Systematized water content calculation in cartilage using T1-mapping MR estimations: design and validation of a mathematical model.

BACKGROUND: Up to 80 % of cartilage is water; the rest is collagen fibers and proteoglycans. Magnetic resonance (MR) T1-weighted measurements can be employed to calculate the water content of a tissue using T1 mapping. In this study, a method that translates T1 values into water content data was tested statistically. MATERIALS AND METHODS: To develop a predictive equation, T1 values were obtained for tissue-mimicking gelatin samples. 1.5 T MRI was performed using inverse angle phase and an inverse sequence at 37 (±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated in arbitrary units. Data were collected and modeled using linear regression. To validate the method, articular cartilage from six healthy pigs was used. The experiment was conducted in accordance with the Danish Animal Experiment Committee. Double measurements were performed for each animal. Ex vivo, all water in the tissue was extracted by lyophilization, thus allowing the volume of water to be measured. This was then compared with the predicted water content via Lin's concordance correlation coefficient at the 95 % confidence level. RESULTS: The mathematical model was highly significant when compared to a null model (p < 0.0001). 97.3 % of the variation in water content can be explained by absolute T1 values. Percentage water content could be predicted as 0.476 + (T1 value) × 0.000193 × 100 %. We found that there was 98 % concordance between the actual and predicted water contents. CONCLUSION: The results of this study demonstrate that MR data can be used to predict percentage water contents of cartilage samples. LEVEL OF EVIDENCE: 3 (case-control study).

Does radiofrequency ablation (RFA) epiphysiodesis affect adjacent joint cartilage?

PURPOSE: To test the hypothesis that epiphysiodesis made with radiofrequency ablation (RFA) is a safe procedure that disrupts the growth plate without damaging the adjacent joint articular cartilage. METHODS: RFA epiphysiodesis was done during 8 min in vivo in 40 growing pig tibia physis. In addition, three tibiae were ablated for 16 min and three more for 24 min. As a burned cartilage reference, six tibiae were ablated on the joint articular cartilage for 8 min. After the procedure, the animals were terminated and the tibiae were harvested. Magnetic resonance imaging (MRI) was done ex vivo to evaluate the joint articular cartilage in all samples. We used T1-weighted, T2-weighted, and water content sequences under a 1.5 T magnetic field. RESULTS: On the burned articular cartilage, intensity changes were observed at MRI. We found no evidence of articular cartilage damage on the 40 8-min RFA procedures. The tibiae ablated for 16 min and 24 min showed intact joint cartilage. CONCLUSIONS: Epiphysiodesis using RFA is safe for the adjacent articular cartilage. This study shows that RFA can be done safely in the growing physis of pigs, even with triple duration procedures.

Concomitant changes in cross-sectional area and water content in skeletal muscle after resistance exercise.

This study investigated how one bout (1EX) and three bouts (3EX) of strenuous resistance exercise affected the cross-sectional area (CSA) and water content (WC) of the quadriceps muscle and patella tendon (PT), 4 h and 52 h after the last exercise bout. Ten healthy untrained male subjects performed 1EX with one leg and 3EX with the other leg. CSA and WC were measured with magnetic resonance imaging 10, 20 and 30 cm proximal to the tibia plateau (TP) for the muscle, and at the proximal, central and distal site for the PT prior to exercise, and 4 h and 52 h after the last exercise bout. Ten centimeter above the TP, muscle CSA was significantly increased at 4 h (1EX: 13 ± 5%; 3EX: 13 ± 4%) and 52 h (1EX: 16 ± 5%; 3EX: 16 ± 5%) compared with baseline. Muscle WC was significantly increased at 4 h (1EX: 7 ± 1%; 3EX: 6 ± 2%) and 52 h (1EX: 8 ± 2%; 3EX: 8 ± 3%) compared to baseline. PT central CSA was significantly reduced at 52 h (3EX: 14 ± 2%) compared with baseline and (3EX: 13 ± 1%) compared with 4 h. Present data demonstrate that strenuous resistance exercise results in an acute increase in muscle WC and underlines the importance of ensuring sufficient time between the last exercise bout and the determination of anatomical dimensions in muscles.

Water-content calculation in growth plate and cartilage using MR T1-mapping design and validation of a new method in a porcine model.

