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Purpose To assess the distribution of bone lesions in patients with prostate cancer (PCa) and those with multiple myeloma (MM) using whole-body magnetic resonance imaging (MRI); and to assess the added value of four anatomical regions located outside the thoraco-lumbo-pelvic area to detect the presence of bone lesions in a patient-based perspective. Materials and methods Fifty patients (50 men; mean age, 67 ± 10 [SD] years; range, 59–87 years) with PCa and forty-seven patients (27 women, 20 men; mean age, 62.5 ± 9 [SD] years; range, 47–90 years) with MM were included. Three radiologists assessed bone involvement in seven anatomical areas reading all MRI sequences. Results In patients with PCa, there was a cranio-caudal increasing prevalence of metastases (22% [11/50] in the humeri and cervical spine to 60% [30/50] in the pelvis). When the thoraco-lumbo-pelvic region was not involved, the prevalence of involvement of the cervical spine, proximal humeri, ribs, or proximal femurs was 0% in patients with PCa and ≥ 4% (except for the cervical spine, 0%) in those with MM. Conclusion In patients with PCa, there is a cranio-caudal positive increment in the prevalences of metastases and covering the thoraco-lumbo-pelvic area is sufficient to determine the metastatic status of a patient with PCa. In patients with MM, there is added value of screening all regions, except the cervical spine, to detect additional lesions.

Presented in part at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 27–30 September 2006, San Francisco, CA, USA, Abstract M-1307; International audience; Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) uptake may be observed in the course of active inva-sive fungal infections. The aim of this study was to assess the role of positron emission tomography with [ 18 F]FDG ([ 18 F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [ 18 F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplanta-tion (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidia-sis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomyco-sis in one case each. An increased uptake of [ 18 F]FDG was observed in all areas previously identified by computed tomography and/ or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [ 18 F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [ 18 F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [ 18 F]FDG-PET was performed to assess the evolution of the disease. [ 18 F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [ 18 F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.

International audience; PURPOSE: Partial volume effects (PVEs) are consequences of the limited spatial resolution in emission tomography leading to underestimation of uptake in tissues of size similar to the point spread function (PSF) of the scanner as well as activity spillover between adjacent structures. Among PVE correction methodologies, a voxel-wise mutual multiresolution analysis (MMA) was recently introduced. MMA is based on the extraction and transformation of high resolution details from an anatomical image (MR/CT) and their subsequent incorporation into a low-resolution PET image using wavelet decompositions. Although this method allows creating PVE corrected images, it is based on a 2D global correlation model, which may introduce artifacts in regions where no significant correlation exists between anatomical and functional details. METHODS: A new model was designed to overcome these two issues (2D only and global correlation) using a 3D wavelet decomposition process combined with a local analysis. The algorithm was evaluated on synthetic, simulated and patient images, and its performance was compared to the original approach as well as the geometric transfer matrix (GTM) method. RESULTS: Quantitative performance was similar to the 2D global model and GTM in correlated cases. In cases where mismatches between anatomical and functional information were present, the new model outperformed the 2D global approach, avoiding artifacts and significantly improving quality of the corrected images and their quantitative accuracy. CONCLUSIONS: A new 3D local model was proposed for a voxel-wise PVE correction based on the original mutual multiresolution analysis approach. Its evaluation demonstrated an improved and more robust qualitative and quantitative accuracy compared to the original MMA methodology, particularly in the absence of full correlation between anatomical and functional information.

