Brain perfusion in sepsis.

Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. Reduction of CBF may be caused by cerebral vasoconstriction, either induced by inflammation or hypocapnia. Endothelial dysfunction associated with sepsis leads to impairment of microcirculation and cerebral metabolic uncoupling that may further reduce brain perfusion so that CBF becomes inadequate to satisfy brain cellular needs. The natural autoregulatory mechanisms that protect the brain from reduced/ inadequate CBF can be impaired in septic patients, especially in those with shock or delirium, and this further contributes to cerebral ischemia if blood pressure drops below critical thresholds. Sedative agents alter cerebro-vascular reactivity and may significantly reduce CBF. Although disorders of brain perfusion and alteration of CBF and cerebral autoregulation are frequently observed in humans with sepsis, their exact role in the pathogenesis of SAE remains unknown. Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.

A pilot feasibility, safety and biological efficacy multicentre trial of therapeutic hypercapnia after cardiac arrest: study protocol for a randomized controlled trial.

BACKGROUND: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. METHODS/DESIGN: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. DISCUSSION: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000690853 .

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

Assessment of metabolic fluxes in the mouse brain in vivo using 1H-[13C] NMR spectroscopy at 14.1 Tesla.

(13)C magnetic resonance spectroscopy (MRS) combined with the administration of (13)C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity (1)H-[(13)C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-(13)C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the (13)C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit (13)C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate V(gln) (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor K(dil) (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate V(Lac)/V(Ala) (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

Delay-sensitive and delay-insensitive deconvolution perfusion-CT: similar ischemic core and penumbra volumes if appropriate threshold selected for each.

INTRODUCTION: Perfusion-CT (PCT) processing involves deconvolution, a mathematical operation that computes the perfusion parameters from the PCT time density curves and an arterial curve. Delay-sensitive deconvolution does not correct for arrival delay of contrast, whereas delay-insensitive deconvolution does. The goal of this study was to compare delay-sensitive and delay-insensitive deconvolution PCT in terms of delineation of the ischemic core and penumbra. METHODS: We retrospectively identified 100 patients with acute ischemic stroke who underwent admission PCT and CT angiography (CTA), a follow-up vascular study to determine recanalization status, and a follow-up noncontrast head CT (NCT) or MRI to calculate final infarct volume. PCT datasets were processed twice, once using delay-sensitive deconvolution and once using delay-insensitive deconvolution. Regions of interest (ROIs) were drawn, and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in these ROIs were recorded and compared. Volume and geographic distribution of ischemic core and penumbra using both deconvolution methods were also recorded and compared. RESULTS: MTT and CBF values are affected by the deconvolution method used (p < 0.05), while CBV values remain unchanged. Optimal thresholds to delineate ischemic core and penumbra are different for delay-sensitive (145 % MTT, CBV 2 ml × 100 g(-1) × min(-1)) and delay-insensitive deconvolution (135 % MTT, CBV 2 ml × 100 g(-1) × min(-1) for delay-insensitive deconvolution). When applying these different thresholds, however, the predicted ischemic core (p = 0.366) and penumbra (p = 0.405) were similar with both methods. CONCLUSION: Both delay-sensitive and delay-insensitive deconvolution methods are appropriate for PCT processing in acute ischemic stroke patients. The predicted ischemic core and penumbra are similar with both methods when using different sets of thresholds, specific for each deconvolution method.

