onset of ischaemia were compared to a control group. Both intervention groups showed a more rapid recovery of PCr and ATP than the control group, but there were no significant differences for intracellular pH.

31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma xenograft lines: tumour bioenergetic status and blood supply.

Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to search for possible relationships between 31P-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The latter parameter was measured by using the 86Rb uptake method. Tumour bioenergetic status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per viable tumour cell decreased with increasing tumour volume for five of the six xenograft lines. The decrease in tumour bioenergetic status was due to a decrease in the (PCr + NTP beta)/total resonance ratio as well as an increase in the Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTP beta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTP beta)/total resonance ratio and the magnitude of the decrease in tumour pH were correlated to the magnitude of the decrease in blood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was larger for the tumour lines showing a high than for those showing a low blood supply per viable tumour cell. No correlations across the tumour lines were found between tumour pH and tumour bioenergetic status or any other resonance ratio on the one hand and blood supply per viable tumour cell on the other. The differences in the 31P-NMR spectrum between the tumour lines were probably caused by differences in the intrinsic biochemical properties of the tumour cells rather than by the differences in blood supply per viable tumour cell. Biochemical properties of particular importance included rate of respiration, glycolytic capacity and tolerance to hypoxic stress. On the other hand, tumour bioenergetic status and tumour pH were correlated to blood supply per viable tumour cell within individual tumour lines. These observations suggest that 31P-NMR spectroscopy may be developed to be a clinically useful method for monitoring tumour blood supply and parameters related to tumour blood supply during and after physiological intervention and tumour treatment. However, clinically useful parameters for prediction of tumour treatment resistance caused by insufficient blood supply can probably not be derived from a single 31P-NMR spectrum since correlations across tumour lines were not detected; additional information is needed.

NMR relaxation studies with MnDPDP.

PURPOSE: Our studies were designed to compare the efficacy of mangafodipir trisodium (MnDPDP, Teslascan) as a tissue-specific MR agent with that of manganese chloride (MnCl2), to compare the efficacy of different doses and rates of administration of MnDPDP, and to collect the data needed for predicting optimum pulse sequences. MATERIAL AND METHODS: The dose response for the relaxation rates R1 and R2 at 0.47 T, and the manganese (Mn) concentrations in rat liver and in the liver, pancreas, heart and adrenals of pigs was determined for both MnDPDP and MnCl2 administered i.v. Computer simulations were carried out to model the effects of different tissue Mn concentrations and TR on signal intensities and contrast-to-noise ratios. RESULTS: In rat liver and pig organs both compounds produced a positive dose-response in R1 and tissue Mn concentration, and only small or no response in R2. The Mn concentration in rat liver was positively correlated with R1, regardless of the form in which Mn was given, or the rate of administration. Optimal imaging parameters are therefore expected to be different pre- and post-MnDPDP administration. CONCLUSION: The added cardiovascular safety of MnDPDP compared with MnCl2 does not result in loss of efficacy in increasing RI at the intended clinical dose of 5 mumol/kg MnDPDP. The changes in R2 were too small to affect T2-weighted images. The data give the basis for choosing the appropriate pulse sequences for MnDPDP-enhanced MR imaging.

Use of the mean transit time of an intravascular contrast agent as an exchange-insensitive index of myocardial perfusion.

A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.