Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice.

The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1-13C]glucose and [1,2-13C]acetate injection with ex vivo 13C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4-13C]glutamate and [4-13C]glutamine, and percent enrichment in [4-13C]glutamate were detected in the α-syn KO mice. [1,2-13C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites.

DynaCT in pre-treatment evaluation of aortic aneurysm before EVAR.

OBJECTIVE: DynaCT(®) is a method for obtaining computed tomography (CT)-like images using a C-arm system. Our aim was to compare the accuracy of these images to multidetector CT (MDCT) images prior to endovascular aortic repair (EVAR). METHODS: A non-consecutive group of 20 elective patients were prospectively exposed to MDCT and one additional DynaCT before EVAR. Six arterial measurements and nine anatomical areas were chosen to: (1) visualise the peri-aortic soft tissue and assess the possibility to diagnose a potential haemorrhage from a ruptured aneurysm and (2) make the pre-treatment measurements before insertion of stent graft. Differences between modalities and readers were statistically compared using a linear mixed model. RESULTS: For maximum aortic diameter, a significant difference of 1.3 mm was found between techniques (p = 0.043). Visibility scores were significantly better for all areas in MDCT data. Pre-treatment evaluation with DynaCT before EVAR was possible for all areas; evaluation of the iliac arteries were suboptimal due to a limited imaging volume size. Significant inter-reader differences were found for all anatomical areas. CONCLUSION: The result indicates that DynaCT gives sufficient information to determine the correct treatment and for selecting the proper stent graft before EVAR. A limited volume size reduces the evaluation of the iliac arteries.

DynaCT during EVAR--a comparison with multidetector CT.

OBJECTIVES: We have explored the usefulness of an on-table, cross-sectional radiological imaging (DynaCT) in endovascular aortic repair (EVAR). DynaCT images were compared to images from a regular multidetector (16 slice) CT. In the comparison, we tested the accordance of firstly 5 relevant clinical measurements and secondly the visibility of 9 anatomical areas in the two different types of images. This imaging was carried out in addition to the usual angiographic imaging. DESIGN, MATERIAL AND METHOD: 20 patients with infrarenal abdominal aortic aneurysm (AAA) were prospectively enrolled in the study. We compared Images from DynaCT with two different doses of contrast medium to MDCT-images in two different ways. Firstly relevant arterial diameters and lengths and secondly, 9 anatomical areas were evaluated regarding visibility which was scored on a 4-point scale. RESULTS: There were no significant differences in the measured arterial diameters and lengths. MDCT had a significantly higher visibility score than both DynaCT investigations. However, with the highest contrast medium dose we found acceptable diagnostic quality in 78-94% of the cases for 8 of the 9 investigated anatomical areas. CONCLUSION: Our findings indicate that on-table DynaCT are of sufficient quality to give relevant information of arterial measurements, needed in endovascular repair of infrarenal aortic aneurysms.

Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight.

Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight

NG2 expression regulates vascular morphology and function in human brain tumours.

Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and the host tissue. The underlying mechanisms that regulate such interactions remain largely unknown. NG2 is a transmembrane proteoglycan whose presence on transformed cells has been demonstrated to increase proliferation in vitro and angiogenesis in vivo. To study the effects of NG2 during tumour growth and progression, we engineered an NG2 positive human glioma cell line (U251-NG2) from parental NG2 negative cells (U251-WT) and implanted both cell types stereotactically into immunodeficient nude rat brains. The tumours were longitudinally monitored in vivo using multispectral MRI employing two differently sized contrast agents (Gd-DTPA-BMA and Gadomer) to assess vascular leakiness, vasogenic oedema, tumour volumes and necrosis. Comparisons of Gd-DTPA-BMA and Gadomer revealed differences in their spatial distribution in the U251-NG2 and U251-WT tumours. The U251-NG2 tumours exhibited a higher leakiness of the larger molecular weight Gadomer and displayed a stronger vasogenic oedema (69.9 +/- 15.2, P = 0.018, compared to the controls (10.7 +/- 7.7). Moreover, immunohistochemistry and electron microscopy revealed that the U251-NG2 tumours had a higher microvascular density (11.81 +/- 0.54; P = 0.0010) compared to controls (5.76 +/- 0.87), with vessels that displayed larger gaps between the endothelial cells. Thus, tumour cells can regulate both the function and structure of the host-derived tumour vasculature through NG2 expression, suggesting a role for NG2 in the cross-talk between tumour-host compartments.

Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method.

Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight

New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer.

