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Optics Express

Optics Express

  • Editor: Andrew M. Weiner
  • Vol. 22, Iss. 2 — Jan. 27, 2014
  • pp: 1500–1511

Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo

Zhenyuan Yang, Jianhua Chen, Junjie Yao, Riqiang Lin, Jing Meng, Chengbo Liu, Jinhua Yang, Xiang Li, Lihong Wang, and Liang Song  »View Author Affiliations

Optics Express, Vol. 22, Issue 2, pp. 1500-1511 (2014)

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Many diseases involve either the formation of new blood vessels (e.g., tumor angiogenesis) or the damage of existing ones (e.g., diabetic retinopathy) at the microcirculation level. Optical-resolution photoacoustic microscopy (OR-PAM), capable of imaging microvessels in 3D in vivo down to individual capillaries using endogenous contrast, has the potential to reveal microvascular information critical to the diagnosis and staging of microcirculation-related diseases. In this study, we have developed a dedicated microvascular quantification (MQ) algorithm for OR-PAM to automatically quantify multiple microvascular morphological parameters in parallel, including the vessel diameter distribution, the microvessel density, the vascular tortuosity, and the fractal dimension. The algorithm has been tested on in vivo OR-PAM images of a healthy mouse, demonstrating high accuracy for microvascular segmentation and quantification. The developed MQ algorithm for OR-PAM may greatly facilitate quantitative imaging of tumor angiogenesis and many other microcirculation related diseases in vivo.

© 2014 Optical Society of America

OCIS Codes
(170.0180) Medical optics and biotechnology : Microscopy
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.5120) Medical optics and biotechnology : Photoacoustic imaging

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: October 28, 2013
Revised Manuscript: December 1, 2013
Manuscript Accepted: December 5, 2013
Published: January 15, 2014

Virtual Issues
Vol. 9, Iss. 3 Virtual Journal for Biomedical Optics

Zhenyuan Yang, Jianhua Chen, Junjie Yao, Riqiang Lin, Jing Meng, Chengbo Liu, Jinhua Yang, Xiang Li, Lihong Wang, and Liang Song, "Multi-parametric quantitative microvascular imaging with optical-resolution photoacoustic microscopy in vivo," Opt. Express 22, 1500-1511 (2014)

