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Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease.

International audience; The controlled design of robust, well reproducible, and functional nanomaterials made according to simple processes is of key importance to envision future applications. In the field of porous materials, tuning nanoparticle features such as specific area, pore size and morphology by adjusting simple parameters such as pH, temperature or solvent is highly needed. In this work, we address the tunable control of the pore morphology of mesoporous silica (MS) nanoparticles (NPs) with the sol-gel reaction temperature (Tsg). We show that the pore morphology of MS NPs alone or of MS shell covering iron oxide nanoparticles (IO NPs) can be easily tailored with Tsg orienting either towards stellar (ST) morphology (large radial pore of around 10 nm) below 80 °C or towards a worm-like (WL) morphology (small randomly oriented pores channel network, of 3–4 nm pore size) above 80 °C. The relaxometric and magnetothermal features of IO@STMS or IO@WLMS core shell NPs having respectively stellar or worm-like morphologies are compared and discussed to understand the role of the pore structure for MRI and magnetic hyperthermia applications.

BackgroundThe weekend effect has been extensively observed for different diseases and countries and recognized as a fact but without obvious causes.ObjectivesIn this paper we first aimed at investigating the existence of a periodicity in the death count due to Covid-19, and second, at opening the discussion concerning the reality of this effect in this particular context.MethodsDaily statistics of deaths due to the Covid-19 pandemic were subjected to a discrete Fourier transform spectral analysis for France and the world, over the periods from March 29 to May 16, 2020 and from January 22 to May 18, 2020 respectively.ResultsIn both cases, a frequency peak of one harmonic corresponding to a period of 7.11 days was observed for France and the world. In France, this weekly frequency corresponds to a decrease in deaths every Sunday, whereas for the world the systematic decrease is shifted on average by 1.5 days and corresponds to Saturday or Friday.ConclusionAt the world scale and for the epidemic period we confirm the existence of a consecutive weekend effect in the context of the Covid-19 pandemic.

Background: The weekend effect has been extensively observed for different diseases and countries and recognized as a fact but without obvious causes. Objectives: In this paper we first aimed at investigating the existence of a periodicity in the death count due to Covid-19, and second, at opening the discussion concerning the reality of this effect in this particular context. Methods: Daily statistics of deaths due to the Covid-19 pandemic were subjected to a discrete Fourier transform spectral analysis for France and the world, over the periods from March 29 to May 16, 2020 and from January 22 to May 18,2020 respectively. Results: In both cases, a frequency peak of one harmonic corresponding to a period of 7·11 days was observed for France and the world. In France, this weekly frequency corresponds to a decrease in deaths every Sunday, whereas for the world the systematic decrease is shifted on average by 1·5 days and corresponds to Saturday or Friday. Conclusion: At the world scale and for the epidemic period we confirm the existence of a consecutive weekend effect in the context of the Covid-19 pandemic. Funding Statement: None. Declaration of Interests: All authors declare no competing interests.

Different environmental conditions under anesthesia may lead to unstable homeostatic conditions in rodents and therefore may alter kinetics. In this study, the impact of different heating conditions on PET imaging quantification was evaluated. Methods: Two groups of 6 adult female BALB/c nude mice with subcutaneously implanted tumors underwent microPET imaging after injection of 18F-labeled tetrafluoroborate or 18F-FDG. Dynamic scans were acquired under optimal and suboptimal heating conditions. Time-activity curves were analyzed to calculate uptake and washout time constants. Results: With 18F-labeled tetrafluoroborate, optimal animal heating led to a stable heart rate during acquisition (515 ± 35 [mean ± SD] beats/min), whereas suboptimal heating led to a lower heart rate and a higher SD (470 ± 84 beats/min). Both uptake and washout time constants were faster (P < 0.01) in animals maintained with optimal heating. Conclusion: Although the difference in heart rates was slight, optimal heating yielded significantly faster uptake and washout kinetics than suboptimal heating in all organs for both tracers.

OBJECTIVE While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). METHODS The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. RESULTS We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. CONCLUSION The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.

