Amide proton transfer-weighted CEST MRI for radiotherapy target delineation of glioblastoma: a prospective pilot study

Background: Extensive glioblastoma infiltration justifies a 15-mm margin around the gross tumor volume (GTV) to define the radiotherapy clinical target volume (CTV). Amide proton transfer (APT)-weighted imaging could enable visualization of tumor infiltration, allowing more accurate GTV delineation. We quantified the impact of integrating APT-weighted imaging into GTV delineation of glioblastoma and compared two APT-weighted quantification methods-magnetization transfer ratio asymmetry (MTR_asym) and Lorentzian difference (LD) analysis-for target delineation.

Methods: Nine glioblastoma patients underwent an extended imaging protocol prior to radiotherapy, yielding APT-weighted MTR_asym and LD maps. From both maps, biological tumor volumes were generated (BTV_MTRasym and BTV_LD) and added to the conventional GTV to generate biological GTVs (GTV_bio,MTRasym and GTV_bio,LD). Wilcoxon signed-rank tests were performed for comparisons.

Results: The GTV_bio,MTRasym and GTV_bio,LD were significantly larger than the conventional GTV (p ≤ 0.022), with a median volume increase of 9.3% and 2.1%, respectively. The GTV_bio,MTRasym and GTV_bio,LD were significantly smaller than the CTV (p = 0.004), with a median volume reduction of 72.1% and 70.9%, respectively. There was no significant volume difference between the BTV_MTRasym and BTV_LD (p = 0.074). In three patients, BTV_MTRasym delineation was affected by elevated signals at the brain periphery due to residual motion artifacts; this elevation was absent on the APT-weighted LD maps.

Conclusion: Larger biological GTVs compared to the conventional GTV highlight the potential of APT-weighted imaging for radiotherapy target delineation of glioblastoma. APT-weighted LD mapping may be advantageous for target delineation as it may be more robust against motion artifacts.

Relevance statement: The introduction of APT-weighted imaging may, ultimately, enhance visualization of tumor infiltration and eliminate the need for the substantial 15-mm safety margin for target delineation of glioblastoma. This could reduce the risk of radiation toxicity while still effectively irradiating the tumor.

Trial registration: NCT05970757 (ClinicalTrials.gov).

Key points: Integration of APT-weighted imaging into target delineation for radiotherapy is feasible. The integration of APT-weighted imaging yields larger GTVs in glioblastoma. APT-weighted LD mapping may be more robust against motion artifacts than APT-weighted MTR_asym.