Metsäteollisuusintegraatin energiaraportoinnin kehittäminen

Työn tavoitteena on Stora Enso Oyj:n Imatran tehtaiden energiaraportoinnin luotettavuuden parantaminen. Raportoinnissa esiintyvää tase-eroa lämmön tuotannon ja kulutuksen välillä on erilaisten selvitysten perusteella pyritty pienentämään. Höyryn ja lauhteen mittausten virheellisyyttä on tutkittu erilaisten osasto- ja höyrylinja- kohtaisten lämpötaseiden avulla. Taseiden lisäksi mittauksen oikeellisuutta selvitettäessä on käytetty tunnuslukuina lämmön ominaiskulutuksia, joita on verrattu Suomen metsäteollisuuden keskimääräisiin arvoihin. Työssä on tarkistettu myös raportointijärjestelmän laskenta ja päivitetty tarvittavat muutokset. Osa raportoinnin tase-erosta johtuu höyryn virtausmittauksen epävarmuudesta. Tässä työssä on esitetty erilaisia vaihtoehtoja sille, mistä mittauksen epävarmuus johtuu. Samalla on selvitetty virtausmittauksen periaatetta ja siihen tarvittavaa laitteistoa.

Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function.

Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of N(G)-monomethyl-l-arginine (l-NMMA, 0.3 mg·kg(-1)·min(-1)), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ∼8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. l-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 ± 2.5 (mean ± SE, placebo) vs. -0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P < 0.0001) and CBF (P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients.

Development of cardiovascular magnetic resonance imaging techniques for improved characterization of atherosclerotic disease

