La anticoncepción en la mujer obesa / Contraception in obese women

La creciente prevalencia de mujeres obesas en edad fértil es una crisis de salud pública y social. La anticoncepción es un tema clave en mujeres con obesidad. Las mujeres obesas tienen una actividad sexual similar a las mujeres de peso normal y en ellas se considera que el uso de anticoncepción es menos eficaz, teniendo mayor riesgo de embarazo no deseado. Debido a una variedad de alteraciones del metabolismo, la obesidad es un factor de riesgo cardiovascular que puede aumentar, cuando se combina con la anticoncepción hormonal. Todos estos factores deben considerarse al elegir un método anticonceptivo en una mujer obesa. El objetivo de esta revisión es evaluar el riesgo-beneficio de cada tipo de anticoncepción disponible y la problemática de anticoncepción después de la cirugía bariátrica, proporcionando al médico una guía práctica sobre el uso de píldoras anticonceptivas orales en mujeres obesas

The increasing prevalence of obese women of childbearing age is a public and social health crisis. Contraception is a key issue in women with obesity. Obese women have a sexual activity no different from women of normal weight, and the use of contraception is considered less effective, as there is a higher risk of having an unwanted pregnancy. Due to a variety of metabolic disorders, obesity is a cardiovascular risk factor that can increase when combined with hormonal contraception. All these factors should be considered when choosing a contraceptive method in an obese woman. The objective of this review is to evaluate the risk-benefit of each type of available contraception, and the problem of contraception after bariatric surgery, in order to provide doctors with a practical guide on the use of oral contraceptive pills in obese women

IMAGING OF NEURO-INFLAMMATION: PAST, PRESENT AND FUTURE.

The investigation of dynamic processes with long time profiles can profit from longitudinal noninvasive imaging modalities. In this contribution the potential and limits of in vivo imaging modalities are discussed as regards monitoring neuro-inflammation. Complementary information derived from magnetic resonance imaging (MRI), positron emission tomography (PET) and bioluminescence imaging (BLI) will be presented.

Overexpression of protein phosphatase 2A in a murine model of chronic myocardial infarction leads to increased adverse remodeling but restores the regulation of ß-catenin by glycogen synthase kinase 3ß.

BACKGROUND/OBJECTIVES: Increased activity of cardiac protein phosphatases is an important feature in human heart failure. Several different protein phosphatases (PP) are involved in the regulation of excitation-contraction-coupling of the myocardium. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase consisting of a dimeric core enzyme and tissue-specific subunits. In this study we used transgenic mice overexpressing PP2A to further investigate the role of PP2A in cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Adult male CD-1 mice overexpressing the catalytic subunit α of PP2A (αMHC-PP2A; TG) underwent chronic LAD-ligation or sham surgery, respectively; wildtype littermates (WT) were used as controls. Cardiac function was determined by echocardiography before and 28 days after LAD-ligation. 28 days after MI, the animals were sacrificed and cardiac remodeling was analyzed in histological sections and by Western blots. PP2A overexpression leads to dilated cardiomyopathy in mice, and increased cardiomyocyte hypertrophy and fibrosis of the remote myocardium can be seen after myocardial infarction. However, we found an improved survival of TG in the subacute phase after MI in comparison to WT. On the molecular level, TG shows reduced expression of SERCA and CaMKII alpha both under basal condition as well 28 days after MI. Additionally, the regulation of the Akt/GSK3ß/ß-catenin pathway is severely disturbed in TG at baseline where a significant activation of Akt is found that coincides with the typical phosphorylation of GSK3ß. However, this does not lead to the accumulation of ß-catenin - on the contrary: phosphorylation-induced degradation of ß-catenin is significantly enhanced. CONCLUSION: Transgenic overexpression of myocardial PP2A causes adverse remodeling which coincides with a disruption of the classical Akt/GSK3/ß-catenin pathway under baseline conditions that is restored to normal values in chronic myocardial infarction. Even so overall survival of TG after myocardial infarction was not constrained and survival after day 2 post MI was improved.

In vivo analysis of neuroinflammation in the late chronic phase after experimental stroke.

