Wearable 3-D Photoacoustic Tomography for Functional Brain Imaging in Behaving Rats

Understanding the relationship between brain function and behavior remains a major challenge in neuroscience. Photoacoustic tomography (PAT) is an emerging technique that allows for noninvasive in vivo brain imaging at micrometer-millisecond spatiotemporal resolution. In this article, a novel, miniaturized 3D wearable PAT (3D-wPAT) technique is described for brain imaging in behaving rats. 3D-wPAT has three layers of fully functional acoustic transducer arrays. Phantom imaging experiments revealed that the in-plane X-Y spatial resolutions were ~200 μm for each acoustic detection layer. The functional imaging capacity of 3D-wPAT was demonstrated by mapping the cerebral oxygen saturation via multi-wavelength irradiation in behaving hyperoxic rats. In addition, we demonstrated that 3D-wPAT could be used for monitoring sensory stimulus-evoked responses in behaving rats by measuring hemodynamic responses in the primary visual cortex during visual stimulation. Together, these results show the potential of 3D-wPAT for brain study in behaving rodents.

[1]  Axel Nimmerjahn,et al.  Functional imaging in freely moving animals , 2012, Current Opinion in Neurobiology.

[2]  Quing Zhu,et al.  A real-time photoacoustic tomography system for small animals. , 2009, Optics express.

[3]  Tao Zhang,et al.  Noninvasive real time tomographic imaging of epileptic foci and networks , 2013, NeuroImage.

[4]  Hao Zhang,et al.  Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy , 2007 .

[5]  Tao Zhang,et al.  Noninvasive High-Speed Photoacoustic Tomography of Cerebral Hemodynamics in Awake-Moving Rats , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  R A Kruger,et al.  Thermoacoustic computed tomography--technical considerations. , 1999, Medical physics.

[7]  Naoshige Uchida,et al.  A wireless multi-channel neural amplifier for freely moving animals , 2011, Nature Neuroscience.

[8]  B. Slotnick,et al.  A stereotaxic atlas of the rat olfactory system , 1980, Brain Research Bulletin.

[9]  L. Pellegrino,et al.  stereotaxic atlas of the rat brain , 1967 .

[10]  Bola Ayeni,et al.  Concepts and Techniques in Urban Analysis , 1979 .

[11]  Huabei Jiang,et al.  4-D Photoacoustic Tomography , 2013, Scientific Reports.

[12]  Tao Zhang,et al.  Towards real-time detection of seizures in awake rats with GPU-accelerated diffuse optical tomography , 2015, Journal of Neuroscience Methods.

[13]  Maik C. Stüttgen,et al.  The Head-fixed Behaving Rat—Procedures and Pitfalls , 2010, Somatosensory & motor research.

[14]  Hua-bei Jiang,et al.  Single Element-Based Dual Focused Photoacoustic Microscopy , 2015 .

[15]  C. Ferris,et al.  Imaging brain activity in conscious animals using functional MRI , 1998, Journal of Neuroscience Methods.

[16]  Jin Young Kim,et al.  Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing MEMS scanner , 2015, Scientific Reports.

[17]  Huabei Jiang,et al.  Photoacoustic tomography system for noninvasive real-time three-dimensional imaging of epilepsy , 2012, Biomedical optics express.

[18]  Lei Xi,et al.  Photoacoustic computed microscopy , 2014, Scientific Reports.

[19]  D. Tank,et al.  Intracellular dynamics of hippocampal place cells during virtual navigation , 2009, Nature.

[20]  Jonathan W. Peirce,et al.  PsychoPy—Psychophysics software in Python , 2007, Journal of Neuroscience Methods.

[21]  Paul M. Matthews,et al.  Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and α-chloralose anesthesia , 2005, NeuroImage.

[22]  David S. Greenberg,et al.  Visually evoked activity in cortical cells imaged in freely moving animals , 2009, Proceedings of the National Academy of Sciences.

[23]  H. Azhari Basics of Biomedical Ultrasound for Engineers , 2010 .

[24]  D.N. Stephens,et al.  Miniaturized circular array [for intravascular ultrasound] , 2000, 2000 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.00CH37121).

[25]  F. Foster,et al.  A history of medical and biological imaging with polyvinylidene fluoride (PVDF) transducers , 2000, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[26]  Laurie D. Burns,et al.  High-speed, miniaturized fluorescence microscopy in freely moving mice , 2008, Nature Methods.

[27]  E. Miller,et al.  All My Circuits: Using Multiple Electrodes to Understand Functioning Neural Networks , 2008, Neuron.

[28]  Lihong V. Wang,et al.  Photoacoustic tomography: principles and advances. , 2016, Electromagnetic waves.

[29]  R. Gruetter,et al.  Neuroglial Metabolism in the Awake Rat Brain: CO2 Fixation Increases with Brain Activity , 2004, The Journal of Neuroscience.

[30]  J. Disterhoft,et al.  Light Stimulus Frequency Dependence of Activity in the Rat Visual System as Studied With High-Resolution BOLD fMRI , 2006 .

[31]  Don H. Johnson,et al.  Array Signal Processing: Concepts and Techniques , 1993 .

[32]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[33]  A. Dale,et al.  Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal , 2010, Proceedings of the National Academy of Sciences.

[34]  Huabei Jiang,et al.  Wearable scanning photoacoustic brain imaging in behaving rats , 2016, Journal of biophotonics.

[35]  J. Pratte,et al.  Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph , 2011, Nature Methods.

[36]  G. Phillips,et al.  Principles and Advances , 1970, Nature.

[37]  P. Beard Biomedical photoacoustic imaging , 2011, Interface Focus.

[38]  I. Kanno,et al.  Anesthesia and the Quantitative Evaluation of Neurovascular Coupling , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[39]  Lihong V. Wang,et al.  Technical considerations in quantitative blood oxygenation measurement using photoacoustic microscopy in vivo , 2006, SPIE BiOS.

[40]  Haim Azhari,et al.  Basics of Biomedical Ultrasound for Engineers: Azhari/Ultrasound , 2010 .