Improvements in high-field localized MRS of the medial temporal lobe in humans using new deformable high-dielectric materials.

The intrinsic nonuniformities in the transmit radiofrequency field from standard quadrature volume resonators at high field are particularly problematic for localized MRS in areas such as the temporal lobe, where a low signal-to-noise ratio and poor metabolite quantification result from destructive B1⁺ field interference, in addition to line broadening and signal loss from strong susceptibility gradients. MRS of the temporal lobe has been performed in a number of neurodegenerative diseases at clinical fields, but a relatively low signal-to-noise ratio has prevented the reliable quantification of, for example, glutamate and glutamine, which are thought to play a key role in disease progression. Using a recently developed high-dielectric-constant material placed around the head, localized MRS of the medial temporal lobe using the stimulated echo acquisition mode sequence was acquired at 7 T. The presence of the material increased the signal-to-noise ratio of MRS by a factor of two without significantly reducing the sensitivity in other areas of the brain, as shown by the measured B1⁺ maps. An increase in the receive sensitivity B1⁻ was also measured close to the pads. The spectral linewidth of the unsuppressed water peak within the voxel of interest was reduced slightly by the introduction of the dielectric pads (although not to a statistically significant degree), a result confirmed by using a pad composed of lipid. Using LCmodel for quantitative analysis of metabolite concentrations, the increase in signal-to-noise ratio and the slight decrease in spectral linewidth contributed to statistically significant reductions in the Cramer-Rao lower bounds (CRLBs), also allowing the levels of glutamate and glutamine to be quantified with CRLBs below 20%.

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study.

AIMS/HYPOTHESIS: We compared in vivo changes in liver glycogen concentration during exercise between patients with type 1 diabetes and healthy volunteers. METHODS: We studied seven men with type 1 diabetes (mean +/- SEM diabetes duration 10 +/- 2 years, age 33 +/- 3 years, BMI 24 +/- 1 kg/m(2), HbA(1c) 8.1 +/- 0.2% and VO(2) peak 43 +/- 2 ml [kg lean body mass](-1) min(-1)) and five non-diabetic controls (mean +/- SEM age 30 +/- 3 years, BMI 22 +/- 1 kg/m(2), HbA(1c) 5.4 +/- 0.1% and VO(2) peak 52 +/- 4 ml [kg lean body mass](-1) min(-1), before and after a standardised breakfast and after three bouts (EX1, EX2, EX3) of 40 min of cycling at 60% VO(2) peak. (13)C Magnetic resonance spectroscopy of liver glycogen was acquired in a 3.0 T magnet using a surface coil. Whole-body substrate oxidation was determined using indirect calorimetry. RESULTS: Blood glucose and serum insulin concentrations were significantly higher (p < 0.05) in the fasting state, during the postprandial period and during EX1 and EX2 in subjects with type 1 diabetes compared with controls. Serum insulin concentration was still different between groups during EX3 (p < 0.05), but blood glucose concentration was similar. There was no difference between groups in liver glycogen concentration before or after the three bouts of exercise, despite the relative hyperinsulinaemia in type 1 diabetes. There were also no differences in substrate oxidation rates between groups. CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes, hyperinsulinaemic and hyperglycaemic conditions during moderate exercise did not suppress hepatic glycogen concentrations. These findings do not support the hypothesis that exercise-induced hypoglycaemia in patients with type 1 diabetes is due to suppression of hepatic glycogen mobilisation.

Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes.

Liver and skeletal muscle triglyceride stores are elevated in type 2 diabetes and correlate with insulin resistance. As postprandial handling of dietary fat may be a critical determinant of tissue triglyceride levels, we quantified postprandial fat storage in normal and type 2 diabetes subjects. Healthy volunteers (n = 8) and diet-controlled type 2 diabetes subjects (n = 12) were studied using a novel 13C magnetic resonance spectroscopy protocol to measure the postprandial increment in liver and skeletal muscle triglyceride following ingestion of 13C-labeled fatty acids given with a standard mixed meal. The postprandial increment in hepatic triglyceride was rapid in both groups (peak increment controls: +7.3 +/- 1.5 mmol/l at 6 h, P = 0.002; peak increment diabetics: +10.8 +/- 3.4 mmol/l at 4 h, P = 0.009). The mean postprandial incremental AUC of hepatic 13C enrichment between the first and second meals (0 and 4 h) was significantly higher in the diabetes group (6.1 +/- 1.4 vs. 1.7 +/- 0.6 mmol x l(-1) x h(-1), P = 0.019). Postprandial increment in skeletal muscle triglyceride in the control group was small compared with the diabetic group, the mean 24-h postprandial incremental AUC being 0.2 +/- 0.3 vs. 1.7 +/- 0.4 mmol x l(-1) x h(-1) (P = 0.009). We conclude that the postprandial uptake of fatty acids by liver and skeletal muscle is increased in type 2 diabetes and may underlie the elevated tissue triglyceride stores and consequent insulin resistance.