BACKGROUND AND PURPOSE: In vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis. To our knowledge, this is the first study providing USPIO-MRI data in the chronic phase up to 8 weeks after stroke. RESULTS: Phagocytes with internalized USPIOs induced MRI-T2(∗) signal alterations in the brain. Combined analysis with [(11)C]PK11195-PET allowed quantification of phagocytic activity and other neuroinflammatory processes. From 4 weeks after induction of ischemia, inflammation was dominated by phagocytes. Immunohistochemistry revealed colocalization of Iba1+ microglia with [(11)C]PK11195 and ED1/CD68 with USPIOs. USPIO-related iron was distinguished from alternatively deposited iron by assessing MRI before and after USPIO application. Tissue affected by non-phagocytic inflammation during the first week mostly remained in a viably vital but remodeled state after 4 or 8 weeks, while phagocytic activity was associated with severe injury and necrosis accordingly. CONCLUSIONS: We conclude that the combined approach of USPIO-MRI and [(11)C]PK11195-PET allows to observe post-stroke inflammatory processes in the living animal in an intraindividual and longitudinal fashion, predicting long-term tissue fate. The non-invasive imaging methods do not affect the immune system and have been applied to human subjects before. Translation into clinical applications is therefore feasible.

Endovascular therapy in trauma.

The practice of medicine has experienced a revolution in the use of catheter-based or endovascular techniques to manage age-related vascular disease over the past 15 years. In many scenarios the less invasive, endovascular method is associated with reduced morbidity and mortality than the traditional open surgical approach. Although somewhat delayed, the use of endovascular approaches in the management of certain trauma scenarios has also increased dramatically. With improvements in catheter-based and imaging technologies and a broader acceptance of the value of the endovascular approach, this trend is likely to continue to the benefit of patients. The use of endovascular techniques in trauma can be considered in three broad categories: (1) large-vessel repair (e.g. covered stent repair), (2) mid- to small-vessel hemostasis (e.g. coils, plugs, and hemostatic agents), and (3) large-vessel balloon occlusion for resuscitation (e.g. resuscitative endovascular balloon occlusion of the aorta). While not exclusive, these categories provide a framework from which to consider establishing a trauma-specific endovascular inventory and performance of these techniques in the setting of severe injury. The aim of this review is to use this framework to provide a current appraisal of endovascular techniques to manage various forms: vascular injury, bleeding, and shock; including injury patterns in which an endovascular approach is established and scenarios in which it is nascent and evolving.

Effects of minocycline on endogenous neural stem cells after experimental stroke.

Minocycline has been reported to reduce infarct size after focal cerebral ischemia, due to an attenuation of microglia activation and prevention of secondary damage from stroke-induced neuroinflammation. We here investigated the effects of minocycline on endogenous neural stem cells (NSCs) in vitro and in a rat stroke model. Primary cultures of fetal rat NSCs were exposed to minocycline to characterize its effects on cell survival and proliferation. To assess these effects in vivo, permanent cerebral ischemia was induced in adult rats, treated systemically with minocycline or placebo. Imaging 7 days after ischemia comprised (i) Magnetic Resonance Imaging (MRI), assessing the extent of infarcts, (ii) Positron Emission Tomography (PET) with [(11)C]PK11195, characterizing neuroinflammation, and (iii) PET with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT), detecting proliferating endogenous NSCs. Immunohistochemistry was used to verify ischemic damage and characterize cellular inflammatory and repair processes in more detail. In vitro, specific concentrations of minocycline significantly increased NSC numbers without increasing their proliferation, indicating a positive effect of minocycline on NSC survival. In vivo, endogenous NSC activation in the subventricular zone (SVZ) measured by [(18)F]FLT PET correlated well with infarct volumes. Similar to in vitro findings, minocycline led to a specific increase in endogenous NSC activity in both the SVZ as well as the hippocampus. [(11)C]PK11195 PET detected neuroinflammation in the infarct core as well as in peri-infarct regions, with both its extent and location independent of the infarct size. The data did not reveal an effect of minocycline on stroke-induced neuroinflammation. We show that multimodal PET imaging can be used to characterize and quantify complex cellular processes occurring after stroke, as well as their modulation by therapeutic agents. We found minocycline, previously implied in attenuating microglial activation, to have positive effects on endogenous NSC survival. These findings hold promise for the development of novel treatments in stroke therapy.

Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle.

The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1α expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors.

