Abstract
Precise demarcation of brain tumor boundaries is critical for optimizing treatment strategies and improving patient outcomes. In vivo characterization of tumor using PET/CT and MRI is clinical standard. PET/CT highlights the metabolic aspects of the tumor, while MRI provides information on functional, metabolic and structural changes. Even with technological advancements in both PET/CT and MRI, a method that can precisely delineate infiltrative tumor boundaries from normal-appearing brain regions (NABR) in vivo is still lacking. To address this limitation, we explored a relatively new MR imaging method, the Nuclear Overhauser Effect Magnetization Transfer Ratio (NOE (MTR) ), in conjunction with a gadolinium-based contrast agent (Gd-DOTA), to precisely delineate the tumor boundaries in a rat model of infiltrative gliosarcoma. NOE (MTR) imaging was performed in the rat model (n=5) before and after Gd-DOTA administration. The post-Gd-DOTA NOE (MTR) map was subtracted from the pre-Gd-DOTA map and compared with contrast-enhanced T (1) -weighted images and immuno-histological findings. The resulting NOE (MTR) difference map clearly highlighted both the tumor core and infiltrative boundaries, which was not discernible on the post-contrast T (1) -weighted images. The extended tumor boundaries observed on the NOE (MTR) difference map corroborated with the IHC image, which confirmed the presence of infiltrative tumor cells and macrophages in these regions. Guided by the NOE (MTR) difference map, regions of interest (ROI) were drawn to quantify NOE (MTR) signal changes in the tumor core, tumor boundaries, and NABR post-Gd-DOTA. Tumor core showed a significant ∼43% reduction in NOE (MTR) signal (plJ=lJ0.003), while the tumor periphery exhibited a moderate reduction of ∼10%, (plJ=lJ0.045). No appreciable change in was observed in the NABR (plJ=lJ0.371). In contrast, the post contrast T (1) -weighted signal changes in tumor core, tumor periphery and NABR were, 33.32% (p = 0.092), 3.8% (p = 0.478), and 8.7% (p = 0.464) respectively. These findings suggest that NOE (MTR) imaging provides enhanced tumor contrast, particularly at the infiltrative tumor margins, where conventional contrast enhanced T (1) -weighted MRI may underestimate tumor extent. Histological validation confirmed the presence of infiltrative tumor cells and macrophages in the tumor periphery, as highlighted by the NOE (MTR) difference map. Overall, NOE (MTR) imaging, in combination with Gd-DOTA administration, demonstrates superior delineation of brain tumor boundaries compared to conventional MRI. As NOE (MTR) imaging is a fast acquisition scan (under 10 minutes) and performed on standard 3 Tesla, it can be easily integrated into clinical protocols. By improving visualization of tumor infiltration and distinguishing tumor regions from NABR, NOE (MTR) imaging holds promise for advancing neuro-oncological diagnostics and treatment planning.