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Hardware Innovations and Biomedical Applications of Magnetic Particle Imaging
Get PDFMagnetic particle imaging (MPI) shows extraordinary promise for biomedical applications: it is highly sensitive, linearly quantitative anywhere in the body, has zero signal from biological tissue, and is safe for patients. One of the major challenges in MPI is spatial resolution, which is fundamentally governed by selection field gradient strength and nanoparticle properties. In Chapter 3 of this dissertation, I describe the design and construction of a high gradient field-free line (FFL) scanner for improved spatial resolution. This is the world's first iron return MPI scanner, and the highest resolution FFL imager in the world. Armed with MPI-tailored nanoparticles created by our collaborators at the University of Washington and Lodespin Labs, we were able to achieve 700 micron resolution in vivo. We also successfully demonstrated dynamic projection MPI as well as 3D projection reconstruction MPI with this scanner. In addition to hardware innovations, I have also demonstrated the use of MPI in two very important applications, namely cancer imaging and gastrointestinal (GI) bleed detection. In Chapter 2 of this dissertation, I demonstrated the first use of MPI for in vivo cancer imaging with systemic tracer administration. Due to the enhanced permeability and retention (EPR) effect, the tumor was highlighted with tumor-to-background ratio of up to 50. The nanoparticle dynamics in the tumor was also well appreciated, with initial wash-in on the tumor rim, peak uptake at 6 hours, and eventual clearance beyond 48 hours. In Chapter 4 of this dissertation, I demonstrated the first use of MPI along with long-circulating, PEG-stabilized SPIOs for rapid in vivo detection and quantification of GI bleed. MPI-tailored, long-circulating SPIOs were systemically administered into a disease model of GI bleed. The tracer biodistribution was then tracked over time using our custom-built high resolution FFL MPI scanner which was described in Chapter 3. Dynamic MPI projection images captured tracer accumulation in the lower GI tract with excellent contrast. The robust contrast, sensitivity, safety, ability to image anywhere in the body, along with our MPI-tailored long-circulating SPIOs, demonstrates the outstanding promise of MPI as a clinical diagnostic tool
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Applications of Magnetic Particle Imaging to Brain Imaging
Get PDFMagnetic Particle Imaging is a novel imaging modality with many applications in the preclinical, and soon, clinical space. In particular, MPIshows promise for imaging of various brain related pathologies, such as stroke, hemmorhage, and traumatic brain injury. In this thesis, wedemonstrate a series of first-in-animal proof-of-concept experiments that MPI could soon be superior to our conventional imaging technologies, including X-ray CT, MRI, ultrasounds and nuclear medicine for particular neuroimaging applications. In the process, we will develop algorithmic enhancements to the image reconstruction of MPI signals in order to achieve real time interventional imaging, much like X-ray fluoroscopic imaging, but without ionizing radiation and significant risksof catheter and iodinated contrast media
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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Tissue Magnetic Susceptibility Matched Pyrolytic Graphite Foam for Improved MRI
Get PDFIn MRI, a powerful and uniform static B0 field is responsible for image signal and contrast. However, regions of different magnetic susceptibilities in the static field give rise to field inhomogeneities that cause image artifacts. For example, air and tissue interfaces for a patient in a MRI study induce up to ±5 ppm static B0 field perturbations within the patient. Unfortunately shim coils are too large to compensate for the very steep field variations found near the breast, cervical spine, shoulders, occipital lobe, and other regions of the body. Many MRI applications are vulnerable to B0 inhomogeneity, including robust fat suppression, which requires better than ±1 ppm homogeneity. To address this challenge, we have developed a flexible, conforming composite foam with magnetic susceptibility matched to human tissue. We surround the region with enough matching material to move the field gradients outside of the body where they cannot cause MRI artifacts. Our matching material is a pyrolytic graphite (PG) composite foam. It has many advantages over existing matching agents: it is lightweight; it adds no noise; and it is safe to embed receiver coils within the PG foam. In this thesis, we propose theory that describes the magnetic susceptibility matching properties of composite PG foam. We show experimental proof of concept susceptibility matching and safety in phantom experiments. We also experimentally demonstrate that PG foam cushions improve the B0 field uniformity to the critical threshold of ±1 ppm in both phantoms and in the neck of 6 normal volunteers at 3T. The tissue susceptibility matched PG foams consistently mitigate signal drop out, improve image SNR, and enable far more robust frequency selective fat suppression in T1-weighted FLASH images in volunteers. PG foam has many practical applications in MR applications that require a pristine B0 field
