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

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.

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

In vivo injection of [1-13C]glucose and [1,2-13C]acetate combined with ex vivo 13C nuclear magnetic resonance spectroscopy: a novel approach to the study of middle cerebral artery occlusion in the rat.

Astrocytes play a pivotal role in cerebral glutamate homeostasis. After 90 minutes of middle cerebral artery occlusion in the rat, the changes induced in neuronal and astrocytic metabolism and in the neuronal-astrocytic interactions were studied by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy and HPLC analysis of amino acids of the lateral caudoputamen and lower parietal cortex, representing the putative ischemic core, and the upper frontoparietal cortex, corresponding to the putative penumbra. In the putative ischemic core, evidence of compromised de novo glutamate synthesis located specifically in the glutamatergic neurons was detected, and a larger proportion of glutamate was derived from astrocytic glutamine. In the same region, pyruvate carboxylase activity, representing the anaplerotic pathway in the brain and exclusively located in astrocytes, was abolished. However, astrocytic glutamate uptake and conversion to glutamine took place, and cycling of intermediates in the astrocytic tricarboxylic acid cycle was elevated. In the putative penumbra, glutamate synthesis was improved compared with the ischemic core, the difference appeared to be brought on by better neuronal de novo glutamate synthesis, combined with normal levels of glutamate formed from astrocytic glutamine. In both ischemic regions, gamma-aminobutyric acid synthesis directly from glucose was reduced to about half, indicating impaired pyruvate dehydrogenase activity; still, gamma-aminobutyric acid reuptake and cycling was increased. The results obtained in the current study demonstrate that by combining in vivo injection of [1-13C]glucose and [1,2-13C]acetate with ex vivo 13C nuclear magnetic resonance spectroscopy, specific metabolic alterations in small regions within the rat brain suffering a focal ischemic lesion can be studied.

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.

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.

Neuroprotective effect of the novel glutamate AMPA receptor antagonist YM872 assessed with in vivo MR imaging of rat MCA occlusion.

The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was evaluated by using MR imaging and histopathology of rats subjected to permanent MCA occlusion. Two treatment groups with continuous i.v. infusion of 20 mg kg-1 h-1 YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n=9) and 24 h YM872 treatment group (n=8) respectively, were compared to a control group (n=8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of the ischemic tissue damage was studied by diffusion weighted MR imaging 412 and 24 h after MCA occlusion. The volume of ischemic tissue damage as assessed by diffusion weighted MR imaging 412 h after MCA occlusion was significantly smaller in both YM872 treatment groups (99+/-52 mm3 and 102+/-44 mm3 compared to 186+/-72 mm3 in the control group, +/-S.D. and p=0.008). The infarct volume as assessed by T2 weighted MR imaging 24 h after MCA occlusion was significantly smaller only in the 24 h YM872 treatment group (262+/-57 mm3 compared to 366+/-49 mm3 in the control group, +/-S.D. and p=0.01) while the infarct volume in the 4 h YM872 treatment group (357+/-88 mm3) was similar to the control group. YM872 treatment significantly reduced the infarct volume 24 h after MCA occlusion when the drug was administered as continuous infusion during the 24-h observation period.

Analysis of dynamic magnetic resonance images.

Dynamic magnetic resonance (MR) imaging with contrast agents is a very promising technique for studying tissue perfusion in vivo. A temporal series of magnetic resonance images of the same slice are acquired following the injection of a contrast agent into the blood stream. The image intensity depends on the local concentration of the contrast agent, so that tissue perfusion can be studied by the image series. A new method of analyzing such series is described here. Nonparametric linear regression is used for modeling the image intensity along the series on a pixel by pixel basis. After modeling, some relevant quantities describing the time series are obtained and displayed as images. Due to its flexibility, this approach is preferred to parametric modeling when pathology is present since this can induce a wide spread of patterns for the pixel image intensity along time. Results of the application of the method to series of dynamic magnetic resonance images from ischaemic rat brains after the injection of the susceptibility agent Sprodiamide Inj. (Dy-DTPA-BMA) are shown and compared to results from a related known method.

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.

A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.

The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.

Comparison of MR perfusion imaging and microsphere measurements of regional cerebral blood flow in a rat model of middle cerebral artery occlusion.

The purpose of this investigation was to correlate magnetic resonance (MR) perfusion measurements with absolute regional cerebral blood flow (rCBF) in a rat model of focal ischemia. The MR perfusion measurements were made using dynamic first-pass bolus tracking of a susceptibility contrast agent, whereas rCBF was measured using radioactive microspheres. Two simple MR perfusion parameters, the maximum change in R2* (m delta R2*) and time delay to m delta R2* (t delta R2*), were derived from the signal intensity versus time curves on a pixel-to-pixel basis, without applying curve-fitting procedures or tracer kinetic theory. In each hemisphere, m delta R2* and t delta R2* were compared with the rCBF measurements in four selected regions of interest. Sixteen MR bolus tracking series were performed in 12 rats with occlusion of the middle cerebral artery. In all of the individual series there was a significant correlation (.0001 < or = p < or = .02) between m delta R2* and the microsphere rCBF measurements, with correlation coefficients ranging from .784 to .983. Pooling the m delta R2* data resulted in a correlation coefficient of .809 (p = .0001). There was a nonlinear correlation between the t delta R2* and rCBF. For both parameters there was considerable variation between different measurements regarding both the slope of the regression line and its intercept with the y-axis. Our results justify the use of m delta R2* as a relative measure of perfusion during acute cerebral ischemia. Because of the interindividual variation, calibration of MR perfusion measurements for the estimation of absolute flow values must be considered unreliable. The t delta R2* may have physiological relevance as a marker of collateral flow.

