PIXSIC: A Pixellated Beta-Microprobe for Kinetic Measurements of Radiotracers on Awake and Freely Moving Small Animals

Abstract

We present a design study of PIXSIC, a new B^+ radiosensitive microprobe implantable in rodent brain dedicated to in vivo and autonomous measurements of local time activitycurves of beta radiotracers in a small (a few mm^3 ) volume of brain tissue. This project follows the initial β microprobe previously developed at IMNC, which has been validated in several neurobiological experiments. This first prototype has been extensively used on anesthetized animals, but presents some critical limits for utilization on awake and freely moving animals. Consequently, we propose to develop a wireless setup that can be worn by an animal without constraints upon its movements. To that aim, we have chosen a Silicon-based detector, highly β sensitive, which allows for the development of a compact pixellated probe (typically 600 X 200 X1000 μm^3), read out with miniaturized wireless electronics. Using Monte-Carlo simulations, we show that high resistive Silicon pixels are appropriate for this purpose, assuming that the pixel dimensions are adapted to our specific signals. More precisely, a tradeoff has to be found between the sensitivity to β^+ particles and to the 511 keV γ background resulting from annihilations of β^+ with electrons. We demonstrate that pixels with maximized surface and minimized thickness can lead to an optimization of their β^+ sensitivity with a relative transparency to the annihilation backgroun

MAPSSIC, a Novel CMOS Intracerebral Positrons Probe for Deep Brain Imaging in Awake and Freely Moving Rats: A Monte Carlo Study

“…Beyond electronic and physical testing of the sensor, the future probe developments will focus of the integration of the sensor into a robust and autonomous system. The probe also shall be adapted to be used with stereotaxic surgical tools and we plan to ensure biocompatibility by covering the sensor with a layer parylene C polymer as previously done for PIXSIC [9]. The first in vivo testings will aim to validate the surgical implantation procedure, the biocompatibility and the detection performances on anesthetized animals.…”

“…The first probes used a scintillation detector coupled to an external photomultiplier tube [7,8], then extended to fully autonomous systems thanks to reverse-biased, high-resistivity silicon diodes and wireless communication [9].…”

A wireless beta-microprobe based on pixelated silicon forin vivobrain studies in freely moving rats

“…The sensitivity values determined in these beaker experiments were validated against GATE Monte Carlo simulations. GATE (Jan et al 2004(Jan et al , 2011 was already used for the conception of the sensor and initial sensitivity considerations (Godart et al 2010). The pixels were simulated as cubic sensitive volumes embedded in the silicon sensor.…”

“…Monte Carlo simulations for the beta-microprobe using a realistic voxelized rat brain and whole-body phantoms have evidenced that the background contribution is less than a few per cents for a probe implanted in the brain, even for a tracer such as [ 18 F]-FDG, which is distributed in every organ (Pain et al 2008). Initial simulations had helped to optimise the design of PIXSIC regarding its pixel dimensions in terms of beta + sensitivity versus relative transparency to the gamma background (Godart et al 2010). However, the 511 keV gammas and the related Compton electrons still lead to a substantial noise background added to the signal of the silicon detector in the beaker experiment geometry (15-25% depending on the threshold).…”

“…Despite these limitations, the beta-microprobe was validated in various different neurobiological studies especially in the neuropharmacological community for competitive binding studies (Zimmer et al 2002a, 2002b, Millet et al 2004, Desbrée et al 2008, but also as an alternative for arterial input function measurement (Pain et al 2004). However, as both the RatCAP and the beta-microprobe approaches still suffer from some important conceptual constraints for the neurobiological investigation of awake and freely moving animals, the pixelated intracerebral probe (PIXSIC) proposes a novel strategy for in vivo recording of the local time-activity curves of isotope-labelled molecules (Godart et al 2010). It relies on a submillimetric pixelated probe based on a reverse-biased, high-resistivity silicon diode for beta + radiotracer detection.…”