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced MR imaging with a new intravascular contrast agent in grading human breast cancer. MATERIAL AND METHODS: 23 patients with 27 breast tumors (21 carcinomas and 6 fibroadenomas) were examined with dynamic MR imaging after administration of Clariscan, an iron oxide nanoparticle with large T1 relaxivity and a long plasma half life. A 3D T1-weighted gradient echo sequence with an acquisition time of 60 s was repeated at regular intervals of 3-5 min before and up to 1 h after injection of 2 mg/kg b.w. of Clariscan. The endothelial transfer constant, Kps, which reflects overall vascular permeability, and the fractional plasma volume, fPV, were estimated from time-intensity curves acquired from three separate regions of interest (ROIs): whole tumor, a permeability hot spot, and a blood volume hot spot. Kps and fPV were compared to the results of histologic tumor grading (Scarff-Bloom-Richardson, SBR) and microvascular density, MVD. RESULTS: A statistically significant correlation between the MR-derived Kps parameters and the SBR score was obtained for the whole tumor ROI (R = 0.70), and for the permeability hot spot ROIs (R = 0.67). A correlation between fPV and SBR was detected for the blood volume hot spot ROIs (R = 0.48). There was no statistically significant correlation between Kps or fPV with MVD. CONCLUSION: The results support the hypothesis that dynamic MR with the intravascular contrast agent Clariscan may be used for non-invasive tumor grading.

Hyperbaric oxygen and neutrophil accumulation/tissue damage during permanent focal cerebral ischaemia in rats.

The use of hyperbaric oxygenation (HBO) for the treatment of severe brain ischaemia remains controversial. The HBO may interfere with destructive neutrophil (PMN) infiltration following ischaemia/reperfusion. The effects of HBO on PMN accumulation and the area of ischaemic tissue damage were investigated in rats having permanent focal ischaemia (4 h). The right middle cerebral arteries of a group of Wistar rats were permanently occluded. The rats were then randomly divided into those ( n=7) to be treated with HBO at 2 atm for 230 min and those ( n=8) to breathe air at atmospheric pressure for an equivalent period. The HBO had no effect on permanent ischaemia, as there was no significant difference in the area of ischaemic tissue damage between HBO-treated [mean (SD)] [331 (88) mm(3)] and non-treated animals [322 (111) mm(3)]. Moreover, the increase in myeloperoxidase [5.4 (4.1) compared to 2.4 (1.2) pg x g(-1) wet weight of brain] was not significantly different. The results indicate that HBO did not reduce tissue damage during 4 h of permanent focal ischaemia.

Differences in neurotransmitter synthesis and intermediary metabolism between glutamatergic and GABAergic neurons during 4 hours of middle cerebral artery occlusion in the rat: the role of astrocytes in neuronal survival.

Astrocytes are intimately involved in both glutamate and gamma-aminobutyric acid (GABA) synthesis, and ischemia-induced disruption of normal neuroastrocytic interactions may have important implications for neuronal survival. The effects of middle cerebral artery occlusion (MCAO) on neuronal and astrocytic intermediary metabolism were studied in rats 30, 60, 120, and 240 minutes after MCAO using in vivo injection of [1-13C]glucose and [1,2- 13C]acetate combined with ex vivo 13C magnetic resonance spectroscopy and high-performance liquid chromatography analysis of the ischemic core (lateral caudoputamen and lower parietal cortex) and penumbra (upper frontoparietal cortex). In the ischemic core, both neuronal and astrocytic metabolism were impaired from 30 minutes MCAO. There was a continuous loss of glutamate from glutamatergic neurons that was not replaced as neuronal glucose metabolism and use of astrocytic precursors gradually declined. In GABAergic neurons astrocytic precursors were not used in GABA synthesis at any time after MCAO, and neuronal glucose metabolism and GABA-shunt activity declined with time. No flux through the tricarboxylic acid cycle was found in GABAergic neurons at 240 minutes MCAO, indicating neuronal death. In the penumbra, the neurotransmitter pool of glutamate coming from astrocytic glutamine was preserved while neuronal metabolism progressively declined, implying that glutamine contributed significantly to glutamate excitotoxicity. In GABAergic neurons, astrocytic precursors were used to a limited extent during the initial 120 minutes, and tricarboxylic acid cycle activity was continued for 240 minutes. The present study showed the paradoxical role that astrocytes play in neuronal survival in ischemia, and changes in the use of astrocytic precursors appeared to contribute significantly to neuronal death, albeit through different mechanisms in glutamatergic and GABAergic neurons.

Analysis of contrast-enhanced dynamic MR images of the lung.

