Imaging thrombosis with 99mTc-labeled RAM.1-antibody in vivo.

INTRODUCTION: Platelets play a major role in thrombo-embolic diseases, notably by forming a thrombus that can ultimately occlude a vessel. This may provoke ischemic pathologies such as myocardial infarction, stroke or peripheral artery diseases, which represent the major causes of death worldwide. The aim of this study was to evaluate the specificity of radiolabeled Rat-Anti-Mouse antibody (RAM.1). METHODS: We describe a method to detect platelets by using a RAM.1 coupled with the chelating agent hydrazinonicotinic acid (HYNIC) conjugated to 99mTc, for Single Photon Emission Computed Tomography (SPECT). To induce platelet accumulation at a site of interest, we used a mouse model of FeCl3 induced injury of the carotid artery. 90 min after i.v. injection of [99mTc][Tc(HYNIC)-RAM.1], biodistribution of the radiolabeled RAM.1 was assessed, SPECT imaging and histological analysis were performed on the mice that underwent FeCl3-induced vessel damage. RESULTS: We demonstrated a quick and strong affinity of the radiolabeled RAM.1 for the platelet thrombus. Results clearly demonstrated the ability of this radioimmunoconjugate for detecting thrombi from 10 min post injection with an exceptional thrombi uptake. Using FeCl3, the median ratio between the thrombus and the background was 12.4 (range 9.3-42.3) as compared to 1.0 (range: 0.86-2.7) p < 0.05 when using 0.9% NaCl. CONCLUSION: Thanks to the high sensitivity of SPECT, we provided evidence that [99mTc][Tc(HYNIC)-RAM.1] represents a powerful tool to detect localized platelet thrombi which could potentially be used in humans. Because of the relative low cost and high sensitivity, these results encourage further study like the detection of non-induced thrombus and further developments toward clinical application. This is further supported by the fact that RAM.1 recognizes human platelets.

A fast experimental beam hardening correction method for accurate bone mineral measurements in 3D µCT imaging system.

Bone mineral density plays an important role in the determination of bone strength and fracture risks. Consequently, it is very important to obtain accurate bone mineral density measurements. The microcomputerized tomography system provides 3D information about the architectural properties of bone. Quantitative analysis accuracy is decreased by the presence of artefacts in the reconstructed images, mainly due to beam hardening artefacts (such as cupping artefacts). In this paper, we introduced a new beam hardening correction method based on a postreconstruction technique performed with the use of off-line water and bone linearization curves experimentally calculated aiming to take into account the nonhomogeneity in the scanned animal. In order to evaluate the mass correction rate, calibration line has been carried out to convert the reconstructed linear attenuation coefficient into bone masses. The presented correction method was then applied on a multimaterial cylindrical phantom and on mouse skeleton images. Mass correction rate up to 18% between uncorrected and corrected images were obtained as well as a remarkable improvement of a calculated mouse femur mass has been noticed. Results were also compared to those obtained when using the simple water linearization technique which does not take into account the nonhomogeneity in the object.

A detector response function design in pinhole SPECT including geometrical calibration.

Clinical single photon emission computed tomography (SPECT) equipped with pinhole collimators have a magnification factor that results in high spatial resolution images for small animal imaging. Using Monte Carlo simulations to model the acquisition process and the propagation of the photons from their point of emission to their detection point then integrating the model into an iterative reconstruction algorithm improves the signal-to-noise ratio, the contrast and the spatial resolution in the reconstructed images. However, pinhole SPECT systems are known to be very sensitive to geometrical misalignments. Geometrical misalignments are defined as the radial or axial shift of the collimator pinhole and/or twist and tilt of the detector heads and are introduced in the system each time the collimation device is changed (pinhole to parallel holes or vice versa). In this work, we present a flexible detector response function table (DRFT) design that takes into account the geometrical misalignments and avoids performing new Monte Carlo simulations for each exam in order to calculate a geometrical study-dependent system matrix. The utilization of the DRFT for the calculation of the system matrix speeds up its computation time by two orders of magnitude making it acceptable for preclinical and clinical applications.

Effect of prior treatment with resveratrol on density and structure of rat long bones under tail-suspension.