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Linearity, Shift-Invariance and Resolution Improvement for Quantitative Magnetic Particle Imaging
Get PDFMagnetic Particle Imaging (MPI) is an emerging tracer imaging modality that utilizes safe, low-frequency magnetic fields and an existing, human-safe, superparamagnetic iron oxide (SPIO) nanoparticle tracer. MPI already shows high contrast and high sensitivity in small animal imaging. The technique exploits the nonlinear magnetization response of SPIO nanoparticles to time-varying magnetic fields at very low frequencies (VLF). Hence, for medical imaging, MPI only detects a signal from the tracers and not from the diamagnetic biological tissue. Moreover, since tissue is completely transparent to VLF magnetic fields, there is no depth attenuation of the MPI signal. Thus, the physics of MPI shows that it has the ideal contrast for tracer imaging, and is ideally suited for clinical applications such as angiography, cancer imaging, inflammation imaging, and in vivo stem cell therapy tracking.The fundamental advantages of MPI as a tracer imaging modality are its superb tracer sensitivity, ideal image contrast, and safety of the tracer and modality. Our lab has already shown experimentally that MPI can detect a minuscule sample of 10 nanogram (100 nM) of tracer in a prototype scanner. In principle, there is another 2 orders of magnitude achievable improvement before the sensitivity reaches the physical limit of the technique. MPI is currently shown to have 200x higher net signal-to-noise ratio (SNR) than magnetic resonance imaging (MRI), and this sensitivity is approaching that of the nuclear medicine, such as positron emission tomography (PET) and single-photon emission computerized tomography (SPECT). Moreover, because MPI tracer is not radioactive, the dose-limited sensitivity can easily exceed PET and SPECT and effectively be more sensitive. MPI has ideal image contrast because the contrast is positive, quantitative, has no tissue background, and independent of depth. Lastly, MPI has ideal tracer and modality safety. MPI tracers, notably SPIO nanoparticles, have been shown to be much safer for patients with chronic kidney disease than currently available tracers (iodine and gadolinium) used in planar X-ray imaging, X-ray computed tomography (CT), and MRI. In addition, MPI uses no ionizing radiation, and thus is safer than X-ray, CT, PET and SPECT.MPI is still a young technology in the medical imaging field. With 10 years of development since the first introduction of the technique in 2005, the current state of MPI research is very much like MRI in the 1980s. There remain many open challenges to be addressed, which makes this field very exciting. In this thesis, we will investigate and address three major challenges in MPI that are crucial for the preclinical and clinical adoption. These challenges are: 1) Restoration of MPI's linearity and shift-invariance (LSI), which are hallmarks of almost all clinically relevant imaging modalities; 2) Achieving isotropic resolution,which is an indispensable characteristic for any diagnostic and quantitative imaging technique; and 3) Understanding the source of the background image haze and eliminate it, which is essential for further improving image resolution, contrast and conspicuity.We begin by investigating the LSI properties in MPI. In MPI, high-pass filters designed to remove unavoidable direct feedthrough interference also remove information crucial to ensuring LSI in MPI scans. We present a complete theoretical and experimental description of the image artifacts from filtering, and propose and validate a robust algorithm to completely restore the lost information for the x-space MPI method. We provide the theoretical, simulated, and experimental proof that our algorithm indeed restores the LSI properties of MPI, which is indispensable for quantification and diagnostic utility.We then detailed an investigation into one of MPI's unique resolution challenge: MPI's point spread function (PSF) is highly dependent on the scanning parameters, and every experimental MPI scan ever created lacks desirable isotropic resolution, which leads to ambiguous and inaccurate diagnosis. In this thesis, we generalized a tensor imaging theory for multidimensional x-space MPI to explore the physical source of this anisotropy, presented a multichannel hardware and scanning trajectory to remove anisotropy, and designed and constructed two orthogonal excitation and detector coils to enable isotropic resolution. We experimentally verified the resolution improvement with the new hardware and reconstruction, and showed that isotropic resolution enabled accurate diagnosis of stenosis in small human arterial phantoms.Lastly, we investigated on MPI's reduced image contrast due to significant background image haze. We have found that the image haze comes from the undesirable rotation of the nanoparticle magnetic moment in response to the applied field outside of the scanning region. Consequently, the