Vascular hydraulic conductivity imaging in cancers in vivo based on spatiotemporal ultrasound elastography

Vascular hydraulic conductivity ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi> <mml:mi>p</mml:mi></mml:msub> </mml:math> ) plays important roles in cancer metastasis, progression, and treatments. To date, there are a few noninvasive methods to image <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi> <mml:mi>p</mml:mi></mml:msub> </mml:math> in cancers, and these methods rely on several assumptions. Common assumptions include that vascular conductivity is dominant over interstitial conductivity inside the tumor and that interstitial effects in the background are dominant over interstitial effects inside the tumor, limiting their applicability to cancers with a narrow range of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi> <mml:mi>p</mml:mi></mml:msub> </mml:math> . In this article, we propose a new method to image a wide range of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi> <mml:mi>p</mml:mi></mml:msub> </mml:math> in cancers using ultrasound spatiotemporal elastography data, without the limitations of existing methods. The method is based on the knowledge of Young's modulus, Poisson's ratio, and volumetric strain. This method shows superior performance with respect to the previous methods in terms of percent-relative-error in simulation studies. In vivo experimental results in an orthotopic mouse model of breast cancer show that <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>L</mml:mi> <mml:mi>p</mml:mi></mml:msub> </mml:math> estimated by ultrasound imaging using the proposed method is highly correlated with histological CD31 data. The proposed imaging methods can thus provide clinically significant information noninvasively and cost-effectively.