Periodic Reporting for period 1 - GLIOBID (Guiding glioblastoma treatments by decrypting tumor biomechanics via Magnetic Resonance Elastography.)
Período documentado: 2023-04-01 hasta 2025-03-31
Glioblastoma multiforme (GBM) is the most aggressive and deadly form of brain tumour. Despite surgery, radiotherapy and chemotherapy, most patients experience tumour recurrence within months, and overall survival remains dismally low. One of the key challenges in treating GBM is that standard imaging tools do not capture the full complexity of the tumour microenvironment — particularly the physical barriers that block drug delivery and promote tumour progression.
GLIOBID addresses this problem by developing and applying advanced imaging techniques to non-invasively measure the biomechanical properties of brain tumours, such as tissue stiffness, viscosity, and pressure. These properties are deeply linked to the biological processes that drive tumour invasion, vascular collapse, and therapy resistance. By mapping how tumours change mechanically in response to treatment, GLIOBID aims to create a new way to monitor whether therapies are working — much earlier and more precisely than what current MRI scans allow.
The project uses Magnetic Resonance Elastography (MRE), an imaging technique that uses Magnetic resonance Imaging to measure how tissue behave when vibrations are sent. The resulting data provide a “biomechanical fingerprint” of the tumour. The main objectives of GLIOBID are:
1. To measure how therapy affects tumour stiffness, viscosity, and vascular structure.
2. To use MRE to estimate tumour pressure non-invasively.
3. To translate these advanced MRE tools into the clinical setting.
Ultimately, GLIOBID aims to support better treatment planning and monitoring in glioblastoma — a critical unmet medical need in Europe and worldwide.
GLIOBID addresses this problem by developing and applying advanced imaging techniques to non-invasively measure the biomechanical properties of brain tumours, such as tissue stiffness, viscosity, and pressure. These properties are deeply linked to the biological processes that drive tumour invasion, vascular collapse, and therapy resistance. By mapping how tumours change mechanically in response to treatment, GLIOBID aims to create a new way to monitor whether therapies are working — much earlier and more precisely than what current MRI scans allow.
The project uses Magnetic Resonance Elastography (MRE), an imaging technique that uses Magnetic resonance Imaging to measure how tissue behave when vibrations are sent. The resulting data provide a “biomechanical fingerprint” of the tumour. The main objectives of GLIOBID are:
1. To measure how therapy affects tumour stiffness, viscosity, and vascular structure.
2. To use MRE to estimate tumour pressure non-invasively.
3. To translate these advanced MRE tools into the clinical setting.
Ultimately, GLIOBID aims to support better treatment planning and monitoring in glioblastoma — a critical unmet medical need in Europe and worldwide.
During the outgoing phase at Stanford Medicine, the project successfully established a dedicated preclinical MRE platform capable of high-resolution brain imaging in small animals. A custom-built vibration setup and optimised imaging sequence were implemented on a 7 Tesla MRI system, enabling longitudinal studies in mice with orthotopic brain tumours.
As part of GLIOBID, the fellow developed a novel enzyme-activated theranostic nanoparticle (TNP) that combines the MRI contrast agent Ferumoxytol with the matrix-degrading enzyme Collagenase IV, linked via a cleavable peptide responsive to enzymes overexpressed in GBM. This smart design allows the TNP to actively remodel the tumour's extracellular matrix, enhancing drug penetration while simultaneously enabling real-time MRI tracking. The TNP functions both as a therapeutic tool and a quantitative biomarker of drug delivery.
In vivo MRE revealed that tumour viscosity — a measure of resistance to deformation — significantly influences nanoparticle uptake. These findings confirm that MRE can detect changes in the tumour’s physical structure that directly impact treatment efficacy.
Additionally, the fellow pioneered a new approach to use mechanical wave propagation to infer vascular architecture within the tumour. This breakthrough demonstrates that MRE not only characterises tissue mechanics but also provides insights into vascular organisation — information that is crucial for personalised tumour grading, therapy planning, and understanding treatment resistance.
As part of GLIOBID, the fellow developed a novel enzyme-activated theranostic nanoparticle (TNP) that combines the MRI contrast agent Ferumoxytol with the matrix-degrading enzyme Collagenase IV, linked via a cleavable peptide responsive to enzymes overexpressed in GBM. This smart design allows the TNP to actively remodel the tumour's extracellular matrix, enhancing drug penetration while simultaneously enabling real-time MRI tracking. The TNP functions both as a therapeutic tool and a quantitative biomarker of drug delivery.
In vivo MRE revealed that tumour viscosity — a measure of resistance to deformation — significantly influences nanoparticle uptake. These findings confirm that MRE can detect changes in the tumour’s physical structure that directly impact treatment efficacy.
Additionally, the fellow pioneered a new approach to use mechanical wave propagation to infer vascular architecture within the tumour. This breakthrough demonstrates that MRE not only characterises tissue mechanics but also provides insights into vascular organisation — information that is crucial for personalised tumour grading, therapy planning, and understanding treatment resistance.
GLIOBID is pioneering a new field of mechanical biomarkers for brain tumours. While conventional imaging focuses on anatomy or metabolism, Magnetic Resonance Elastography (MRE) provides a unique lens into how tumours physically resist therapy and infiltrate surrounding brain tissue.
A key innovation of the project is the development of a theranostic nanoparticle — a single agent that combines therapeutic activity with MRI visibility. This nanoparticle responds to both tumour stiffness and enzyme activity, enabling personalised drug delivery strategies guided by imaging. It represents a significant step forward in integrating diagnosis and therapy.
The project’s findings pave the way for biopsy-free tumour stratification, allowing clinicians to predict therapeutic response based on a tumour’s biomechanical fingerprint. This approach has the potential to spare patients from ineffective treatments and advance personalised oncology.
GLIOBID also introduced a non-invasive method to estimate tumour pressure, a key marker of aggressiveness in GBM, which until now could only be measured invasively. Additionally, the project demonstrated that MRE can be used to infer vascular architecture by analysing shear wave scattering — an important breakthrough, as abnormal vasculature is a defining feature of malignant tumours.
The return phase will focus on translating these advanced MRE biomarkers to the clinic, using data from an ongoing brain cancer trial to validate their predictive value in patients.
The long-term vision is to integrate these tools into routine clinical workflows, ultimately improving treatment selection and outcomes for patients with GBM and, potentially, other solid tumours.
A key innovation of the project is the development of a theranostic nanoparticle — a single agent that combines therapeutic activity with MRI visibility. This nanoparticle responds to both tumour stiffness and enzyme activity, enabling personalised drug delivery strategies guided by imaging. It represents a significant step forward in integrating diagnosis and therapy.
The project’s findings pave the way for biopsy-free tumour stratification, allowing clinicians to predict therapeutic response based on a tumour’s biomechanical fingerprint. This approach has the potential to spare patients from ineffective treatments and advance personalised oncology.
GLIOBID also introduced a non-invasive method to estimate tumour pressure, a key marker of aggressiveness in GBM, which until now could only be measured invasively. Additionally, the project demonstrated that MRE can be used to infer vascular architecture by analysing shear wave scattering — an important breakthrough, as abnormal vasculature is a defining feature of malignant tumours.
The return phase will focus on translating these advanced MRE biomarkers to the clinic, using data from an ongoing brain cancer trial to validate their predictive value in patients.
The long-term vision is to integrate these tools into routine clinical workflows, ultimately improving treatment selection and outcomes for patients with GBM and, potentially, other solid tumours.