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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.

Resume L’imagerie preoperatoire des hyperparathyroidismes primaires a pour objectif premier de determiner avec precision et fiabilite la position et les rapports de la glande pathologique afin d’orienter le geste operatoire du chirurgien et de proposer des methodes de chirurgie moins invasives. La scintigraphie planaire de soustraction presente de bonnes performances diagnostiques mais dans ce cadre preoperatoire pour lequel un reperage anatomique optimal est souhaitable, on peut s’interroger sur la valeur ajoutee d’une imagerie multimodale avec fusion anatomique et fonctionnelle. Nous avons entrepris de comparer – au sein d’une population de 23 patients presentant un hyperparathyroidisme primaire – un protocole d’acquisition planaire cervicomediastinal et pinhole cervical anterieur a un protocole tomographique (TEMP) cervicomediastinal de soustraction ( 123 I/ 99m Tc-MIBI) couple a une tomodensitometrie (TDM). Le compte-rendu chirurgical et l’examen histologique constituaient les references pour la population incluse afin de mesurer les performances diagnostiques respectives. Le protocole d’acquisition TEMP/TDM de soustraction que nous avons mis en œuvre s’est revele plus sensible et plus specifique que le protocole d’acquisition planaire a la fois pour le diagnostic et la localisation precise de la glande parathyroide pathologique ; les sensibilites etaient evaluees respectivement a 76 et 56 %, les specificites a 100 et 80 %. Le protocole tomographique est apparu particulierement performant pour les glandes parathyroides d’origine superieure et pour les patients inclus qui presentaient un goitre nodulaire associe.

Many animal viruses exhibit proficient growth in transformed cells, a property that has been harnessed for the development of novel therapies against cancer. Despite overwhelming evidence for this phenomenon, understanding of the molecular mechanisms enabling tumor-cell killing is rudimentary for most viruses. We report here that growth and cytotoxicity of the prototype oncolytic poliovirus (PV), PVSRIPO, in glioblastoma multiforme (GBM) is promoted by mitogen-activated protein kinases (MAPKs) converging on the MAPK signal-integrating kinase 1 (Mnk1) and its primary substrate, the eukaryotic initiation factor (eIF) 4E. Inducing Mnk1-catalyzed eIF4E phosphorylation through expression of oncogenic Ras substantially enhanced PVSRIPO translation, replication, and cytotoxicity in resistant cells. This effect was mimicked by expression of constitutively active forms of Mnk1 and correlated with enhanced translation of subgenomic reporter RNAs. Our findings implicate Mnk1 activity in stimulation of PVSRIPO cap-independent translation, an effect that can be synergistically enhanced by inhibition of the phosphoinositide-3 kinase (PI3K).

PVS-RIPO is a genetically recombinant, non-pathogenic poliovirus chimera with a tumor-specific conditional replication phenotype. Consisting of the genome of the live attenuated poliovirus type 1 (Sabin) vaccine with its cognate IRES element replaced with that of human rhinovirus type 2, PVS-RIPO displays an inability to translate its genome in untransformed neuronal cells, but effectively does so in cells originating from primary tumors in the central nervous system or other cancers. Hence, PVS-RIPO unleashes potent cytotoxic effects on infected cancer cells and produces sustained anti-tumoral responses in animal tumor models. PVS-RIPO presents a novel approach to the treatment of patients with glioblastoma multiforme, based on conditions favoring an unconventional viral translation initiation mechanism in cancerous cells. In this review, we summarize advances in the understanding of major molecular determinants of PVS-RIPO oncolytic efficacy and safety and discuss their implications for upcoming clinical investigations.

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.

Resume Objectif Developper la methodologie d'acquisition et de traitement des donnees scintigraphiques fonctionnelles hepatobiliaires chez la souris normale. Materiel et methodes L'etude scintigraphique a ete realisee a l'aide d'une gamma-camera dediee a l'imagerie du petit animal sur 11 souris femelles adultes CD1 sous anesthesie gazeuse. L'acquisition comportait une serie dynamique de 40 images sequentielles d'une minute apres injection intraveineuse de mebrofenine technetiee. Deux individus ont ete utilises pour des acquisitions morphologiques tomodensitometriques par microscanner X avec injection de produit de contraste et ont contribue au choix du placement des regions d'interet scintigraphiques. Quatre modeles analytiques : hepatogramme corrige et deconvolue (A), modele bicompartimental (B), modele a cinetique rapide (C) et analyse factorielle (D) ont ete appliques aux donnees scintigraphiques a partir des regions d'interet centrees sur les cavites cardiaques et le foie. Resultats La cinetique hepatobiliaire de la mebrofenine est caracterisee par un temps du maximum tmax compris entre 4,5 et 4,6 minutes, un temps du centre de gravite tcdg de 6,2 a 7,0 minutes et une demi-vie de decroissance exponentielle t1/2decr de 5,4 a 6,8 minutes, une fraction d'extraction hepatique de 100 %. Les temps de captation et d'excretion sont de 2,3 et 5,8 minutes pour le modele bicompartimental et de 3,2 et 3,3 minutes pour le modele a cinetique rapide. Les comparaisons ne retrouvent pas de difference significative entre les foies droit et gauche ni entre les modeles A, B, C et D pour les constantes de captation ni entre les modeles A, B et D pour les constantes de d'excretion. Conclusion Differentes modelisations compartimentales ont permis d'obtenir des valeurs de reference de la fonction hepatobiliaire pour la souris normale CD1.