Recent studies have demonstrated the potential of dynamic contrast-enhanced magnetic resonance imaging (MRI) describing pulmonary perfusion. However, breathing motion, susceptibility artifacts, and a low signal-to-noise ratio (SNR) make automatic pixel-by-pixel analysis difficult. In the present work, we propose a novel method to compensate for breathing motion. In order to test the feasibility of this method, we enrolled 53 patients with pulmonary embolism (N = 24), chronic obstructive pulmonary disease (COPD) (N = 14), and acute pneumonia (N = 15). A crucial part of the method, an automatic diaphragm detection algorithm, was evaluated in all 53 patients by two independent observers. The accuracy of the method to detect the diaphragm showed a success rate of 92%. Furthermore, a Bayesian noise reduction technique was implemented and tested. This technique significantly reduced the noise level without removing important clinical information. In conclusion, the combination of a motion correction method and a Bayesian noise reduction method offered a rapid, semiautomatic pixel-by-pixel analysis of the lungs with great potential for research and clinical use.

Local endostatin treatment of gliomas administered by microencapsulated producer cells.

We describe a technique for the treatment of malignant brain tumors based on local delivery of the anti-angiogenic protein endostatin from genetically engineered cells encapsulated in ultrapure sodium alginate. Alginate consists of L-guluronic and D-mannuronic acid, which in the presence of divalent cations forms an extended gel network, in which cells reside and remain immunoisolated, when implanted into the rat brain. Here, we show that endostatin-transfected cells encapsulated in alginate maintain endostatin secretion for at least four months after intracerebral implantation in rats. During the implantation period 70% of the encapsulated cells remained viable, as opposed to 85% in in vitro-cultured capsules. Rats that received transplants of BT4C glioma cells, together with endostatin-producing capsules (0.2 microg/ml per capsule), survived 84% longer than the controls. The endostatin released from the capsules led to an induction of apoptosis, hypoxia, and large necrotic avascular areas within 77% of the treated tumors, whereas all the controls were negative. The encapsulation technique may be used for many different cell lines engineered to potentially interfere with the complex microenvironment in which tumor and normal cells reside. The present work may thus provide the basis for new therapeutic approaches toward brain tumors.

Feature extraction and classification of dynamic contrast-enhanced T2*-weighted breast image data.

UNLABELLED: The relatively low specificity of dynamic contrast-enhanced T1-weighted magnetic resonance imaging (MR) imaging of breast cancer has lead several groups to investigate different approaches to data acquisition, one of them being the use of rapid T2*-weighted imaging. Analyses of such data are difficult due to susceptibility artifacts and breathing motion. MATERIALS AND METHODS: One-hundred-twenty-seven patients with breast tumors underwent MR examination with rapid, single-slice T2*-weighted imaging of the tumor. Different methods for classifying the image data set using leave-one-out cross validation were tested. Furthermore, a semi-automatic region of interest (ROI) definition tool was presented and compared with manual ROI definitions from a previous study. Finally, pixel-by-pixel analysis was done and compared with ROI analysis. The analyses were done with and without noise reduction. RESULTS: The minimum enhancement parameter was the most robust and accurate of the parameters tested. The semi-automatic ROI definition method was fast and produced similar results as the manually defined ROIs. Noise reduction improved both sensitivity and specificity, but the improvement was not statistically significant. The pixel-based analysis methods used in the present study did not improve classification results. CONCLUSIONS: Analysis of T2*-weighted breast images can be done in a rapid and robust manner by using semi-automatic ROI definition tools in combination with noise reduction. Minimum enhancement gives an indication of malignancy in T2*-weighted imaging.

(13)C MR spectroscopy study of lactate as substrate for rat brain.

In order to address the question whether lactate in blood can serve as a precursor for cerebral metabolites, fully awake rats were injected intravenously with [U-(13)C]lactate or [U-(13)C]glucose followed 15 min later by decapitation. Incorporation of label from [U-(13)C]glucose was seen mainly in glutamate, GABA, glutamine, aspartate, alanine and lactate. More label was found in glutamate than glutamine, underscoring the predominantly neuronal metabolism of pyruvate from [U-(13)C]glucose. It was estimated that the neuronal metabolism of acetyl CoA from glucose accounts for at least 66% and the glial for no more than 34% of the total glucose consumption. When [U-(13)C]lactate was the precursor, label incorporation was similar to that observed from [U-(13)C]glucose, but much reduced. Plasma analysis revealed the presence of approximately equal amounts of [1,2,3-(13)C]- and [1,2-(13)C]glucose, showing gluconeogenesis from [U-(13)C]lactate. It was thus possible that the labeling seen in the cerebral amino acids originated from labeled glucose, not [U-(13)C]lactate. However, the presence of significantly more label in [U-(13)C]- than in [2,3-(13)C]alanine demonstrated that [U-(13)C]lactate did indeed cross the blood-brain barrier, and was metabolized further in the brain. Furthermore, contributions from pyruvate carboxylase (glial enzyme) were detectable in glutamine, glutamate and GABA, and were comparatively more pronounced in the glucose group. This indicated that relatively more pyruvate from lactate than glucose was metabolized in neurons. Surprisingly, the same amount of lactate was synthesized via the tricarboxylic acid cycle in both groups, indicating transfer of neurotransmitters from the neuronal to the astrocytic compartment, as previous studies have shown that this lactate is synthesized primarily in astrocytes. Taking into consideration that astrocytes take up glutamate more avidly than GABA, it is conceivable that neuronal lactate metabolism was more prominent in glutamatergic neurons.