The present work compares intravenous (IV) and subcutaneous (SC) routes for contrast-enhanced MRI (CE-MRI) in mice. For that purpose, we selected two contrast media used in clinical practice. MRI acquisitions were performed at 1.5 T on five adult mice (Swiss, 41 g +/- 3 g). On each animal, four acquisitions were achieved with IV and SC administration of either Gd-DOTA or MS-325 (1 acquisition per week). For each route, 0.1 mL of NaCl and 0.1 mL of contrast agent were injected. For each acquisition, 200 T1-weighted images were acquired in a 2 h 34 min time lapse. For each route and contrast medium, dynamic contrast enhancement (DCE) curves were obtained. Time-to-peak (TTP), uptake, and washout constant-time values and contrast-to-noise ratio (CNR) were extracted. IV route TTP value was 4.9 min with Gd-DOTA and 5.4 min with MS-325. SC route TTP was 43.3 min with Gd-DOTA and 45.0 min with MS-325. Despite slower uptake constant-time, we show that SC is a potentially valuable alternative to the IV route in mouse preclinical CE-MRI.

International audience; Background/objectives: We previously observed that selective agonists of the sympatho-inhibitory I1 imidazoline receptors (LNP ligands) have favorable effects on several cardiovascular and metabolic disorders defining the metabolic syndrome, including body weight. The objectives of this study were to explore the effects of LNPs on adiposity and the mechanisms involved, and to evaluate their impact on metabolic homeostasis.Methods: Young Zucker fa/fa rats were treated with LNP599 (10 mg/kg/day) for 12 weeks. Effects on body weight, adiposity (regional re-distribution, morphology, and function of adipose tissues), cardiovascular and metabolic homeostasis, and liver function were evaluated. Direct effects on insulin and AMP-activated protein kinase (AMPK) signaling were studied in human hepatoma HepG2 cells.Results: LNP599 treatment limited the age-dependent remodeling and inflammation of subcutaneous, epididymal, and visceral adipose tissues, and prevented total fat deposits and the development of obesity. Body-weight stabilization was not related to reduced food intake but rather to enhanced energy expenditure and thermogenesis. Cardiovascular and metabolic parameters were also improved and were significantly correlated with body weight but not with plasma norepinephrine. Insulin and AMPK signaling were enhanced in hepatic tissues of treated animals, whereas blood markers of hepatic disease and pro-inflammatory cytokine levels were reduced. In cultured HepG2 cells, LNP ligands phosphorylated AMPK and the downstream acetyl-CoA carboxylase and prevented oleic acid-induced intracellular lipid accumulation. They also significantly potentiated insulin-mediated AKT activation and this was independent from AMPK.Conclusions: Selective I1 imidazoline receptor agonists protect against the development of adiposity and obesity, and the associated cardio-metabolic disorders. Activation of I1 receptors in the liver, leading to stimulation of the cellular energy sensor AMPK and insulin sensitization, and in adipose tissues, leading to improvement of morphology and function, are identified as peripheral mechanisms involved in the beneficial actions of these ligands.

The assessment of the three-dimensional architecture of collagen fibers inside vessel walls constitutes one of the bases for building structural models for the description of the mechanical behavior of these tissues. Multiphoton microscopy allows for such observations, but is limited to volumes of around a thousand of microns. In the present work, we propose to observe the collagenous network of vascular tissues using micro-CT. To get a contrast, three staining solutions (phosphotungstic acid, phosphomolybdic acid and iodine potassium iodide) were tested. Two of these stains were showed to lead to similar results and to a satisfactory contrast within the tissue. A detailed observation of a small porcine iliac vein sample allowed assessing the collagen fibers orientations within the medial and adventitial layers of the vein. The vasa vasorum network, which is present inside the adventitia of the vein, was also observed. Finally, the demonstrated micro-CT staining technique for the three-dimensional observation of thin soft tissues samples, like vein walls, contributes to the assessment of their structure at different scales while keeping a global overview of the tissue.

