Periodic Reporting for period 2 - BREAKBEN (Breaking the Nonuniqueness Barrier in Electromagnetic Neuroimaging)
Reporting period: 2017-01-01 to 2019-05-31
BREAKBEN aimed at attacking a fundamental limitation of electromagnetic brain imaging when MEG or EEG is used: the inverse problem is non-unique. This means that additional information (“a priori information”) is needed to determine locations of brain activity when using these techniques. BREAKBEN technology combines measurement of brain activity with magnetoencephalography (MEG) and the measurement of brain structure with so-called ultra-low-field magnetic resonance imaging (ULF MRI) methodology. We developed a hybrid instrument that uses a new generation of extremely sensitive superconducting quantum interference devices (SQUIDs) for these two purposes. If brain MEG and MRI are measured with the same SQUID sensors essentially at the same time, the accuracy and reliability of determining the locations and waveforms of brain activity can be improved. This would be extremely useful for clinical applications such as determining the origin (location) of epileptic activity in the brain prior to surgery.
In addition to MEG and its combination with accurate anatomical data, another ambitious goal of BREAKBEN was to measure brain activity directly with MRI. This has been predicted to be within reach, since the neuronally generated electric currents change the local magnetic fields, affecting MRI signals. Success in this endeavor would be a breakthrough and would enable one to further improve the accuracy of locating brain activity.
In addition to MEG and its combination with accurate anatomical data, another ambitious goal of BREAKBEN was to measure brain activity directly with MRI. This has been predicted to be within reach, since the neuronally generated electric currents change the local magnetic fields, affecting MRI signals. Success in this endeavor would be a breakthrough and would enable one to further improve the accuracy of locating brain activity.
During the first year of the projects, the following work has been done:
1) User specifications have been defined.
2) Guidelines for safety and regulatory requirements for the devices have been written.
3) Test to be used later to validate the systems have been specified.
4) The magnetometer array (SQUID sensor array) has been investigated; comparisons between wire-wound and more traditional integrated magnetometer designs have been analyzed.
5) A test dewar has been designed and fabricated.
6) A new generation of SQUIDs to obtain a lower noise level and better field tolerance has been fabricated.
7) Ultra-low-noise electronics for MRI coils have been investigated.
8) Methods for direct current imaging have been further developed.
9) Phantoms for testing the systems have been developed.
10) The effect of improved coregistration of MEG and MRI on source localization accuracy has been quantitatively studied.
11) A web page has been prepared.
12) Video and other material about the project have been produced.
13) The project and initial results have been reported in conferences and in publications.
As a result of the final period (M13-M41):
1) A novel MEG-MRI device including 120 new SQUID sensors was built. This MEG-MRI system will allow one to locate electrical brain activity more reliably and more accurately than before. This is expected to be beneficial for the characterization of epileptic activity in patients as well as abnormal activity in other brain disorders. The new system is also expected to be useful in basic studies of brain function.
2) A novel type of measurement, Current Density Imaging or CDI, was demonstrated. Here the 3-dimensional flow pattern of electric current injected in an object (eventually via scalp electrodes to the brain) is uniquely determined from the changes in MRI signals due to the magnetic field produced by the current flow.
3) Using the same principles as in CDI but now aiming to measure neuronally generated currents in the brain, progress was made but it was found that neuronal signals are not quite as strong as would be necessary for them to be seen with the thus far developed technology.
4) Phantoms that approximate the physical properties of the head and its internal structure were developed. These were tested experimentally and modeled with computer simulations.
5) It was shown that for locating brain activity and in particular for determining area-to-area connectivity with MEG, an improvement in MEG-MRI coregistration to approximately 2-mm range is needed. This accuracy is not possible with current techniques but can be easily achieved with the new technology.
6) Algorithms were developed and tested for solving the MEG inverse problem when very good co-registration is available and in the case when neuronal current imaging data would be available.
7) Market analysis including potential use cases was performed.
Although not all planned work could not be done during the project because of delays in SQUID sensor production (the device developers and fabrication facilities had to prioritize the European Space Agency ESA in their work due to ESA’s strict deadlines), overall BREAKBEN can be considered a success. This work will continue with Innovation Launchpad and Business Finland funding in order to prepare the technology for commercial exploitation.
