Tiran Elodie, Ferrier Jérémy, Deffieux Thomas, Gennisson Jean-Luc, Pezet Sophie, Lenkei Zsolt, Tanter Mickaël
INSERM U979, Paris, France; Institut Langevin, CNRS UMR 7587, Paris, France; ESPCI Paris, Paris, France; PSL Research University, Paris, France.
ESPCI Paris, Paris, France; PSL Research University, Paris, France; Brain Plasticity Unit, CNRS UMR 8249, Paris, France.
Ultrasound Med Biol. 2017 Aug;43(8):1679-1689. doi: 10.1016/j.ultrasmedbio.2017.03.011. Epub 2017 May 4.
Functional ultrasound (fUS) imaging by ultrasensitive Doppler detection of blood volume was previously reported to measure adult rat brain activation and functional connectivity with unmatched spatiotemporal sampling (100 μm, 1 ms), but skull-induced attenuation of ultrasonic waves imposed skull surgery or contrast agent use. Also, fUS feasibility remains to be validated in mice, a major pre-clinical model organism. In the study described here, we performed full-depth ultrasensitive Doppler imaging and 3-D Doppler tomography of the entire mouse brain under anesthesia, non-invasively through the intact skull and skin, without contrast agents. Similar results were obtained in anesthetized young rats up to postnatal day 35, thus enabling longitudinal studies on postnatal brain development. Using a newly developed ultralight ultrasonic probe and an optimized ultrasonic sequence, we also performed minimally invasive full-transcranial fUS imaging of brain vasculature and whisker stimulation-induced barrel cortex activation in awake and freely moving mice, validating transcranial fUS for brain imaging, without anesthesia-induced bias, for behavioral studies.
功能超声（fUS）成像通过超灵敏多普勒检测血容量，此前有报道称其可测量成年大鼠脑激活和功能连接，具有不匹配的时空采样（100μm，1ms），但颅骨引起的超声波衰减需要进行颅骨手术或使用造影剂。此外，fUS在小鼠（一种主要的临床前模式生物）中的可行性仍有待验证。在本文所述的研究中，我们在麻醉状态下对整个小鼠脑进行了全深度超灵敏多普勒成像和三维多普勒断层扫描，无需使用造影剂，通过完整的颅骨和皮肤进行非侵入性操作。在出生后35天内的麻醉幼鼠中也获得了类似结果，从而能够对出生后脑发育进行纵向研究。使用新开发的超轻型超声探头和优化的超声序列，我们还对清醒且自由活动的小鼠进行了微创全颅fUS脑脉管系统成像以及触须刺激诱导的桶状皮层激活成像，验证了用于脑成像的经颅fUS在行为研究中不存在麻醉诱导偏差。
