Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.

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Abstract. Optical properties of fresh and frozen tissues of rat heart, kidney, brain, liver, and muscle were measured in the 450-to 700-nm range. The total reflectance and transmittance were measured using a well-calibrated integral sphere set-up. Absorption coefficient μ a and reduced scattering coefficient μ 0 s were derived from the experimental measurements using the inverse adding doubling technique. The influence of cryogenic processing on optical properties was studied. Interindividual and intraindividual variations were assessed. These new data aim at filling the lack of validated optical properties in the visible range especially in the blue-green region of particular interest for fluorescence and optogenetics preclinical studies. Furthermore, we provide a unique comparison of the optical properties of different organs obtained using the same measurement set-up for fresh and frozen tissues as well as an estimate of the intraindividual and interindividual variability.

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Abstract. Rodent brain is studied to understand the basics of brain function. The activity of cell populations and networks is commonly recorded in vivo with wide-field optical imaging techniques such as intrinsic optical imaging, fluorescence imaging, or laser speckle imaging. These techniques were recently adapted to unrestrained mice carrying transcranial windows. Furthermore, optogenetics studies would benefit from optical stimulation through the skull without implanting an optical fiber, especially for longitudinal studies. In this context, the knowledge of bone optical properties is requested to improve the quantitation of the depth and volume of imaged or stimulated tissues. Here, we provide experimental measurements of absorption and reduced scattering coefficients of freshly excised mice skull for wavelengths between 455 and 705 nm. Absorption coefficients from 6 to 8 months mice skull samples range between 1.67 AE 0.28 mm −1 at 455 nm and 0.47 AE 0.07 mm −1 at 705 nm, whereas reduced scattering coefficients were in the range of 2.79 AE 0.26 mm −1 at 455 nm up to 2.29 AE 0.12 mm −1 at 705 nm. In comparison, measurements carried out on 4 to 5 weeks mice showed similar spectral profiles but smaller absorption and reduced scattering coefficients by a factor of about 2 and 1.5, respectively. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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...

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The Geant4 Application for Emission Tomography (GATE) is an advanced open-source software dedicated to Monte-Carlo (MC) simulations in medical imaging involving photon transportation (Positron emission tomography, single photon emission computed tomography, computed tomography) and in particle therapy. In this work, we extend the GATE to support simulations of optical imaging, such as bioluminescence or fluorescence imaging, and validate it against the MC for multilayered media standard simulation tool for biomedical optics in simple geometries. A full simulation set-up for molecular optical imaging (bioluminescence and fluorescence) is implemented in GATE, and images of the light distribution emitted from a phantom demonstrate the relevance of using GATE for optical imaging simulations.