Y. Charon

SIC, an intracerebral radiosensitive probe for in vivo neuropharmacology investigations in small laboratory animals: theoretical considerations and practical characteristics

Although high-resolution tomographs provide a new approach that strongly simplifies the measurement of in vivo tracer biodistribution and kinetics in small animals, they suffer from an important drawback: the need for animal anesthesia or immobilization, which restricts the neurophysiological investigations. Furthermore, quantitative in vivo experiments realized on the brain sometimes only require a simple measurement of the radioactivity achieved on a few local points and do not necessarily imply the use of a tomograph, which is a detector of high cost. These constraints led the authors to develop an interacerebral /spl beta/ sensitive probe, sonde intracerebrate (SIC) (French acronym of intracerebral probe) that will allow chronic measurements of the neurophysiological activity in awake and unrestrained small animals. The volume to which the probe is sensitive and the noise contributions to the relevant signal have been evaluated through Monte Carlo simulations. Characterizations of a first prototype based on a small piece of scintillating fiber (500-/spl mu/m diameter and 1-mm length) fused to a same diameter optical fiber coupled in turn to a photomultiplier are also presented. A first configuration of the detector is finally proposed.

POCI: a compact high resolution /spl gamma/ camera for intra-operative surgical use

The development of a hand-held /spl gamma/ imaging probe for inside body localization of small tumors is of first interest for radio-guided operative cancer surgery. In that context, we have developed a sub-millimeter spatial resolution, small field of view, /spl gamma/ per-operative compact imager (POCI). It consists of a head module composed of a high resolution tungsten collimator and a YAP:Ce crystal plate, optically coupled to an intensified position sensitive diode (HSD). We report here the essential imaging performance characteristics of the POCI camera (spatial resolution, position linearity, efficiency and energy response). These were obtained by studying the influence of the collimator and the crystal design to evaluate the optimal configuration. The present version of POCI has a 24 mm diameter usable field of view and an intrinsic spatial resolution of 0.9 mm to 1.2 mm FWHM at 120 keV. These good detection performance characteristics combined with the small size of the camera make the device well suited to provide intra-operative monitoring in several medical procedures, such as thyroid and breast tumor removal.

Mobile gamma cameras in breast cancer care - a review.

BACKGROUND Currently, due to progress in detection and to extended screening, surgeons have to deal with increasing numbers of non-palpable lesions in breast cancer. These lesions can be treated by radio-guided surgery in the lumpectomy associated with sentinel lymph node (SLN) procedures. Thanks to advances in detector technology, mini gamma cameras are now available, that can perform real-time lymphoscintigraphy during surgery, or at bedside. AIM In this article, we review the clinical literature on these dedicated cameras used in breast cancer surgery. The goal is to show how these cameras are used in breast cancer treatment and in SLN biopsy and what kind of benefits they offer. METHODS We conducted our search on MEDLINE and EMBASE databases. We performed a comprehensive review to identify clinical studies or cases using mobile gamma cameras in breast cancer surgery. RESULTS We collected 14 articles published between January 2000 and March 2012. We analysed the use of the mobile cameras and the obtained results. CONCLUSION Mobile gamma cameras seem to be useful imaging tools either used pre-operatively or during surgery. They assist surgeons with accurate localization of SLNs and/or radio-labelled tumours, and in verification that all radioactive nodes have been excised.

A Novel Rat Tyrosine Hydroxylase mRNA Species Generated by Alternative Splicing

Abstract: Tyrosine hydroxylase (TH) catalyzes the first and rate‐limiting step in the biosynthesis of catecholamines. Among the various mechanisms implicated in the regulation of TH activity, alternative splicing of TH primary transcript has been described as a characteristic of higher primates and Drosophila. We investigated whether there is such a regulatory mechanism in the rat. Reverse transcriptase‐PCR experiments were performed with RNA from PC12 cells. A new TH mRNA species was evidenced, resulting from the use of an alternative donor site in exon 2. RNase protection assays and in situ hybridization experiments detected this mRNA species in the adrenal medulla but not in the main catecholaminergic nuclei of the CNS. The corresponding putative protein lacks 33 amino acids in the N‐terminal regulatory domain. A recombinant protein was produced in E. coli. Its in vitro specific activity was similar to that of the previously identified TH protein.