OBJECTIVE: To establish a chronic mouse model of critical limb ischemia (CLI) with in vivo and ex vivo validation, closely mimicking human pathology. METHODS: Swiss mice (n = 28) were submitted to sequential unilateral femoral (day 0) and iliac (day 4) ligatures. Ischemia was confirmed by clinical scores (tissue and functional damages) and methoxyisobutylisonitrile (MIBI) scintigraphies at days 0, 4, 6, 10, 20, and 30. At days 10, 20, and 30, muscle mitochondrial respiration, calcium retention capacity (CRC), and production of reactive oxygen species (ROS) were investigated, together with transcripts of mitochondrial biogenesis and antioxidant enzymes. Histological analysis was also performed. RESULTS: Clinical and functional damage confirmed CLI. MIBI scintigraphies showed hypoperfusion of the ischemic limb, which remained stable until day 30. Mitochondrial respiration was impaired in ischemic muscles compared with controls (Vmax = 7.93 +/- 0.99 vs. 10.09 +/- 2.87 mmol/L O2/minute/mg dry weight [dw]; p = .01), together with impaired CRC (7.4 +/- 1.6 mmol/L minute/mg dw vs. 11.9 +/- 0.9 mmol/L minute/mg dw; p < .001) and biogenesis (41% decrease in peroxisome proliferator-activated receptor gamma coactivator [PGC]-1alpha, 49% decrease in PGC-1beta, and 41% decrease in nuclear respiratory factor-1). Ischemic muscles also demonstrated increased production of ROS under electron paramagnetic resonance (0.084 +/- 0.029 vs. 0.051 +/- 0.031 mmol/L minute/mg dw; p = .03) and with dihydroethidium staining (3622 +/- 604 arbitrary units of fluorescence vs. 1224 +/- 324; p < .01), decreased antioxidant enzymes (32% decrease in superoxide dismutase [SOD]1, 41% decrease in SOD2, and 49% decrease in catalase), and myopathic features (wider range in fiber size, rounded shape, centrally located nuclei, and smaller cross-sectional areas). All defects were stable over time. CONCLUSION: Sequential femoral and iliac ligatures closely mimic human functional, clinical, scintigraphic, and skeletal muscle mitochondrial characteristics, and could prove useful for testing therapeutic approaches.

International audience; We use high-resolution [Formula: see text] data in multiple experiments to estimate the sources of error during coregistration of images acquired on separate preclinical instruments. In combination with experiments with phantoms, we completed in vivo imaging on mice, aimed at identifying the possible sources of registration errors, caused either by transport of the animal, movement of the animal itself, or methods of coregistration. The same imaging cell was used as a holder for phantoms and animals. For all procedures, rigid coregistration was carried out using a common landmark coregistration system, placed inside the imaging cell. We used the fiducial registration error and the target registration error to analyze the coregistration accuracy. We found that moving an imaging cell between two preclinical devices during a multimodal procedure gives an error of about [Formula: see text] at most. Therefore, it could not be considered a source of coregistration errors. Errors linked to spontaneous movements of the animal increased with time, to nearly 1 mm at most, excepted for body parts that were properly restrained. This work highlights the importance of animal intrinsic movements during a multiacquisition procedure and demonstrates a simple method to identify and quantify the sources of error during coregistration.

Owing to the great potential of iron oxide nanoparticles (NPs) for nanomedicine, large efforts have been made to better control their magnetic properties, especially their magnetic anisotropy to provide NPs able to combine imaging by MRI and therapy by magnetic hyperthermia. In that context, the design of anisotropic NPs appears as a very promising and efficient strategy. Furthermore, their bioactive coating also remains a challenge as it should provide colloidal stability, biocompatibility, furtivity along with good water diffusion for MRI. By taking advantage of our controlled synthesis method of iron oxide NPs with different shapes (cubic, spherical, octopod and nanoplate), we demonstrate here that the dendron coating, shown previously to be very suitable for 10 nm sized iron oxide, also provided very good colloidal, MRI and antifouling properties to the anisotropic shaped NPs. These antifouling properties, demonstrated through several experiments and characterizations, are very promising to achieve specific targeting of disease tissues without affecting healthy organs. On the other hand, the magnetic hyperthermia properties were shown to depend on the saturation magnetization and the ability of NPs to self-align, confirming the need of a balance between crystalline and dipolar magnetic anisotropies.

A series of four multimodal ligands incorporating one porphyrin moiety and one or more dota-like macrocycles all-in-one in the same molecular architecture have been synthesized and full characterized. The corresponding gadolinium(III) complexes were also synthesized and heterometallic complexes incorporating both gadolinium(III) and copper(II) ions were prepared as potential MRI/PET multimodal contrast agents. One ligand (L4) includes an amine moiety that can be activated for easy conversion into an isothiocyanate group for further anchoring to a biological vector. Preliminary relaxivity, cytotoxicity, and MRI studies showed that the complexes developed in this work are very promising medical-imaging agents for the enhancement of contrast in bimodal MRI techniques.