Axillary lymph node metastases in breast cancer: preoperative detection with dynamic contrast-enhanced MRI.

Metastatic involvement of axillary lymph nodes is one of the most important prognostic variables in breast cancer. The aim of our work was to study the value of dynamic contrast-enhanced MR imaging in revealing axillary lymph node metastases from breast cancer. A total of 65 patients with invasive breast cancer treated with axillary lymph node dissection were preoperatively evaluated by MRI. T1-weighted dynamic contrast-enhanced 3D images were acquired using a coil covering the breast and the axilla. The dynamic contrast enhancement, size, and morphology of the axillary lymph nodes were registered. Histopathological examination revealed axillary lymph node metastases in 24 patients. When using a signal intensity increase in the lymph nodes of >100% during the first postcontrast image as a threshold for malignancy, 57 of 65 patients were correctly classified (sensitivity 83%, specificity 90%, accuracy 88%). These results were not improved when lymph node size and morphology were used as additional criteria. Axillary lymph nodes can be evaluated as a part of an MR-mammography study without substantial increase in examination time, and provide the surgeon with knowledge about the localization of possible metastatic lymph nodes.

Perfusion magnetic resonance imaging of the lung: characterization of pneumonia and chronic obstructive pulmonary disease. A feasibility study.

Perfusion magnetic resonance (MR) imaging is a promising new method for detection of perfusion defects in the diagnosis of pulmonary embolism. In the present study we evaluated the first-pass characteristics of perfusion MR imaging in patients with pneumonia or chronic obstructive pulmonary disease (COPD), frequent differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD were acquired in both the coronal and transaxial planes (an inversion recovery prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR images and the signal intensity (SI) versus time curves were characterized for each disease entity and compared with normal lung and the findings in pulmonary embolism from our previous study. The perfusion MR images of pneumonia showed distinct regions of increased contrast enhancement; in COPD with signs of emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with signs of emphysema, and normal lung were statistically different, the respective pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4 (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR imaging of pneumonia and COPD with signs of emphysema showed first-pass that were characteristics promising for diagnostic use. Both the MR images and the SI versus time curves were different from the perfusion characteristics in normal lung and pulmonary embolism shown previously.

Breast lesions: evaluation with dynamic contrast-enhanced T1-weighted MR imaging and with T2*-weighted first-pass perfusion MR imaging.

PURPOSE: To evaluate the diagnostic value of an imaging protocol that combines dynamic contrast-enhanced T1-weighted magnetic resonance (MR) imaging and T2*-weighted first-pass perfusion imaging in patients with breast tumors and to determine if T2*-weighted imaging can provide additional diagnostic information to that obtained with T1-weighted imaging. MATERIALS AND METHODS: One hundred thirty patients with breast tumors underwent MR imaging with dynamic contrast-enhanced T1-weighted imaging of the entire breast, which was followed immediately with single-section, T2*-weighted imaging of the tumor. RESULTS: With T2*-weighted perfusion imaging, 57 of 72 carcinomas but only four of 58 benign lesions had a signal intensity loss of 20% or more during the first pass, for a sensitivity of 79% and a specificity of 93%. With dynamic contrast-enhanced T1-weighted imaging, 64 carcinomas and 19 benign lesions showed a signal intensity increase of 90% or more in the first image obtained after the administration of contrast material, for a sensitivity of 89% and a specificity of 67%. CONCLUSION: T2*-weighted first-pass perfusion imaging can help differentiate between benign and malignant breast lesions with a high level of specificity. The combination of T1-weighted and T2*-weighted imaging is feasible in a single patient examination and may improve breast MR imaging.

Measurement of cell density and necrotic fraction in human melanoma xenografts by diffusion weighted magnetic resonance imaging.

