The somatostatin analog octreotide as potential treatment for re-stenosis and chronic rejection.
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Angioplasty↗
Biomedical subjects
N Beckmann
Publications and source records attributed to N Beckmann.
Analysis of tracer transit in rat brain after carotid artery and femoral vein administrations using linear system theory.
Determination of tissue perfusion rates by MRI bolus tracking methods relies on the central volume principle which states that tissue blood flow is given by the tissue blood volume divided by the mean tracer transit time (MTT). Accurate determination of the MTT requires knowledge of the arterial input function which in MRI experiments is usually not known, especially when using small animals. The problem of unknown arterial input can be circumvented in animal experiments by directly injecting the contrast agent into a feeding artery of the tissue of interest. In the present article the passage of magnetite nanoparticles through the rat cerebral cortex is analyzed after injection into the internal carotid artery. The results are discussed in the framework of linear system theory using a one-compartment model for brain tissue and by using the well characterized gamma-variate function to describe the tissue concentration profile of the contrast agent. The results obtained from the intra-arterial tracer administration experiments are then compared with the commonly used intra-venous injection of the contrast agent in order to estimate the contribution of the peripheral circulation to the MTT values in the latter case. The experiments were analyzed using a two-compartment model and the gamma-variate function. As an application perfusion rates in normal and ischemic cerebral cortex of hypertensive rats were estimated in a model of focal cerebral ischemia. The results indicate that peripheral circulation has a significant influence on the MTT values and thus on the perfusion rates, which cannot be neglected.
Animals↗
Magnetic resonance imaging for the evaluation of rejection of a kidney allograft in the rat.
Orthotopic DA (RT1a) into Lewis (RT1l) rat kidney allografts and control Lewis-into-Lewis grafts were assessed by magnetic resonance imaging (MRI) and perfusion measurement after intravenous injection of a superparamagnetic contrast agent. MRI anatomical scores (range 1-6) and perfusion rates were compared with graft histology (rank of rejection score 1-6). Not only acute rejection, but also chronic events were monitored after acute rejection was prevented by daily cyclosporine (Sandimmune) treatment during the first 2 weeks after transplantation. In acute allograft rejection (n = 11), MRI scores reached the maximum value of 6 and perfusion rates were severely reduced within 5 days after transplantation; histology showed severe acute rejection (histologic score 5-6). In the chronic phase (100-130 days after transplantation), allografts (n = 5) manifested rejection (in histology cellular rejection and vessel changes), accompanied by MRI scores of around 2-3 and reduced perfusion rates. Both in the acute and chronic phases, the MRI anatomical score correlated significantly with the histological score (Spearman rank correlation coefficient rs 0.89, n = 30, P < 0.01), and perfusion rates correlated significantly with the MRI score or histological score (rs values between -0.60 and -0.87, n = 23, P < 0.01). It is concluded that MRI represents an interesting tool for assessing the anatomical and hemodynamical status of a kidney allograft in the acute and chronic phases after transplantation.
Acute Disease↗
Absolute quantification of the hepatic glycogen content in a patient with glycogen storage disease by 13C magnetic resonance spectroscopy.
Using natural-abundance 13C magnetic resonance spectroscopy (MRS) on a conventional whole-body system operating at 1.5 T, the absolute hepatic glycogen concentration was noninvasively determined in a patient with type Ia glycogen storage disease. Furthermore, to assess the reliability of glycogen determination, hepatic glycogen content was assessed after an overnight fasting period in 35 healthy volunteers divided into two groups, one with a carbohydrate-rich diet, the other without any particular dietary preparation. In the patient, the glycogen concentration was found to be 458 mM. In the healthy subjects, average glycogen concentrations were 229 +/- 34 mM (mean +/- standard deviation) and 257 +/- 31 mM for the group without and with dietary preparation, respectively. The 13C-MRS results are in agreement with those obtained by conventional liver biopsy. 13C MRS in natural abundance may thus serve as a straightforward, fast, and noninvasive tool for quantification of the liver glycogen content in patients.
Adult↗
Early glycogenolysis and late glycogenesis in human liver after intravenous administration of galactose.
Galactose is incorporated by a different metabolic pathway than glucose. Its contribution to glycogen synthesis has not been studied in humans. We administered galactose (0.5 g/kg iv) to overnight-fasted normal human volunteers and examined its effects on hepatic glycogen synthesis and hepatic glucose output (HGO). Hepatic glycogenesis was assessed noninvasively, determining glycogen concentration by 13C magnetic resonance spectroscopy (MRS) and liver volume by magnetic resonance imaging. HGO was determined by [6,6-2H2]glucose and gluconeogenesis calculated by adding the amount of hepatic glycogenesis to the HGO. After galactose administration, liver glycogen concentration (baseline 254 +/- 11 mmol/l) decreased in the first 45 min to 207 +/- 15 mmol/l (P < 0.05) and increased thereafter to 313 +/- 7 mmol/l (P < 0.01). Net hepatic glycogenesis was 101 +/- 12 mmol over 150 min. HGO (baseline 14.3 +/- 1.9 mumol.kg-1.min-1) increased threefold in the first 15 min and then returned to baseline. The average rate of gluconeogenesis was 12.3 mumol.kg-1.min-1. Intravenous galactose leads to an increase in hepatic glycogen and hepatic glucose output in normal humans. Competitive inhibition of UDP-glucose pyrophosphorylase by UDP-galactose could explain the apparent glycogenolysis observed early after galactose administration. 13C MRS in combination with a stable isotope tracer is a noninvasive and safe method to study hepatic carbohydrate metabolism in humans.