Acute treatment of whiplash neck sprain injuries. A randomized trial of treatment during the first 14 days after a car accident.

STUDY DESIGN: A single-blinded, randomized treatment study with a follow-up period of 6 months. OBJECTIVE: To study the long-term consequences of whiplash neck sprain injuries in patients treated with two different regimes during the first 14 days after the car accident. Patients in the first group were encouraged to act as usual, i.e., continue to engage in their normal, pre-injury activities; that group was compared with another group of patients who were given time off from work and who were immobilized using a soft neck collar. The end point of the comparison was the evaluation of subjective symptoms 6 months after the accident. SUMMARY OF BACKGROUND DATA: Few randomized treatment studies have been performed to evaluate the clinical outcome for patients with neck sprain. METHOD: Patients who participated in the study were recruited from the Emergency Clinic at the University Hospital in Trondheim, Norway. The study group included 201 patients (47% of the study group) with neck sprain that resulted from a car accident. Neck and shoulder movements and subjective symptoms, which were assessed using several different measurements, were assessed during the follow-up period. RESULTS: There was a significant reduction of symptoms from the time of intake to 24 weeks after the treatment period in both groups. There was a significantly better outcome for the act-as-usual group in terms of subjective symptoms, including pain localization, pain during daily activities, neck stiffness, memory, and concentration, and in terms of visual analog scale measurements of neck pain and headache. CONCLUSIONS: The outcome was better for patients who were encouraged to continue engaging in their normal, pre-injury activities as usual than for patients who took sick leave from work and who were immobilized during the first 14 days after the neck sprain injury.

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.

Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F.

We used phosphorus-31 nuclear magnetic resonance spectroscopy in a rat model of 10 minutes' severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to study the effects of preischemic and postischemic treatment with 3 mg/kg i.v. U74006F on the recovery of high-energy phosphates and intracellular pH during early reperfusion. The mean +/- SD time to 85% recovery of phosphocreatine was 14.1 +/- 8.4 minutes in the control group (n = 10) compared with 6.6 +/- 3.5 minutes (p less than 0.05) in the preischemic (n = 8) and 4.2 +/- 1.0 minutes (p less than 0.001) in the postischemic (n = 11) treatment groups. The mean +/- SD time to 80% recovery of adenosine triphosphate was 15.4 +/- 8.5 minutes in the control group compared with 6.3 +/- 1.8 (p less than 0.005) and 5.4 +/- 2.8 (p less than 0.001) minutes in the preischemic and postischemic treatment groups, respectively. There were no differences in intracellular pH between the control and either of the treatment groups. We conclude that U74006F led to quicker recovery of high-energy phosphates during early reperfusion, and this beneficial effect was also seen with postischemic treatment.

Characterization of the microcirculation during ischemia and reperfusion in the penumbra of a rat model of temporary middle cerebral artery occlusion: a laser Doppler flowmetry study.

The dynamic changes in microcirculation were investigated with laser Doppler flowmetry in two selected regions of interest (ROI) of a stroke lesion during ischemia and early reperfusion using a rat model of temporary middle cerebral artery (MCA) occlusion. In each ROI measurements were made either during 30 min or 2 h of MCA occlusion followed by 1 h of reperfusion. On the periphery of the MCA territory, an area of mild ischemia with a mean reduction of flow to 38% (39.9% in the group with 30 min MCA occlusion and 35.9% in the group with 2 h MCA occlusion) of preischemic values was demonstrated. Closer to the center of the MCA territory, more severe ischemia with a mean reduction of flow to 21% (19.9% in the 30-min group and 22.9% in the 2-hour group) was seen. In the two groups with laser Doppler flowmetry in the ROI of mild ischemia, a compensatory increase in flow during the first 3-6 min after MCA occlusion could be seen. All rats displayed a peak hyperperfusion immediately after re-establishing of flow which then stabilized above, below, or equal to the preischemic level. This peak hyperemia was most abundant in the group in which flow was measured in the ROI of more severe ischemia after the 30-min MCA occlusion. In the same area a short hyperemic peak was followed by a significant hypoperfusion of 60% of preischemic flow after 2 h of MCA occlusion. In the groups with flow measurements in the ROI of mild ischemia, there was a return to preischemic flow after the 30-min ischemia and a tendency of preserved hyperemia after 2 h of MCA occlusion.

Contrast-enhanced pulmonary MR imaging.

The present paper reports our own experience with MR perfusion imaging and gives an overview of contrast-enhanced pulmonary MR perfusion imaging, MR angiography, and ventilation MR imaging using hyperpolarized gases or oxygen as contrast agent. These methods are discussed within the context of their possible role in the diagnosis of pulmonary diseases, particularly embolism and emphysema.

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.