The Usefulness of a Preoperative Compact Imager, a Hand-Held γ-Camera for Breast Cancer Sentinel Node Biopsy: Final Results of a Prospective Double-Blind, Clinical Study

The aim of this study was to compare the effectiveness of a hand-held preoperative compact imager (POCI) camera with conventional lymphoscintigraphy using a γ-camera for sentinel lymph node (SLN) detection in breast cancer. Methods: The main objective was to demonstrate the noninferiority of the POCI relative to conventional lymphoscintigraphy and to compare the number of SLNs detected by the 2 imaging devices. Our study, a clinical prospective, double-blind, noninferiority study, planned to include 200 patients with early breast cancer and started in January 2006. A standard SLN protocol (4 periareolar injections of 37 MBq of 99mTc-nanocolloids, 2 h before lymphoscintigraphy) was performed preoperatively using a conventional γ-camera and then the POCI camera. Scans were obtained by 2 different nuclear medicine physicians unaware of each others results. The day after, in the operating room, the surgeon, after receiving the previous results, used the counting probe for surgical SLN biopsy. The number and localization of axillary SLNs obtained by lymphoscintigraphy and the POCI and the duration of the whole procedure were determined. Results: Among the 162 patients included, 138 were evaluable. The POCI detected more SLNs than did lymphoscintigraphy in 50 patients (36%), the same number of in 54 patients (39%), and fewer SLNs in 34 patients (25%), representing 84 (61%) discordant pairs. The noninferiority of preoperative compact imaging of axillary SLNs numbers was found to be statistically significant (95% confidence interval, 30%–52%, P = 0.025) using the McNemar test. The duration of acquisition was shorter using the POCI (<10 min in 84% [n = 117] of patients; mean, 7.5 ± 3.3 min) than lymphoscintigraphy (13% [n = 18] of patients; mean, 15.7 ± 3.4 min), with P < 0.001 using the McNemar test for paired proportions. Conclusion: Preoperative compact imaging using a hand-held camera was able to predict the number and localization of breast cancer SLNs and was not inferior to conventional lymphoscintigraphy in this study. Further studies will determine whether preoperative compact imaging could replace lymphoscintigraphy, especially in surgical centers without an on-site nuclear medicine department.

A self triggered intensified CCD (STIC)

We are developing a new device based on the results reported previously of the successful coincidence detection of β− particles with a high spatial resolution. The novelty of the device consists in triggering and intensified CCD, i.e. a CCD coupled to an image intensifier (II), by an electrical signal collected from the II itself. This is a suitable procedure for detecting low light and rare events with high efficiency and high resolution. The trigger pulse is obtained from the secondary electrons produced by multiplication in a double microchannel plate (MCP) and collected on the aluminized layer protecting the phosphor screen in the II. Triggering efficiencies up to 80% have already been achieved.

Performance characterization and first clinical evaluation of a intra-operative compact gamma imager

The growing interest of cancer surgeons for intra-operative probes has led to the development of several prototypes of high resolution mini gamma cameras. The aim of this paper is to present a global characterization of the one the authors developed and the corresponding first evaluation in a clinical context. The current prototype of POCI (peroperative compact imager) is a 24 mm diameter intensified position sensitive diode. In order to face the various clinical situations, two sets of collimator/scintillator imaging head have been developed either for high spatial resolution or high efficiency purposes, Both of them have been first optimized for /sup 99m/Tc labeled tumor detection. Intrinsic performances are the following: the spatial resolution ranges from 1 mm up to 1.9 mm (without significant distortion) and the corresponding efficiency ranges from 6.10/sup -h/ up to 2.10/sup -4/. Phantom studies illustrating these results are proposed. First clinical evaluation of POCI concerned sentinel lymph node imaging which is included in melanoma and breast cancer staging protocols. Preliminary results already show that performances of POCI are compatible with intra-operative imaging purposes and suggest how such mini-cameras can improve the success rate of tumor removal surgeries.

