X-ray phase-contrast CO2 angiography for sub-10 μm vessel imaging

X-ray in-line phase contrast has recently been combined with CO(2) angiography for high-resolution small-animal vascular imaging at low radiation dose. In this paper we further investigate the potential and limitations of this method and demonstrate observation of vessels down to 8 μm in diameter, considerably smaller than the 60 μm previously reported. Our in-line phase-contrast imaging system is based on a liquid-metal-jet-anode x-ray source and utilizes free-space propagation to convert phase shifts, caused by refractive index variations, into intensity differences. Enhanced refractive index variations are obtained through injection of CO(2) gas into the vascular system to replace the blood. We show rat-kidney images with blood vessels down to 27 μm in diameter and mouse-ear images with vessels down to 8 μm. The minimum size of observable blood vessels is found to be limited by the penetration of gas into the vascular system and the signal-to-noise ratio, i.e. the allowed dose. The diameters of vessels being gas-filled depend on the gas pressure and follow a simple model based on surface tension. A theoretical signal-to-noise comparison shows that this method requires 1000 times less radiation dose than conventional iodine-based absorption contrast for observing sub-50 μm vessels.

[1]  Irvin F. Hawkins,et al.  Carbon Dioxide Angiography: Principles, Techniques, and Practices , 2007 .

[2]  E. Kvašňák,et al.  Temperature dependence of blood surface tension. , 2007, Physiological research.

[3]  Richard J. Fitzgerald,et al.  Phase‐Sensitive X‐Ray Imaging , 2000 .

[4]  J. H. Hubbell,et al.  Tables of X-Ray Mass Attenuation Coefficients and Mass Energy-Absorption Coefficients 1 keV to 20 MeV for Elements Z = 1 to 92 and 48 Additional Substances of Dosimetric Interest , 1995 .

[5]  Benjamin J Vakoc,et al.  Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging , 2009, Nature Medicine.

[6]  Anna Burvall,et al.  Phase Retrieval in X-ray Phase-contrast Imaging Suitable for Tomography , 2022 .

[7]  O. Bunk,et al.  Phase retrieval and differential phase-contrast imaging with low-brilliance X-ray sources , 2006 .

[8]  H M Hertz,et al.  X-ray phase contrast for CO2 microangiography , 2012, Physics in medicine and biology.

[9]  B. Funaki Carbon dioxide angiography. , 2008, Seminars in interventional radiology.

[10]  P. Choyke,et al.  Imaging of angiogenesis: from microscope to clinic , 2003, Nature Medicine.

[11]  Harrison H. Barrett,et al.  Foundations of Image Science , 2003, J. Electronic Imaging.

[12]  D. Mattson,et al.  Comparison of arterial blood pressure in different strains of mice. , 2001, American journal of hypertension.

[13]  Zoltan Derdak,et al.  Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue , 2008, Physics in medicine and biology.

[14]  G. Johnson,et al.  In vivo small-animal imaging using micro-CT and digital subtraction angiography , 2008, Physics in medicine and biology.

[15]  A. Momose Recent Advances in X-ray Phase Imaging , 2005 .

[16]  H M Hertz,et al.  A 24 keV liquid-metal-jet x-ray source for biomedical applications. , 2011, The Review of scientific instruments.

[17]  Olivier Stéphan,et al.  Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles. , 2011, Journal of biomedical optics.

[18]  R. Lewis,et al.  Medical phase contrast x-ray imaging: current status and future prospects. , 2004, Physics in medicine and biology.

[19]  S. Wilkins,et al.  Phase-contrast imaging using polychromatic hard X-rays , 1996, Nature.

[20]  T Takeda,et al.  Blood vessels: depiction at phase-contrast X-ray imaging without contrast agents in the mouse and rat-feasibility study. , 2000, Radiology.

[21]  Hans M. Hertz,et al.  Liquid-metal-jet anode electron-impact x-ray source , 2003 .

[22]  G. Nikiforidis,et al.  In vivo small animal imaging: current status and future prospects. , 2010, Medical physics.

[23]  Gyula Faigel,et al.  X-Ray Holography , 1999 .