Quantification of tumor characteristics with MRI for tumor characterization and therapy evaluation

• Applicant: Dr. Mirjam Gerwing
• Subject Area: Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446302350

While the effects of classical cytotoxic chemotherapeutic can reliably be analyzed using conventional cross-sectional imaging like computed tomography or magnetic resonance imaging, those techniques are limited in the assessment of “targeted therapies”. Modern, precise tumor therapeutics frequently do not attack the tumor cells directly, but tumor features or components of the tumor microenvironment. Therapeutic changes in the tumor microenvironment thus do not primarily influence the size of the tumor and its metastases. Thus, measurement of changes in the tumor size do not reflect the mode of action of these new therapeutics and their therapy response adequately. Innovative imaging techniques, which quantitatively asses specific tumor traits and therapy-associated alterations, are therefore of major importance. Novel, targeted therapeutics influence inter alia neoangiogenesis, vascular permeability, the immune cell infiltrate in the tumor area, and cause, due to their immune-modulating activity, an associated edema, as well as an intratumoral hemorrhage. The quantitative assessment of these characteristics has to be the goal of modern oncologic imaging, as it enables individual therapy options and optimized response assessment. Within the project, a comprehensive MR imaging protocol is used to characterize tumors regarding their heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability, immune-cell infiltrate and metabolism. A combination of the MR imaging approaches diffusion-weighted imaging (DWI), T1 and T2 mapping, oscillating gradient spin echo (OGSE), dynamic contrast-enhanced (DCE) and chemical exchange saturation transfer (CEST) enables to not only sufficiently characterize the tumors, but also quantify these characteristics. To assess the endothelial permeability, the MRI scan is conducted with the albumin-binding contrast medium gadofosveset, which only extravasates in the interstitium in case of leaky vessels, where it shortens the T1 relaxivity. It is afterwards detected and quantified ex vivo with laser- ablation inductively coupled mass spectrometry (LA-ICP-MS) with a high spatial resolution of up to 5 µm. The tumor features endothelial permeability and immune cell infiltrate are specifically altered to assure that changes in the tumor features can be detected. Furthermore, treatment groups with two different targeted therapies are analyzed for changes in their tumor characteristics.With the knowledge from the MRI scan, the tumor’s leading features can be chosen for an individual, optimized targeted therapy. Furthermore, the development of these features after treatment initiation can be monitored over time. Thus, treatment failure can be noticed early, allowing a fast change in the treatment regimen if needed. The assessed tumor features and their changes are validated with different ex vivo methods, including LA-ICP-MS, histology and electron microscopy.

• DFG Programme: Research Grants