The aim of this study was to investigate whether apparent diffusion coefficients (ADCs) could be used as measures of cell density and necrotic fraction of tumors. Tumors of four human melanoma xenograft lines were subjected to diffusion-weighted magnetic resonance imaging (DWI). ADCs were calculated from the images and related to cell density and necrotic fraction, as determined from histological sections. A significant correlation was found between the ADC of the viable tissue and cell density, regardless of whether tumors of different lines or different regions within individual tumors were considered. Necrosis was found in two of the lines. A single region of massive necrosis that could be differentiated from the viable tissue in ADC maps was found in one line, whereas a number of smaller necrotic regions that could not be identified in ADC maps were found in the other line. Tumor ADC was significantly correlated with the necrotic fraction of the former, but not of the latter line. Our results suggest that ADCs can be used as measures of cell density and necrotic fraction of some but not of all tumors, depending on whether the individual necrotic regions are large enough to be differentiated from the viable tissue with the obtained spatial resolution of the DW images. Magn Reson Med 43:828-836, 2000.

[Diagnosis of breast diseases with magnetic resonance tomography]. / Brystdiagnostikk med magnetisk resonanstomografi.

Magnetic resonance imaging (MRI) of the breast is currently used for evaluation of both parenchymal disease and silicone gel implants. MRI is widely recognised as the most accurate imaging method for evaluation of breast implant integrity. Knowledge of the MRI appearance of the different types of implants and the possible complications of their use is important for diagnosis in these patients. The use of contrast-enhanced MRI in breast cancer diagnosis has been investigated thoroughly during the last decade. It is a sensitive imaging method to detect breast pathology, and may have an important diagnostic impact in carefully selected patient groups. The development of new MR techniques may improve the utility of MR in breast cancer diagnosis, treatment and research.

A closed-chest pulmonary artery occlusion/reperfusion model in the pig: detection of experimental pulmonary embolism with MR angiography and perfusion MR imaging.

RATIONALE AND OBJECTIVES: To establish a pig model suitable for imitating pulmonary emboli to facilitate research in the diagnosis of pulmonary embolism. METHODS: Thirteen animals were anesthetized, mechanically ventilated, and subjected to pulmonary artery catheterization initiated from the right external jugular vein. With the use of a Swan-Ganz catheter, repetitive occlusion/reperfusion maneuvers were done at different locations of the pulmonary arterial tree. Conventional pulmonary angiography, MR angiography, and perfusion MR imaging were performed. RESULTS: The model remained hemodynamically stable throughout the 13 experiments, without any significant difference between the blood pressure measurements at the start and at the end of the right-heart and pulmonary artery catheterizations. In each of the nine animal experiments that investigated MR imaging, four of four using perfusion MR imaging (proximal and distal occlusions) and five of five using MR angiography (larger pulmonary artery occlusions), all repeated pulmonary artery occlusions were successfully performed (reproducibility of 100%). CONCLUSIONS: The closed-chest pulmonary artery occlusion/reperfusion model in the pig allowed repetitive, controlled imitations of pulmonary emboli at different levels of the pulmonary artery in the same experiment. MR angiography and perfusion MR imaging were adequate to detect the pulmonary artery occlusions and the nonperfused lung regions, respectively. The model may be a helpful tool for future research in this field.

In vivo effects of adenosine A1 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13C NMR spectroscopy.

Adenosine is a neuromodulator, and it has been suggested that cerebral acetate metabolism induces adenosine formation. In the present study the effects that acetate has on cerebral intermediary metabolism, compared with those of glucose, were studied using the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Fasted rats received an intravenous injection of CCPA, DPCPX, or vehicle. Fifteen minutes later either [1,2-13C]acetate or [1-13C]glucose was given intraperitoneally; after another 30 min the rats were decapitated. Cortical extracts were analyzed with 13C NMR spectroscopy and HPLC analysis. DPCPX affected neuronal and astrocytic metabolism. De novo synthesis of GABA from neuronal and astrocytic precursors was significantly reduced. De novo syntheses of glutamate and aspartate were at control levels, but their degradation was significantly elevated. In glutamine the anaplerotic activity and the amount of label in the position representing the second turn in the tricarboxylic acid cycle were significantly increased, suggesting elevated metabolic activity in astrocytes. CCPA did not influence GABA, aspartate, or glutamine synthesis. In glutamate the contribution from the astrocytic anaplerotic pathway was significantly decreased. In the present study the findings in the [1,2-13C]acetate and [1-13C]glucose control, CCPA, and DPCPX groups were complementary, and no adenosine A1 agonist effects arising from cerebral acetate metabolism were detected.