Understanding brain disorders, the neural processes implicated in cognitive functions and their alterations in neurodegenerative pathologies, or testing new therapies for these diseases would benefit greatly from combined use of an increasing number of rodent models and neuroimaging methods specifically adapted to the rodent brain. Besides magnetic resonance (MR) imaging and functional MR, positron-emission tomography (PET) remains a unique methodology to study in vivo brain processes. However, current high spatialresolution tomographs suffer from several technical limitations such as high cost, low sensitivity, and the need of restraining the animal during image acquisition. We have developed a  ؉ -sensitive high temporal-resolution system that overcomes these problems and allows the in vivo quantification of cerebral biochemical processes in rodents. This -MICROPROBE is an in situ technique involving the insertion of a fine probe into brain tissue in a way very similar to that used for microdialysis and cell electrode recordings. In this respect, it provides information on molecular interactions and pathways, which is complementary to that produced by these technologies as well as other modalities such as MR or fluorescence imaging. This study describes two experiments that provide a proof of concept to substantiate the potential of this technique and demonstrate the feasibility of quantifying brain activation or metabolic depression in individual living rats with 2-[ 18 F]fluoro-2-deoxy-D-glucose and standard compartmental modeling techniques. Furthermore, it was possible to identify correctly the origin of variations in glucose consumption at the hexokinase level, which demonstrate the strength of the method and its adequacy for in vivo quantitative metabolic studies in small animals.A lterations in local cerebral metabolic rate of glucose (lCMRglc) have been reported in several human brain conditions such as psychiatric disorders or neurodegenerative diseases. Understanding the cellular mechanisms involved in these diseases and the development of new therapeutic strategies will advance more rapidly through the use of animal models. The quantitation of metabolic rates in the rodent brain was achieved initially by using the 2-deoxy-D-[ 14 C]glucose autoradiographic method (1). Although efficient, this technique requires the sacrifice of several animals to obtain each time point and thus can provide only ex vivo, averaged kinetic constants calculated from values obtained from various animals. As an alternative, positron-emission tomography (PET), an imaging technology designed to use compounds labeled with positron-emitting radioisotopes to image and measure biochemical processes in vivo, has been adapted to use in small animals. The implementation of several high spatial-resolution PET scanners within the last several years (2-9) has enabled the adaptation of the 2-deoxy-D-[ 14 C]glucose method to in vivo imaging of small animals by using 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) as a tracer. However, such PE...
The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for (18)F was 1.1 cps kBq(-1) ml(-1) for the small head and 3.4 cps kBq(-1) ml(-1) for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The gamma-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.
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