Localised mapping of water movement and hydration inside a developing bioadhesive bond.

Few studies have investigated the internal processes involved in bioadhesive bond formation, particularly where mucus and hydrated polymer contribute jointly to bond structure. This paper reports the first study to spatially map the internal environment within a developing bioadhesive bond, utilising nuclear magnetic resonance (NMR) microscopy to measure localised water self-diffusion coefficients (SDC) and confocal laser scanning microscopy (CLSM) to estimate mucin concentration. In a model bioadhesive bond formed between an alginate matrix and mucin gel, characteristic profiles were observed in which fluorescence measurements showed a region of increasing mucin concentration in the mucus layer region adjacent to the matrix, corresponding closely with a zone of restricted water SDC in the diffusion profiles. These regions extended 144 microm (a normal human gastric layer thickness [Clin. Sci. 95 (1998) 97]) into the mucin layer after just 30 s, increasing to 800 microm after 30 min. The formation of a hydrated polymer layer at the matrix surface, confirmed visually, was also reflected in corresponding gradient changes. The results suggest a progressive dehydration of the mucus gel during bond formation, and the study demonstrates how together, these microscopies can provide non-invasive, quantitative, spatial and time-resolved evidence of internal hydration behaviour during bioadhesive bond formation.

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects.

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.

A novel application of NMR microscopy: measurement of water diffusion inside bioadhesive bonds.

The self-diffusion coefficient of water (D) inside bioadhesive bonds formed by dry and prehydrated hydrophilic matrices has been spatially resolved using nuclear magnetic resonance (NMR) microscopy. One-dimensional profiles showing the variation of D inside bioadhesive bonds were calculated from nine diffusion-weighted profiles obtained immediately after bond formation and every 5 min for 30 min. The resulting data indicated that the hydration state of a hydrophilic matrix can significantly and dramatically influence the dynamics of water movement inside a bioadhesive bond.

Strong gradients for spatially resolved diffusion measurements.

A new multilayer approach to gradient coil design, which allows the production of very strong gradient coils with reasonable resistance and consequent power dissipation, has been developed. Using this approach we have designed and built a strong z-gradient coil that will accommodate vertically mounted samples contained in 5-mm nuclear magnetic resonance tubes. The coil has an efficiency of 1.73 Tm-1A-1, an inductance of 49 microH, and a resistance of 1.8 omega, with a homogeneous volume consisting of a central cylinder of 4.5-mm length and diameter. This coil has been used to monitor the diffusion of water in Nylon 6.6 at room temperature, during desorption. This system is difficult to monitor via nuclear magnetic resonance (NMR), because the diffusion coefficients are typically less than 10(-13) m2s-1, while the T2 relaxation time is less than 1 ms even when the sample is fully saturated. The resulting measurements show a strong concentration dependence of the T2 relaxation time and self-diffusion coefficient of the absorbed water. The measured concentration profiles are consistent with a Fickian diffusion process with a concentration-dependent diffusion coefficient. The measured self-diffusion values are in reasonable agreement with those inferred from the variation of the concentration profiles as a function of time, using the one-dimensional Fickian diffusion equation.

Self-diffusion and molecular mobility in PVA-based dissolution-controlled systems for drug delivery.

Nuclear magnetic resonance (NMR) microscopy has been used to monitor the hydration of poly(vinyl alcohol) (PVA) samples of varying molecular weight. One-dimensional profiles weighted to predominantly show the variation of water concentration were acquired every 3 min during the first 30 min of hydration and subsequently at 1 and 2 h. Diffusion-weighted profiles obtained after 30 min and 1 and 2 h were used to calculate the spatial variation of the water self-diffusion coefficient. The resulting data provide supporting evidence for the hypothesis that phenomena such as reptation are important near the glassy/rubbery interface of polymers during dissolution, while the diffusion gradually changes to Zimm type near the rubbery/solvent interface.