native PSF contains a hazy component that falls off as 1/Gr, where G is the gradient field strength, and r is the radially symmetric spatial coordinate. This haze resembles the haze seen in CT images reconstructed with non-filtered backprojection. We propose that we can reshape the MPI PSF with k-space equalization filter that dehazes the image without any noise amplification. We demonstrate experimentally that equalization dramatically increases image contrast and enables the first quantitative measurements of lumen size in a sub-millimeter diameter blood vessel phantom.In conclusion, this thesis work has proposed significant advancement in imaging theory, hardware and algorithm for MPI that ensures LSI properties, and improves image resolution, contrast and conspicuity. Taken together, these are major contributions to the fundamental imaging science of MPI. LSI and sharp isotropic resolution is essential for quantitative imaging, and could foster clinical adoption of MPI
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Exploiting Magnetic Relaxation in x-Space Magnetic Particle Imaging
Get PDFMagnetic particle imaging (MPI) is a new and rapidly developing imaging modality. Here we explore new ways to use MPI for molecular imaging and theranostic applications. A major focus is exploring methods to leverage the magnetic relaxation dynamics associated with the tracers used in MPI. In the context of canonical MPI implementations, these dynamics can reduce resolution and signal; however, they are also a source of molecular imaging contrast. In the first part of this thesis, we experimentally characterize relaxation in the canonical sinusoidal MPI implementation and explore novel ways to exploit this relaxation for colorized imaging and theranostic applications. In the second part, we describe a new approach to signal encoding in MPI that we call pulsed MPI (pMPI). We show that pMPI can allow one to fully prevent relaxation-induced resolution loss and can even provide ways to improve resolution over traditional continuous wave encoding techniques. Furthermore, pMPI can be leveraged to directly quantify magnetic relaxation that does occur and report this information in an imaging format as relaxation images (in contrast to the standard tracer mass/concentration images). Such approaches may pave the way for greatly improved color MPI and related molecular imaging methods. We believe a major takeaway from this work is that there remains significant untapped potential in MPI by way of unexploited physics. We believe development of these possibilities will be an exciting part of our field's future
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Towards clinical immuno-MPI: Optimizing magnetic particle imaging of superferromagnetic iron oxide nanoparticles and developing MPI leukocyte tracking
Get PDFMagnetic particle imaging (MPI) is a sensitive, high contrast tracer modality that directly images superparamagnetic iron oxide nanoparticles (SPIOs), enabling radiation-free theranostic imaging. With zero tissue signal, persistent biosafe tracers, and no ionizing radiation, MPI has shown great promise for cell tracking, vascular imaging, and imaging applications. Indeed, its capability for multi-month studies and exquisite contrast position itself uniquely for immune-cell based diagnoses and extended monitoring of immunotherapies. However, MPI resolution is currently limited by scanner and particle constraints. Recent tracers have experimentally shown 10x resolution and signal improvements, with dramatically sharper M-H curves. Experiments suggest that this results from interparticle interactions, conforming to literature definitions of superferromagnetism. We thus call our tracers superferromagnetic iron oxide nanoparticles (SFMIOs). While SFMIOs provide excellent signal and resolution, they exhibit hysteresis, with non-negligible remanence and coercivity.
In my dissertation I provide the first report on MPI scanning with remanence and coercivity, including the first quantitative measurements of SFMIO remanence decay and reformation using a novel multi-echo pulse sequence. We also describe an SNR-optimized pulse sequence for SFMIOs under human electromagnetic safety limitations.
I separately investigate ex vivo and in situ labeling neutrophils and macrophages and tracking to inflammation and immune activity with XY Zhou and P Chandrasekharan. I demonstrate the first antibody MPI (Ab-MPI) images using antibody-conjugated SPIOs (Ab-SPIOs), showing bone marrow and sites of lipopolysaccharide-induced myositis. Through bioluminescent imaging, electron microscopy, flow cytometry and histopathology, I confirm labeling and tracking of neutrophils and macrophages. Excitingly, our images are able to differentiate between the acute inflammation response from neutrophils, and the chronic response from macrophages.
With the resolution improvements from SFMIOs, which could be used to reduce hardware costs by 100x, and the demonstrated applications of Ab-SPIOs, MPI demonstrates incredible potential for clinical diagnosis and immunotherapy monitoring
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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