Non-ionizing Metabolic Imaging for predicting the effect of and guiding Therapeutic Interventions

Project Information

MITI

Grant agreement ID: 101058229

DOI

10.3030/101058229

Project closed

EC signature date 2 March 2022

Start date 1 April 2022

End date 30 September 2025

Funded under

• The European Innovation Council (EIC)

Total cost

€ 2 100 238,75

EU contribution

€ 2 100 238,00

Coordinated by

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands

Periodic Reporting for period 2 - MITI (Non-ionizing Metabolic Imaging for predicting the effect of and guiding Therapeutic Interventions)

Reporting period: 2023-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

Non-ionizing metabolic imaging represents a paradigm shift compared to both traditional magnetic resonance imaging (MRI) and alternative technologies for mapping metabolic activity. MITI will develop and mature a novel, ground-breaking technology for high precision non-ionizing metabolic imaging, enabling fast and non-invasive detection of the markers of metabolic processes e.g. cell proliferation and energy metabolism. Using the results of metabolic imaging, medical specialists will be able to establish the effectiveness of therapies and determine the specific disease months sooner than is possible with currently available technologies.

Objectives:

1. Further develop the basic double tuned metabolic imaging concept for usage on 7T MRI platforms. This concerns the development of demonstrators consisting of hardware components, the integrated system, and the specialised processing software, standardized phantoms and pulse sequences.
2. Broaden the potential technological applications by developing a testing model and testing a quadruple tuned imaging set for 7T MRI scanners (Philips). With this, we will be able to measure in parallel three groups of metabolic biomarkers: phosphorus (31P), sodium (23Na), and deuterium (2H).
3. Validate the capability of the technology to map and visualize relevant metabolic processes with four clinical use cases: lung tumours, heart disease, muscle disorders, and quadruple tuned feasibility evaluation of liver
metastases. We will carry out small clinical studies to show the benefit of the application of metabolic MRI in each of these use cases.
4. Develop the business case, business model and further exploitation and commercialisation plan for MITI

The MITI partners aim to commercialize the technology, by providing it to clinicians in research centres and within 3 years after MITI to general medical centres. At present, more than 100 7T MRI machines have been installed worldwide, all embedded in (clinical) research environments. With an expected increase in sales-rate of 7T MRIs, the manufacturing capacity is likely the limiting factor on up-scaling for the foreseeable future. In MITI, 100% of the highfield MRI vendors are involved and engaged, bringing awareness of the potential and possibilities of metabolic MRI worldwide.

The specific impact areas are:

1. Increase in business generated for MRI manufacturers (by increasing the usefulness of and therefore demand for the 7T MRI machine) and pharmaceutical companies (by enabling better mechanisms for drug development and discovery
2. Metabolic MRI in the clinic will improve and speed up diagnosis of diseases and the evaluation of therapies, resulting in therapies better suited to patients and less unnecessary side effects from ineffective treatment.
3. Reduce healthcare costs by stopping ineffective treatment earlier and by speeding up recovery times
4. Establishes the basis for a new research area: the study of human biochemistry using non-invasive biochemical imaging

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The MITI project is divided into 6 workpackages, of which 4 will deliver significant scientific outputs; these are:

WP1: The development of demonstrators for basic double tuned metabolic imaging set
The output will be to develop metabolic imaging from a research tool to a product suitable for clinical use. To achieve this, we will improve hardware and software on robustness, ease of use, connectivity, user interfaces, data storage, and integration into the MRI system.

The necessary coils have been delivered to all MITI sites and are undergoing testing. We note that SNR is currently sub-optimal and sites are investigating possible causes and troubleshooting solutions.

Plugin components have been developed and have been included in TDCs Compass software tool. These plugins can handle data acquired in the scanner to post-process it and correctly display it.

WP2: Development of testing model for advanced quadruple tuned metabolic imaging set

Tesla Dynamic Coils has been working closely with the University Medical Centre Utrecht for the definition of the specifications needed for the RF coils. It has been mostly worked on the design of the triple tuned bore coil, RF shield and triple tuned body array. Simulations have been performed on several RF shield designs to determine its safety (mostly on temperature) when used in the 7T scanner.
TDC has already ordered the tube carrier to place the triple tuned birdcage and the RF shield carrier. A testing model of the triple tuned bore coil has been developed and integrated in a patient tube for parallel detection of 31P-phosphorus, 23Na-sodium, and 2H-deuterium for the Philips 7T system located at UMCU.


WP3: Finetuning and testing of demonstrators and testing models for specific use cases

Here we will further validate metabolic imaging for 4 clinical use cases. This will be done via clinical trials at 3 participating partner sites. We have obtained ethical approval and trials are in the start-up phase at each MITI site for their respective use-cases.

General progress workflow from all sites:

1. implement suitable coils for UHF (7T) studies

2. optimize sequences to perform a qualitative analysis of the biochemical profiles in the healthy controls and in the patients

3. evaluate the potential of MRS methods showing the pathological alteration patients compared to healthy controls.

Midterm patient recruitment reports and the reporting of eventual results will follow.


WP4: Development of final prototype and production process for basic double tuned metabolic imaging set

Finally, WP4 will focus on bringing the basic metabolic imaging set to Technology Readiness Level 6 (prototype system verified). For this, the production procedure for bore coils will be defined. Documentation compliant to relevant standards will be integrated into Siemens, GE and Philips platforms. We will deliver pre-procuduction models of the basic metabolic imaging sets and update the Compass software tool to be able to process resulting data for different vendor platforms.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

MITI is a game changing breakthrough to MRI imaging, because it reveals causative information and provides information early. Importantly, MITI will enable clinical domain experts (e.g. oncologists, neurologists, and internists) and radiologists to faster draw conclusions on diseases and the effectiveness of treatment. Where the current techniques mainly allow for morphologic imaging based on water and fat, metabolic imaging represents a paradigm shift towards non-invasive imaging of biochemical processes in the human body. This is expected to open a new and effective window for understanding human biology, drug pathways, diseases and their treatment without the need for any radioactive tracers.

In order to maximize chances for update and success we will do the following:

1. Investigate reimbursement routes of cancer therapies and clinical imaging of muscle dystrophy patients. Meetings with insurance companies and relevant governments will be conducted.
2. Engage with drug companies in order to discuss the technology for usage in cardio-diseases
3. Explore possibilities with OEM MRI vendors to include metabolic insert in standard MRI systems
4. Market research and fine-tuning of business plan with support from ERC innovation services and a solid tech-to-market-transition plan
5. Dissemination and communication via scientific publications, collaborations and meetings/symposia.