Atherosclerosis is a chronic cardiovascular disease that involves the thicken¬ing of the artery walls as well as the formation of plaques (lesions) causing the narrowing of the lumens, in vessels such as the aorta, the coronary and the carotid arteries. Magnetic resonance imaging (MRI) is a promising modality for the assessment of atherosclerosis, as it is a non-invasive and patient-friendly procedure that does not use ionizing radiation. MRI offers high soft tissue con¬trast already without the need of intravenous contrast media; while modifica¬tion of the MR pulse sequences allows for further adjustment of the contrast for specific diagnostic needs. As such, MRI can create angiographic images of the vessel lumens to assess stenoses at the late stage of the disease, as well as blood flow-suppressed images for the early investigation of the vessel wall and the characterization of the atherosclerotic plaques. However, despite the great technical progress that occurred over the past two decades, MRI is intrinsically a low sensitive technique and some limitations still exist in terms of accuracy and performance. A major challenge for coronary artery imaging is respiratory motion. State- of-the-art diaphragmatic navigators rely on an indirect measure of motion, per¬form a ID correction, and have long and unpredictable scan time. In response, self-navigation (SM) strategies have recently been introduced that offer 100% scan efficiency and increased ease of use. SN detects respiratory motion di¬rectly from the image data obtained at the level of the heart, and retrospectively corrects the same data before final image reconstruction. Thus, SN holds po-tential for multi-dimensional motion compensation. To this regard, this thesis presents novel SN methods that estimate 2D and 3D motion parameters from aliased sub-images that are obtained from the same raw data composing the final image. Combination of all corrected sub-images produces a final image with reduced motion artifacts for the visualization of the coronaries. The first study (section 2.2, 2D Self-Navigation with Compressed Sensing) consists of a method for 2D translational motion compensation. Here, the use of com- pressed sensing (CS) reconstruction is proposed and investigated to support motion detection by reducing aliasing artifacts. In healthy human subjects, CS demonstrated an improvement in motion detection accuracy with simula¬tions on in vivo data, while improved coronary artery visualization was demon¬strated on in vivo free-breathing acquisitions. However, the motion of the heart induced by respiration has been shown to occur in three dimensions and to be more complex than a simple translation. Therefore, the second study (section 2.3,3D Self-Navigation) consists of a method for 3D affine motion correction rather than 2D only. Here, different techniques were adopted to reduce background signal contribution in respiratory motion tracking, as this can be adversely affected by the static tissue that surrounds the heart. The proposed method demonstrated to improve conspicuity and vi¬sualization of coronary arteries in healthy and cardiovascular disease patient cohorts in comparison to a conventional ID SN method. In the third study (section 2.4, 3D Self-Navigation with Compressed Sensing), the same tracking methods were used to obtain sub-images sorted according to the respiratory position. Then, instead of motion correction, a compressed sensing reconstruction was performed on all sorted sub-image data. This process ex¬ploits the consistency of the sorted data to reduce aliasing artifacts such that the sub-image corresponding to the end-expiratory phase can directly be used to visualize the coronaries. In a healthy volunteer cohort, this strategy improved conspicuity and visualization of the coronary arteries when compared to a con¬ventional ID SN method. For the visualization of the vessel wall and atherosclerotic plaques, the state- of-the-art dual inversion recovery (DIR) technique is able to suppress the signal coming from flowing blood and provide positive wall-lumen contrast. How¬ever, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. In response and as a fourth study of this thesis (chapter 3, Vessel Wall MRI of the Carotid Arteries), a phase-sensitive DIR method has been implemented and tested in the carotid arteries of a healthy volunteer cohort. By exploiting the phase information of images acquired after DIR, the proposed phase-sensitive method enhances wall-lumen contrast while widens the window of opportunity for image acquisition. As a result, a 3-fold increase in volumetric coverage is obtained at no extra cost in scanning time, while image quality is improved. In conclusion, this thesis presented novel methods to address some of the main challenges for MRI of atherosclerosis: the suppression of motion and flow artifacts for improved visualization of vessel lumens, walls and plaques. Such methods showed to significantly improve image quality in human healthy sub¬jects, as well as scan efficiency and ease-of-use of MRI. Extensive validation is now warranted in patient populations to ascertain their diagnostic perfor¬mance. Eventually, these methods may bring the use of atherosclerosis