Circulating bacterial lipopolysaccharide-induced inflammation reduces flow in brain-irrigating arteries independently from cerebrovascular prostaglandin production

International audienceBrain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cere-bral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-jB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as pros-taglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals. Time-resolved TOF MRA revealed no differences in blood flow in the internal carotids upstream of the circle of Willis, but indicated lower flow in its lateral parts as well as in the middle and anterior cerebral arteries after intravenous LPS injection as compared to saline administration. Although LPS did not increase c-Fos expression in ventral forebrain structures of these animals, it did induce NF-jB in meningeal blood vessels. LPS also increased cerebral expression of cyclooxygenase-2 and prostaglandin E syn-thase mRNAs, but de novo expression occurred in veins rather than in arteries. In conclusion, our work indicates that LPS-induced systemic inflammation does not necessarily affect filling of the circle of the Willis from the periphery, but that circulating LPS alters outflow from the circle of Willis to the middle and anterior cerebral arteries. These modifications in arterial flow were not related to increased cerebral synthesis of prostaglandins, but may instead be the consequence of the action of circulating prostaglandins and other vasoactive mediators on brain-irrigating arteries during systemic inflammation

Improved Energy Supply Regulation in Chronic Hypoxic Mouse Counteracts Hypoxia-Induced Altered Cardiac Energetics

Hypoxic states of the cardiovacular system are undoubtedly associated with the most frequent diseases of modern time. Therefore, understanding hypoxic resistance encountered after physiological adaptation such as chronic hypoxia, is crucial to better deal with hypoxic insult. In this study, we examine the role of energetic modifications induced by chronic hypoxia (CH) in the higher tolerance to oxygen deprivation.P-NMR), and to describe the integrated changes in cardiac energetics regulation by using Modular Control Analysis (MoCA). Oxygen reduction induced a concomitant decrease in RPP (−46%) and in [PCr] (−23%) in Control hearts while CH hearts energetics was unchanged. MoCA demonstrated that this adaptation to hypoxia is the direct consequence of the higher responsiveness (elasticity) of ATP production of CH hearts compared with Controls (−1.88±0.38 vs −0.89±0.41, p<0.01) measured under low oxygen perfusion. This higher elasticity induces an improved response of energy supply to cellular energy demand. The result is the conservation of a healthy control pattern of contraction in CH hearts, whereas Control hearts are severely controlled by energy supply.As suggested by the present study, the mechanisms responsible for this increase in elasticity and the consequent improved ability of CH heart metabolism to respond to oxygen deprivation could participate to limit the damages induced by hypoxia

Invest Radiol

The magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence provides quantitative T1 maps in addition to high-contrast morphological images. Advanced acceleration techniques such as compressed sensing (CS) allow its acquisition time to be compatible with clinical applications. To consider its routine use in future neuroimaging protocols, the repeatability of the segmented brain structures was evaluated and compared with the standard morphological sequence (magnetization-prepared rapid gradient echo [MPRAGE]). The repeatability of the T1 measurements was also assessed. Thirteen healthy volunteers were scanned either 3 or 4 times at several days of interval, on a 3 T clinical scanner, with the 2 sequences (CS-MP2RAGE and MPRAGE), set with the same spatial resolution (0.8-mm isotropic) and scan duration (6 minutes 21 seconds). The reconstruction time of the CS-MP2RAGE outputs (including the 2 echo images, the MP2RAGE image, and the T1 map) was 3 minutes 33 seconds, using an open-source in-house algorithm implemented in the Gadgetron framework.Both precision and variability of volume measurements obtained from CAT12 and VolBrain were assessed. The T1 accuracy and repeatability were measured on phantoms and on humans and were compared with literature.Volumes obtained from the CS-MP2RAGE and the MPRAGE images were compared using Student t tests (P < 0.05 was considered significant). The CS-MP2RAGE acquisition provided morphological images of the same quality and higher contrasts than the standard MPRAGE images. Similar intravolunteer variabilities were obtained with the CS-MP2RAGE and the MPRAGE segmentations. In addition, high-resolution T1 maps were obtained from the CS-MP2RAGE. T1 times of white and gray matters and several deep gray nuclei are consistent with the literature and show very low variability (<1%). The CS-MP2RAGE can be used in future protocols to rapidly obtain morphological images and quantitative T1 maps in 3-dimensions while maintaining high repeatability in volumetry and relaxation times.Translational Research and Advanced Imaging LaboratoryDéveloppement de l'IRM ultra-rapide pour la mesure des temps de relaxation : Apllication à la thérapide guidée par IR