Objectives: Quantitative and qualitative image quality evaluation of two different dental CBCT scanners.Methods: Two CBCT systems were evaluated in this study: one small field-of-view (FOV) (50-mm diameter) system that also allows two-dimensional (2D) dental panoramic imaging and one large FOV CBCT system (60-180-mm diameter). These devices were all tested with installed acquisition default modes and proprietary reconstruction software, enabling high-resolution bone imaging. Quantitative analyses were carried out to measure spatial resolution, linearity and homogeneity. Small-size phantoms and a human dry skull were used to evaluate intrinsic performances. Visual qualitative analyses of specific anatomical parts were blindly performed by 10 operators.Results: Concerning spatial resolution, small-voxel size protocols provide equivalent results on the two apparatus. In terms of linearity, all systems are highly linear (0.98 < r2 < 0.99) over the range of signal intensities encountered. Our results, coming from either phantoms or the dry skull, demonstrate that the small FOV CBCT suffers from a lack of homogeneity.Conclusions: For limited oral and maxillofacial volume imaging (diameter < 50 mm), the polyvalent small FOV CBCT (2D and three-dimensional imaging) system used in this study could reach performances similar to those of the large FOV CBCT.

An universal tool was designed for small animal SPECT/CT/MR coregistration. It was tested on a preclinical MRI (OPTImouse, RS2D, Bischwiller, France) and a micro-SPECT/CT (eXplore speCZT Vision 120, GE, Waukesha, USA), closed to each other, thanks to the short extension of the MRI magnet fringe field. The tool consists of a curved catheter describing many rigid loops, and fixed on a plastic sheet. During acquisitions, it is placed around the animal, in an isolated imaging cell, and filled with a solution containing iodine, copper sulfate and radioisotope. Multimodality imaging is achieved sequentially by moving the cell from one system to the other, in about 20 s. Acquisitions on phantom demonstrate the resolution accuracy of the coregistration process. Whole body trimodal SPECT/CT/MR acquisitions on live mice were coregistrated as well. A simple, cheap tool, easy to fill, could efficiently help for rigid coregistration of preclinical images, acquired on separate imaging apparatus.

The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.

The eXplore CT 120 is the latest generation micro-CT from General Electric. It is equipped with a high-power tube and a flat-panel detector. It allows high resolution and high contrast fast CT scanning of small animals. The aim of this study was to compare the performance of the eXplore CT 120 with that of the eXplore Ultra, its predecessor for which the methodology using the vmCT phantom has already been described [1] . The phantom was imaged using typical a rat (fast scan or F) or mouse (in vivo bone scan or H) scanning protocols. With the slanted edge method, a 10% modulation transfer function (MTF) was observed at 4.4 (F) and 3.9–4.4 (H) mm−1 corresponding to 114 μm resolution. A fairly larger MTF was obtained by the coil method with the MTF for the thinnest coil (3.3 mm−1) equal to 0.32 (F) and 0.34 (H). The geometric accuracy was better than 0.3%. There was a highly linear (R2>0.999) relationship between measured and expected CT numbers for both the CT number accuracy and linearity sections of the phantom. A cupping effect was clearly seen on the uniform slices and the uniformity-to-noise ratio ranged from 0.52 (F) to 0.89 (H). The air CT number depended on the amount of polycarbonate surrounding the area where it was measured; a difference as high as approximately 200 HU was observed. This hindered the calibration of this scanner in HU. This is likely due to the absence of corrections for beam hardening and scatter in the reconstruction software. However in view of the high linearity of the system, the implementation of these corrections would allow a good quality calibration of the scanner in HU. In conclusion, the eXplore CT 120 achieved a better spatial resolution than the eXplore Ultra (based on previously reported specifications) and future software developments will include beam hardening and scatter corrections that will make the new generation CT scanner even more promising.