OBJECTIVE: There is a close relation between cartilage health and its hydration state. Current magnetic resonance methods allow visualizing this tissue. However, a quantitative analysis is more useful when studying disease. The purpose of this study was to quantify water content in cartilage using magnetic resonance without contrast agents. MATERIALS AND METHODS: Water-content estimations using T1 magnetic resonance mapping were done first in eight gelatin samples where the water content was previously known. The same method was used in the physeal areas of eight skeletally immature 30-kg pigs. To calculate accuracy, T1 calculations were compared to dry-freeze, which is considered the gold standard because it can remove the total water content form a tissue. Four fresh cartilage and seven gelatin samples were dry-frozen. Water content obtained from dry-freeze was compared to the one calculated from T1 map values. A mathematical model and statistical analysis were used to calculate the predictive value of the method and its significance. RESULTS: T1-map-based magnetic resonance method can calculate water content in cartilage with an accuracy of 97.3 %. We calculated a coefficient of variance for this method against dry-frozen sample of 3.68 (SD = 1.2) in gelatin samples, and 2.73 (SD = 1.3) in in vivo samples. Between two independent observers, the coefficient of variance was 0.053, which suggests it can be easily reproduced. CONCLUSIONS: Magnetic resonance was able to calculate, with high accuracy, the cartilage water content using T1 mapping sequences.

Controlled longitudinal bone growth by temporary tension band plating: an experimental study.

Permanent growth arrest of the longer bone is an option in the treatment of minor leg-length discrepancies. The use of a tension band plating technique to produce a temporary epiphysiodesis is appealing as it avoids the need for accurate timing of the procedure in relation to remaining growth. We performed an animal study to establish if control of growth in a long bone is possible with tension band plating. Animals (pigs) were randomised to temporary epiphysiodesis on either the right or left tibia. Implants were removed after ten weeks. Both tibiae were examined using MRI at baseline, and after ten and 15 weeks. The median interphyseal distance was significantly shorter on the treated tibiae after both ten weeks (p = 0.04) and 15 weeks (p = 0.04). On T1-weighted images the metaphyseal water content was significantly reduced after ten weeks on the treated side (p = 0.04) but returned to values comparable with the untreated side at 15 weeks (p = 0.14). Return of growth was observed in all animals after removal of implants. Temporary epiphysiodesis can be obtained using tension band plating. The technique is not yet in common clinical practice but might avoid the need for the accurate timing of epiphysiodesis.

Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels - results from a randomized trial.

BACKGROUND: Low plasma 25-hydroxy-vitamin D (25OHD) is associated with obesity. Vitamin D (VD) may be implicated in obesity and its complications such as insulin resistance, hypertension, and low-grade inflammation. We investigated the effects of VD supplementation on fat distribution and on obesity complications in obese adults with low plasma levels of 25OHD. METHODS: In a double-blind design 52 subjects aged 18 to 50years with BMI>30kg/m(2) and plasma 25OHD <50nmol/l were randomized to 26weeks of treatment with 7000IU of VD daily or placebo. Body composition was assessed by DXA and subcutaneous (SAT) and visceral adipose tissue (VAT), intrahepatic (IHL) and intramyocellular lipids (IMCL) were evaluated by magnetic resonance imaging and magnetic resonance spectroscopy. Insulin resistance (HOMA-IR), blood pressure, plasma lipids, and circulating inflammatory markers were also investigated. RESULTS: VD treatment increased mean plasma levels of 25OHD from 33nmol/l to 110nmol/l (P<0.0001) and decreased median parathyroid hormone levels from 5.3 to 4.5pmol/l (P<0.01) in the intervention group. Treatment did not change body fat, SAT, VAT, IHL, or IMCL compared with placebo. Neither did treatment affect HOMA, blood pressure, plasma lipids or any of several inflammatory markers investigated including hsCRP. CONCLUSION: Increasing 25OHD levels by VD treatment for 26weeks have no effects on obesity complications in obese adults with low baseline plasma 25OHD.

Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle.

During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast.

Longitudinal MR study of brain structure and hippocampus volume in major depressive disorder.

OBJECTIVE: To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume. METHOD: An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model. RESULTS: Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome. CONCLUSION: Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.