MRI closer to the clinical practice. Résumé L'athérosclérose est une maladie cardiovasculaire chronique qui implique le épaississement de la paroi des artères, ainsi que la formation de plaques (lé¬sions) provoquant le rétrécissement des lumières, dans des vaisseaux tels que l'aorte, les coronaires et les artères carotides. L'imagerie par résonance magné¬tique (IRM) est une modalité prometteuse pour l'évaluation de l'athérosclérose, car il s'agit d'une procédure non-invasive et conviviale pour les patients, qui n'utilise pas des rayonnements ionisants. L'IRM offre un contraste des tissus mous très élevé sans avoir besoin de médias de contraste intraveineux, tan¬dis que la modification des séquences d'impulsions de RM permet en outre le réglage du contraste pour des besoins diagnostiques spécifiques. À ce titre, l'IRM peut créer des images angiographiques des lumières des vaisseaux pour évaluer les sténoses à la fin du stade de la maladie, ainsi que des images avec suppression du flux sanguin pour une première enquête des parois des vais¬seaux et une caractérisation des plaques d'athérosclérose. Cependant, malgré les grands progrès techniques qui ont eu lieu au cours des deux dernières dé¬cennies, l'IRM est une technique peu sensible et certaines limitations existent encore en termes de précision et de performance. Un des principaux défis pour l'imagerie de l'artère coronaire est le mou¬vement respiratoire. Les navigateurs diaphragmatiques de pointe comptent sur une mesure indirecte de mouvement, effectuent une correction 1D, et ont un temps d'acquisition long et imprévisible. En réponse, les stratégies d'auto- navigation (self-navigation: SN) ont été introduites récemment et offrent 100% d'efficacité d'acquisition et une meilleure facilité d'utilisation. Les SN détectent le mouvement respiratoire directement à partir des données brutes de l'image obtenue au niveau du coeur, et rétrospectivement corrigent ces mêmes données avant la reconstruction finale de l'image. Ainsi, les SN détiennent un poten¬tiel pour une compensation multidimensionnelle du mouvement. A cet égard, cette thèse présente de nouvelles méthodes SN qui estiment les paramètres de mouvement 2D et 3D à partir de sous-images qui sont obtenues à partir des mêmes données brutes qui composent l'image finale. La combinaison de toutes les sous-images corrigées produit une image finale pour la visualisation des coronaires ou les artefacts du mouvement sont réduits. La première étude (section 2.2,2D Self-Navigation with Compressed Sensing) traite d'une méthode pour une compensation 2D de mouvement de translation. Ici, on étudie l'utilisation de la reconstruction d'acquisition comprimée (compressed sensing: CS) pour soutenir la détection de mouvement en réduisant les artefacts de sous-échantillonnage. Chez des sujets humains sains, CS a démontré une amélioration de la précision de la détection de mouvement avec des simula¬tions sur des données in vivo, tandis que la visualisation de l'artère coronaire sur des acquisitions de respiration libre in vivo a aussi été améliorée. Pourtant, le mouvement du coeur induite par la respiration se produit en trois dimensions et il est plus complexe qu'un simple déplacement. Par conséquent, la deuxième étude (section 2.3, 3D Self-Navigation) traite d'une méthode de cor¬rection du mouvement 3D plutôt que 2D uniquement. Ici, différentes tech¬niques ont été adoptées pour réduire la contribution du signal du fond dans le suivi de mouvement respiratoire, qui peut être influencé négativement par le tissu statique qui entoure le coeur. La méthode proposée a démontré une amélioration, par rapport à la procédure classique SN de correction 1D, de la visualisation des artères coronaires dans le groupe de sujets sains et des pa¬tients avec maladies cardio-vasculaires. Dans la troisième étude (section 2.4,3D Self-Navigation with Compressed Sensing), les mêmes méthodes de suivi ont été utilisées pour obtenir des sous-images triées selon la position respiratoire. Au lieu de la correction du mouvement, une reconstruction de CS a été réalisée sur toutes les sous-images triées. Cette procédure exploite la cohérence des données pour réduire les artefacts de sous- échantillonnage de telle sorte que la sous-image correspondant à la phase de fin d'expiration peut directement être utilisée pour visualiser les coronaires. Dans un échantillon de volontaires en bonne santé, cette stratégie a amélioré la netteté et la visualisation des artères coronaires par rapport à une méthode classique SN ID. Pour la visualisation des parois des vaisseaux et de plaques d'athérosclérose, la technique de pointe avec double récupération d'inversion (DIR) est capa¬ble de supprimer le signal provenant du sang et de fournir un contraste posi¬tif entre la paroi et la lumière. Pourtant, il est difficile d'obtenir un contraste optimal car cela est soumis à la variabilité du rythme cardiaque. Par ailleurs, l'imagerie DIR est inefficace du point de vue du temps et les acquisitions "mul- tislice" peuvent conduire à des temps de scan prolongés. En réponse à ce prob¬lème et comme quatrième étude de cette thèse (chapitre 3, Vessel Wall MRI of the Carotid Arteries), une méthode de DIR phase-sensitive a été implémenté et testé