Ultrasound-based transient elastography (TE) and magnetic resonance elastography (MRE) are increasingly used methods for the clinical evaluation of soft tissue mechanical properties and their alteration under diseased conditions. This study proposes a comparison between magnetic resonance elastography (MRE) and ultrasound-based transient elastography (TE). Both methods were tested on the same soft tissue-mimicking gels in a common frequency range in order to allow for direct quantitative comparison. For the four gels tested, relatively good agreement was found between the shear moduli measured by both methods, with an averaged relative difference of 23%. This study demonstrates that under the assumption of homogeneous media that are significantly more elastic than viscous, quantitative results obtained by both methods are comparable.

International audience; The rationale of this work is to point out the relevance of in vivo MR images of mice obtained using a dedicated low-field system. For this purpose a small 0.1 T water-cooled electro-magnet and solenoidal radio frequency (RF) transmit–receive coils were used. All MR images were acquired in three-dimensional (3D) mode. An isolation cell was designed allowing easy placement of the RF coils and simple delivery of gaseous anesthesia as well as warming of the animal. Images with and without contrast agent were obtained in total acquisition times on the order of half an hour to four hours on normal mice as well as on animals bearing tumors. Typical in plane pixel dimensions range from 200 × 200 to 500 × 500 µm2 with slice thicknesses ranging between 0.65 and 1.50 mm. This work shows that, besides light installation and low cost, dedicated low-field MR systems are suitable for small rodents imaging, opening this technique even to small research units.

The peritoneal contact surface area (PCSA), which represents the area parameter in the mass transfer area coefficient (MTAC), is a crucial marker in the evaluation of peritoneal dialysis effectiveness. However, the capacity to recruit a larger PCSA has only been rarely demonstrated in vivo and, in most cases, changes in MTAC are interpreted as permeability changes and not as surface area variations. Here, we report the use of micro-computerized tomography (muCT) for the measurement of PCSA changes to various fill volumes. Using this three-dimensional imaging method, PCSA was measured in vivo in 26 healthy Wistar rats receiving intraperitoneally increasing fill volumes of peritoneal dialysis solutions: 5 mL (group 1, n = 8), 10 mL (group 2, n = 8) and 15 mL (group 3, n = 10) per 100 g of body weight. A non-ionic iodinated contrast agent was added to the dialysis solution in order to distinguish the intraperitoneal dialysis solutions from soft tissues. The normalized PCSA/weight ratio (cm(2)/g) increased with fill volume: 1.12 +/- 0.10 cm(2)/g (range 0.98-1.25) in group 1; 1.74 +/- 0.08 cm(2)/g (range 1.64-1.87) in group 2; 2.13 +/- 0.09 cm(2)/g(range 1.90-2.30) in group 3. With this muCT method, PCSA recruited in vivo with a 10 mL/100 g fill volume was in the range 94-107%) of ex vivo total peritoneal surface area (evPSA), as calculated with the Kuzlan's formula. With a 15 mL/100 g fill volume, the in vivo-measured PCSA, the exchange surface area, surpassed the evPSA (range 113-139%).

Objective This work aims at demonstrating the interest of low field magnetic resonance imaging (MRI) for in vivo imaging in rat. Material and methods MRI is performed using an open resistive 0.1 T magnet with a homogeneous zone measuring 6 cm × 10 cm × 10 cm. Rats under isoflurane gaseous anesthesia are placed in a technical cell for small animal imaging. Radio frequency solenoidal coils are developed for each application. Gradient echo T1 and T2-weighted sequences are programmed to acquire 3D data in vivo in rats. Results Acquisition times are comprised between 1 min for scout sequences and 2 h 10 min to acquire volumes with in-plane pixel size ranging from 0.37 to 1 mm and a slice thickness between 0.37 mm and 1.88 mm. Information obtained from our acquisitions are comparable to those reported in the literature about five applications: 1: intracerebral glioma; 2: cerebral contrast enhancement using manganese; 3: description of knee joint anatomy; 4: cardiac dynamic acquisition synchronized on cardiac rhythm; 5: whole body (thorax and abdomen) acquisition. Conclusion Rat MRI using an 0.1 T device allows to answer to the biological questions studied in this work at the expense of long acquisition times compared to high field MRI. Low field MRI offers economical and technical characteristics that could make it attractive to a non-specialized scientific community aiming at realizing daily MRI in vivo in rat.

