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Biomedical subjects

H Stødkilde-Jørgensen

Publications and source records attributed to H Stødkilde-Jørgensen.

At least 19 recordsLinked to original sources
PubMed2004

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.

Anatomy, Cross-Sectional↗
PubMed2003

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.

Blood↗
PubMed2003

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.

Acidosis, Respiratory↗
PubMed2002

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.

Animals↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Analysis of Variance↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Animals↗
PubMed2000

In vivo measurements of relaxivities in the rat kidney cortex.

The aim of this study was to implement a novel noninvasive method to derive the in vivo T1 relaxivity (R1) and T2 relaxivity (R2) in the rat kidney cortex. A two-compartment gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) distribution model was established to estimate the bolus and infusion dosages of Gd-DTPA necessary for obtaining the required steady-state concentration levels. After a single bolus injection of (99m)Tc-DTPA, several blood samples were collected. Based on considerations from the applied two-compartment model, a steady-state concentration was predicted approximately 5-10 minutes after the bolus injection. The plasma concentration levels of Gd-DTPA were measured by simultaneous injection of (99m)Tc-DTPA. Three regions in the cortex (upper, central, and lower) of both rat kidneys were used. A statistical evaluation resulted in the following in vivo relaxivities found at 7 T: R1 = 1.04 +/- 0.08 mM(-1)s(-1) and R2 = 10.78 +/- 0.83 mM(-1)s(-1). Using a 95% confidence interval, no intracortical differences were detected. The relaxivities R1 and R2 calculated in the intact rat kidney cortex were distinctly different from relaxivities found in human plasma: (22 degrees C) 4.42 +/- 0.07 mM(-1)s(-1) (r2> 0.98) and R2 = 5.75 +/- 0.17 mM(-1)s(-1) (r2> 0.98), respectively. The measurements showed a marked difference between in vitro and in vivo relaxivities. Comparison of the distribution rates in pig, human, and rats shows a distinct proportionality between size and renal function.

Animals↗
PubMed2000

Evaluation of renal function in normal and hydronephrotic kidneys in rats using gadolinium diethylenetetramine-pentaacetic acid enhanced dynamic magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) is becoming established as a modality complementary to computerized tomography and ultrasound for evaluating kidney function. The evaluation of renal function during ureteral obstruction may be improved by contrast enhanced MRI. We evaluated dynamic changes in relative signal intensity in normal and hydronephrotic rat kidneys after intravenous injection of gadolinium (Gd) diethylenetetramine-pentaacetic acid (DTPA). MATERIALS AND METHODS: Using Gd-DTPA enhanced dynamic MRI we evaluated 35, 1-year-old rats, including 10 with partial and complete unilateral ureteral obstruction, respectively, and 15 with sham operated nonobstructed kidneys. Partial obstruction was created in 2-day-old rats by embedding the left ureter into the psoas muscle. Complete obstruction was created 10 days before MRI by placing a ligature around the upper third of the left ureter. MRI was performed before and 0.1 to 60 minutes after and intravenous injection of Gd-DTPA. We calculated relative signal intensity per time interval in the renal cortex, medulla and pelvis. RESULTS: Dynamic relative signal intensity patterns differed significantly among normal, and partially and completely obstructed kidneys. In normal kidneys signal intensity changes were divided into 3 phases after Gd-DTPA administration. During phase 1 rapid parenchymal uptake of Gd-DTPA within the initial minute after injection produced a rapid signal intensity decrease in the cortex, which achieved a minimum of 28% of pre-injection intensity. During phase 2 signal intensity decreased in the medulla and pelvis to a minimum of 18% and 22%, respectively, of pre-injection intensity within 5 minutes. During phase 3 significant relative signal intensity recovery began in the cortex at 7 minutes, and in the medulla and pelvis at 10 to 15 minutes, and lasted 30 to 60 minutes. In partially obstructed kidneys the 3 phases were significantly slower than in controls. In completely obstructed kidneys only phase 1 occurred within 60 minutes. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI provides useful information for distinguishing obstructed from nonobstructed and partially from completely obstructed kidneys.