Tunnel positioning assessment after anterior cruciate ligament reconstruction at 12 months: Comparison between 3D CT and 3D MRI. A pilot study

Background: Tunnel positioning assessment is a major issue after anterior cruciate ligament (ACL) reconstruction surgery. Historically, it used plain X-ray and, more recently, CT with 3D reconstruction. MRI is a reliable method of assessing ACL graft integrity and postoperative complications. To our knowledge, there have been no studies of efficacy in tunnel positioning assessment. The aim of this study was to assess the efficacy of 3D MRI in assessing femoral and tibial tunnel positioning after ACL reconstruction. The hypothesis was that 3D MRI sequences with reconstruction are as accurate as 3D CT for tunnel positioning assessment in ACL reconstruction. Methods: Twenty-two patients who underwent an arthroscopic ACL reconstruction using hamstring graft were included in a prospective study. All patients were examined on 3D CT and 3D MRI at 12 months post-surgery. Tunnel positioning was assessed on both imaging systems by a musculoskeletal radiologist and an orthopedic surgeon specialized in knee arthroscopy, both blind to all clinical data. Results: No statistically significant difference was found between 3D CT and 3D MRI on coronal and sagittal reconstructions. For coronal assessment of tibial tunnel orifice, sagittal assessment of tibial tunnel orifice and sagittal assessment of femoral tunnel orifice, P-values ranged from 0.37 to 0.99, 0.051 to 0.64 and 0.19 to 0.59, respectively. For tibial and femoral tunnel angulation, P-values were respectively 0.52 and 0.29. Conclusion: 3D MRI is a reliable method to assess femoral and tibia tunnel positioning in ACL reconstruction , compared to 3D CT as gold standard. Indeed, in our opinion 3D MRI could in the future replace CT for ACL reconstruction assessment, concerning not only the meniscus and ligaments but also tunnel position. Level of evidence: Level 3; comparative prospective study

Magn Reson Med

To propose a quantitative 3D double-echo steady-state (DESS) sequence that offers rapid and repeatable T mapping of the human brain using different encoding schemes that account for respiratory B variation. A retrospective self-gating module was firstly implemented into the standard DESS sequence in order to suppress the respiratory artifact via data binning. A compressed-sensing trajectory (CS-DESS) was then optimized to accelerate the acquisition. Finally, a spiral Cartesian encoding (SPICCS-DESS) was incorporated to further disrupt the coherent respiratory artifact. These different versions were compared to a standard DESS sequence (fully DESS) by assessing the T distribution and repeatability in different brain regions of eight volunteers at 3 T. The respiratory artifact correction was determined to be optimal when the data was binned into seven respiratory phases. Compared to the fully DESS, T distribution was improved for the CS-DESS and SPICCS-DESS with interquartile ranges reduced significantly by a factor ranging from 2 to 12 in the caudate, putamen, and thalamus regions. In the gray and white matter areas, average absolute test-retest T differences across all volunteers were respectively 3.5 ± 2% and 3.1 ± 2.1% for the SPICCS-DESS, 4.6 ± 4.6% and 4.9 ± 5.1% for the CS-DESS, and 15% ± 13% and 7.3 ± 5.6% for the fully DESS. The SPICCS-DESS sequence's acquisition time could be reduced by half (<4 min) while maintaining its efficient T mapping. The respiratory-resolved SPICCS-DESS sequence offers rapid, robust, and repeatable 3D T mapping of the human brain, which can be especially effective for longitudinal monitoring of cerebral pathologies.Développement de l'IRM ultra-rapide pour la mesure des temps de relaxation : Apllication à la thérapide guidée par IR