Constant gradient stimulated echo studies of diffusion in porous materials at high spectrometer fields.

A high field strength, constant gradient stimulated-echo pulse sequence is applied to a model heterogeneous system consisting of randomly packed beds of glass microspheres. A multiple exponential analysis of the dependence of the stimulated echo amplitude on diffusion time, delta, yields coefficients that depend explicitly on both the wavevector, q and on the time delay, delta. The wavevector and delta- dependence of the coefficients is analyzed both theoretically and experimentally and shown to be sensitive to the effects of coupled relaxation and diffusion. It is proposed that these effects could be exploited as a new probe of microstructure.

Combined relaxation and diffusion studies of porous media using the multigrade CPMG sequence.

A new approach to q-space NMR studies of microstructure is proposed that exploits the combined information contained in the water proton transverse relaxation time distribution and the frequency dependence of the apparent water diffusivity. A simple protocol is used to eliminate undesirable crossterms in background susceptibility gradients. Local, microscopic nonlinearity in the applied field gradients is shown to lead to enhancement of the apparent water diffusivity in small pores at high frequencies. The relationships between NMR relaxation studies of pore emptying with sorption isotherms, electrical conductivity, and microbiological survival are indicated.

Dynamic NMR Q-space studies of microstructure with the multigrade CPMG sequence.

A new approach to q-space studies of microstructure is proposed, which exploits the combined information contained in the water proton transverse relaxation time distribution and the frequency dependence of the apparent water diffusivity in heterogeneous systems. Using an automated two-dimensional multigrade CPMG sequence, both the pulse spacing and the amplitude of the applied field gradient are varied systematically and used to measure the frequency and wave vector dependence of the multiple exponential echo decay constants and amplitudes. Undesirable crossterms in the applied and background field gradients are eliminated by a simple procedure involving a sign reversal in the applied gradient. Nonlinear, local susceptibility-induced field gradients are shown to lead to enhanced, frequency-dependent apparent water diffusivities that are sensitive to the local microstructure.

Quantitative measurement and imaging of transport processes in plants and porous media by 1H NMR.

NMR and MRI have been applied to transport processes, that is, net flow and diffusion/perfusion, of water in whole plants, cells, and porous materials. By choosing proper time windows and pulse sequences, magnetic resonance imaging can be made selective for each of the two transport processes. For porous media and plant cells the evolution of the spatial distribution of excited spins has been determined by q-space imaging, using a 20 MHz pulsed 1H NMR imager. The results of these experiments are explained by including spin-relaxation and exchange at boundaries. A 10 MHz portable 1H NMR spectrometer is described, particularly suitable to study the response of net flow in plants and canopies to changing external conditions.

Probing water compartments and membrane permeability in plant cells by H NMR relaxation measurements.

(1)H NMR relaxation times (T(1) and T(2)) in parenchyma tissue of apple can identify three populations of water with different relaxation characteristics. By following the uptake of Mn(2+) ions in the tissue it is shown that the observed relaxation times originate from particular water compartments: the vacuole, the cytoplasm, and the cell wall/extracellular space.Proton exchange between these compartments is controlled by the plasmalemma and tonoplast membranes. During the Mn(2+) penetration experiment, conditions occur that cause the relaxation times of protons of cytoplasmic water to be much shorter than their residence time in the cytoplasm. Then the tonoplast permeability coefficient P(d) for water can be calculated from the vacuolar T(1) and T(2) values to be 2.44 10(-5) m.s(-1).

Localized real time blood flow measurements.

A novel method for real time, localized, flow measurements is applied to blood flow in human fingers. Results for arterial and venous flow in normal subjects and patients with abnormal blood circulation are presented. Effects of blood flow regulation by the autonomic nervous system have been observed. Stricture of the digital arteries could be clearly demonstrated in a patient with Raynaud's phenomenon. Experimental signals due to pulsatile flow in a model system can be simulated in a quantitative way. The calibration, however, depends on the actual spin-spin relaxation time and the shape of the pulsatile flow vs. time curve. Due to these limitations, the volume flow rate can be measured with a relative error of approximately +/- 25%.