Summary
Despite vast drug development efforts, brain tumors remain the leading cause of pediatric cancer deaths. Noninvasive monitoring of treatment response is crucial to reveal the mechanisms behind tumor-drug interactions and optimize patient care. However, standard magnetic resonance imaging (MRI) methods involve injecting metals, have severe difficulties in differentiating treatment response from tumor progression, are qualitative, and mandate prolonged anesthesia due to the lengthy acquisition. I propose to develop a transformative molecular MRI technology, based on the chemical exchange saturation transfer (CEST) contrast mechanism that will enable specific, quantitative, rapid, contrast-material free, treatment monitoring of pediatric brain cancer. Recently I revealed that a combination of mathematical CEST models and AI can generate quantitative biomarker maps of pH and protein concentration changes across the brain, two known hallmarks of cancer. Inspired by these results, I now propose to adopt a previously unconsidered perspective and to represent the underlying physics of CEST MRI as a computational graph, enabling an automatic AI-based optimization of molecular imaging. I hypothesize that the combination of biophysical models with a new AI framework, and their synergetic integration throughout the entire imaging pipeline will provide accurate noninvasive treatment monitoring. First, I will establish a method for automated optimization of MRI protocols for early determination of the tumor response to mainstream chemotherapy. Next, I will shorten the 3D scan time by an order of magnitude and quantify the response to next generation immunotherapy. Third, I will translate the method to clinical scanners and validate it in a human pediatric pilot study. This research will yield a fundamental understanding of the molecular mechanisms underlying treatment response and establish an innovative precision medicine methodology that will transform pediatric cancer imaging.
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| Web resources: | https://cordis.europa.eu/project/id/101115639 |
| Start date: | 01-04-2024 |
| End date: | 31-03-2029 |
| Total budget - Public funding: | 1 497 669,00 Euro - 1 497 669,00 Euro |
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Original description
Despite vast drug development efforts, brain tumors remain the leading cause of pediatric cancer deaths. Noninvasive monitoring of treatment response is crucial to reveal the mechanisms behind tumor-drug interactions and optimize patient care. However, standard magnetic resonance imaging (MRI) methods involve injecting metals, have severe difficulties in differentiating treatment response from tumor progression, are qualitative, and mandate prolonged anesthesia due to the lengthy acquisition. I propose to develop a transformative molecular MRI technology, based on the chemical exchange saturation transfer (CEST) contrast mechanism that will enable specific, quantitative, rapid, contrast-material free, treatment monitoring of pediatric brain cancer. Recently I revealed that a combination of mathematical CEST models and AI can generate quantitative biomarker maps of pH and protein concentration changes across the brain, two known hallmarks of cancer. Inspired by these results, I now propose to adopt a previously unconsidered perspective and to represent the underlying physics of CEST MRI as a computational graph, enabling an automatic AI-based optimization of molecular imaging. I hypothesize that the combination of biophysical models with a new AI framework, and their synergetic integration throughout the entire imaging pipeline will provide accurate noninvasive treatment monitoring. First, I will establish a method for automated optimization of MRI protocols for early determination of the tumor response to mainstream chemotherapy. Next, I will shorten the 3D scan time by an order of magnitude and quantify the response to next generation immunotherapy. Third, I will translate the method to clinical scanners and validate it in a human pediatric pilot study. This research will yield a fundamental understanding of the molecular mechanisms underlying treatment response and establish an innovative precision medicine methodology that will transform pediatric cancer imaging.Status
SIGNEDCall topic
ERC-2023-STGUpdate Date
12-03-2024
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