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IN SITU IMAGING OF LIVING TISSUES WITH CELLULAR SPATIAL RESOLUTION

Periodic Reporting for period 2 - HISTO-MRI (IN SITU IMAGING OF LIVING TISSUES WITH CELLULAR SPATIAL RESOLUTION)

Reporting period: 2019-01-01 to 2021-03-31

The main objective of HISTO-MRI project is to develop the technologies that will enable the non-invasive visualization of individual human cells in vivo and in real time, based on a radical new Magnetic Resonance Imaging concept: High Frequency Pulsed MRI. To accomplish this ambitious objective, several new challenging multidisciplinary technologies will have to be developed: 1) new method for the production of magnet coils, based on additive manufacturing technology, in order to stand very high currents at very high frequencies; 2) novel high frequency high voltage pulse power sources, based of semiconductor switches, to feed those magnet coils; and new pulse sequencing and computer algorithms to deal with and analyse the enormous amount of data. Therefore, this project has a foundational character, establishing the basis for a new field of research, pulsed MRI in the high frequency regime, which will radically advance MRI performance to micron resolution.

A Proof of Concept of the new technology will be accomplished through the visualization of a mouse brain at the neuron level. This new technology will enable transformative research in the fields of neurosciences, bioengineering, biophysics and experimental oncology.

The new technologies under development have the potential of fulfilling the long awaited neuroscientists’ dream of examining the human brain at the neuron level. It will also enable bridging in vivo imaging with ex vivo tissue microscopy or performing a histological examination without the need of a biopsy. In the long term, our new pulsed approach is expected to lead to new capabilities and benefits in the MRI field, such as real time visualization of every single cell of the human body.
The main achievements in this period are:

- Determination of the requirements and finalized the design of the main magnet, gradient coils and radiofrequency system,
- Definition of the requirements for the pulsed powers supply and the power amplifiers,
- Development of the sequence programming interface,
- Design and manufacture of the mechanical structure for the main magnet, gradient system and radiofrequency amplifier,
- Installation and characterization of the performance of the main magnet,
- Installation and characterization of the performance of the magnetic gradient coils,
- All tasks involving radio-frequency electronics completed
- Availability of the preliminary working version of a high power supply which we now know how to scale up to meet the project’s demands,
- Close to completing the development of a general imaging platform allowing for flexible image orientations as well as sequences providing standard T1/T2 contrasts in multi-slice and 3D mode,
- Succeess to image the hardest human tissues at low field strength (0.3 T),
- Design of an experimental setup for characterizing Peripheral Nerve Stimulation thresholds in the extreme operating opened up by the power supplies developed in this project,
- Invention and patent of MASSIF, a new technology for real-time, high resolution Magnetic Resonance Imaging.
SCIENTIFIC IMPACT

HISTO-MRI will enable the launch of new bioengineering devices capable of producing images with cellular resolution, a topic of intense interest to biomedical researchers around the World. The new technology will provide access to high-resolution deep tissue imaging for the broader scientific community, a capability that is not currently available to scientists. It will broaden the use of MRI from modest resolution to deep tissue single cell imaging and will enable transformative research in the fields of neurosciences, bioengineering, biophysics, experimental oncology and nano-therapeutic targeting. In particular, Neuroscience research might experience a giant leap forward through the visualization of all 100 billion neurons of the human brain and their mutual connections.

MEDICAL IMPACT

Oncology. The technology developed by HISTO-MRI will produce a deep impact in Oncologic diagnosis and follow-up. Precise examinations will improve early detection of aggressive cancers with impact on survival rate, treatment costs (shorter) and indirect costs related to early mortality. Accurate, safe and harmless repeated imaging will monitor tumour progression and determine tumour aggressiveness. The novel imaging technology may replace biopsies in many cases, reducing mortality (for instance, death probability from brain biopsy is higher than 1%), injuries from medical misadventures , and healthcare costs, pain and psychological trauma to the patient.

Hard Tissue Contrast. Conventional MRI cannot distinguish between hard tissue and air and many radiologists believe that the bones or teeth do not emit a signal with MRI. However, both teeth and bones do emit an MRI signal, which is very difficult to detect because it is much faster than soft tissue signals. Due to its fast imaging capabilities, the new technology exhibits excellent hard tissue detail. This will enable the development of a Dental-MRI scanner in the future.

Real Time Monitoring of RadioTherapy. Radiation oncologists will be able to immediately verify that treatment plans were correct by viewing the distribution of free-radicals generated in the body from beam therapy. This is possible through the Overhauser mechanism, by which some of the excited electrons transfer their energy to protons in the sample, thus allowing quantitative measurement of free radicals in vivo. There is a need for such real-time feedback.

IMPACT ON AEROSPACE, AUTOMOTIVE AND FOOD INDUSTRIES

Aerospace, Automotive and Food industries move several trillions of euros every year only in Europe. Together, they represent an important contribution to the GDP of the EU. The deep imaging capabilities enabled with the pulsed technology would definitely trigger a revolution in the quality control chain of the aerospace, automotive and food industries through automatic inspection of factory-produced parts at very high rate and with micron resolution quality.

ECONOMIC IMPACT

Cancer-related health care costs in Europe amount to more than 50 B€ yearly. A recent study found wide differences between countries and identified the need for cost-effective measures to prevent cancer and to improve early detection. The sustainability of health care systems will depend strongly on a cost-effective implementation of cancer diagnostics and monitoring. Imaging is one tool in this domain and the new technologies could be instrumental for early detection and therapy monitoring in cancer patients.
In the case of Prostate Cancer, for example, the primary users of the new technology will be urologists, who would purchase the new technology for use in their office practices. There are about 40,000 practicing urologists worldwide . An important selling point for the product is that no cryogens or special rooms will be needed to operate the scanner, since the magnetic fields are generated using pulsed power technologies. The typical hazards of MRI would be reduced, since the system would not have a static field. Costs considerably lower than whole-body MRI scanners enable higher spread of the new technology especially in smaller hospitals enabling shorter time for waiting and lower cost of more precise examination.
HISTO-MRI magnet assembly