Peritoneal dialysis (PD) uses the dynamic dialysis properties of the peritoneal membrane. The fraction of the anatomic peritoneal surface area (PSA) recruited is of importance for maximizing exchanges and is potentially impacted by parameters such as fill volume. We describe an in vivo assessment of the contact surface area by micro-computed tomography (μCT) using an iodinated contrast medium added to the PD fluid, a contrast agent presumed without surfactant property. In the isotropic volume (reconstructed voxel size 186 μm x 186 μm x 186 μm), the iodinated PD fluid is automatically selected, thanks to its contrast difference with soft tissues, and its surface area is computed. The method was first tested on phantoms showing the ability to select the PD fluid volume and to measure its surface area. In vivo experiments in rat consisted of μCT acquisition of rat abdomen directly after intraperitoneal administration (10 mL/100 g rat body weight) of a dialysis fluid containing 10% by volume iodinated contrast agent. Fluorescein isothiocyanate albumin was used as dilution marker. We found a strong linear relationship ( R2 = 0.98) between recruited PSA (cm2) and rat weight (g) in the range of 235 to 435 g: recruited PSA = (1.61 weight + 40.5) cm2. Applying μCT with a fill volume of 10 mL/100 g rat body weight, the in vivo measured PSA was in the order of magnitude of the ex vivo anatomic PSA as determined by Kuzlan's formula, considered in most instances as the maximal surface area that can be recruited by PD fluid. This new methodology was the first to give an in vivo high-resolution isotropic three-dimensional (3-D) determination of the PSA in contact with dialysate. Its sensitivity allows us to take into account the recruitment of fine 3-D structures of the PSA membrane that were not accessible to previous 2-D-based imaging methodologies. Its in vivo application also integrates the physiological natural tensile stress of tissues.

This article reviews and explains the basic physical principles of metal-induced MRI artifacts, describes simple ways to reduce them, and presents specific reduction solutions. Artifacts include signal loss, pile-up artifacts, geometric distortion, and failure of fat suppression. Their nature and origins are reviewed and explained though schematic representations that ease the understanding. Then, optimization of simple acquisition parameters is detailed. Lastly, dedicated sequences and options specifically developed to reduce metal artifacts (VAT, SEMAC, and MAVRIC) are explained.

This overview first summarizes the last decade of continuous developments and improvements in pre-clinical imaging methods that are now essential tools for in vivo evaluation of cardiac morphology and function in living mice, involving nuclear emission of labeled molecules (micro-PET and micro-SPECT) and electromagnetic wave interactions with biological tissues (micro-CT and micro-MRI). In the following, and for better understanding, the basic physical principles and specific technical innovations of the aforementioned imaging methods are reviewed. Specificity, sensitivity, and spatial and temporal resolutions, together with the corresponding advantages and weaknesses of each method are then discussed, and cardiac image-acquisition protocols and illustrative examples are given for each modality. Emerging hybrid cardiac imaging is also presented and illustrated. Then, recent biological insights provided by mouse cardiac imaging are presented. Finally, imaging strategies in mouse cardiac phenotyping involving the aforementioned methods, adding metabolic and molecular information to morphological data, are emphasized and discussed. Curr. Protoc. Mouse Biol. 2:129-144 © 2012 by John Wiley & Sons, Inc.

Laser polarised (hyperpolarised) 129Xe offers a new potential way for assessment of cerebral blood flow (CBF) by nuclear magnetic resonance (NMR). We present the basic physical principles underlying noble gases'laser polarisation. Distinguishing characteristics of 129Xe NMR properties as well as theoretical basis for CBF measurement using laser polarised 129Xe are emphasized. Recent results are briefly presented and potential applications as well as current limitations of 129Xe in CBF studies are discussed.

