Gold-nanorod contrast-enhanced photoacoustic micro-imaging of focused-ultrasound induced blood-brain-barrier opening in a rat model.

In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ≈ 800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.

[1]  A. Ghose,et al.  A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. , 1999, Journal of combinatorial chemistry.

[2]  Natalia Vykhodtseva,et al.  MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. , 2005, Ultrasound in medicine & biology.

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

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

[5]  Jianjun Liu,et al.  SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells , 2010, Particle and Fibre Toxicology.

[6]  Erik C. Dreaden,et al.  Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. , 2008, Cancer letters.

[7]  Hong Ding,et al.  Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications , 2010, Nanotechnology.

[8]  Yi-Cheng Chen,et al.  DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. , 2006, Journal of the American Chemical Society.

[9]  Wei Wang,et al.  Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography , 2008, Proceedings of the IEEE.

[10]  Xinmai Yang,et al.  Nanoparticles for photoacoustic imaging. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[11]  Mustafa Sarimollaoglu,et al.  In vivo ultra‐fast photoacoustic flow cytometry of circulating human melanoma cells using near‐infrared high‐pulse rate lasers , 2011, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[12]  Younan Xia,et al.  Gold nanocages as contrast agents for photoacoustic imaging. , 2011, Contrast media & molecular imaging.

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

[14]  H. Winn,et al.  High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo. , 2002, Ultrasound in medicine & biology.

[15]  Jer-Junn Luh,et al.  In vivo photoacoustic micro-imaging of microvascular changes for Achilles tendon injury on a mouse model , 2011, Biomedical optics express.

[16]  Steen J. Madsen,et al.  Photothermal ablation of malignant brain tumors by nanoparticle loaded macrophages , 2011, BiOS.

[17]  F. Jolesz,et al.  Current status and future potential of MRI‐guided focused ultrasound surgery , 2008, Journal of magnetic resonance imaging : JMRI.

[18]  F A Jolesz,et al.  Non-invasive opening of BBB by focused ultrasound. , 2003, Acta neurochirurgica. Supplement.

[19]  Lihong V. Wang,et al.  In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature. , 2009, Journal of biomedical optics.

[20]  G. Farhat,et al.  Diagnostic ultrasound Imaging : Inside out , 2004 .

[21]  D D Allen,et al.  Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier , 2002, Drug development and industrial pharmacy.

[22]  Po-Chun Chu,et al.  Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage , 2009, Journal of magnetic resonance imaging : JMRI.

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

[24]  A. Perretti,et al.  Diagnostic ultrasound imaging. , 1990, Rays.

[25]  Chin-Teng Lin,et al.  Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy , 2010, NeuroImage.

[26]  Natalia Vykhodtseva,et al.  Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI‐guided focused ultrasound , 2007, International journal of cancer.

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

[28]  K. Hynynen,et al.  Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. , 2001, Radiology.

[29]  Ton G van Leeuwen,et al.  Oxygen saturation-dependent absorption and scattering of blood. , 2004, Physical review letters.

[30]  S. Emelianov,et al.  Silica-coated gold nanorods as photoacoustic signal nanoamplifiers. , 2011, Nano letters.

[31]  C. R. Chris Wang,et al.  Gold Nanorods: Electrochemical Synthesis and Optical Properties , 1997 .

[32]  K. Hynynen,et al.  Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models , 2008, PloS one.

[33]  A. Marmarou,et al.  Brain Edema XII , 2003, Acta Neurochirurgica Supplements.

[34]  Vasilis Ntziachristos,et al.  Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging , 2010, Particle and Fibre Toxicology.

[35]  Ferenc A. Jolesz,et al.  Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications , 2005, NeuroImage.

[36]  Roger E. Price,et al.  Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model , 2009, BiOS.