Rainer Siebert

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

Optical phantoms with variable properties and geometries for diffuse and fluorescence optical spectroscopy

Abstract. Growing interest in optical instruments for biomedical applications has increased the use of optically calibrated phantoms. Often associated with tissue modeling, phantoms allow the characterization of optical devices for clinical purposes. Fluorescent gel phantoms have been developed, mimicking optical properties of healthy and tumorous brain tissues. Specific geometries of dedicated molds offer multiple-layer phantoms with variable thicknesses and monolayer phantoms with cylindrical inclusions at various depths and diameters. Organic chromophores are added to allow fluorescence spectroscopy. These phantoms are designed to be used with 405 nm as the excitation wavelength. This wavelength is then adapted to excite large endogenous molecules. The benefits of these phantoms in understanding fluorescence tissue analysis are then demonstrated. In particular, detectability aspects as a function of geometrical and optical parameters are presented and discussed.

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.

The Tumor Resection Camera (TReCam), a multipixel imaging probe for radio-guided surgery

Using the POCI camera, we recently demonstrated the clinical impact of per-operative imaging techniques thanks to a successful clinical trial. Taking advantage of both the POCI experience and the availability of new pixelated detectors, we are developing a new hand held gamma camera TReCam (tumor resection camera). The first prototype offers a 49 × 49 mm2 field of view. It combines a 15 mm thick parallel hole collimator (with an efficiency of 5.10-4 and a spatial resolution of 7.5 mm at 50 mm), a 5 mm thick LaBr3:Ce crystal optically coupled to a Hamamatsu H9500 flat panel multianode photomultiplier tube (MAPMT). The read-out of the MAPMT is ensured thanks to a new specific integrated circuit called HARDROC2 (hadronic Rpc detector readout chip). This chip was initially designed for the digital hadronic calorimeter (DHCAL) of the linear collider. The TReCam presents an intrinsic spatial resolution of 0.65 mm (FWHM) and an energetic resolution of 17.4% at 122 keV. The new read-out by the HARDROC2 chip is currently being implemented and using this new device energetic resolution is expected to be better.

Dynamics of single-stranded DNA migration in denaturing polyacrylamide slab-gel electrophoresis.

We describe an original apparatus for the study of the dynamics of single stranded DNA migration. Four detectors based on laser‐induced fluorescence (LIF) are equidistantly placed on one migration lane, allowing repeated measurements of the same DNA band at different positions along migration. This article presents the characteristics and performances of this system and focuses on the data analysis, showing how the multiple detection scheme enables the study of band broadening and band resolution during a migration run. Our results suggest the existence of anomalous (nonthermal) diffusion of DNA molecules during the electrophoretic process.

Spectral and lifetime domain measurements of rat brain tumours

During glioblastoma surgery, delineation of the brain tumour margins remains difficult especially since infiltrated and normal tissues have the same visual appearance. This problematic constitutes our research interest. We developed a fibre-optical fluorescence probe for spectroscopic and time domain measurements. First measurements of endogenous tissue fluorescence were performed on fresh and fixed rat tumour brain slices. Spectral characteristics, fluorescence redox ratios and fluorescence lifetime measurements were analysed. Fluorescence information collected from both, lifetime and spectroscopic experiments, appeared promising for tumour tissue discrimination. Two photon measurements were performed on the same fixed tissue. Different wavelengths are used to acquire two-photon excitation-fluorescence of tumorous and healthy sites.

Development of an autofluorescent probe designed to help brain tumor removal: study on an animal model

The complete resection of the brain tumour is crucial to the patient life quality and prognosis. An autofluorescence probe aiming at helping the surgeon to improve the completeness of the removal is being developed. Autofluorescence spectroscopy is a promising approach to define whether the tissue is cancerous or not. First ex vivo measurements have been realised on an animal model. After tumorous cell injection in rat brain, autofluorescence intensity is revealed from the extracted brain. These autofluorescence data are compared to results from a histological analysis of same brains. First indicators are identified that may have the ability to differentiate tumorous and healthy tissues.

Designing the scintillation module of a pixelated mini gamma camera: The spatial spreading behaviour of light

Designing the scintillation module of a mini gamma camera requests good understanding of how the scintillation light signal spreads within the crystal and how photons are finally collected on the PMT. For a given scintillation process, the key parameters are the geometry of the crystal, its optical coating and the interface between the crystal and the PMT. In order to optimize the design of our gamma camera TReCam, we studied the shape of the spatial distribution of the scintillation light for different values and combinations of these key parameters. Our approach was to produce computer simulations, for which the optical simulation transport software DETECT2000 was used. Three major parameters were investigated: optical coatings for the crystal (aluminum, Teflon, corner cube retro-reflectors), the thickness of the crystal (ranging from 1 mm up to 5 mm) and the interfaces (air, optical grease). In addition to the FWHM of the light spot distribution, specific figures of merit were implemented to further characterize photon spreading. In order to evaluate the influence of these parameters on the imaging performances of the TReCam, the whole scintillation module (including the PMT) was also simulated with GATE v4.0.0 based on GEANT 4.9.1.p02. It appears that the best configuration is a 5 mm thick LaBr3:Ce crystal plate covered on the top with Teflon optical coating coupled optically with a PMT.

Post-capillary laser-induced fluorescence detection without sheath-flow

The sensitivity of laser-induced fluorescence detection in capillary electrophoresis is generally limited by noise due to scattering of the excitation beam on the capillary walls. The highest sensitivities have been obtained with post-capillary detection in a sheath-flow cuvette. In this paper, we report a new method for post-capillary detection, avoiding the hydrodynamic buffer flow at the capillary outlet. In our detection scheme, the analytes coming out of the individual capillaries are kept well separated from their neighbours in the outlet detection chamber because of an adequate electric field surrounding the capillary extremities.