[Abstract] A series composed of a tetra-, a tris- and a bisphosphonated ligand based on a pyridine scaffold (L4, L3 and L2, respectively) was studied within the frame of lanthanide (Ln) coordination. The stability constants of the complexes formed with lanthanide cations (Ln=La, Nd, Eu, Gd, Tb, Er and Lu) were determined by potentiometry in aqueous solutions (25.0 °C, 0.1 M NaClO4), showing that the tetraphosphonated complexes are among the most stable LnIII complexes reported in the literature. The complexation of L4 was further studied by different titration experiments using mass spectrometry and various spectroscopic techniques including UV/Vis absorption, and steady state and time-resolved luminescence (Ln=Eu and Tb). Titration experiments confirmed the formation of highly stable [LnL4] complexes. 31P NMR experiments of the LuL4 complex revealed an intramolecular interconversion process which was studied at different temperatures and was rationalized by DFT modelling. The relaxivity properties of the GdIII complexes were studied by recording their 1H NMRD profiles at various temperatures, by temperature dependent 17O NMR experiments (GdL4) and by pH dependent relaxivity measurements at 0.47 T (GdL3 and GdL2). In addition to the high relaxivity values observed for all complexes, the results showed an important second-sphere contribution to relaxivity and pH dependent variations associated with the formation of aggregates for GdL2 and GdL3. Finally, intravenous injection of GdL4 to a mouse was followed by dynamic MRI imaging at 1.5 T, which showed that the complex can be immediately found in the blood stream and rapidly eliminated through the liver and in large part through the kidneys. Torino. Compagnia di San Paolo; CSP-2012 NANOPROGLY

Our aim was to conduct a quantitative and qualitative evaluation of high-resolution skull-bone imaging for dentistry and otolaryngology using different architectures of recent X-ray computed tomography systems.Three multi-slice computed tomography (MSCT) systems and one Cone-beam computed tomography (CBCT) system were used in this study. All apparatuses were tested with installed acquisition modes and proprietary reconstruction software enabling high-resolution bone imaging. Quantitative analyses were performed with small fields of view with the preclinical vmCT phantom, which permits to measure spatial resolution, geometrical accuracy, linearity and homogeneity. Ten operators performed visual qualitative analyses on the vmCT phantom images, and on dry human skull images.Quantitative analysis showed no significant differences between protocols in terms of linearity and geometric accuracy. All MSCT systems present a better homogeneity than the CBCT. Both quantitative and visual analyses demonstrate that CBCT acquisitions are not better than the collimated helical MSCT mode.Our results demonstrate that current high-resolution MSCT protocols could exceed the performance of a previous generation CBCT system for spatial resolution and image homogeneity.• Quantitative evaluation is a prerequisite for comparison of imaging equipment. • Bone imaging quality could be objectively assessed with a phantom and dry skull. • The current MSCT shows better image quality than a dental CBCT system. • CBCT remains a work-in-progress technology.

The high xenon solubility in blood and tissues makes hyperpolarized 129 Xe a potential MR tracer for tissue perfusion studies. Two biocompatible fluids were studied with a view to be used as delivery media for hyperpolarized xenon injection: the carrier agents were 129 Xe micro-bubbles in Echovist (2–3 μm in diameter), and Intralipid 129 Xe suspension. Xenon chemical shifts and longitudinal relaxation time T 1 were measured at 2.35 T in both fluids. Xenon chemical shift of the dissolved phase in Echovist was 204.1 ± 0.5 ppm from the micro-bubbles gas phase resonance data (0 ppm). Xenon T 1 was 20.0 s in micro-bubbles in Echovist and 19.0 s for the dissolved phase. Xenon chemical shift in Intralipid was 194.6 ± 0.5 ppm. T 1 was 15.2 ± 4.9 s ( n = 5) in Intralipid 20 % and 20.9 ± 2.9 s ( n = 4) in Intralipid 30 %. Using an intra-carotid injection of a small volume (0.15 mL) of hyperpolarized xenon dissolved in Intralipid 30 %, cerebral blood flow was measured in rats (160 ± 30 mL·(100 g) –1 ·min –1 , n = 10). Rat brain xenon images were performed with 2-D projection–reconstruction pulse sequence, enabling regional blood flow measurements.

Although the practice of perinatal autopsy has increased in recent years, examination of the fetus and especially of the fetal brain during the first trimester or the beginning of the second trimester remains difficult. Postmortem high-resolution images of the brain of a normal and an abnormal fetus of the same gestational age (22 weeks) were obtained with a low-field (0.1 T) dedicated magnetic resonance imaging (MRI) system. We demonstrated that a small MRI machine supplemented data from classical necropsy and may help in the interpretation of in utero ultrasound and magnetic resonance images for the antenatal diagnosis of fetal malformations.

