Abstract
.Solid tumors are typically supplied nutrients by a network of irregular blood vessels. By targeting these vascular networks, it might be possible to hinder cancer growth and metastasis. Vascular disrupting agents induce intertumoral hemorrhaging, making photoacoustic (PA) imaging well positioned to detect bleeding due to its sensitivity to hemoglobin and its various states. We introduce a fractal-based numerical model of intertumoral hemorrhaging to simulate the PA signals from disrupted tumor blood vessels. The fractal model uses bifurcated cylinders to represent vascular trees. To mimic bleeding from blood vessels, hemoglobin diffusion from microvessels was simulated. In the simulations, the PA signals were detected by a linear array transducer (30 MHz center frequency) of four different vascular trees. The power spectrum of each beamformed PA signal was computed and fitted to a straight line within the bandwidth of the receiving transducer. The spectral slope and midband fit (MBF) based on the fit decreased by and 2.12 dB, respectively, 1 h post bleeding, while the -intercept increased by 1.21 dB. The results suggest that spectral PA analysis can be used to measure changes in the concentration and spatial distribution of hemoglobin in tissue without the need to resolve individual vessels. The simulations support the feasibility of using PA imaging and spectral analysis in cancer treatment monitoring by detecting microvessel disruption.
Highlights
A class of cancer therapeutic drugs targeting blood vessels, known as vascular disrupting agents (VDAs), induces intertumoral hemorrhage.[1]
The drugs are activated at the location of the tumor to disrupt endothelial and/or intravascular cells, which results in hemoglobin leakage into the surrounding tissues.[1,2,3]
We modeled hemorrhaging of tumor blood vessels post VDA to assess the potential of PA RF analysis for monitoring this process
Summary
A class of cancer therapeutic drugs targeting blood vessels, known as vascular disrupting agents (VDAs), induces intertumoral hemorrhage.[1]. Ultrasound frequency analysis of the PA signals has been shown to detect changes smaller than the system resolution,[11,12,13] and this analysis may permit assessment of microvessel bleeding. Simulations were undertaken to model the generation of PA signals from vascular trees This would allow us to examine the feasibility of detecting the effects of VDAs on the PA signals from tissue. We perform simulations that can provide insights into PA spectral analysis parameters to assess the effectiveness of cancer therapy. This could potentially improve the therapeutic outcome and reduce the tumor reoccurrence rate noninvasively and without the need of contrast agents, to provide timely feedback on the effectiveness of the drug/therapeutic approach
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