Evaluation of complete and partially obstructed kidneys using Gd-DTPA enhanced dynamic MRI in adolescent swine.

PURPOSE: Aim of this study was to evaluate the dynamic changes in renal relative signal intensity (RSI) following the administration of Gd-DTPA in adolescent pigs with complete and partial unilateral ureteric obstruction. METHODS: Pigs were divided into 3 groups: partial and complete unilateral ureteric obstruction and controls. Complete unilateral ureteric obstruction (CUUO) was created by ligating the left ureter, whereas partial unilateral ureteric obstruction (PUUO) was created in pigs of 2 weeks of age by embedding the left ureter into the psoas muscle. Dynamic MRI was performed before and at 0 - 60 min after an intravenous bolus injection of Gd-DTPA. Mean RSI of the renal cortex, medulla and pelvis was measured and interpreted as an indirect measure of the renal function. In addition, renography was performed, and renal morphology was examined IN VITRO. RESULTS: Three phases of RSI were identified. The dynamic RSI patterns differed markedly between obstructed and control kidneys. In PUUO kidneys, Phase 1 of the mean RSI of the cortex and medulla demonstrated a decreased amplitude and prolonged duration, whereas in Phase 2 the mean RSI of the pelvis was increased. In acute CUUO kidneys, the mean RSI patterns were similar to those of controls, except for a significant increase of the pelvic mean RSI. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI allowed a characterization and differentiation of renal function and morphology of normal and obstructed kidneys, and secondly, provided potentially important information on renal concentrative and filtration availability.

Changes in levator ani anatomical configuration following physiotherapy in women with stress urinary incontinence.

PURPOSE: We quantified the effect of pelvic floor muscle training on the anatomical configuration of the levator ani using magnetic resonance imaging. MATERIALS AND METHODS: Five female participants with stress urinary incontinence underwent magnetic resonance imaging before and after participating in a pelvic floor muscle physiotherapy program. Axial T1-weighted images of the levator ani were taken with the participant in a supine position. Source images were then manually segmented and surface modeling was applied to build a 3-dimensional model of the levator ani. Models were then measured to determine the levator ani surface area as well as the encircled volume at rest and during voluntary contraction. The percentage of levator ani retraction and symphysis pubis movement during voluntary contraction before and after physiotherapy were also measured. RESULTS: After physiotherapy the levator ani surface area at rest was significantly smaller than before physiotherapy, decreasing from 677.11 +/- 45.00 to 620.48 +/- 36.14 mm(2) (p = 0.04). The relative reduction in volume encircled by the levator ani during contraction increased significantly from -11.66 +/- 7.42 to -26.02 +/- 13.52 mm(3) (p = 0.04). Levator ani surface retraction during a voluntary contraction increased significantly from 65.61% +/- 17.07% to 81.70% +/- 16.30% (p = 0.02). Symphysis pubis movement during pelvic floor muscle contraction decreased from 1.45 +/- 1.32 to 0.44 +/- 0.61 mm (p = 0.05). CONCLUSIONS: Findings from this preliminary study indicate that pelvic floor muscle training results in anatomical changes in the levator ani and reduction of pubic movement. These results provide insight into the possible anatomical mechanisms through which physiotherapy enables the pelvic floor muscle to minimize urine leakage.

Reading with the ears.

We studied the cortical networks of Morse code reading with functional magnetic resonance imaging (fMRI). Four expert radio telegraphists performed two closely matched reading experiments, one in binaurally presented high speed Morse code and one in print. Performance was equal for both conditions. Reading single nouns in Morse code resulted in predominantly left-sided activation of the frontal and temporal perisylvian language areas, prefrontal cortex, and premotor cortex. In a within-subject comparison between reading Morse code and reading print, the activation pattern in the left temporoparietal association cortex was similar for both forms of reading, suggesting that reading Morse code shares part of its cortical networks with reading print.

Tension and stress calculations in a 3-D Fourier model of gall bladder geometry obtained from MR images.

