In the treatment of solid tumors, low perfusion and the resulting hypoxic microenvironment remain major barriers to therapeutic efficacy. Poor blood supply within tumors creates a “desert of oxygen,” limiting drug delivery and undermining the effectiveness of chemo-, radio-, and immunotherapies.

A research team from the Department of Ultrasound at Xinqiao Hospital, Army Medical University, has made a significant advance in tackling this challenge. Their study, recently published in Academic Radiology, demonstrates that combining ultrasound-stimulated microbubble cavitation (USMC) with nitric oxide (NO) pathway activation—specifically using sodium nitrite (SN)—can synergistically improve tumor perfusion and alleviate hypoxia in a mouse MC38 tumor model.

Key Findings

• Synergistic effect: SN + USMC increased tumor perfusion parameters far more than either treatment alone, with notable improvements in vessel density, blood flow velocity, and overall perfusion index.
• Hypoxia relief: Co-therapy significantly reduced expression of hypoxia-inducible factor-1α (HIF-1α), indicating meaningful alleviation of tumor hypoxia.
• Mechanistic insight: The benefits were mediated through NO signaling, with SN contributing both via hypoxia-dependent nitrite reduction and potentiating the L-Arg/NO pathway.
• Clinical readiness: Both the ultrasound platform and sodium nitrite have clinical applicability, suggesting high translational potential.

Technology Enabling the Breakthrough

This study was powered by the ULTIMUS 9E ultrasound system, integrating:

• VFlash low-intensity ultrasound therapy mode — delivering precisely controlled acoustic energy to stimulate microbubble cavitation within the tumor microvasculature.
• Ultra-Resolution Microscopy (URM) — enabling visualization and quantification of microvascular changes with near-microscopic detail, capturing parameters such as vessel ratio, mean velocity, and perfusion index.

By combining therapeutic modulation and high-resolution imaging in a single platform, the research team achieved both precise intervention and comprehensive assessment — creating a 1+1>2 synergy in both experimental capability and scientific insight.

Read the full article here: https://pubmed.ncbi.nlm.nih.gov/40234163/