Kaasuturbiinin polttoainesuuttimien virtausmittaus

Tässä diplomityössä suunniteltiin ja rakennettiin kaasuturbiinin kaasusuuttimien virtausmittauslaitteisto. Suuttimien epätasainen toiminta kasvattaa kaasuturbiinin poistolämpötilahajontaa. Virtausmittauksien perusteella voidaan määrittää suuttimien efektiivinen virtauspoikkipinta-ala. Suuttimien asennusjärjestys opti-moidaan suuttimien välisten pinta-alaerojen mukaisesti, jolloin polttoainevirtaus polttokammioihin on mahdollisimman tasainen ja poistolämpötilahajonta pienenee. Kaasuturbiinin MS6001 esittelyssä keskityttiin tärkeimpiin komponentteihin sekä polttoainesuuttimien testauksen kannalta oleellisiin osiin ja niiden toimintaan. Teoriaosuudessa tarkasteltiin tilavuusvirran sekä suutinvirtauksen laskennassa käytettäviä yhtälöitä. Mittalaitteiston suunnittelu ja toteutus olivat tämän työn laajin osa-alue. Laitteiston keskeiset osat ovat kuristuselin ja suutintestausosa. Kuristuselintyypiksi valittiin rengaskammiollinen kuristuslaippa, joka suun-niteltiin standardin SFS-EN ISO 5167:2003 mukaisesti. Standardissa annettujen yhtälöiden antamia tuloksia verrattiin numeerisella virtauslaskentamallilla lasket-tuihin tuloksiin. Suutinrunkojen ja -kärkien mittauksien suunnittelussa sovellettiin samaa standardia sekä numeerista virtauslaskentaa optimaalisen sijainnin löytämiseksi paineyhteelle. Mittauksissa syntyvien epävarmuuksien arviointiin kiinnitettiin erityistä huomiota. Kokeellisessa osuudessa mitattiin yhden kunnostetun suuttimen, käytetyn suut-timen ja suutinrungon virtausta. Tuloksien perusteella laskettiin efektiiviset pinta-alat, joita verrattiin turbiinivalmistajan ilmoittamiin pinta-aloihin. Lopuksi arvioitiin mittaustulosten perusteella laitteiston toimivuutta. Virhe-arvioinnin ja mittaustulosten perusteella laadittiin teknisiä parannusehdotuksia suutintestauslaitteiston luotettavan toiminnan varmistamiseksi.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Application of contrast media in post-mortem imaging (CT and MRI).

The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.

Metabolic connectivity as index of verbal working memory.

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [(18)F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metabolism, no difference between groups was found. The results encourage examination of covariant patterns in FDG-PET data from non-neurodegenerative populations.

Fetal laser therapy: applications in the management of fetal pathologies.

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy.

Ventricularisation of the left atrium: a rare cause of left ventricular dysfunction in a patient with mitral valve prolapse

Case: A 11 yo girl with Marfan syndrome was referred to cardiac MR (CMR) to measure the size of her thoracic aorta. She had a typical phenotype with arachnodactyly, abnormally long arms, and was tall and slim (156 cm, 28 kg, body mass index 11,5 kg/m2). She complained of no symptoms. Cardiac auscultation revealed a prominent mid-systolic click and an end-systolic murmur at the apex. A recent echocardiogram showed a moderately dilated left ventricle with normal function and a mitral valve prolapse with moderate mitral valve regurgitation. CMR showed a dilatation of the aortic root (38 mm, Z-score 8.9) and a severe prolapse of the mitral valve with regurgitation. The ventricular cavity was moderately dilated (116 ml/m2) and its contraction was hyperdynamic (stroke volume (SV): 97 ml; LVEF 72%, with the LV volumes measured by modified Simpson method from the apex to the mitral annulus). In this patient however, the mitral prolapse was characterized by a severe backward movement of the valve toward the left atrium (LA) in systole and the dyskinetic movement of the atrioventricular plane caused a ventricularisation of a part of the LA in systole (Figure). This resulted in a significant reduction of LVEF: more than ¼ of the apparent SV was displaced backwards into the ventricularized LA volume, reducing the effective LVEF to 51% (effective SV 69ml). Moreover, by flow measurement, the SV across the ascending aorta was 30 ml (cardiac index 2.0 l/min/m2) allowing the calculation of a regurgitant fraction across the mitral valve of 56%, which was diagnostic for a severe mitral valve insufficiency. Conclusion: This case illustrates the phenomenon of a ventricularisation of the LA where the severe prolapse gives the illusion of a higher attachement of the mitral leaflets within the atrial wall. Besides the severe mitral regurgitation, this paradoxical backwards movement of the valve causes an intraventricular unloading during systole reducing the apparent LVEF of 72% to an effective LVEF of only 51%. In addition, forward flow fraction is only 22% after accounting for the regurgitant volume, as well. This combined involvement of the mitral valve could explain the discrepancy between a low output state and an apparently hyperdynamic LV contraction. Due to its ability to precisely measure flows and volumes, CMR is particularly suited to detect this phenomenon and to quantify its impact on the LV pump function.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.