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Magnetic Resonance Methods Development and Applications for Life Sciences

Final Report Summary - EUROCANMRI (Magnetic Resonance Methods Development and Applications for Life Sciences)

The project aimed at the improvement of current diagnostic capabilities of MR in the areas of cancer, spinal cord and Alzheimer diseases as well as the development of new MR imaging methods. These tasks were accomplished with the support from the IBD NRC facilities and researchers. The combination of Canadian expertise and the experience of Polish (INP PAN) and Czech (UPT CAS)
partners in these areas was a perfect match that allowed further advancements of science.
Collaboration among the above institutions in the following areas was realised during the project duration:
1. Development of new Magnetic Resonance Imaging (MRI) methods.
2. Application of Magnetic Resonance to the study of structure, function and pathology of the Central Nervous System.
3. Development of Molecular MRI for early cancer diagnosis.
The specific workpackages within the area 1 of the collaboration included:
- Development of a low cost console for MRI and MRS
- Gradient free MRI for silent and low cost MR imaging.
Within the area 2 specific workpackages were:
- Application of the simultaneous brain and spinal cord fMRI and spinal cord DTI in the animal model of the spinal cord injury,
- Implementation of fMRI for studying cortical plasticity in rat's brain
- In vivo MRI/MRS study of an animal model of sporadic Alzheimer disease.

During the course of the project the MRI console was designed and built at NRC IBD and succesfully installed at INP PAN site, integrated with 4.7T magnet and tested with a range of phantoms for hydrogen and phosphorus resonances. The INP PAN team with the help of UPT CAS team developed software packages for different imaging methods including cardiac, fMRI, diffusion and spectroscopy, test the hardware and software and applied it for ongoing projects in preclinical MR imaging in vivo as well as material science. With this work we demonstrated feasibility of designing a low cost MRI/MRS system, which can be used for a range of applications.

Moreover the gradient free MRI (RF MRI) methodology was set up to the extent allowing for demontration of its practical use. Conventionally, MR images are formed by applying gradients to the main static magnetic field (B0). However, the B0 gradient equipment is expensive, power-hungry, complex, and noisy and can induce eddy currents in nearby conducting structures, including the patient. The obtained experimental results with RF MRI approach demonstrated one-dimensional and two-dimensional imaging capabilities and slice selection using a single-channel, transmit/receive, 0.2 T, permanent magnet, human MR system. Potential applications are those in which one or more of the features of simplified equipment, lower costs, silent MRI, or the different physics of the image formation process are particularly advantageous, one of them being possibility of using MRI at space station.

Among the research activities during the project a novel animal model of neurodegeneration, similar to the molecular and pathological features of Alzheimer's disease was proposed based on the intracerebroventricular injection of streptozotocin (STZ) in rats. We used 1H Magnetic Resonance Spectroscopy (1H-MRS) at 9.4T for quantification of the metabolites changes during the course of experiment. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 18 brain metabolites. Comparing the research based on biochemical studies and the results of our experiment we concluded that high field in vivo 1H-MRS accurately reflects the neurochemical changes induced by a subdiabetogenic dose of STZ. The localized 1H-MRS technique provides new input into better understanding of the neuropathological processes that underlie the neurodegeneration of Alzheimer's type. The proposed non-invasive method enables as well monitoring the development and possible treatment modalities of the Alzheimer's disease in the animal models.

A development of effective method for early diagnosis of glioma was the aim of other workpackage in the project. We have investigated the molecular targeting of a contrast agent to brain tumor vessels in a mouse model of glioblastoma multiforme. We also tested magnetic properties of different nanoparticles (NP) as potential contrast agents for MRI. NPs with different core/shell composition were tested and their T2 relaxation times were measured. A mouse model of glioblastoma multiforme was used to determine the accumulation of a targeted contrast agent in tumor vessels. T2 relaxation time was used to measure the accumulation of the contrast agent in the tumor. Changes in tumor to brain contrast due to active targeting were compared to a non-targeted contrast agent. These results were confirmed with near infra-red measurements. The study showed, that the developed anti-IGFBP7-iron oxide single domain antibody-targeted MRI contrast agent selectively binds to abnormal vessels within a glioblastoma. In addition we assessed feasibility of using different pulse sequences for NP imaging in tumor. Gradient echo (GE), flow compensated gradient echo (GEFC) and susceptibility weighted (SWI) MR images prior to injection of the NP in our study showed very low contrast between tumor and healthy brain tissues. Post-injection of the NP demonstrated significantly increased CNR for the GE, GEFC and especially the SW images.

Feasibility study of functional MRI (fMRI) on rats using 4.7T MRI scanner were conducted as well during the course of the project. It was concluded however that signal to noise ratio possible to achieve is too low for effective in vivo animal fMRI experiments, thus leaving 9.4T scanner as an only option for further continuation of these type of experiments.

In addition to research and development work, two workshops were organised: in 2009 in Banff, Canada and in 2011 in Krakow, Poland. Both events were well attended by numerous scientists from Canada, USA as well as Poland and other European countries, being good opportunities for exchange of ideas and knowledge between them.