Characterization of Anti-Angiogenic Chemo-Sensitization via Longitudinal Ultrasound Localization Microscopy in Colorectal Carcinoma Tumor Xenografts

Abstract

Super-resolution ultrasound localization microscopy (ULM) has unprecedented vascular resolution at clinically relevant imaging penetration depths. This technology can potentially screen for the transient microvascular changes that are thought to be critical to the synergistic effect(s) of combined chemotherapy-antiangiogenic agent regimens for cancer. Methods: In this paper, we apply this technology to a highthroughput colorectal carcinoma xenograft model treated with either the antiangiogenic agent sorafenib, FOLFOX-6 chemotherapy, a combination of the two treatments, or vehicle control. Results: Longitudinal ULM demonstrated morphological changes in the antiangiogenic treated cohorts, and evidence of vascular disruption caused by chemotherapy. Gold-standard histological measurements revealed reduced levels of hypoxia in the sorafenib treated cohort for both of the human cell lines tested (HCT-116 and HT-29). Therapy resistance was associated with an increase in tumor vascular fractal dimension as measured by a box-counting technique on ULM images. Conclusion: These results imply that the morphological changes evident on ULM signify a functional change in the tumor microvasculature, which may be indicative of chemo-sensitivity. Significance: ULM provides additional utility for tumor therapy response evaluation by offering a myriad of morphological and functional quantitative indices for gauging treatment effect(s).

Fundamentals of Bowel Cancer for Biomedical Engineers

“… 19 , 29 , 45 , 73 The measurement is to examine how quickly these vibrations move through the organ, and then this information will be used to create a visual map revealing the differences in the elastic properties of soft tissues for further diagnosis. On the other hand, conventional ultrasound diagnostic images can only visualise the differences in soft tissue acoustic properties through the echogenicity of ultrasound waves passing through the soft tissue, 62 , 68 , 75 whereas ultrasound elastography (USE) images (Fig. 5 d) are able to reveal the differences in the elastic properties of soft tissues.…”

Nanodroplet-Based Super-Resolution Ultrasound Localization Microscopy

“…Due to the low cost, wide accessibility, and safety, ultrasound has the latent capacity to turn into the preferred method of cancer imaging. 80 Doppler ultrasound techniques or conventional B-mode are challenged to demonstrate microvascular characteristics on the scale of early tumor angiogenesis. ULM is not limited to diffraction-limited resolution, which makes this technique a potentially forceful technique.…”

Contrast-free Super-resolution Doppler (CS Doppler) based on Deep Generative Neural Networks

“…Early studies conducted by Viessmann et al [1], Desailly et al [2][3], and O'Reilly et al [4] showed that one can break the resolution limit of acoustic waves by localizing microbubbles in the blood stream. The seminal papers by Errico et al [5] and Christensen-Jeffries et al [6] catalyzed the growth of the field, leading to many subsequent reports with successful in vivo applications [7][8][9][10][11][12][13][14][15][16] and technical advancements of super-resolution ultrasound imaging [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”