In vivo MRI stem cell tracking requires balancing of detection limit and cell viability.

Cell-based therapy using adult mesenchymal stem cells (MSCs) has already been the subject of clinical trials, but for further development and optimization the distribution and integration of the engrafted cells into host tissues have to be monitored. Today, for this purpose magnetic resonance imaging (MRI) is the most suitable technique, and micron-sized iron oxide particles (MPIOs) used for labeling are favorable due to their low detection limit. However, constitutional data concerning labeling efficiency, cell viability, and function are lacking. We demonstrate that cell viability and migratory potential of bone marrow mesenchymal stromal cells (BMSCs) are negatively correlated with incorporated MPIOs, presumably due to interference with the actin cytoskeleton. Nevertheless, labeling of BMSCs with low amounts of MPIOs results in maintained cellular function and sufficient contrast for in vivo observation of single cells by MRI in a rat glioma model. Conclusively, though careful titration is indicated, MPIOs are a promising tool for in vivo cell tracking and evaluation of cell-based therapies.

Bid-induced release of AIF from mitochondria causes immediate neuronal cell death.

Mitochondrial dysfunction and release of pro-apoptotic factors such as cytochrome c or apoptosis-inducing factor (AIF) from mitochondria are key features of neuronal cell death. The precise mechanisms of how these proteins are released from mitochondria and their particular role in neuronal cell death signaling are however largely unknown. Here, we demonstrate by fluorescence video microscopy that 8-10 h after induction of glutamate toxicity, AIF rapidly translocates from mitochondria to the nucleus and induces nuclear fragmentation and cell death within only a few minutes. This markedly fast translocation of AIF to the nucleus is preceded by increasing translocation of the pro-apoptotic bcl-2 family member Bid (BH3-interacting domain death agonist) to mitochondria, perinuclear accumulation of Bid-loaded mitochondria, and loss of mitochondrial membrane integrity. A small molecule Bid inhibitor preserved mitochondrial membrane potential, prevented nuclear translocation of AIF, and abrogated glutamate-induced neuronal cell death, as shown by experiments using Bid small interfering RNA (siRNA). Cell death induced by truncated Bid was inhibited by AIF siRNA, indicating that caspase-independent AIF signaling is the main pathway through which Bid mediates cell death. This was further supported by experiments showing that although caspase-3 was activated, specific caspase-3 inhibition did not protect neuronal cells against glutamate toxicity. In conclusion, Bid-mediated mitochondrial release of AIF followed by rapid nuclear translocation is a major mechanism of glutamate-induced neuronal death.

Efficient stem cell labeling for MRI studies.

Iron oxide particles are especially suited for cell tracking experiments due to their extraordinarily molar relaxivity as compared with other paramagnetic nuclei. We have compared different iron oxide particles (Sinerem, Endorem and magnetic microspheres) for their suitability to label embryonic stem cells (D3 cell line). In addition to detectability thresholds, particular attention has been paid to the evaluation of long-term stability of the labelling procedure (up to 4 weeks) as well as to toxic and other adverse effects on cell viability. Comparative studies were performed using neural progenitor cells (C17.2) and dendritic cells. The present study indicates strong dependence of the label efficiency and stability on the iron oxide particles and cell lines in use.

The tales of two geckos: does dispersal prevent extinction in recently fragmented populations?

Although habitat loss and fragmentation threaten species throughout the world and are a major threat to biodiversity, it is apparent that some species are at greater risk of extinction in fragmented landscapes than others. Identification of these species and the characteristics that make them sensitive to habitat fragmentation has important implications for conservation management. Here, we present a comparative study of the population genetic structure of two arboreal gecko species (Oedura reticulata and Gehyra variegata) in fragmented and continuous woodlands. The species differ in their level of persistence in remnant vegetation patches (the former exhibiting a higher extinction rate than the latter). Previous demographic and modelling studies of these two species have suggested that their difference in persistence levels may be due, in part, to differences in dispersal abilities with G. variegata expected to have higher dispersal rates than O. reticulata. We tested this hypothesis and genotyped a total of 345 O. reticulata from 12 sites and 353 G. variegata from 13 sites at nine microsatellite loci. We showed that O. reticulata exhibits elevated levels of structure (FST=0.102 vs. 0.044), lower levels of genetic diversity (HE=0.79 vs. 0.88), and fewer misassignments (20% vs. 30%) than similarly fragmented populations of G. variegata, while all these parameters were fairly similar for the two species in the continuous forest populations (FST=0.003 vs. 0.004, HE=0.89 vs. 0.89, misassignments: 58% vs. 53%, respectively). For both species, genetic structure was higher and genetic diversity was lower among fragmented populations than among those in the nature reserves. In addition, assignment tests and spatial autocorrelation revealed that small distances of about 500 m through fragmented landscapes are a barrier to O. reticulata but not for G. variegata. These data support our hypothesis that G. variegata disperse more readily and more frequently than O. reticulata and that dispersal and habitat specialization are critical factors in the persistence of species in habitat remnants.