Physical inactivity during space flight or prolonged bed rest causes rapid and marked loss of bone mass in humans. Resveratrol, a red wine polyphenol that is currently under study for its therapeutic antioxidant properties, has been shown to significantly modulate biomarkers of bone metabolism, i.e., to promote osteoblast differentiation and to prevent bone loss induced by estrogen deficiency. However, there is no direct evidence supporting its inhibitory effect toward bone loss during physical inactivity. In the present study, effects of resveratrol on bone mineral density (BMD), bone mineral content, and bone structure were examined in the femora and tibiae of tail-suspended and unsuspended rats using X-ray micro-computed tomography (micro-CT). Rats were treated with 400 mg/kg/day of resveratrol for 45 days and half of them were suspended during the last 2 weeks of treatment. Suspension caused a decrease in tibial and femoral BMD and deterioration of trabecular and cortical bone. Bone deterioration during suspension was paralleled by increased bone marrow area, which could be caused by an increase in stromal cells with osteoclastogenic potential or in adipocytes. Resveratrol had a preventive effect against bone loss induced by hindlimb immobilization. In particular, trabecular bone in the proximal tibial metaphysis was totally preserved in rats treated with resveratrol before tail-suspension.

Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer.

PURPOSE: The aim of this prospective study was to analyze the safety of methylene blue dye (MBD) and compare its efficacy with that of isotopic mapping for sentinel lymph node (SLN) identification in breast cancer. PATIENTS AND METHODS: The SLN procedure, involving isotopic mapping and MBD (subareolar intraparenchymal injections of 2 mL, 10 mg/mL), was performed on 100 patients with early breast cancer. RESULTS: The procedure was safe with a success rate of 99%; SLNs were, respectively, found in 65% by MBD, in 73% by lymphoscintigraphy and in 94% by gamma-probe. Out of 40 metastatic SLNs, 37 were "hot" and 32 stained. Digital examination allowed the detection of 2 additional metastatic LNs. CONCLUSION: MBD is safe and combination mapping associated with digital examination is the superior method. Modification of the procedure, favouring injections of dilute MBD (4 mL, 1.25 mg/mL) increases MBD efficiency (90%) and maintains low rates of complications.

Red wine polyphenols prevent acceleration of neovascularization by angiotensin II in the ischemic rat hindlimb.

Studies in both animals and humans indicate that angiogenesis is implicated in the development of atherosclerotic lesions. Thus, inhibition of angiogenesis may provide a novel therapeutic approach for the treatment of atherosclerosis. Because epidemiological studies have indicated an inverse relation between red wine intake and coronary disease, we determined the antiangiogenic potential of red wine polyphenols (RWPs) in the ischemic hindlimb model. Neovascularization was accelerated by the chronic infusion of angiotensin II (Ang II; 0.1 mg/kg/day). RWPs (25 mg/kg/day) or vehicle were administrated in the drinking water 7 days before the ligation. After 21 days, Ang II potentiated the ischemia-induced neovascularization in the hindlimb, as assessed by microangiography and measurement of microvessel density. This effect was associated with an increased formation of reactive oxygen species (ROS) and increased expression of hypoxia-inducible factor (HIF)-2alpha, endothelial nitric-oxide synthase (eNOS), and vascular endothelial growth factor (VEGF). RWPs intake significantly prevented the angiogenic process, the formation of ROS and nitrated proteins, and the expression HIF-2alpha, eNOS, and VEGF induced by Ang II. Similar preventive effects were observed with the antioxidant and NADPH oxidase inhibitor apocynin. These findings indicate that RWPs have potent antiangiogenic properties in vivo by preventing the expression of proangiogenic factors, including VEGF and eNOS most likely by inhibiting oxidative stress. Thus, the antiangiogenic properties of red wine polyphenols might contribute to their protective effect against coronary disease.

A new intraoperative gamma camera for the sentinel lymph node procedure in breast cancer.

AIM: This study aimed at evaluating the performance of an intraoperative gamma camera, named CarolIReS, to detect axillary drainage and to assess the removal of sentinel lymph nodes (SLN) in breast surgery. PATIENTS AND METHODS: SLN biopsy was performed on 25 patients and the CarolIReS camera was used preoperatively to localize SLNs. During surgery, individual removal of SLNs was performed using a gamma probe and their activity was measured with a gamma ray counter. At the end of surgery, the CarolIReS camera was used again to check the quality of surgery which was followed by surgical excision for remaining SLNs. RESULTS: The detection efficiency of the CarolIReS camera was 2.2 cps/kBq for 99"Tc activity in SLNs. In one case, it allowed the detection of a residual SLN with a low activity (0.5 kBq) which was massively metastatic. CONCLUSION: Intraoperative cameras could be used to improve the efficiency of the SLN procedure.