Biliary tract obstruction results in dilatation of the biliary tract including the gall bladder and induction of symptoms such as abdominal pain. Since the pain receptors are likely mechano-sensitive receptors, it is important to develop tools for studying the distributions of tension and stress in the wall of the gall bladder. Wall tension and stress can be determined using Laplace's equation and the three-dimensional (3-D) geometry of a thin walled organ under equilibrium conditions. The objective of this study was to develop an analytical method to describe the 3-D geometry of the porcine gall bladder. The Fourier series method was used to describe the organ surface geometry obtained from magnetic resonance (MR) images. MR images of nine normal and three obstructed porcine gall bladders were analyzed. The curvature was computed throughout the gall bladder surface and the wall tension was computed using Laplace's equation. The spatial distributions of principal curvatures, tensions, and stresses were nonhomogeneous in the gall bladder because of its complex geometry. The extremum values of curvatures did not differ between normal and 2-day obstructed gall bladders. The pressure, tension, and stress were significantly higher, however, in the obstructed gall bladders (p < 0.05). This study provides an analytical tool for characterizing the complex 3-D geometry of an organ obtained from a clinical imaging modality.

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study.

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.

CO2 induced acute respiratory acidosis and brain tissue intracellular pH: a 31P NMR study in swine.

High concentration carbon dioxide (CO(2)) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO(2) anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO(2) is not known. Based on (31)P NMR spectroscopy, we describe CO(2)-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO(2) in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P(CO2), O(2) saturation and HCO(3)(-) concentration. The intracellular pH paralleled the arterial pH and P(CO2) during inhalation of CO(2); and it is suggested that the acute reaction to CO(2) inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H(+)/HCO(3)(-). The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO(2) inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO(2) leads to anaesthesia soon after the start of inhalation.

Dynamic gadolinium-enhanced MRI evaluation of porcine femoral head ischemia and reperfusion.

OBJECTIVE: To examine the potential of gadolinium (Gd)-enhanced dynamic MRI in the detection of early femoral head ischemia. Furthermore, to apply a three-compartment model to achieve a clinically applicable MR index for femoral head perfusion during the steady state and arterial hip joint tamponade. DESIGN AND MATERIALS: In a porcine model femoral head perfusion was measured by radioactive tracer microspheres and by using a dynamic Gd-enhanced MRI protocol. Femoral head perfusion measurements and MRI tests were performed unilaterally before, during and after the experimentally induced ischemia of one of the hip joints. Ischemia was induced by increasing intra-articular pressure to 250 mmHg. RESULTS: All pigs showed ischemia of the femoral head epiphysis under hip joint tamponade followed by reperfusion to the same level as before joint tamponade. In two cases perfusion after removal of tamponade continued to be low. In dynamic MRI measurements increases in signal intensity were seen after intravenous infusion of Gd-DTPA, followed by a slow decrease in signal intensity. The signal-intensity curve during femoral head ischemia had a minor increase. Also the coefficient determined was a helpful indicator of femoral head ischemia. CONCLUSIONS: Femoral head blood flow as measured by microspheres fell significantly under joint tamponade. Early detection of this disturbed regional blood flow was possible using a dynamic MRI procedure. A biomathematical model resulted from the evaluation of the intervals of signal intensity over time which allows detection of bone blood flow changes at a very early stage. Using this new method earlier detection of femoral head necrosis may be possible.

Post mortem energy metabolism and pH development in porcine M. longissimus dorsi as affected by two different cooling regimes. A (31)P-NMR spectroscopic study.

(31)P-NMR spectroscopy was carried out on M. longissimus dorsi samples chilled by two different cooling profiles corresponding to commercial batch and tunnel chilling. The half-life of post mortem phosphocreatine (PCr) degradation was found to be significantly less in muscle samples exposed to tunnel chilling (rapid) compared with muscle samples exposed to batch chilling (soft) conditions, while no difference in the post mortem ATP degradation was found. Moreover, the post mortem pH development in the muscle samples differed considerably between the two cooling regimes. A maximum difference of approx. 0.25 pH units between the two cooling profiles was observed around 150 min post mortem. Theoretical calculations of the registered pH difference between rapid and soft chilling of muscle samples revealed that the temperature effect on the buffer capacity of muscle is the major determining factor in the detected difference in intracellular pH between the two cooling profiles, while any contribution from a temperature-induced delayed progress in the lactate formation post mortem seems negligible. Moreover, calculations on the effect of the registered pH difference between rapid and soft chilling of muscle samples resemble a 2.5 times greater denaturation of myosin in samples which were chilled softly compared with samples chilled more rapidly. Finally, the relationship to the functionality of meats from soft and rapid chilled pork carcasses is discussed.