A responsive MRI contrast agent to monitor functional cell status.

It has been shown that insoluble Gd chelates are suitable MRI contrast agents for conditional activation by intracellular lipases. The DTPA-based, insoluble, inactive contrast agent was internalized into dendritic cells by phagocytosis. Cleavage of long aliphatic side chains by intracellular lipase activity leads to the contrast agents solubility and hereby its activation depending on the enzyme expression. Uptake and activation of the contrast agent was much reduced in Flt3+ CD11b+ progenitor cells. Detectability limits in the T(1)-weighted MR images were estimated in phantoms and in vivo in the rat brain. Marginal toxic effects were only observed at very high concentrations of the contrast agent. The chelate can easily be modified to be targeted by enzymes expressed during specific change of cell status like activation or differentiation. Such a system is suitable for functional cellular in vivo MR imaging.

Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism: an MRI investigation in rat brain.

BACKGROUND AND PURPOSE: Thrombolytic treatment of stroke carries the risk of hemorrhagic transformation. Therefore, the potential of MRI for prediction of recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to identify patients in whom rtPA treatment may provoke such complications. METHODS: Spontaneously hypertensive rats (SHR) (n=9) were submitted to middle cerebral artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of 10 mg/kg rtPA. Untreated SHR (n=9) were infused with saline. MRI imaging was performed before treatment and included apparent diffusion coefficient (ADC), T2, and perfusion mapping and contrast enhancement with gadolinium-DTPA. The distribution of intracerebral hemorrhages was studied 3 days later by histological staining. RESULTS: Clot embolism led to the rapid decline of ADC in the territory of the occluded artery. Tissue lesion volume derived from ADC imaging increased by 155+/-69% in the untreated animals and by 168+/-87% in the treated animals (P=NS), determined on the histological sections after 3 days. This same lesion growth in both groups indicated absence of therapeutic effect after 3-hour treatment delay. Hemorrhagic transformations were significantly more frequent in treated SHR (P<0.05). In untreated rats, hemorrhages were found in the border zone of the ischemic territory; in treated animals, hemorrhagic transformations occurred in the ischemic core region. rtPA-induced hemorrhages were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or perfusion imaging. The region of contrast enhancement colocalized with subsequent bleeding in these animals. CONCLUSIONS: The disturbance of blood-brain barrier but not of other MR parameters allows risk assessment for hemorrhagic transformation induced by subsequent thrombolytic treatment.

Dynamic changes of ADC, perfusion, and NMR relaxation parameters in transient focal ischemia of rat brain.

The potential of multiparametric MRI parameters for differentiating between reversibly and irreversibly damaged brain tissue was investigated in an experimental model of focal brain ischemia in the rat. The middle cerebral artery (MCA) was occluded by intraluminal suture insertion for 60 or 90 min, followed by 4.5 h of reperfusion. The apparent diffusion coefficient (ADC) of brain water, T(1) and T(2) relaxation times, and CBF(i), an MR-derived index of cerebral perfusion, were repeatedly measured and correlated with the outcome from the ischemic impact. A novel user-independent approach for segmentation of ADC maps into classes of increasing injury was introduced to define regions of interest (ROIs) in which these parameters were evaluated. MCA occlusion led to a graded decline of ADC, which corresponded with both the severity of flow reduction and an increase in T(1) and T(2) relaxation times. Removal of the suture led to a triphasic restitution of blood flow consisting of a fast initial rise, a secondary decline, and final normalization. Postischemic reperfusion led to a rise of ADC irrespective of the duration of ischemia. However, the quality of recovery declined with increasing severity of the ischemic impact. Throughout the observation time, T(1) and T(2) showed a continuous increase, the intensity of which correlated with the severity of ADC decline during ischemia. Particularly with longer ischemia time, elevated T(2) in combination with reduced ADC yielded a lower probability of recovery during recirculation, while intraischemic perfusion information contributed less to the prediction of outcome. In conclusion, the combination of MR parameters at the end of ischemia correlated with the probability of tissue recovery but did not permit reliable differentiation between reversibly and irreversibly damaged tissue.

