Diffusion MRI and Novel Texture Analysis in Osteosarcoma Xenotransplants Predicts Response to Anti-Checkpoint Therapy

Abstract

Combinations of targeted drugs have been employed to treat sarcomas, however, response rates have not improved notably, therefore emphasizing the need for novel treatments. In addition, imaging approaches to assess therapeutic response is lacking, as currently measurable indices, such as volume and/or diameter, do not accurately correlate with changes in tumor biology. In this study, quantitative and profound analyses of magnetic resonance imaging (MRI) were developed to evaluate these as imaging biomarkers for MK1775 and Gem in an osteosarcoma xenotransplant model at early time-points following treatment. Notably, we showed that Gem and Gem+MK1775 groups had significantly inhibited tumor growth by day 4, which was presaged by elevations in mean ADC by 24 hours post treatment. Significant differences were also observed at later time points for the Gem+MK1775 combination and MK1775 therapy. ADC distribution and entropy (randomness of ADC values) were also elevated by 24 hours following therapy. Immunohistochemistry demonstrated that these treatment-related increases in ADC correlated with apoptosis and observed cell condensations (dense- and exploded bodies). These findings underline the role of ADC as a quantitative imaging biomarker for therapy-induced response and show promising clinical relevance in the sarcoma patient population.

Study of diffusion‐weighted magnetic resonance imaging in the evaluation of the response to AAV2‐VEGF‐Trap neoadjuvant treatment in a triple‐negative breast cancer animal model

“…Therefore, how the ADC value changes after effective anti‐angiogenesis therapy remains controversial. Using a higher b‐value, the ADC value is less affected by perfusion . In the present study, a b ‐value of 1000 s/mm 2 that was sufficient to retain image quality and avoided the influence of perfusion.…”

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

“…These novel texture analyses have also been applied to other imaging modalities, e.g. MRI, 21,22 and will be discussed later (section on Simultaneous positron emission tomography/MR and textural analysis).…”

Diagnostic assessment of osteosarcoma chemoresistance based on Virtual Clinical Trials

“…Similar quantitative algorithms have been developed for the automated quantification of IHC-determined protein expressions in melanocytes (27), for the automated assessment of the extent of malignant nuclei in colon cancer histology images (28), and for quantifying the architectural complexity in breast and prostate cancer specimens (29, 30). Our group also used quantitative segmentation algorithms to automatically determine scores for HER2-positive, ER-positive, and PR-positive cells within digitized histology images of breast cancer tissues (31), to correlate patient ER statuses with spatial distributions of ER-positive and ER-negative cells, as well as tumor vascular density and vascular area (32), and to determine the extent of the drug-mediated cytotoxic and apoptotic effects in osteosarcoma xenotransplants (33). …”