Here we engineered transgenic Leishmania infantum that express luciferase, the objectives being to more easily monitor in real time their establishment either in BALB/c mice—the liver and spleen being mainly studied—or in vitro. Whatever stationary phase L. infantum promastigotes population—wild type or engineered to express luciferase—the parasite burden was similar in the liver and the spleen at day 30 post the intravenous inoculation of BALB/c mice. Imaging of L. infantum hosting BALB/C mice provided sensitivity in the range of 20,000 to 40,000 amastigotes/mg tissue, two tissues—liver and spleen—being monitored. Once sampled and processed ex vivo for their luciferin-dependent bioluminescence the threshold sensitivity was shown to range from 1,000 to 6,000 amastigotes/mg tissue. This model further proved to be valuable for in vivo measurement of the efficiency of drugs such as miltefosine and may, therefore, additionally be used to evaluate vaccine-induced protection., Author Summary Leishmania infantum/L. chagasi parasites are inoculated in the skin of mammals by sand flies. Though most often these L. infantum-mammal interactions are asymptomatic, they can proceed, in some individuals, to a systemic disease known as visceral leishmaniasis. If left untreated this disease is fatal. The lack of protective or curative vaccines and the limited number of parasite-targeting drugs were incentive to set up experimental conditions that could allow easy monitoring of the fluctuation of the population size of parasites in living laboratory animals. Thus, in the present report, we depict two distinct readout assays that rely on a population of L. infantum we genetically engineered for stably expressing the firefly luciferase gene. These transgenic parasites were either inoculated to BALB/c mice or added to a culture of monocytic cells. Post intravenous inoculation, BALB/c mice were imaged over time, with special attention being given to the liver and the spleen. The sensitivity of this technique ranged from 20,000 to 40,000 parasites/mg of tissue and from 1,000 to 6,000 parasites/mg tissue, for in vivo and ex vivo measurements, respectively. Though preliminary, the data, relying on monocytic cells, are promising for further in vitro screening of small compound libraries.

International audience; OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients.

International audience; Antibiotic-resistant bacteria threaten life worldwide. Although new antibiotics are scarce, the use of bacteriophages, viruses that infect bacteria, is rarely proposed as a means of offsetting this shortage. Doubt also remains widespread about the efficacy of phage therapy despite recent encouraging results. Using a bioluminescent Pseudomonas aeruginosa strain, we monitored and quantified the efficacy of a bacteriophage treatment in mice during acute lung infection. Bacteriophage treatment not only was effective in saving animals from lethal infection, but also was able to prevent lung infection when given 24 h before bacterial infection, thereby extending the potential use of bacteriophages as therapeutic agents to combat bacterial lung infection.

International audience; PURPOSE: Partial volume effects (PVEs) are consequences of the limited resolution of emission tomography. The aim of the present study was to compare two new voxel-wise PVE correction algorithms based on deconvolution and wavelet-based denoising. MATERIALS AND METHODS: Deconvolution was performed using the Lucy-Richardson and the Van-Cittert algorithms. Both of these methods were tested using simulated and real FDG PET images. Wavelet-based denoising was incorporated into the process in order to eliminate the noise observed in classical deconvolution methods. RESULTS: Both deconvolution approaches led to significant intensity recovery, but the Van-Cittert algorithm provided images of inferior qualitative appearance. Furthermore, this method added massive levels of noise, even with the associated use of wavelet-denoising. On the other hand, the Lucy-Richardson algorithm combined with the same denoising process gave the best compromise between intensity recovery, noise attenuation and qualitative aspect of the images. CONCLUSION: The appropriate combination of deconvolution and wavelet-based denoising is an efficient method for reducing PVEs in emission tomography.

International audience; Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.0 mM(-1) s(-1) for GdDOTA at 9.4 T, 37 degrees C, in H(2)O). Here we report an in vivo MRI feasibility study, complemented with dynamic gamma scintigraphic imaging and biodistribution experiments using the (153)Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd(3)L and the commercial contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd(3)L was well tolerated by the animals at the dose of 8 micromol Gd kg(-1) body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd(3)L injection than after GdDOTA injection at an identical dose. The relaxation rates, DeltaR(1), were calculated from the IR TrueFISP data. During the excretory phase, the DeltaR(1) for various tissues was similar for Gd(3)L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 micromol Gd kg(-1) body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd(3)L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd(3)L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd(3)L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are also indicative of a fast elimination via the kidneys.

Real-time visualization of calcium (Ca(2+)) dynamics in the whole animal will enable important advances in understanding the complexities of cellular function. The genetically encoded bioluminescent Ca(2+) reporter green fluorescent protein-aequorin (GA) allows noninvasive detection of intracellular Ca(2+) signaling in freely moving mice. However, the emission spectrum of GA is not optimal for detection of activity from deep tissues in the whole animal. To overcome this limitation, two new reporter genes were constructed by fusing the yellow fluorescent protein (Venus) and the monomeric red fluorescent protein (mRFP1) to aequorin. Transfer of aequorin chemiluminescence energy to Venus (VA) is highly efficient and produces a 58 nm red shift in the peak emission spectrum of aequorin. This substantially improves photon transmission through tissue, such as the skin and thoracic cage. Although the Ca(2+)-induced bioluminescence spectrum of mRFP1-aequorin (RA) is similar to that of aequorin, there is also a small peak above 600 nm corresponding to the peak emission of mRFP1. Small amounts of energy transfer between aequorin and mRFP1 yield an emission spectrum with the highest percentage of total light above 600 nm compared with GA and VA. Accordingly, RA is also detected with higher sensitivity from brain areas. VA and RA will therefore improve optical access to Ca(2+) signaling events in deeper tissues, such as the heart and brain, and offer insight for engineering new hybrid molecules.