Application of magnetic resonance to animal models of cerebral ischemia.

The present review has been compiled to highlight the role of magnetic resonance imaging (MRI) and MR spectroscopy (MRS) for the investigation of cerebral ischemia in the animal experimental field of basic research. We have focused on stroke investigations analyzing the pathomechanisms of the disease evolution and on new advances in both nuclear MR (NMR) methodology or genetic engineering of transgenic animals for the study of complex molecular relationships and causes of the disease. Furthermore, we have tried to include metabolic and genetic aspects, as well as the application of functional imaging, for the investigation of the disturbance or restitution of functional brain activation under pathological conditions as relates to controlled animal experiments.

Intensive voice treatment (LSVT) for patients with Parkinson's disease: a 2 year follow up.

OBJECTIVES: To assess long term (24 months) effects of the Lee Silverman voice treatment (LSVT), a method designed to improve vocal function in patients with Parkinson's disease. METHODS: Thirty three patients with idiopathic Parkinson's disease were stratified and randomly assigned to two treatment groups. One group received the LSVT, which emphasises high phonatory-respiratory effort. The other group received respiratory therapy (RET), which emphasises high respiratory effort alone. Patients in both treatment groups sustained vowel phonation, read a passage, and produced a monologue under identical conditions before, immediately after, and 24 months after speech treatment. Change in vocal function was measured by means of acoustic analyses of voice loudness (measured as sound pressure level, or SPL) and inflection in voice fundamental frequency (measured in terms of semitone standard deviation, or STSD). RESULTS: The LSVT was significantly more effective than the RET in improving (increasing) SPL and STSD immediately post-treatment and maintaining those improvements at 2 year follow up. CONCLUSIONS: The findings provide evidence for the efficacy of the LSVT as well as the long term maintenance of these effects in the treatment of voice and speech disorders in patients with idiopathic Parkinson's disease.

MR angiographic investigation of transient focal cerebral ischemia in rat.

Contrast agent free time-of-flight magnetic resonance angiography (TOF-MRA) was applied to the intraluminal thread occlusion model of experimental stroke in rat. It was combined with perfusion- and diffusion-weighted imaging (PWI and DWI) sequences to correlate occlusion and reopening of the middle cerebral artery with alterations in these well-established magnetic resonance sequences. Since TOF-MRA can be repeated without limitations, the time course of vascular patency is demonstrated during an experimental period of up to 8 h (2 h control, 1 h ischemia, 3-6 h reperfusion). With an acquisition time of 10 min, TOF-MRA proved to be suitable to analyze the vascular state of occlusion and reperfusion repetitively in longitudinal studies. Spatial resolution was sufficient to observe neurovascular structural details. In eight out of 10 animals complete vessel occlusion by the intraluminal thread could be validated by an entirely extinguished signal of the ipsilateral middle cerebral artery (MCA) in the angiograms. This was in accordance with a perfusion deficit in the MCA vascular territory detected by PWI (reduction to 30.4 +/- 7.4% relative to contralateral side) and a disturbance of water ion homeostasis monitored by DWI in this area. One animal showed a delayed occlusion after 30 min of MCA occlusion, in another animal vessel occlusion failed. In seven out of the eight successful occlusion experiments there was immediate reperfusion after withdrawal of the thread. One animal showed a delayed reperfusion after suture retraction. Remarkable hemispheric differences in vascular branching of the MCA could be recognized in three out of 10 animals. In conclusion, TOF-MRA is considered a helpful method to survey even in small laboratory animals the correct time course of vascular occlusion and reopening in experimental ischemia, and provides complementary information to the tissue perfusion status monitored by PWI and the ischemic lesion territory detected by DWI.

