Biogenic gas nanostructures as ultrasonic molecular reporters.

Ultrasound is among the most widely used non-invasive imaging modalities in biomedicine, but plays a surprisingly small role in molecular imaging due to a lack of suitable molecular reporters on the nanoscale. Here, we introduce a new class of reporters for ultrasound based on genetically encoded gas nanostructures from microorganisms, including bacteria and archaea. Gas vesicles are gas-filled protein-shelled compartments with typical widths of 45-250 nm and lengths of 100-600 nm that exclude water and are permeable to gas. We show that gas vesicles produce stable ultrasound contrast that is readily detected in vitro and in vivo, that their genetically encoded physical properties enable multiple modes of imaging, and that contrast enhancement through aggregation permits their use as molecular biosensors

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

High-Resolution, In Vivo Magnetic Resonance Imaging of Drosophila at 18.8 Tesla

High resolution MRI of live Drosophila was performed at 18.8 Tesla, with a field of view less than 5 mm, and administration of manganese or gadolinium-based contrast agents. This study demonstrates the feasibility of MR methods for imaging the fruit fly Drosophila with an NMR spectrometer, at a resolution relevant for undertaking future studies of the Drosophila brain and other organs. The fruit fly has long been a principal model organism for elucidating biology and disease, but without capabilities like those of MRI. This feasibility marks progress toward the development of new in vivo research approaches in Drosophila without the requirement for light transparency or destructive assays

Line-Scanning Particle Image Velocimetry: An Optical Approach for Quantifying a Wide Range of Blood Flow Speeds in Live Animals

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

Magnetic Particle Imaging for the Evaluation of Gastrointestinal Health by Measuring Gastrointestinal Permeability

Various diseases and immune-related issues have been associated with the gastrointestinal system’s health. Gastrointestinal permeability - a measure of transport across the GI tract’s cell lining from the lumen - is a functional parameter that is affected and is a viable factor in GI health assessment. Current diagnosis of GI-related disease involves the use of invasive exploratory surgery to minimally invasive colonoscopy. Magnetic particle imaging (MPI) is a non-radioactive and highly sensitive tracer imaging modality. The nanoparticle tracers used for MPI are FDA approved and can readily be translated into the clinic. In this research, we provide the first proof-of-concept using MPI to evaluate GI permeability in an in vitro model of the epithelial barrier lining of the GI tract

In vivo therapeutic cell tracking using magnetic particle imaging

White blood cells (WBCs) are a key component of our immune system. They play an essential role in surveillance, defense and adaptation against foreign pathogens during an immune response. Immunotherapies and immunomodulatory medications have become indispensable for treating cancer and immune disorders. Hence, imaging the immune response could help medicine diagnose and treat infections, inflammatory diseases like cardiovascular disease, and cancer. Currently, doctors rely on imaging tools like In-111 WBC scans to visualize the immune response. However, these tools destroy CAR-T and CAR-NK cells with radiation before they home to a tumor. A new biomedical imaging tool, Immuno-MPI, could remedy this pitfall and help doctors and researchers optimize immunotherapy for solid tumors. MPI uses no radiation to track cells. Its tracers also have infinite persistence. Here, we compare the effects and sensitivity limits of MPI to In111-WBC scintigraphy

Design of a more easily shimmable gradiometric coil using linear programming

Magnetic particle imaging (MPI) is a tracer imaging modality that detects superparamagnetic iron oxide nanoparticles (SPIOs), enabling sensitive, radiation-free imaging of cells and disease pathologies. The arbitrary waveform relaxometer (AWR) is an indispensable platform for developing magnetic nanoparticle tracers and evaluating tracer performace for magnetic particle imaging applications. One of the biggest challenges in arbitrary waveform excitation is direct feedthrough interference, which is usually six orders of magnitude larger than the signal from magnetic nanoparticles. Direct feedthrough is often mitigated with a gradiometric cancellation coil which requires extremely precise placement in order to achieve adequate decoupling from the transmit excitation coil. This work will showcase a coil design of a transmit coil that meets excitation capability requirements with an order of magnitude more forgiving mechanical tolerance