Sci Rep

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r relaxivities (100 mM s) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de Glioblastom

Exploring the Allen mouse connectivity experiments with new neuroinformatic tools for neurophotonics, diffusion MRI and tractography applications

International audienceThe Allen Mouse Brain Connectivity Atlas (AMBCA) o↵ers a high-resolution map of neural connections detailing axonal projections labeled by viral tracers. It is a unique tool for studying structural connectivity and better understanding the white matter pathways of the gene mouse brain. But, the analysis and comparison of these data are limited to a simple visualization on the Allen website and have no direct relationship with specific User data. Here, we propose a series of python-based tools to operate with AMBCA data in the User's data space. Our method is based on "back and forth" actions between Allen and User data using the Allen Software Development Kit (AllenSDK) to import data from the Allen Institute and the Python package ANTsPyX for registration. A transformation matrix is calculated with ANTsPyX to overlay, for instance, Allen's projection density maps with a di↵usion MRI-based tractography in the User space. Conversely, applying the inverse transformation to a specific location along a white matter bundle within the User space allows us to recover which experiments were done at this particular location in the Allen Mouse brain Common Coordinate Framework (CCFv3). Thus, both data can be used in a natural interaction, e.g., by inspecting them in a visualization tool such as the MI-Brain software. This series of tools will o↵er an attractive solution for researchers with neural tracing and/or tractography data to be combined with the AMBCA. The code is available at: https: //github.com/linum-uqam/m2m

Early Achilles Enthesis Involvement in a Murine Model of Spondyloarthropathy: Morphological Imaging with Ultrashort Echo-Time Sequences and Ultrasmall Superparamagnetic Iron Oxide (USPIO) Particle Evaluation in Macrophagic Detection

Purpose. To confirm the interest of 3-dimensional ultrashort echo-time (3D-UTE) sequences to assess morphologic aspects in normal and pathological Achilles entheses in a rat model of spondyloarthropathy (SpA) with histological correlations, in comparison with conventional RARE T2 Fat-Sat sequences, and, furthermore, to evaluate the feasibility of a 3D multiecho UTE sequence performed before and after the intravenous injection of ultrasmall superparamagnetic iron oxide (USPIO) particles to assess macrophagic involvement in the Achilles enthesis in the same rat model of SpA. Materials and Methods. Fourteen rats underwent in vivo MRI of the ankle at 4.7 T, including a 3D RARE T2 Fat-Sat sequence and a 3D ultrashort echo-time (UTE) sequence for morphologic assessment at baseline and day 3 after induction of an SpA model, leading to Achilles enthesopathy in the left paw (right paw serving as a control). A 3D multiecho UTE sequence was also performed at day 3 before and then 24 (4 rats) and 48 (2 rats) hours after intravenous injection of USPIO. Visual analysis and signal intensity measurements of all images were performed at different locations of the Achilles enthesis and preinsertional area. Visual analysis and T2∗ measurements were performed before and after USPIO injection, on the 3D multiecho UTE sequence in the same locations. Normal and pathological values were compared by Wilcoxon signed-rank tests. MR findings were compared against histological data. Results. 3D-UTE sequences enabled morphologic identification of the anterior fibrocartilage and posterior collagenic areas of the Achilles enthesis. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at day 3 (P=0.02). After administration of USPIO, no differences in signals were detected. Similarly, both visual analysis and signal T2∗ measurements in the enthesis were unable to distinguish the SpA-affected tendons from healthy ones (P=0.914). Neither the normal anatomy of the enthesis nor its pathological pattern could be distinguished using the standard RARE sequence. Histology confirmed the absence of USPIO in Achilles entheses, despite marked signs of inflammation. Conclusion. Unlike conventional RARE T2 Fat-Sat sequences, 3D-UTE sequences enable morphologic assessment of normal enthesis anatomy and early detection of abnormalities in pathological conditions. However, 3D multiecho UTE sequences combined with USPIO injections with T2∗ measurements were unable to detect macrophagic involvement in these pathological conditions