Adult↗
Magnetic resonance imaging in assessment of rejection of a kidney allograft in the rat: effect of the somatostatin analogue SMS 201-995.
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Animals↗
Noninvasive 3D MR microscopy as a tool in pharmacological research: application to a model of rheumatoid arthritis.
Magnetic resonance microscopy (MRM) was applied to noninvasively image skeletal structures in the hindpaw of the live rat to characterize the progression of a heterologous type II collagen-induced arthritic process. Using a resonator, with optimized filling factor, three-dimensional (3D) gradient-echo images with voxel dimensions of 94 x 81 x 60 micron3 were acquired in 54.6 min. Three-dimensional MRM reduces the slice positioning problem, which is critical in longitudinal studies. Moreover, due to the much smaller slice thickness of images derived from 3D data sets, partial volume effects are less pronounced than in corresponding 2D images. Distinct pathomorphological changes associated with the collagen-induced arthritic process (e.g., increase of metatarsophalangeal joint space, and bone and cartilage erosion) could thus be analyzed under in vivo conditions.
Animals↗
Noninvasive observation of hepatic glycogen formation in man by 13C MRS after oral and intravenous glucose administration.
The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C magnetic resonance spectroscopy (MRS) under two different conditions: a) intravenous infusion of [1-13C]glucose under hyperglycemic and hyperinsulinemic clamp conditions, and b) oral intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of alpha- and beta-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by 13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 +/- 34 mM (minimum = 160 mM; maximum = 274 mM).
Administration, Oral↗
Relationship between the degree of unsaturation of dietary fatty acids and adipose tissue fatty acids assessed by natural-abundance 13C magnetic resonance spectroscopy in man.
Natural-abundance 13C magnetic resonance spectroscopy was used for determining noninvasively the relative concentration of mono- and polyunsaturated fatty acids of adipose tissue in two groups of volunteers. The first consisted of subjects who had followed a fat-reduced diet for at least half a year before the 13C measurements. The second were control subjects who were on a usual high-fat diet. The ratio of unsaturated to total fatty acids in adipose tissue determined by 13C MRS correlated significantly with the same ratio in fat of the diet composition estimated by a dietician according to food records. The results indicate that 13C MRS is capable of assessing the degree of unsaturation of dietary fatty acids consumed during the preceding months.
Adipose Tissue↗
13C NMR for the assessment of human brain glucose metabolism in vivo.
Proton-decoupled 13C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1-13C]glucose in normal volunteers. In addition to 13C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1-13C]glucose, the signals of alpha- and beta-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 min. The spatial localization of the different regions of interest was confirmed by 13C NMR spectroscopic imaging with a time resolution of 9 min. Increasing the enrichment level to 99% [1-13C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1-13C]glucose. The time course of 13C label incorporation into the C2, C3, and C4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body.
Adult↗
Analysis of glycogen storage disease by in vivo 13C NMR: comparison of normal volunteers with a patient.
Broadband proton-decoupled natural abundance 13C spectra of the human calf, liver, and head were obtained from normal volunteers and a patient with glycogen type IIIA storage disease. Two concentric and coplanar surface coils of diameters 8.0 cm and 13.0 cm were used for 13C (at 16.0 MHz) and 1H (at 63.6 MHz), respectively. A WALTZ-8 sequence lead to homogeneous decoupling over a large volume. In addition to lipid resonances a variety of other metabolite resonances could be resolved. The glycogen concentration in the muscle and the liver of normal volunteers varied considerably depending on dietary preparation and physical exercise. The glycogen level in the liver and the calf of a patient with glycogen type IIIA storage disease was increased by a factor of 2-3 compared to normal, well-trained volunteers. Proton-decoupled 13C spectra of human head are reported for the first time. The spectra are dominated by lipid resonances but an additional resonance at 54.0 ppm is clearly visible. The proton-decoupled 13C head spectrum of a patient with glycogen type IIIA storage disease revealed additional resonances between 71.0 and 85.0 ppm.
Abdominal Muscles↗
Comparison of the signal-to-noise ratio at 1.5 and 2.0 T using a whole-body system.
Signal-to-noise ratios for 1H, 31P, and 13C signals at 1.5 and 2.0 T were compared using a whole-body system with a fast rampable magnet. Results indicate that SNR lies within the predicted values of linear and 7/4th power dependency with the applied magnetic field, for lossy and lossless samples, respectively.
Carbon Isotopes↗
13C spectroscopic imaging. A simple approach to in vivo 13C investigations.
13C spectroscopic imaging (SI) is implemented and tested on a Siemens whole-body MR instrument for in vivo localized 13C spectroscopy. The method provides spectroscopic maps of extended regions of interest. It is found that 13C SI is an ideal field of application for the spectroscopic imaging technique since most other localization methods suffer from chemical-shift or offset artifacts for this nucleus. Applications of 13C SI with a single 13C rf channel as well as in combination with polarization transfer experiments and heteronuclear broadband decoupling are shown.
Carbon Isotopes↗