An Intraoperative Beta Probe Dedicated to Glioma Surgery: Design and Feasibility Study

Surgery is considered as the primary therapeutic procedure for gliomas and several recent clinical studies have shown that total tumor resection is directly associated with longer survival when compared to subtotal resection. In order to refine the resection in the boundaries of gliomas, we are developing an intraoperative probe specifically dedicated to the localization of residual tumor labeled with positron emitters. The probe is designed to be compact and electrically safe in order to be directly coupled to the excision tool leading to simultaneous detection and removal of tumor tissues. It is built with clear and plastic scintillating fibers held in a closed packed annular arrangement ensheathing the excision tool. The annihilation gamma ray background is eliminated by a real-time subtraction method. Validation of the technical choice and optimization of the probe geometry were performed by preliminary measurements and Monte Carlo simulations based on the MCNP-4C code and an anthropomorphic brain phantom. The theoretical probe sensitivity was found to be 82 cps/muCi/ml with a gamma ray rejection efficiency of 99.6%. The expected minimum radiotracer detectable concentration for tumors labeled with 18 F-FET was 0.10 muCi/ml. When compared to the 0.29 muCi/ml average concentration in the bulk of the tumor, this result demonstrate the potential ability of the probe to define more accurately the extent of brain tumor resection

Physical Performance of an Intraoperative Beta Probe Dedicated to Glioma Radioguided Surgery

The precise delineation and excision of brain tumor extent allows to improve survival outcome and quality of life of surgically treated patients. In order to refine the resection of gliomas, we are developing a novel intraoperative probe specifically dedicated to the localization of residual tumor after the bulk has been excised. The probe, built around clear and plastic scintillating fibers, was designed to detect positrons emitted from radiolabeled brain tissue in order to discriminate more specifically neoplastic from normal tissues. The probe was also built to be directly coupled to the excision tool leading to simultaneous detection and removal of tumor. We report here performances of the first radio-isotopic configuration of the intraoperative probe which consists of a detection head composed of eight detection elements held around the excision tool in a closed packed annular arrangement. This head is coupled to an optic fiber bundle that exports the scintillating light to a multi-channel photomultiplier tube. The gamma ray background generated by the annihilation of beta+ in tissues is eliminated by a real-time subtraction method. The detector exhibits a beta sensitivity of 139 cps/kBq and a gamma ray rejection efficiency of 99.5%. The ability of the probe to detect residual lesions was evaluated with a realistic brain phantom representing the surgical cavity and the boundaries of the tumor. We showed that lesions as small as 5 mm in diameter can be detected for tumor to normal tissue uptake ratios of fluorinated tracers greater than 3.5. This ratio is achieved with radiopharmaceuticals like 18F-FET or 18F-choline. These promising results suggest that the features of our system are compatible with in situ localization of residual radiolabeled tumors.

HRRI: A high-resolution β− imager for biological applications

We have developed a high-resolution β− position detector which combines a thin scintillator sheet and an intensified CCD. This device has been designed for molecular biology purposes (“in situ” hybridization). Therefore, the absolute detection efficiency, S/N ratio and spatial resolution have been studied in particular. With the first version of our detector, we achieved an intrinsic resolution of 10 μm with a relative efficiency for 35S of 99% (i.e. 18% absolute efficiency). We now present results in which another scintillator and a new triggering system have been adopted. The main result is that the absolute efficiency has been improved (up to ≈ 60% for 35S) and the background influence has been significantly reduced. These improvements can be observed on the biological image displayed in this paper.