Cancer remains one of the leading causes of death worldwide. Biomedical imaging plays a crucial role in all phases of cancer management. Physicians often need to choose the ideal diagnostic imaging ...modality for each clinical presentation based on complex trade-offs among spatial resolution, sensitivity, contrast, access, cost, and safety. Magnetic particle imaging (MPI) is an emerging tracer imaging modality that detects superparamagnetic iron oxide (SPIO) nanoparticle tracer with high image contrast (zero tissue background signal), high sensitivity (200 nM Fe) with linear quantitation, and zero signal depth attenuation. MPI is also safe in that it uses safe, in some cases even clinically approved, tracers and no ionizing radiation. The superb contrast, sensitivity, safety, and ability to image anywhere in the body lends MPI great promise for cancer imaging. In this study, we show for the first time the use of MPI for in vivo cancer imaging with systemic tracer administration. Here, long circulating MPI-tailored SPIOs were created and administered intravenously in tumor bearing rats. 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 h, and eventual clearance beyond 48 h. Lastly, we demonstrate the quantitative nature of MPI through compartmental fitting in vivo.
The magnetic particle imaging (MPI) imaging process is a new method of medical imaging with great promise. In this paper we derive the 1-D MPI signal, resolution, bandwidth requirements, ...signal-to-noise ratio (SNR), specific absorption rate, and slew rate limitations. We conclude with experimental data measuring the point spread function for commercially available SPIO nanoparticles and a demonstration of the principles behind 1-D imaging using a static offset field. Despite arising from the nonlinear temporal response of a magnetic nanoparticle to a changing magnetic field, the imaging process is linear in the magnetization distribution and can be described as a convolution. Reconstruction in one dimension is exact and has a well-behaved quasi-Lorentzian point spread function. The spatial resolution improves cubically with increasing diameter of the SPIO domain, inverse to absolute temperature, linearly with saturation magnetization, and inversely with gradient. The bandwidth requirements approach a megahertz for reasonable imaging parameters and millimeter scale resolutions, and the SNR increases with the scanning rate. The limit to SNR as we scale MPI to human sizes will be patient heating. SAR and magnetostimulation limits give us surprising relations between optimal scanning speeds and scanning frequency for different types of scanners.
Image-guided treatment of cancer enables physicians to localize and treat tumors with great precision. Here, we present in vivo results showing that an emerging imaging modality, magnetic particle ...imaging (MPI), can be combined with magnetic hyperthermia into an image-guided theranostic platform. MPI is a noninvasive 3D tomographic imaging method with high sensitivity and contrast, zero ionizing radiation, and is linearly quantitative at any depth with no view limitations. The same superparamagnetic iron oxide nanoparticle (SPIONs) tracers imaged in MPI can also be excited to generate heat for magnetic hyperthermia. In this study, we demonstrate a theranostic platform, with quantitative MPI image guidance for treatment planning and use of the MPI gradients for spatial localization of magnetic hyperthermia to arbitrarily selected regions. This addresses a key challenge of conventional magnetic hyperthermiaSPIONs delivered systemically accumulate in off-target organs (e.g., liver and spleen), and difficulty in localizing hyperthermia results in collateral heat damage to these organs. Using a MPI magnetic hyperthermia workflow, we demonstrate image-guided spatial localization of hyperthermia to the tumor while minimizing collateral damage to the nearby liver (1–2 cm distance). Localization of thermal damage and therapy was validated with luciferase activity and histological assessment. Apart from localizing thermal therapy, the technique presented here can also be extended to localize actuation of drug release and other biomechanical-based therapies. With high contrast and high sensitivity imaging combined with precise control and localization of the actuated therapy, MPI is a powerful platform for magnetic-based theranostics.
Magnetic particle imaging (MPI) is a promising new medical imaging tracer modality with potential applications in human angiography, cancer imaging, in vivo cell tracking, and inflammation imaging. ...Here we demonstrate both theoretically and experimentally that multidimensional MPI is a linear shift-invariant imaging system with an analytic point spread function. We also introduce a fast image reconstruction method that obtains the intrinsic MPI image with high signal-to-noise ratio via a simple gridding operation in x-space. We also demonstrate a method to reconstruct large field-of-view (FOV) images using partial FOV scanning, despite the loss of first harmonic image information due to direct feedthrough contamination. We conclude with the first experimental test of multidimensional x-space MPI.
One quarter of all iodinated contrast X‐ray clinical imaging studies are now performed on Chronic Kidney Disease (CKD) patients. Unfortunately, the iodine contrast agent used in X‐ray is often toxic ...to CKD patients’ weak kidneys, leading to significant morbidity and mortality. Hence, we are pioneering a new medical imaging method, called Magnetic Particle Imaging (MPI), to replace X‐ray and CT iodinated angiography, especially for CKD patients. MPI uses magnetic nanoparticle contrast agents that are much safer than iodine for CKD patients. MPI already offers superb contrast and extraordinary sensitivity. The iron oxide nanoparticle tracers required for MPI are also used in MRI, and some are already approved for human use, but the contrast agents are far more effective at illuminating blood vessels when used in the MPI modality. We have recently developed a systems theoretic framework for MPI called x‐space MPI, which has already dramatically improved the speed and robustness of MPI image reconstruction. X‐space MPI has allowed us to optimize the hardware for five MPI scanners. Moreover, x‐space MPI provides a powerful framework for optimizing the size and magnetic properties of the iron oxide nanoparticle tracers used in MPI. Currently MPI nanoparticles have diameters in the 10‐20 nanometer range, enabling millimeter‐scale resolution in small animals. X‐space MPI theory predicts that larger nanoparticles could enable up to 250 micrometer resolution imaging, which would represent a major breakthrough in safe imaging for CKD patients.
