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      Design analysis of an MPI human functional brain scanner

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          Abstract

          MPI’s high sensitivity makes it a promising modality for imaging brain function. Functional contrast is proposed based on blood SPION concentration changes due to Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in fMRI studies. MPI offers the potential for a direct and more sensitive measure of SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in sensitivity, enhancing the scientific and clinical value of functional imaging. As human-sized MPI systems have not been attempted, we assess the technical challenges of scaling MPI from rodent to human brain. We use a full-system MPI simulator to test arbitrary hardware designs and encoding practices, and we examine tradeoffs imposed by constraints that arise when scaling to human size as well as safety constraints (PNS and central nervous system stimulation) not considered in animal scanners, thereby estimating spatial resolutions and sensitivities achievable with current technology. Using a projection FFL MPI system, we examine coil hardware options and their implications for sensitivity and spatial resolution. We estimate that an fMPI brain scanner is feasible, although with reduced sensitivity (20×) and spatial resolution (5×) compared to existing rodent systems. Nonetheless, it retains sufficient sensitivity and spatial resolution to make it an attractive future instrument for studying the human brain; additional technical innovations can result in further improvements.

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          Tomographic imaging using the nonlinear response of magnetic particles.

          The use of contrast agents and tracers in medical imaging has a long history. They provide important information for diagnosis and therapy, but for some desired applications, a higher resolution is required than can be obtained using the currently available medical imaging techniques. Consider, for example, the use of magnetic tracers in magnetic resonance imaging: detection thresholds for in vitro and in vivo imaging are such that the background signal from the host tissue is a crucial limiting factor. A sensitive method for detecting the magnetic particles directly is to measure their magnetic fields using relaxometry; but this approach has the drawback that the inverse problem (associated with transforming the data into a spatial image) is ill posed and therefore yields low spatial resolution. Here we present a method for obtaining a high-resolution image of such tracers that takes advantage of the nonlinear magnetization curve of small magnetic particles. Initial 'phantom' experiments are reported that demonstrate the feasibility of the imaging method. The resolution that we achieve is already well below 1 mm. We evaluate the prospects for further improvement, and show that the method has the potential to be developed into an imaging method characterized by both high spatial resolution as well as high sensitivity.
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            Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo

            Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R2 = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents.
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              Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast

              We demonstrate that Magnetic Particle Imaging (MPI) enables monitoring of cellular grafts with high contrast, sensitivity, and quantitativeness. MPI directly detects the intense magnetization of iron-oxide tracers using low-frequency magnetic fields. MPI is safe, noninvasive and offers superb sensitivity, with great promise for clinical translation and quantitative single-cell tracking. Here we report the first MPI cell tracking study, showing 200-cell detection in vitro and in vivo monitoring of human neural graft clearance over 87 days in rat brain.
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                Author and article information

                Journal
                101705792
                46521
                Int J Magn Part Imaging
                Int J Magn Part Imaging
                International journal on magnetic particle imaging
                2365-9033
                19 May 2017
                23 March 2017
                2017
                25 July 2017
                : 3
                : 1
                : 1703008
                Affiliations
                [a ]MGH-HST A.A. Martinos Center for Biomedical Imaging, Dept. of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
                [b ]Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA
                [c ]Case Western Reserve University, OH, USA
                [d ]University of California, Berkeley, CA, USA
                [e ]Harvard Medical School, Boston, MA, USA
                Author notes
                [* ]Corresponding author: emason1@ 123456mgh.harvard.edu
                Article
                NIHMS873444
                10.18416/ijmpi.2017.1703008
                5526464
                28752130
                0c0992a9-10bf-47a4-a4a7-3b832f06fb24

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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