In-111 DTPA-D-Phe1-octreotide (In-111 pentetreotide) is a widely used radiotracer for somatostatin receptor (SSTR) in- vestigations in neuroendocrine (NE) pathology. Cellular SSTR den- sity is directly related to the degree of NE cellular differentiation. Poorly differentiated cell lines show a surface reduction of SSTRs, which may lead to misinterpreting the In-111 pentetreotide scintig- raphy results as negative. A case of anorectal small-cell undifferen- tiated neuroendocrine carcinoma is reported. This pathologic finding is rare, highly aggressive, and associated with a dramatic prognosis. The patient was investigated with In-111 pentetreotide SPECT and low-dose computed tomography (CT) for anatomic reference. De- spite its low degree of differentiation, the tumor showed high tracer uptake characterized by a positive incremental trend as shown by comparison of the 4-hour and 24-hour SPECT images, suggesting specific receptorial binding of In-111 pentetreotide.

The understanding of the flow structures and the particle transport/deposition across the human bronchial system remains a challenge to achieve because of the complexity of the geometry of human lungs. This work relies a strong collaboration between physicians, medical imaging researchers, fluid mechanics researcher and CFD researchers. Four configurations of airways (the generic Weibel model, the Human model proposed by Hiroko Kitaoka, a realistic Rat lung obtained by \(\mu \)-CT and a realistic rabbit geometry obtained by a synchrotron based CT) have been generated, meshed and simulated using the CFD commercial package CFD-ACE. Both steady and realistic inflow rates have been studied as well as the associated transport and deposition of particles.

Three glomus tumors of the fingers were detected using a dedicated hand and wrist low field (0.1 T) MR imager equipped with solenoidal coils allowing a FOV of 2 cm. Three-dimensional T1-, T*2-, or T2-weighted images were used (8 contiguous slices of 2 mm thickness). Glomus tumors had low or intermediate signal intensity (2 cases) or no signal (1 case) on T1-weighted images. On T*2- or T2-weighted images they had high signal intensity. MRI findings correlate well with surgery and biopsy.

RATIONALE AND OBJECTIVES Xenon is an inert gas characterized by a nuclear halfspin and a high solubility in lipids. It appears to diffuse freely in biological tissues and, in particular, through the blood-brain barrier. Spin-exchange with optically pumped rubidiu mvapo rincrease sth enuclea rpolarizatio no f 129 Xe gas by several orders of magnitude above the polarization at thermal equilibrium, resulting in “hyperpolarized” (HP) xenon. HP xenon can be used as a magnetic resonance (MR) tracer because of its NMR-enhanced sensitivity combined with its high solubility. This HP tracer is a potential exogenous NMR probe for cerebral imaging studies. The purpose of this paper is to describe the preparation of this HP tracer and to demonstrate that it can be used in NMR for absolute cerebral perfusion measurements.

This study compares different peritoneal dialysis fluids (PDF) in rats over a short contact time. For greater accuracy, net ultrafiltration (UF) and peritoneal transport indices, mass transfer area coefficient (MTAC) were scaled for the in vivo peritoneal surface area recruited (ivPSA) measured by microcomputerized tomography. Wistar rats underwent nephrectomy (5/6ths), were randomized into two groups and given 1.5% glucose PDF, either conventional acidic lactate (n = 14) or pH neutral bicarbonate (BicaVera) (n = 13); MTAC and UF were measured using a 90-min peritoneal equilibrium test (PET), fill volume (IPV) of 10 ml/100 g; small pore fluid transport was determined from sodium balance and used to calculate free water transport (FWT). Each ivPSA value was significantly correlated with the actual IPV, which varied from one rat to another. At 90 min of contact, there was no difference in recruited ivPSA in relation to PDFs. There was a difference (p 0.01) in net UF/ivPSA 0.45 vs. 1.41 cm(2)/ml for bicarbonate versus lactate, as there was in the proportion of FWT with bicarbonate (42 ± 5% of net UF) compared to lactate (29 ± 4% of net UF). Net UF for individual values of ivPSA differs between conventional PDF and more biocompatible solutions, such as bicarbonate PDF. This observed change in UF cannot be fully explained by differences in glucose transport. The changes in FWT may be explained by the impact of the PDF biocompatibility on aquaporin function.