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  1. L. V. Wang, S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012). [CrossRef] [PubMed]
  2. R. Ma, S. Söntges, S. Shoham, V. Ntziachristos, D. Razansky, “Fast scanning coaxial optoacoustic microscopy,” Biomed. Opt. Express 3(7), 1724–1731 (2012). [CrossRef] [PubMed]
  3. K. Maslov, H. F. Zhang, S. Hu, L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett. 33(9), 929–931 (2008). [CrossRef] [PubMed]
  4. L. Song, K. Maslov, L. V. Wang, “Multifocal optical-resolution photoacoustic microscopy in vivo,” Opt. Lett. 36(7), 1236–1238 (2011). [CrossRef] [PubMed]
  5. P. Hajireza, W. Shi, R. Zemp, “Label-free in vivo GRIN-lens optical resolution photoacoustic micro-endoscopy,” Laser Phys. Lett. 10(5), 055603 (2013). [CrossRef]
  6. S. Hu, L. V. Wang, “Photoacoustic imaging and characterization of the microvasculature,” J. Biomed. Opt. 15(1), 011101 (2010). [CrossRef] [PubMed]
  7. S. S. Oladipupo, S. Hu, A. C. Santeford, J. Yao, J. R. Kovalski, R. V. Shohet, K. Maslov, L. V. Wang, J. M. Arbeit, “Conditional HIF-1 induction produces multistage neovascularization with stage-specific sensitivity to VEGFR inhibitors and myeloid cell independence,” Blood 117(15), 4142–4153 (2011). [CrossRef] [PubMed]
  8. S. Oladipupo, S. Hu, J. Kovalski, J. J. Yao, A. Santeford, R. E. Sohn, R. Shohet, K. Maslov, L. V. Wang, J. M. Arbeit, “VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting,” Proc. Natl. Acad. Sci. U. S. A. 108(32), 13264–13269 (2011). [CrossRef] [PubMed]
  9. J. Folkman, “Angiogenesis in cancer, vascular, rheumatoid and other disease,” Nat. Med. 1(1), 27–30 (1995). [CrossRef] [PubMed]
  10. J. Folkman, M. Bach, J. W. Rowe, F. Davidoff, P. Lambert, C. Hirsch, A. Goldberg, H. H. Hiatt, J. Glass, E. Henshaw, “Tumor angiogenesis: therapeutic implications,” N. Engl. J. Med. 285(21), 1182–1186 (1971). [CrossRef] [PubMed]
  11. J. W. Baish, R. K. Jain, “Cancer, angiogenesis and fractals,” Nat. Med. 4(9), 984 (1998). [CrossRef] [PubMed]
  12. R. K. Jain, “Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy,” Nat. Med. 7(9), 987–989 (2001). [CrossRef] [PubMed]
  13. B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009). [CrossRef] [PubMed]
  14. Y. Gazit, J. W. Baish, N. Safabakhsh, M. Leunig, L. T. Baxter, R. K. Jain, “Fractal characteristics of tumor vascular architecture during tumor growth and regression,” Microcirculation 4(4), 395–402 (1997). [CrossRef] [PubMed]
  15. L. Hlatky, P. Hahnfeldt, J. Folkman, “Clinical application of antiangiogenic therapy: Microvessel density, what it does and doesn’t tell us,” J. Natl. Cancer Inst. 94(12), 883–893 (2002). [CrossRef] [PubMed]
  16. E. Bullitt, D. L. Zeng, G. Gerig, S. Aylward, S. Joshi, J. K. Smith, W. L. Lin, M. G. Ewend, “Vessel tortuosity and brain tumor malignancy: A blinded study,” Acad. Radiol. 12(10), 1232–1240 (2005). [CrossRef] [PubMed]
  17. H. Harada, X. J. Xie, S. Itasaka, L. H. Zeng, Y. X. Zhu, A. Morinibu, K. Shinomiya, M. Hiraoka, “Diameter of tumor blood vessels is a good parameter to estimate HIF-1-active regions in solid tumors,” Biochem. Biophys. Res. Commun. 373(4), 533–538 (2008). [CrossRef] [PubMed]
  18. E. Bullitt, G. Gerig, S. M. Pizer, W. L. Lin, S. R. Aylward, “Measuring tortuosity of the intracerebral vasculature from MRA images,” IEEE Trans. Med. Imaging 22(9), 1163–1171 (2003). [CrossRef]
  19. A. F. Frangi, W. J. Niessen, K. L. Vincken, M. A. Viergever, “Multiscale vessel enhancement filtering,” Med. Image Comput. Comput. Assisted Intervention 1496, 130–137 (1998).
  20. C. Li, R. Huang, Z. Ding, J. Gatenby, D. N. Metaxas, J. C. Gore, “A level set method for image segmentation in the presence of intensity inhomogeneities with application to MRI,” IEEE Trans. Image Process. 20(7), 2007–2016 (2011). [CrossRef]
  21. J. Chen, R. Lin, H. Wang, J. Meng, H. Zheng, L. Song, “Blind-deconvolution optical-resolution photoacoustic microscopy in vivo,” Opt. Express 21(6), 7316–7327 (2013). [CrossRef] [PubMed]
  22. R. Fattal, D. Lischinski, M. Werman, “Gradient domain high dynamic range compression,” ACM Trans. Graphics 21, 249–256 (2002).
  23. R. Van Uitert, I. Bitter, “Subvoxel precise skeletons of volumetric data based on fast marching methods,” Med. Phys. 34(2), 627–638 (2007). [CrossRef] [PubMed]
  24. R. K. Jain, N. Safabakhsh, A. Sckell, Y. Chen, P. Jiang, L. Benjamin, F. Yuan, E. Keshet, “Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: role of vascular endothelial growth factor,” Proc. Natl. Acad. Sci. U. S. A. 95(18), 10820–10825 (1998). [CrossRef] [PubMed]
  25. E. Bullitt, D. Zeng, G. Gerig, S. Aylward, S. Joshi, J. K. Smith, W. Lin, M. G. Ewend, “Vessel tortuosity and brain tumor malignancy: a blinded study,” Acad. Radiol. 12(10), 1232–1240 (2005). [CrossRef] [PubMed]
  26. A. H. Parikh, J. K. Smith, M. G. Ewend, E. Bullitt, “Correlation of MR perfusion imaging and vessel tortuosity parameters in assessment of intracranial neoplasms,” Technol. Cancer Res. Treat. 3(6), 585–590 (2004). [PubMed]
  27. J. W. Baish, R. K. Jain, “Fractals and cancer,” Cancer Res. 60(14), 3683–3688 (2000). [PubMed]
  28. S. P. Lalley, D. Gatzouras, “Hausdorff and box dimensions of certain self-affine fractals,” Indiana Univ. Math. J. 41(2), 533–568 (1992). [CrossRef]

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