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Theranostics 2024; 14(3):1312-1324. doi:10.7150/thno.89306 This issue Cite

Research Paper

Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy

Jingyi Yin^1*, Feihong Dong^2,3,4*, Jian An^1*, Tianyu Guo², Heping Cheng^2,3,4,5, Jiabin Zhang^2,3,4✉, Jue Zhang^1,4,5,6✉

1. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
2. College of Future Technology, Peking University, Beijing, China.
3. State Key Laboratory of Membrane Biology, Peking-Tsinghua Center for Life Sciences, and Institute of Molecular Medicine, Peking University, Beijing, China.
4. National Biomedical Imaging Center, Peking University, Beijing, China.
5. Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing, China.
6. College of Engineering, Peking University, Beijing, China.
*J.Y., F.D., and J. A. contributed equally to this work.

✉ Corresponding authors: Jiabin Zhang and Jue Zhang. Email: zhangjiabinedu.cn; zhangjueedu.cn; Tel.: +86 13911405566; Peking University, No.5 Yiheyuan, Beijing, P.R. China 100871. Jue Zhang's ORCID: 0000-0003-0440-1357; ScholarID: CN-B6748SXJ More

Abstract

Rationale: Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations.

Methods: We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles.

Results: PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 μm. Compared with traditional vascular parameters, PARM-derived heterogeneity parameters prove to be more sensitive to microvascular changes following anti-angiogenic therapy. Particularly, PARM-identified “sentinel” microvasculature, exhibiting evident structural changes as early as 24 hours after treatment initiation, correlates significantly with subsequent tumor volume changes (|r| > 0.9, P < 0.05). This provides prognostic insight into tumor response much earlier than clinical criteria.

Conclusions: The ability of PARM to noninvasively quantify tumor vascular heterogeneity at the microvascular level may shed new light on early-stage assessment of cancer therapy.

Keywords: Super-resolution ultrasound imaging, Tumor microvasculature, Tumor heterogeneity, Anti-angiogenic treatment, Pattern recognition

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