Animals↗
PubMed1999

[Magnesium supplementation to patients with type II diabetes].

The purpose of this study was to evaluate Mg status by nuclear magnetic resonance spectroscopy in a group of well-regulated non-insulin-dependent diabetic (NIDDM) patients without angiopathy. Furthermore, to investigate the effect of Mg supplementation on markers of diabetic control, hemostatic function, platelet reactivity and endothelial function in the same patient population. A double-blinded, placebo-controlled and randomized crossover study was carried out, with two 8-weeks treatment periods (360 mg Mg/day) separated by a 4-weeks wash-out period. 11 well-regulated NIDDM patients participated in the study. Eight weeks of Mg supplementation significantly raised the level of free intracellular Mg in the diabetic patients (157.35 +/- 16.53 vs. 197.49 +/- 27.60 microM; p < 0.01). No changes were observed neither in plasma level of von Willebrand factor antigen, fibrinogen and fibronectin nor in platelet release of thromboxane B2 (TxB2). Similarly, markers of diabetic regulation, HbA1c and fructosamine, showed no significant changes. These results suggest that even well regulated NIDDM patients have marked Mg deficiency. Restoring this deficiency had no effect on diabetic control, markers of platelet reactivity, hemostatic function and endothelial function.

Adult↗
PubMed1999

Localized in vivo 1H NMR spectroscopy of murine tumours: effect of blood flow reduction.

Single voxel 1H localized spectroscopy (PRESS at 300 MHz) was used to monitor physiological and biochemical changes induced by hydralazine (5 mg/kg, i.p.) in murine C3H mammary tumours. In addition to a significant increase (by 52%, maximal at 30 min) in the intensity of the 1.32 ppm signal (predominantly from lactate, consistent with a selective reduction in tumour blood supply by hydralazine), downfield shifts in the resonance frequencies of 1H signals were observed. In particular, the signal initially at 3.24 ppm (total choline, tCho) shifted by 0.050 ppm (maximal at 13 min), whereas water shifted by 0.086 ppm. Lactate intensity and water and tCho resonance frequencies returned to control values at approximately 100 min after treatment. No significant changes in the resonance frequencies of water or tCho were observed over this time period in the tumours of mice given saline. In vitro studies showed that, while the resonance frequency of water was temperature dependent, the main components of the tCho signal (choline, phosphorylcholine and glycerophosphorylcholine) were more than 30-fold less sensitive to temperature. It was concluded that the shift in the water resonance frequency was due to the combined effects of tumour temperature reduction and a paramagnetic shift from increased deoxyhaemoglobin levels, whereas the tCho signal was only affected by the paramagnetic shifts.

Animals↗
PubMed1999

Contralateral compensatory kidney growth in rats with partial unilateral ureteral obstruction monitored by magnetic resonance imaging.

PURPOSE: We studied dynamic changes in total volume and renal vein blood flow in the kidneys contralateral to partial ureteral obstruction induced in newborn rats. MATERIALS AND METHODS: Using magnetic resonance imaging we investigated changes in total kidney volume and renal vein blood flow in 20 rats with mild and 18 with severe partial ureteral obstruction that was induced on the left side 2 days after birth. A total of 15 sham operated control rats were also studied. Total kidney volume and renal vein blood flow were monitored sequentially every 2 to 6 weeks for a total of 24 weeks. Renal parenchymal volume measured in vivo by magnetic resonance imaging was compared with that measured in vitro at week 24. RESULTS: Total volume and renal vein blood flow increased significantly in contralateral nonobstructed kidneys from week 14 and thereafter in rats with severe partial unilateral ureteral obstruction. At week 24 volume had increased by 22% and blood flow had increased by 25%. Volume and flow did not increase significantly in contralateral nonobstructed kidneys in rats with mild partial unilateral ureteral obstruction (p = 0.09). Before changes occurred in volume and blood flow in the contralateral nonobstructed kidneys, renal vein blood flow had decreased significantly from week 8 and thereafter in severely obstructed kidneys. In rats with mild partial unilateral ureteral obstruction renal vein blood flow decreased significantly in obstructed kidneys from week 18 and thereafter. Good correlation was noted between MRI in vivo and in vitro kidney volume measurements (r = 0.972, p <0.001). CONCLUSIONS: A significant increase in total volume and renal vein blood flow in contralateral nonobstructed kidneys did not develop immediately after the onset of detectable functional deterioration in partially obstructed kidneys. Therefore, caution should be used when incorporating compensatory growth into surgical decision making.

