The development of magnetic resonance based hypoxia imaging for targeted radiotherapy planning.
Lead Research Organisation:
University College London
Department Name: Oncology
Abstract
Cancer patients that have tumours with low oxygen levels (also known as hypoxic tumours) have a worse prognosis than those with well oxygenated tumours. They are more likely to relapse after treatment with radiotherapy or chemotherapy and a higher chance of developing incurable metastatic disease.
Currently there is no practical method of measuring hypoxia in tumours prior to treatment. This project aims to build on current research in order to develop MRI based imaging of hypoxia as a feasible tool for routine clinical use. The research will predominately be carried out in patients will pelvic malignancies such as prostate and cervical cancer. In order to validate the imaging processes, the MRI maps of hypoxia will be compared with tissue samples obtained from patients during their planned cancer surgery. The hypoxia maps that are generated will then be used to target hypoxic tumour regions using highly focused radiotherapy.
The potential for clinical application is substantial. Hypoxia imaging could be incorporated into staging procedures to provide prognostic information. Strategies to combat hypoxia may be offered on an individualised basis and hypoxia maps offer the prospect of targeted treatments such as highly conformal radiotherapy with dose escalation to the hypoxic regions.
F3B Stem Cell Lay Summary - Before completing this section you MUST refer to the guidance notes. (Up to a maximum of 6 A4l sheets, explain to a lay audience the nature of the proposed research, the prospective outcomes and the expected benefits in terms of improvement to human health).
Currently there is no practical method of measuring hypoxia in tumours prior to treatment. This project aims to build on current research in order to develop MRI based imaging of hypoxia as a feasible tool for routine clinical use. The research will predominately be carried out in patients will pelvic malignancies such as prostate and cervical cancer. In order to validate the imaging processes, the MRI maps of hypoxia will be compared with tissue samples obtained from patients during their planned cancer surgery. The hypoxia maps that are generated will then be used to target hypoxic tumour regions using highly focused radiotherapy.
The potential for clinical application is substantial. Hypoxia imaging could be incorporated into staging procedures to provide prognostic information. Strategies to combat hypoxia may be offered on an individualised basis and hypoxia maps offer the prospect of targeted treatments such as highly conformal radiotherapy with dose escalation to the hypoxic regions.
F3B Stem Cell Lay Summary - Before completing this section you MUST refer to the guidance notes. (Up to a maximum of 6 A4l sheets, explain to a lay audience the nature of the proposed research, the prospective outcomes and the expected benefits in terms of improvement to human health).
Technical Summary
Background
Tumour hypoxia is a recognised cause of treatment failure. Currently there is no reliable method to measure and map the distribution of hypoxia before treatment begins, which has hampered the development of strategies to combat hypoxia. This project will build upon current research to develop MRI protocols that can generate high-resolution hypoxia maps of human tumours for use in routine clinical practice. The project will then proceed to targeting tumour hypoxia, guided by the MR derived hypoxia maps, using highly focused radiotherapy.
Relevance to cancer
The potential for clinical application is substantial. Hypoxia imaging could be incorporated into staging procedures to provide prognostic information. Strategies to combat hypoxia may be offered on an individualised basis and hypoxia maps offer the prospect of targeting treatment to hypoxic tumour regions.
Scientific Rational
Blood Oxygen Level Dependent (BOLD) MRI capitalizes on the differing magnetic properties of oxygenated and deoxygenated haemoglobin. Microscopic magnetic field gradients in the vicinity of perfused vessels are caused by changes in the deoxyhaemoglobin concentration, leading to signal changes in susceptibility-weighted MRI sequences. For BOLD-MRI to be able to depict tissue oxygenation status it is necessary to know that tissues are perfused by red blood cells. Combining MRI based blood volume measurements with BOLD imaging therefore reflects tissue oxygenation more accurately.
Specific aims of the research
To develop magnetic resonance based hypoxia imaging for targeted radiotherapy planning by:
1) Validating blood volume adjusted Blood Oxygen Dependent (BOLD) MRI hypoxia maps.
2) The development of radiobiological models for optimal radiotherapy delivery based on the MRI derived hypoxia maps.
3) Clinical implementation of highly conformal radiotherapy treatment to boost hypoxic targets.
Research Plan
Our previous research has demonstrated the potential for hypoxia imaging using MRI. However, current methodology is impractical for routine clinical use. The first series of experiments will evaluate alternative strategies to generate MR derived blood volume data from human tumours that can then be combined with BOLD images to generate hypoxia maps.
We will develop radiobiological models to show the advantage of selective radiation dose escalation in enhancing tumor control probability by targeting hypoxic tumour regions.
Highly conformal HDR brachytherapy will be used to target hypoxic areas in a dose-escalation clinical trial for patients with prostate cancer. A protocol for this study has already been written. A dose escalation scheme to hypoxic tumour sub-volumes has been calculated using biologically equivalent dose estimations derived from the linear-quadratic model.
Tumour hypoxia is a recognised cause of treatment failure. Currently there is no reliable method to measure and map the distribution of hypoxia before treatment begins, which has hampered the development of strategies to combat hypoxia. This project will build upon current research to develop MRI protocols that can generate high-resolution hypoxia maps of human tumours for use in routine clinical practice. The project will then proceed to targeting tumour hypoxia, guided by the MR derived hypoxia maps, using highly focused radiotherapy.
Relevance to cancer
The potential for clinical application is substantial. Hypoxia imaging could be incorporated into staging procedures to provide prognostic information. Strategies to combat hypoxia may be offered on an individualised basis and hypoxia maps offer the prospect of targeting treatment to hypoxic tumour regions.
Scientific Rational
Blood Oxygen Level Dependent (BOLD) MRI capitalizes on the differing magnetic properties of oxygenated and deoxygenated haemoglobin. Microscopic magnetic field gradients in the vicinity of perfused vessels are caused by changes in the deoxyhaemoglobin concentration, leading to signal changes in susceptibility-weighted MRI sequences. For BOLD-MRI to be able to depict tissue oxygenation status it is necessary to know that tissues are perfused by red blood cells. Combining MRI based blood volume measurements with BOLD imaging therefore reflects tissue oxygenation more accurately.
Specific aims of the research
To develop magnetic resonance based hypoxia imaging for targeted radiotherapy planning by:
1) Validating blood volume adjusted Blood Oxygen Dependent (BOLD) MRI hypoxia maps.
2) The development of radiobiological models for optimal radiotherapy delivery based on the MRI derived hypoxia maps.
3) Clinical implementation of highly conformal radiotherapy treatment to boost hypoxic targets.
Research Plan
Our previous research has demonstrated the potential for hypoxia imaging using MRI. However, current methodology is impractical for routine clinical use. The first series of experiments will evaluate alternative strategies to generate MR derived blood volume data from human tumours that can then be combined with BOLD images to generate hypoxia maps.
We will develop radiobiological models to show the advantage of selective radiation dose escalation in enhancing tumor control probability by targeting hypoxic tumour regions.
Highly conformal HDR brachytherapy will be used to target hypoxic areas in a dose-escalation clinical trial for patients with prostate cancer. A protocol for this study has already been written. A dose escalation scheme to hypoxic tumour sub-volumes has been calculated using biologically equivalent dose estimations derived from the linear-quadratic model.