High-Resolution Imaging of Extracellular pH in Mouse Liver Tumor.

Authors

Jessica Gois Santana, Sara Kurdi, Lisa Marie Helene Peschke, Sandeep Kumar Mishra, Fahmeed Hyder, Julius Chapiro, Daniel Coman

Published in

NMR in biomedicine. Volume 39. Issue 9. Pages e70375.

Abstract

Extracellular acidosis is a biologically important feature of the tumor microenvironment in the liver, promoting immune evasion, angiogenesis, and resistance to therapy, and representing a mechanistically important and potentially targetable axis in liver cancer. Imaging extracellular pH (pH_e) at high resolution is needed to better understand the immuno-metabolic interplay, especially at the transition regions between the tumor core, tumor margin, and background liver, which is critical for any pharmacological or image-guided intervention. Yet, there is a paucity of imaging techniques capable of providing pH_e mapping at high resolution. Here, we demonstrate high-resolution pH_e imaging in a mouse Hepa1-6 liver tumor model using ¹H Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) with REduced Spherical Encoding with GAussian Weighting (RESEGAW). Eight tumor-bearing C57BL/6J mice were used to demonstrate pH_e imaging with RESEGAW using the macrocyclic agent TmDOTP^5- at 0.6 mm isotropic resolution on a 9.4 T scanner, which was validated using ³¹P-MRSI with 3-aminopropylphosphonate (3-APP). pH_e imaging with ¹H-BIRDS-RESEGAW consistently showed acidic tumor regions (pH_e = 6.77 ± 0.14) relative to adjacent normal liver (pH_e = 7.14 ± 0.07). Mean pH_e values measured by ³¹P-MRSI with 3-APP and ¹H-BIRDS-RESEGAW with TmDOTP^5- show no significant differences in tumors (pH_e = 6.81 ± 0.13) and normal liver (pH_e = 7.14 ± 0.06). Voxelwise comparison after co-registration of ³¹P-MRSI with 3-APP to ¹H-BIRDS-RESEGAW using Bland-Altman analysis demonstrated excellent agreement between the two methods, with minimal mean bias (-0.005 pH units) and variance of less than 0.1 pH units. These results demonstrate the feasibility and quantitative reliability of ¹H-BIRDS-RESEGAW for imaging extracellular acidosis in liver tumors at submillimeter resolution, establishing a technical foundation for studying the immuno-metabolic interplay in liver cancer and its response to therapy.

PMID:
42619234
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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