Animals↗
PubMed1999

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Adult↗
PubMed1999

Prosthetic heart valve evaluation by magnetic resonance imaging.

OBJECTIVE: To evaluate the potential of magnetic resonance imaging (MRI) for evaluation of velocity fields downstream of prosthetic aortic valves. Furthermore, to provide comparative data from bileaflet aortic valve prostheses in vitro and in patients. METHODS: A pulsatile flow loop was set up in a 7.0 Tesla MRI scanner to study fluid velocity data downstream of a 25 mm aortic bileaflet heart valve prosthesis. Three dimensional surface plots of velocity fields were displayed. In six NYHA class I patients blood velocity profiles were studied downstream of their St. Jude Medical aortic valves using a 1.5 Tesla MRI whole-body scanner. Blood velocity data were displayed as mentioned above. RESULTS: Fluid velocity profiles obtained from in vitro studies 0.25 valve diameter downstream of the valve exhibited significant details about the cross sectional distribution of fluid velocities. This distribution completely reflected the valve design. Blood velocity profiles in humans were considerably smoother and in some cases skewed with the highest velocities toward the anterior-right ascending aortic wall. CONCLUSION: Display and interpretation of fluid and blood velocity data obtained downstream of prosthetic valves is feasible both in vitro and in vivo using the MRI technique. An in vitro model with a straight tube and the test valve oriented orthogonally to the long axis of the test tube does not entail fluid velocity profiles which are compatible to those obtained from humans, probably due to the much more complex human geometry, and variable alignment of the valve with the ascending aorta. With the steadily improving quality of MRI scanners this technique has significant potential for comparative in vitro and in vivo hemodynamic evaluation of heart valves.

Adult↗
PubMed1998

Effects of combretastatin on murine tumours monitored by 31P MRS, 1H MRS and 1H MRI.

PURPOSE: Combretastatins have tubulin-binding activity and are being investigated for their toxicity against tumour vasculature. We report the use of 31P and 'H magnetic resonance (MR) spectroscopy and 1H MR imaging for monitoring the effects of combretastatin A-4 prodrug (100mg/kg, i.p.) on energy metabolism and necrosis, respectively, in the C3H murine mammary tumour. MATERIALS AND METHODS: The tumours (volume ca. 200mm3) were grown in the hind foot of mice. MR examinations were performed without anaesthesia within a 7.1 Tesla magnet. 31P MRS (TR = 6 s) was performed before treatment and at 1-, 2-, 3-, and 24-h after injection of drug or saline via an i.p. line. 1H MRS (PRESS; 24microl voxel; TR = 2 s; TE = 135 ms) and both T1-weighted (TR = 0.2 s; TE = 0.02 s) and T2-weighted (TR = 2 s; TE = 0.20 s) 1H MRI were performed before treatment and 2.5 and 24 h afterwards. RESULTS: The ratio beta-nucleotide triphosphate/inorganic phosphate fell by 33% within 1 h of treatment and remained constant for a further 2 h. A small but significant fall in pH (by 0.11 units) was observed at 1 h. Although an increase in the 1H MR spectroscopy signal at about 1.32 ppm (predominantly from lactate) was observed in some tumours following combretastatin treatment, this effect was not seen consistently. No changes in the intensity of T2-weighted 1H MR images or in tumour necrosis (measured histologically) were detected within 3 h of treatment. CONCLUSIONS: The reduction in tumour energetics and pH was consistent with a reduction in tumour blood flow but this occurred before any significant incidence of haemorrhagic necrosis was detected. The combretastatin dose used to achieve these effects was less than one tenth of the maximum tolerated dose in mice.

Animals↗