1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components.

In vitro NMR spectroscopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. (31)P- and (1)H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. (31)P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the (1)H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the (31)P- and the (1)H-spectra. Based on the total detectable (31)P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary glioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and -23% (p = 0.0314) change, respectively]. (1)H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the (31)P-spectra, the (1)H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. (1)H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution (1)H- and (31)P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism.

Magnetic resonance prediction of outcome after thrombolytic treatment.

Treatment of clinical stroke with recombinant tissue plasminogen activator (rt-PA) carries the risk of hemorrhagic complications. Hence, predictors of therapeutic outcome with respect to (a) reperfusion and (b) tissue recovery would be very useful to identify potentially salvageable brain tissue. Magnetic resonance (MR) parameters, especially the apparent diffusion coefficient of water (ADC), perfusion-weighted imaging (PWI) and T(2) relaxometry are thought to provide this information. We evaluated the prognostic implications of ADC, PWI and T(2) relaxometry immediately before initiation of thrombolytic treatment in a model of clot embolism in rats. Animals (n = 14) were treated with intraarterial rt-PA (10 mg/kg) at 90 min after embolism. MR imaging was repeatedly performed at 4.7 T before and up to 5.5 h after embolism. ADC was calculated from diffusion-weighted images (b-values: 30, 765, 1500 s/mm(2)), arterial spin tagging was used for PWI, and quantitative T(2) relaxometry was performed with a Carr-Purcell-Meiboom-Gill (CPMG) sequence. A reperfusion index was calculated to assess the quality of thrombolytic recanalization. The decline of ADC at the end of the experiment to below 80% of control was defined as unfavorable outcome. The probability of tissue injury at the end of the experiments increased with the severity of ADC changes before the initiation of treatment (probability of unfavorable outcome: 21%, 44%, 65% for ADC values of 80-90%, 70-80% and <70% of control, respectively). Pretreatment PWI or T(2) relaxometry also correlated with outcome but-alone or in combination with pretreatment ADC maps-did not improve injury prediction over that obtained by ADC alone. Outcome was influenced positively by successful reperfusion the quality of which, however, could not be predicted by pre-treatment MR characteristics. The data demonstrate that ADC mapping performed before the initiation of thrombolytic treatment provides reliable risk assessment of impeding brain injury but due to uncertainties of postischemic reperfusion does not allow precise outcome prediction in individual experiments.

Relation of apparent diffusion coefficient changes and metabolic disturbances after 1 hour of focal cerebral ischemia and at different reperfusion phases in rats.

Changes in apparent diffusion coefficients (ADC) were compared with alterations of adenosine triphosphate (ATP) concentration and pH in different phases of transient focal cerebral ischemia to study the ADC threshold for breakdown of energy metabolism and tissue acidosis during ischemia and reperfusion. Male Wistar rats underwent 1 hour of middle cerebral artery occlusion without recirculation (n = 3) or with 1 hour (n = 4) or 10 hours of reperfusion (n=5) inside the magnet, using a remotely controlled thread occlusion model. ADC maps were calculated from diffusion-weighted images and normalized to the preischemic value to obtain relative ADC maps. Hemispheric lesion volume (HLV) was determined on the last relative ADC maps at different relative ADC thresholds and was compared to the HLV measured by ATP depletion and by tissue acidosis. The HLVs, defined by ATP depletion and tissue acidosis, were 26.0% +/- 10.6% and 38.1% +/- 6.5% at the end of ischemia, 3.3% +/- 2.4% and 4.8% +/- 3.5% after 1 hour of reperfusion, and 11.2% +/- 4.7% and 10.9% +/- 5.2% after 10 hours of recirculation, respectively. The relative ADC thresholds for energy failure were consistently approximately 77% of the control value in the three different groups. The threshold for tissue acidosis was higher at the end of ischemia (86% of control) but was similar to the results obtained for ATP depletion after 1 hour (78% of control) and 10 hours (76% of control) of recirculation. These results indicate that the described relative ADC threshold of approximately 77% of control provides a good estimate for the breakdown of energy metabolism not only during middle cerebral artery occlusion but also at the early phase of reperfusion, when recovery of energy metabolism is expected to occur, or some hours later, when development of secondary energy failure was described.