Magnetic Particle Imaging for Highly Sensitive, Quantitative, and Safe in Vivo Gut Bleed Detection in a Murine Model

Abstract

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) 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.

Towards accurate modeling of the multidimensional magnetic particle imaging physics

“…In contrast to magnetic resonance imaging, the contrast in MPI is positive and the reconstructed images are quantitative. With these properties MPI is an interesting candidate for various medical applications ranging from vascular imaging [2][3][4][5] to targeted imaging [6].…”

Superparamagnetic iron oxides as MPI tracers: A primer and review of early applications

“…Since the iron present in these two bleeding byproducts is not superparamagnetic, it will be able to produce a specific MPI signal. Similarly, MPI can be properly used in abdominal studies [54], where the colon and other parts of the GI system often contain air-filled pockets or food packages that show up hypointense on MRI.…”

Magnetic particle imaging for radiation-free, sensitive and high-contrast vascular imaging and cell tracking

“…Alternative approaches to increasing MPI tracer circulation time include loading SPIOs into red blood cells 7,19,20 . These long-circulating tracers are crucial for applications like cancer imaging via the enhanced permeability and retention (EPR) effect 21•• , brain imaging for traumatic brain injury (TBI) and stroke via visualizing cerebral blood volume and cerebral blood flow 22••,23 , and gastrointestinal (GI) bleed imaging 24 . Each of these applications shown in Fig.…”

“…In cell tracking, researchers have imaged several types of stem cells, and more recently interest has grown in imaging immune cells for infection imaging, immunotherapy tracking and early-stage cancer detection. Scanner schematic adapted with permission from 24 . Copyright 2017 American Chemical Society.…”

“…Dynamic projection MPI and subtraction MPI images, both co-registered to X-ray anatomical reference, allow detection and quantification of GI bleed in a ApcMin/+ mouse model predisposed to GI polyp development. Reprinted with permission from 24 . Copyright 2017 American Chemical Society.…”