Magnetic particle imaging (MPI) is an emerging medical imaging technique that could be a safer alternative to X‐ray and CT using iodinated contrast agents, especially for patients with chronic kidney disease. Here we describe the overall technique, detail the latest advances in MPI theory, and discuss the optimal nanoparticle characteristics for MPI. We also show images taken using our latest MPI hardware, demonstrating MPI's already superb contrast and high sensitivity.
The ability to measure blood velocities is critical for studying vascular development, physiology, and pathology. A key challenge is to quantify a wide range of blood velocities in vessels deep ...within living specimens with concurrent diffraction-limited resolution imaging of vascular cells. Two-photon laser scanning microscopy (TPLSM) has shown tremendous promise in analyzing blood velocities hundreds of micrometers deep in animals with cellular resolution. However, current analysis of TPLSM-based data is limited to the lower range of blood velocities and is not adequate to study faster velocities in many normal or disease conditions.
We developed line-scanning particle image velocimetry (LS-PIV), which used TPLSM data to quantify peak blood velocities up to 84 mm/s in live mice harboring brain arteriovenous malformation, a disease characterized by high flow. With this method, we were able to accurately detect the elevated blood velocities and exaggerated pulsatility along the abnormal vascular network in these animals. LS-PIV robustly analyzed noisy data from vessels as deep as 850 µm below the brain surface. In addition to analyzing in vivo data, we validated the accuracy of LS-PIV up to 800 mm/s using simulations with known velocity and noise parameters.
To our knowledge, these blood velocity measurements are the fastest recorded with TPLSM. Partnered with transgenic mice carrying cell-specific fluorescent reporters, LS-PIV will also enable the direct in vivo correlation of cellular, biochemical, and hemodynamic parameters in high flow vascular development and diseases such as atherogenesis, arteriogenesis, and vascular anomalies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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 (R(2) = 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.
Gastrointestinal (GI) bleeding causes more than 300 000 hospitalizations per year in the United States. Imaging plays a crucial role in accurately locating the source of the bleed for timely ...intervention. Magnetic particle imaging (MPI) is an emerging clinically translatable imaging modality that images superparamagnetic iron-oxide (SPIO) tracers with extraordinary contrast and sensitivity. This linearly quantitative modality has zero background tissue signal and zero signal depth attenuation. MPI is also safe: there is zero ionizing radiation exposure to the patient and clinically approved tracers can be used with MPI. In this study, we demonstrate the use of MPI along with long-circulating, PEG-stabilized SPIOs for rapid in vivo detection and quantification of GI bleed. A mouse model genetically predisposed to GI polyp development (Apc Min/+) was used for this study, and heparin was used as an anticoagulant to induce acute GI bleeding. We then injected MPI-tailored, long-circulating SPIOs through the tail vein, and tracked the tracer biodistribution over time using our custom-built high resolution field-free line (FFL) MPI scanner. Dynamic MPI projection images captured tracer accumulation in the lower GI tract with excellent contrast. Quantitative analysis of the MPI images show that the mice experienced GI bleed rates between 1 and 5 μL/min. Although there are currently no human scale MPI systems, and MPI-tailored SPIOs need to undergo further development and evaluation, clinical translation of the technique is achievable. The robust contrast, sensitivity, safety, ability to image anywhere in the body, along with long-circulating SPIOs lends MPI outstanding promise as a clinical diagnostic tool for GI bleeding.
Magnetic Particle Imaging is an emerging tracer imaging modality with zero background signal and zero ionizing radiation, high contrast and high sensitivity with quantitative images. While there is ...recent work showing that the low amplitude or low frequency drive parameters can improve MPI's spatial resolution by mitigating relaxation losses, the concomitant decrease of the MPI's tracer sensitivity due to the lower drive slew rates was not fully addressed. There has yet to be a wide parameter space, multi-objective optimization of MPI drive parameters for high resolution, high sensitivity and safety. In a large-scale study, we experimentally test 5 different nanoparticles ranging from multi to single-core across 18.5 nm to 32.1 nm core sizes and across an expansive drive parameter range of 0.4 - 416 kHz and 0.5 - 40 mT/μ 0 to assess spatial resolution, SNR, and safety. In addition, we analyze how drive-parameter-dependent shifts in harmonic signal energy away and towards the discarded first harmonic affect effective SNR in this optimization study. The results show that when optimizing for all four factors of resolution, SNR, discarded-harmonic-energy and safety, the overall trends are no longer monotonic and clear optimal points emerge. We present drive parameters different from conventional preclinical MPI showing ~ 2-fold improvement in spatial resolution while remaining within safety limits and addressing sensitivity by minimizing the typical SNR loss involved. Finally, validation of the optimization results with 2D images of phantoms was performed.
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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