At the southern end of the Gregory Rift Valley, Lake Magadi occupies the bottom of a relatively large drainage basin. It is presently covered by a thick trona crust, which overlies two silty-clay units deposited during Late Pleistocene high lake stands. These units consist of a mixture of detrital grains (anorthoclase, amphiboles, quartz), clays (illite, authigenic zeolites), phosphates, and sedimentary sodium silicates and cherts. A late diagenetic calcite is occasionally observed. The authigenic and/or diagenetic mineralogical phases were extracted and analyzed for their uranium and thorium isotope contents. All yielded highly correlated ( 234 U 232 Th vs. 238 U 232 Th ) and ( 230 Th 232 Th vs. 234 U 232 Th ) isochrons defining two-component mixing systems (detrital and authigenic phases). The detrital component is characterized by large excesses of 230Th (over 234U) and by 230 Th 232 Th ratios carrying an imprint of the source rocks (e.g., Precambrian basement vs. volcanics) and indicating efficient uranium-leaching processes during the previous pedologic cycle. The slope of the isochrons defines the 234 U 238 U and 230 Th 234 U ratios of the authigenic component, i.e., the age of the uranium-uptake episode. Zeolites yield an age of 10.4 ± 0.6 ka. This age is in agreement with the 14C chronology already established for the most recent high lake level episode in the basin (10,000–12,000 yr Bp). Sodium-silicates and cherts yield distinct ages of 98.5 ± 20 and 6 ± 3 ka, respectively, for the lower and upper lacustrine units. These ages allow the conclusion that (1) sedimentary silicates are of late diagenetic origin, and (2) that the lower lacustrine unit was deposited during a former high Lake Magadi level, possibly during the lacustrine episode dated at 135 ± 10 ka from uranium-series measurements on littoral stromatolites. Finally, the late diagenetic calcite, which yields an age of about 5 ka, indicates a significant change in the sediment interstitial water chemistry. This is also shown by the occurrence of calcitic oncolites in flat deposits assigned to a mid-Holocene minor oscillation of Lake Magadi level on the basis of their 14C ages. It is concluded that uranium-series measurements in diagenetic minerals may give access to the age of their formation.

Background ST segment/heart rate hysteresis can improve the diagnostic performance of the exercise ECG for prediction of coronary artery disease and cardiovascular mortality. As this simple variable integrates the heart-rate adjusted ST segment depression during exercise and recovery phase, ST/HR hysteresis is related both to ischemia and sympathovagal balance. Microvolt T wave alternans (TWA) measurement during stress testing has been suggested as a predictor of life-threatening cardiac arrhythmia. According to the Coumel's triangle hypothesis, the sympathovagal balance could modulate TWA. Dipyridamol-induced ischemia does not disturb significantly this balance. Purpose We aimed to assess the absence of an elevated TWA under a dipyridamol SPECT imaging. Methods and Results All 339 consecutive patients who were referred for a pharmacological stress test with dipyridamol. The maximum TWA was determined with the modified moving average method. Using for ST/HR hysteresis a cutoff of 0.038 mV, yields a 75% negative predictive value for a TWA above the reported threshold of 47 μV (from holter recordings). ST/HR hysteresis negative predictive value was even better reaching 90% to rule out the occurrence of a higher TWA (65 μV derived from ECG stress testing). Conclusion The absence of significant alterations in sympathovagal balance seems to be associated with low T-wave alternans. ST/HR hysteresis might be useful to exclude the possibility of an elevated T wave alternans.

Purpose Heart rate adjustment of exercise-induced ST-segment depression (ST/HR index and ST/HR hysteresis) has been suggested as an accurate predictor of the presence of a coronary artery disease. Its powerful predictive value for proven coronary artery stenosis is now accepted. The objective of our study was to investigate the sentitivity and specificity of computerized ST/HR index and ST/HR hysteresis to detect significant ischemia. Methods We used a cross-sectional analysis of exercise test and myocardial perfusion stress-rest SPECT data. The study population comprised 710 consecutive patients referred for myocardial perfusion imaging. The threshold of significant ischemia was set above 10% reversibility hypoperfusion area from entire surface of left ventricle using gated-SPECT image analysis (QGS). Diagnostic performance of ST/HR index and ST/HR hysteresis was assessed by receiver operating characteristic (ROC) curve. Results Crude ST/HR hysteresis showed at the same 70% specificity, a sensitivities of 56% and 57%, respectively. Diagnostic performance of ST/HR hysteresis seems slightly better than ST/HR index (AUC = .668 vs .654) with the following cut points .038 mV and 1.625 μV/bpm. Adjusting these variables to body mass index does not improve the diagnostic performance. Combining an independant clinical judgement in the model yields a moderate increase of the diagnostic accuracy the prediction only for ST/HR index as suggested by the AUC (.688). Conclusions ST/HR index and ST/HR hysteresis have a good capability to detect a significant myocardial ischemia evaluated by SPECT, which has therapeutic implications.