Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy

The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models.

[1]  Lihong V. Wang.  Multiscale photoacoustic microscopy and computed tomography. , 2009, Nature photonics.

[2]  Lihong V. Wang,et al.  Noninvasive mapping of the electrically stimulated mouse brain using photoacoustic microscopy , 2008, SPIE BiOS.

[3]  Fu-Shan Jaw,et al.  BOLD fMRI mapping of brain responses to nociceptive stimuli in rats under ketamine anesthesia. , 2008, Medical engineering & physics.

[4]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[5]  Lihong V. Wang,et al.  In vivo imaging of subcutaneous structures using functional photoacoustic microscopy , 2007, Nature Protocols.

[6]  Lihong V. Wang.  Photoacoustic imaging and spectroscopy , 2009 .

[7]  F. Jaw,et al.  A New Scenario for Negative Functional Magnetic Resonance Imaging Signals: Endogenous Neurotransmission , 2009, The Journal of Neuroscience.

[8]  D. Abbott,et al.  Functional imaging of intratumoral hypoxia. , 2004, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[9]  Lihong V. Wang,et al.  Noninvasive, in vivo imaging of blood-oxygenation dynamics within the mouse brain using photoacoustic microscopy. , 2009, Journal of biomedical optics.

[10]  Liang Song,et al.  High-speed dynamic 3D photoacoustic imaging of sentinel lymph node in a murine model using an ultrasound array. , 2009, Medical physics.

[11]  B. Rosen,et al.  Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation , 1998, Magnetic resonance in medicine.

[12]  Lihong V. Wang,et al.  Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels , 2007, Physics in medicine and biology.

[13]  D. Kleinfeld,et al.  Stimulus-Induced Changes in Blood Flow and 2-Deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex , 2008, The Journal of Neuroscience.

[14]  Fu-Shan Jaw,et al.  ISPMER: Integrated system for combined PET, MRI, and electrophysiological recording in somatosensory studies in rats , 2007 .

[15]  Rupeng Li,et al.  Refining the sensory and motor ratunculus of the rat upper extremity using fMRI and direct nerve stimulation , 2007, Magnetic resonance in medicine.

[16]  F. Hyder,et al.  Dynamic Magnetic Resonance Imaging of the Rat Brain during Forepaw Stimulation , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Oraevsky,et al.  Laser optoacoustic imaging system for detection of breast cancer. , 2009, Journal of biomedical optics.

[18]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Erwin Hondebrink,et al.  Photoacoustic determination of blood vessel diameter. , 2004, Physics in medicine and biology.

[20]  T. Duong,et al.  Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia , 2004, Magnetic resonance in medicine.

[21]  Lihong V. Wang,et al.  Tutorial on Photoacoustic Microscopy and Computed Tomography , 2008, IEEE Journal of Selected Topics in Quantum Electronics.

[22]  Lihong V. Wang,et al.  Improved in vivo photoacoustic microscopy based on a virtual-detector concept. , 2006, Optics letters.

[23]  H. Merkle,et al.  BOLD and CBV‐weighted functional magnetic resonance imaging of the rat somatosensory system , 2006, Magnetic resonance in medicine.

[24]  T. Floyd,et al.  Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels , 2009, Magnetic resonance in medicine.

[25]  M. Ingvar,et al.  Functional MRI at 4.7 Tesla of the Rat Brain during Electric Stimulation of Forepaw, Hindpaw, or Tail in Single- and Multislice Experiments , 2000, Experimental Neurology.

[26]  Lihong V. Wang,et al.  Photoacoustic imaging of lacZ gene expression in vivo. , 2007, Journal of biomedical optics.

[27]  David A. Boas,et al.  Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin , 2005, NeuroImage.

[28]  W. Abbott,et al.  Utility of transcutaneous oxygen tension measurements in peripheral arterial occlusive disease. , 1984, Journal of vascular surgery.

[29]  H. Merkle,et al.  Functional MRI of the rodent somatosensory pathway using multislice echo planar imaging , 2004, Magnetic resonance in medicine.

[30]  Lihong V. Wang,et al.  Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging , 2006, Nature Biotechnology.

[31]  Lihong V. Wang,et al.  Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain , 2003, Nature Biotechnology.

[32]  R. Frostig,et al.  Optical imaging of neuronal activity. , 1988, Physiological reviews.

[33]  Junjie Yao,et al.  Transverse flow measurement using photoacoustic Doppler bandwidth broadening: phantom and in vivo studies , 2010, BiOS.

[34]  G. Gratton,et al.  Dynamic brain imaging: Event-related optical signal (EROS) measures of the time course and localization of cognitive-related activity , 1998 .

[35]  Seong-Gi Kim,et al.  Simultaneous Blood Oxygenation Level-Dependent and Cerebral Blood Flow Functional Magnetic Resonance Imaging during Forepaw Stimulation in the Rat , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[36]  Lihong V. Wang,et al.  Biomedical Optics: Principles and Imaging , 2007 .

[37]  John C. Murphy,et al.  Local determination of hemoglobin concentration and degree of oxygenation in tissue by pulsed photoacoustic spectroscopy , 2000, BiOS.

[38]  J R Reichenbach,et al.  In vivo measurement of blood oxygen saturation using magnetic resonance imaging: A direct validation of the blood oxygen level‐dependent concept in functional brain imaging , 1997, Human brain mapping.

[39]  Lihong V. Wang,et al.  In vivo dark-field reflection-mode photoacoustic microscopy. , 2005, Optics letters.

[40]  Greg Zaharchuk,et al.  Quantitative hemodynamic studies in moyamoya disease: a review. , 2009, Neurosurgical focus.

[41]  T. Duong,et al.  Echo‐planar BOLD fMRI of mice on a narrow‐bore 9.4 T magnet , 2004, Magnetic resonance in medicine.

[42]  Joshua E. Motelow,et al.  Negative BOLD with large increases in neuronal activity. , 2008, Cerebral cortex.

[43]  David A Boas,et al.  Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation , 2003, Physics in medicine and biology.

[44]  Thomas A. Mustoe, MD, FACS,et al.  Oxygen in wound healing: More than a nutrient , 2001, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[45]  Dae-Shik Kim,et al.  Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  A. Dale,et al.  Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. , 2003, Optics letters.

[47]  D. Fraker,et al.  Tumor oxygenation status as a prognostic marker. , 2005, Cancer letters.