1) User specifications have been defined.
2) Guidelines for safety and regulatory requirements for the devices have been written.
3) Test to be used later to validate the systems have been specified.
4) The magnetometer array (SQUID sensor array) has been investigated; comparisons between wire-wound and more traditional integrated magnetometer designs have been analyzed.
5) A test dewar has been designed and fabricated.
6) A new generation of SQUIDs to obtain a lower noise level and better field tolerance has been fabricated.
7) Ultra-low-noise electronics for MRI coils have been investigated.
8) Methods for direct current imaging have been further developed.
9) Phantoms for testing the systems have been developed.
10) The effect of improved coregistration of MEG and MRI on source localization accuracy has been quantitatively studied.
11) A web page has been prepared.
12) Video and other material about the project have been produced.
13) The project and initial results have been reported in conferences and in publications.
As a result of the final period (M13-M41):
1) A novel MEG-MRI device including 120 new SQUID sensors was built. This MEG-MRI system will allow one to locate electrical brain activity more reliably and more accurately than before. This is expected to be beneficial for the characterization of epileptic activity in patients as well as abnormal activity in other brain disorders. The new system is also expected to be useful in basic studies of brain function.
2) A novel type of measurement, Current Density Imaging or CDI, was demonstrated. Here the 3-dimensional flow pattern of electric current injected in an object (eventually via scalp electrodes to the brain) is uniquely determined from the changes in MRI signals due to the magnetic field produced by the current flow.
3) Using the same principles as in CDI but now aiming to measure neuronally generated currents in the brain, progress was made but it was found that neuronal signals are not quite as strong as would be necessary for them to be seen with the thus far developed technology.
4) Phantoms that approximate the physical properties of the head and its internal structure were developed. These were tested experimentally and modeled with computer simulations.
5) It was shown that for locating brain activity and in particular for determining area-to-area connectivity with MEG, an improvement in MEG-MRI coregistration to approximately 2-mm range is needed. This accuracy is not possible with current techniques but can be easily achieved with the new technology.
6) Algorithms were developed and tested for solving the MEG inverse problem when very good co-registration is available and in the case when neuronal current imaging data would be available.
7) Market analysis including potential use cases was performed.
Although not all planned work could not be done during the project because of delays in SQUID sensor production (the device developers and fabrication facilities had to prioritize the European Space Agency ESA in their work due to ESA’s strict deadlines), overall BREAKBEN can be considered a success. This work will continue with Innovation Launchpad and Business Finland funding in order to prepare the technology for commercial exploitation.
To succeed, BREAKBEN had to surpass the prevailing state of the art in several subareas. One of them is the quality of the ultra-sensitive SQUIDs. They needed to have and even lower noise than earlier and they must withstand higher magnetic fields than before and recover from them quickly without any shielding that would made the construction impractical. The new SQUIDs that were been developed in the second half of the project for the MEG-MRI system are very close to the target in both sensitivity and field tolerance. Even more sensitive SQUID sensors were developed for the neuronal current imaging. Excellent progress was made and the new levels of sensitivity are well in the sub-femtotesla range (on the order of 100 attotesla). Phantoms were developed to exquisite precision, which allows very reliable comparison of computational simulation results with experimental data. New methods in connectivity studies have paved the way to applying the new technology in brain network studies in unprecedented ways.
The socioeconomic impact and wider societal aspects of the project will be realized mainly after the technology has been taken to neuroscientific and clinical use after the end of the project. The project made it plausible that the ambitious goals of making MEG far more accurate and reliable than presently are realizable. As a result, funding has been secured to prepare the technology for the commercialization stage and for moving the MEG-MRI prototype to a hospital for patient measurements.
The socioeconomic impact and wider societal aspects of the project will be realized mainly after the technology has been taken to neuroscientific and clinical use after the end of the project. The project made it plausible that the ambitious goals of making MEG far more accurate and reliable than presently are realizable. As a result, funding has been secured to prepare the technology for the commercialization stage and for moving the MEG-MRI prototype to a hospital for patient measurements.