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

Abstract

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta(+) radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta(+) sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

MicroPET Outperforms Beta-Microprobes in Determining Neuroreceptor Availability under Pharmacological Restriction for Cold Mass Occupancy

“…A major theoretical advantage of beta-microprobes includes their high temporal resolution to capture the peak of the time-activity curve. However, during time-activity curve pre-processing and in accordance with literature (Pain et al, 2002 ; Zimmer et al, 2002 ; Ginovart et al, 2004 ; Moulin-Sallanon et al, 2005 ; Märk et al, 2013 ; Balasse et al, 2014 ), we were forced to resample the curves to larger time frames due to high signal noise associated with beta-microprobe recordings. We resampled the data to μPET frames: 2 × 10 s, 3 × 20 s, 3 × 30 s, 3 × 60 s, 3 × 150 s, 9 × 300 s. In this way, the beneficial theoretical temporal resolution of 1 s was lost.…”

“…μPET offers a non-invasive alternative, by visualizing radiotracer distribution in the entire brain and enabling longitudinal studies through intra-animal comparisons. Although, incapable of providing information on spatial tracer distribution (Märk et al, 2013 ), beta-microprobes are suggested as a cost-effective alternative to μPET. They possess a higher temporal resolution (Zimmer et al, 2002 ) to estimate the peak of a time-activity curve, higher sensitivity (Pain et al, 2008 ), lower partial volume effect (Ginovart et al, 2004 ), and easier coupling with other in vivo techniques (Desbrée et al, 2004 ).…”

PIXSIC: A Wireless Intracerebral Radiosensitive Probe in Freely Moving Rats

“…The corresponding TACs were normalized for radioactive decay, and the detection sensitivity of each pixel was measured as described elsewhere. 6 The specific binding ratio (B/F) was calculated as described elsewhere 10 with the following equation:…”

“…We have previously shown its ability to measure TACs in anesthetized rats. 6 Here we demonstrate that the probe can provide kinetics measurements of [ 11 C]raclopride, a well-known dopaminergic D 2 receptor tracer, in freely moving rats using chronically implanted wireless probes.…”

“…The probe design is light, compact, energetically autonomous, and based on a wireless radiofrequency data exchange that empowers free behavioral activity during acquisition. 6…”