International audience; The aim of this paper is to develop a registration methodology in order to combine anatomical and functional information provided by thoracic/abdominal computed tomography (CT) and whole-body positron emission tomography (PET) images. The proposed procedure is based on the incorporation of prior anatomical information in an intensity-based nonrigid registration algorithm. This incorporation is achieved in an explicit way, initializing the intensity-based registration stage with the solution obtained by a nonrigid registration of corresponding anatomical structures. A segmentation algorithm based on a hierarchically ordered set of anatomy-specific rules is used to obtain anatomical structures in CT and emission PET scans. Nonrigid deformations are modeled in both registration stages by means of free-form deformations, the optimization of the control points being achieved by means of an original vector field-based approach instead of the classical gradient-based techniques, considerably reducing the computational time of the structure registration stage. We have applied the proposed methodology to 38 sets of images (33 provided by standalone machines and five by hybrid systems) and an assessment protocol has been developed to furnish a qualitative evaluation of the algorithm performance.

International audience; Accurate volume of interest (VOI) estimation in PET is crucial in different oncology applications such as response to therapy evaluation and radiotherapy treatment planning. The objective of our study was to evaluate the performance of the proposed algorithm for automatic lesion volume delineation; namely the fuzzy hidden Markov chains (FHMC), with that of current state of the art in clinical practice threshold based techniques. As the classical hidden Markov chain (HMC) algorithm, FHMC takes into account noise, voxel intensity and spatial correlation, in order to classify a voxel as background or functional VOI. However the novelty of the fuzzy model consists of the inclusion of an estimation of imprecision, which should subsequently lead to a better modelling of the 'fuzzy' nature of the object of interest boundaries in emission tomography data. The performance of the algorithms has been assessed on both simulated and acquired datasets of the IEC phantom, covering a large range of spherical lesion sizes (from 10 to 37 mm), contrast ratios (4:1 and 8:1) and image noise levels. Both lesion activity recovery and VOI determination tasks were assessed in reconstructed images using two different voxel sizes (8 mm3 and 64 mm3). In order to account for both the functional volume location and its size, the concept of % classification errors was introduced in the evaluation of volume segmentation using the simulated datasets. Results reveal that FHMC performs substantially better than the threshold based methodology for functional volume determination or activity concentration recovery considering a contrast ratio of 4:1 and lesion sizes of

International audience; We reported that regioselectively addressable functionalized template (RAFT)-c(-RGDfK-)(4 )presenting four cyclic (Arg-Gly-Asp) (cRGD) peptides targets integrin alpha(V)beta(3) with an improved specificity compared with monomeric cRGD. In this study, we improved this vector by creating a "stealth" molecule in which a fluorescence quencher (Q) is linked to Cy5 via a disulfide bond (-SS-). RAFT-c(-RGDfK-)(4)-Cy5-SS-Q fluorescence is quenched unless activated by reduction during internalization. RAFT-c(-RGDfK-)(4)-Cy5-SS-Q fluorescence was negligible when compared with the control but totally recovered after cleavage of the disulfide bridge. Confocal microscopy showed that only the intracellular Cy5 signal could be detected using RAFT-c(-RGDfK-)(4)-Cy5-SS-Q, confirming that uncleaved extracellular molecules are not visible. Whole-body imaging of mice bearing subcutaneous tumors injected intravenously with RAFT-c(-RGDfK-)(4)-Cy5-SS-Q showed a very significant enhancement of the fluorescent contrast in tumors compared with the unquenched molecule. Histology of the tumor confirmed the intracellular accumulation of Cy5. These results demonstrate that the presence of a labile disulfide bridge between the targeting vector and a drug mimetic is an efficient way to deliver a dye, or a drug, intracellularly. In addition, this quenched RAFT-c(-RGDfK-)(4)-Cy5-SS-Q probe is a very powerful vector for imaging tumor masses and investigating in vivo RGD-mediated internalization.