The Danish PET/depression project: PET findings in patients with major depression.

BACKGROUND: It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression. METHODS: By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain. RESULTS: The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period. CONCLUSION: Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.

Effects of centrally administered arginine vasopressin and atrial natriuretic peptide on the development of brain edema in hyponatremic rats.

OBJECTIVE: Centrally released arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have been shown to participate in brain volume regulation. The aim of the present study was to evaluate the effects of centrally administered AVP and ANP on the time course of development of brain edema in vivo in hyponatremic rats, using diffusion-weighted magnetic resonance imaging. METHODS: We performed intracerebroventricular (ICV) administration of 120 microg AVP, 20 microg ANP, or physiological saline into the right lateral ventricle in 18 rats. Twenty-five minutes after the treatment, we induced systemic hyponatremia by the intraperitoneal administration of 140 mmol/L dextrose solution. Serial diffusion-weighted imaging scans were obtained up to 96 minutes after the start of the hyponatremia. Changes in the brain extra-to intracellular volume fraction ratio were estimated as changes in the apparent diffusion coefficient (ADC). RESULTS: No change in the ADC was observed after the ICV injection of saline or AVP. The onset of hyponatremia induced a rapid and marked ADC reduction in both groups, indicating an increased intracellular space. However, the ADC decrease became significantly more pronounced in the ICV AVP group (83.3+/-4.7% of baseline level, mean +/- standard deviation) than in the saline group (93.7+/-3.3% of baseline, P < 0.001) after 78 minutes of hyponatremia. The ICV injection of ANP induced a prompt ADC increase to 111.5+/-10.0% (P < 0.05) of the baseline level, indicating a rapid reduction in the intracellular compartment. In the initial phase of hyponatremia, the ADC values in the ANP group were consistently higher than those in the saline group, decreasing finally to 86.9+/-9.6% after 96 minutes of hyponatremia. CONCLUSION: Our findings demonstrate the opposite effects of AVP and ANP on the intracellular volume fraction of the brain during the development of cellular brain edema, with an immediate effect on ANP and a delayed effect on AVP. The results emphasize the direct effects of these hormones on the cellular volume regulatory mechanisms in the brain during the development of cerebral edema.

Effect of changing tumor oxygenation on glycolytic metabolism in a murine C3H mammary carcinoma assessed by in vivo nuclear magnetic resonance spectroscopy.

The rate of conversion of D-[1-(13)C]glucose into [3-(13)C]lactate (apparent glycolytic rate) has been determined in C3H murine mammary carcinomas in vivo using tumor-selective (13)C nuclear magnetic resonance spectroscopy with (1)H-(13)C cross-polarization. Under conditions of acute hypoxia induced by breathing carbon monoxide at 660 ppm, the apparent glycolytic rate was 0.0239 +/- 0.0019 min(-1). The proportion of (13)C label incorporated into [4-(13)C]glutamate (measured in tumor extracts) was 25-fold lower than that incorporated into [3-(13)C]lactate, reflecting a very limited oxidative metabolism during this hypoxic episode. For animals breathing air or carbogen (95% O(2) + 5% CO(2)), the calculated glycolytic rates were correspondingly lower (0.0160 +/- 0.0021 min(-1) and 0.0050 +/- 0.0011 min(-1), respectively). Although (13)C labeling of glutamate at C4 was still an order of magnitude lower than that for lactate at C3 (11-fold for air and 9-fold for carbogen), these ratios did show a greater degree of oxidative metabolism than that seen in animals breathing carbon monoxide at 660 ppm. The marked difference in apparent glycolytic rate for this tumor model between well-oxygenated and hypoxic conditions demonstrates a substantial Pasteur effect (inhibition of glycolysis by oxygen). Dynamic (13)C nuclear magnetic resonance spectroscopy provides a noninvasive estimate of tumor glycolysis that can be used to evaluate the relationship between oxygenation and energy metabolism, and this has potential consequences for the sensitivity of hypoxic cells to treatment and their ability to promote angiogenesis.