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

Emerging investigator series: moving beyond resilience by considering antifragility in potable water systems

It is inherently difficult to plan water systems for a future that is non-predictive. This paper introduces a novel perspective for the design and operation of potable water systems under increasing water quality volatility (e.g., a relatively rapid and unpredicted deviation from baseline water quality). Increased water quality volatility and deep uncertainty stress water systems, confound design decisions, and increase the risk of decreased water system performance. Recent emphasis on resilience in drinking water treatment has partly addressed this issue, but still establishes an adversarial relationship with change. An antifragile system benefits from volatile change. By incorporating antifragility, water systems may move beyond resilience and improve performance with extreme events and other changes, rather than survive, or fail and quickly recover. Using examples of algal blooms, wildfires, and the COVID-19 pandemic, this work illustrates fragility, resilience, and antifragility within physicochemical process design including clarification, adsorption and disinfection. Methods for increasing antifragility, both individual process options and new system design tools, are discussed. Novel physicochemical processes with antifragile characteristics include ferrate preoxidation and magnetic iron (nano)particles. New design tools that allow for systematic evaluation of antifragile opportunities include artificial neural networks and virtual jar or pilot “stress testing”. Incorporating antifragile characteristics represents a trade-off with capital and/or operating cost. We present a real options analysis approach to considering costs in the context of antifragile design decisions. Adopting this antifragile perspective will help ensure water system improved performance during extreme events and a general increase in volatility

Monolithically Integrated Multilayer Silicon Nitride-on-Silicon Waveguide Platforms for 3-D Photonic Circuits and Devices

In this paper, we review and provide additional details about our progress on multilayer silicon nitride (SiN)-on-silicon (Si) integrated photonic platforms. In these platforms, one or more SiN waveguide layers are monolithically integrated onto a Si photonic layer. This paper focuses on the development of three-layer platforms for the O- and SCL-bands for very large-scale photonic integrated circuits requiring hundreds or thousands of waveguide crossings. Low-loss interlayer transitions and ultralow-loss waveguide crossings have been demonstrated, along with bilevel and trilevel grating couplers for fiber-to-chip coupling. The SiN and Si passive devices have been monolithically integrated with high-efficiency optical modulators, photodetectors, and thermal tuners in a single photonic platform

Monolithically Integrated Multilayer Silicon Nitride-on-Silicon Waveguide Platforms for 3-D Photonic Circuits and Devices

In this paper, we review and provide additional details about our progress on multilayer silicon nitride (SiN)-on-silicon (Si) integrated photonic platforms. In these platforms, one or more SiN waveguide layers are monolithically integrated onto a Si photonic layer. This paper focuses on the development of three-layer platforms for the O- and SCL-bands for very large-scale photonic integrated circuits requiring hundreds or thousands of waveguide crossings. Low-loss interlayer transitions and ultralow-loss waveguide crossings have been demonstrated, along with bilevel and trilevel grating couplers for fiber-to-chip coupling. The SiN and Si passive devices have been monolithically integrated with high-efficiency optical modulators, photodetectors, and thermal tuners in a single photonic platform

Whither Magnetic Hyperthermia? A Tentative Roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

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

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

Narrowband and x-Space Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is a new method of medical imaging with great promise for rapid angiography, cell tracking, and cancer detection. In this thesis, we approach the development of MPI theory and hardware from two perspectives, frequency space and x- space.We begin our analysis of MPI in frequency space by developing a new theory for narrow- band MPI using intermodulation. MPI, as originally envisioned, requires a high-bandwidth receiver coil and preamplifier, which are difficult to optimally noise match. Narrowband MPI dramatically reduces bandwidth requirements and increases the signal-to-noise ratio for a fixed specific absorption rate. We employ a two-tone excitation (called intermodulation) that can be tailored for a high-Q, narrowband receiver coil. We demonstrate a new MPI instrument capable of full 3D tomographic imaging of SPIO particles by imaging acrylic and tissue phantoms.Using the principles of narrowband MPI, we describe the construction of a system capable of imaging a mouse without requiring movement of the mouse using a moving stage. The system has a high field 6500 mT/m permanent magnet NdFeB gradient, and intermodulation excitation and slow FFP movement in the X, Y, and Z axes. The system excites with a HF field in the Z axis at approximately 250 kHz.Narrowband MPI produces multiple images at intermodulation products of the funda- mental frequency. It is necessary to convert these multiple harmonic images into a single composite image. We describe an efficient method to combine multiple harmonic images in frequency space that scales as O(Nlog(N)), readily scaling to reconstruction of whole-body 3D data sets in real time.We then develop the x-Space theory of MPI. In x-Space theory, we no longer consider signal excitation and reception as a frequency space process, but instead as occurring in real space. We derive the one-dimensional MPI signal, resolution, bandwidth requirements, SNR, specific absorption rate, and slew rate limitations. We follow with experimental data measuring the point spread function for commercially available SPIO nanoparticles and a demonstration of the principles behind one-d imaging using a static offset field. We conclude by generalizing x-Space MPI to multiple dimensions, where we discover that MPI imaging occurs on a reference frame aligned with the FFP velocity vector. We briefly discuss pulse sequences, and finish by presenting experimental results demonstrating the three-dimensional point spread function of the MPI experiment

Narrowband and x-Space Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is a new method of medical imaging with great promise for rapid angiography, cell tracking, and cancer detection. In this thesis, we approach the development of MPI theory and hardware from two perspectives, frequency space and x- space.We begin our analysis of MPI in frequency space by developing a new theory for narrow- band MPI using intermodulation. MPI, as originally envisioned, requires a high-bandwidth receiver coil and preamplifier, which are difficult to optimally noise match. Narrowband MPI dramatically reduces bandwidth requirements and increases the signal-to-noise ratio for a fixed specific absorption rate. We employ a two-tone excitation (called intermodulation) that can be tailored for a high-Q, narrowband receiver coil. We demonstrate a new MPI instrument capable of full 3D tomographic imaging of SPIO particles by imaging acrylic and tissue phantoms.Using the principles of narrowband MPI, we describe the construction of a system capable of imaging a mouse without requiring movement of the mouse using a moving stage. The system has a high field 6500 mT/m permanent magnet NdFeB gradient, and intermodulation excitation and slow FFP movement in the X, Y, and Z axes. The system excites with a HF field in the Z axis at approximately 250 kHz.Narrowband MPI produces multiple images at intermodulation products of the funda- mental frequency. It is necessary to convert these multiple harmonic images into a single composite image. We describe an efficient method to combine multiple harmonic images in frequency space that scales as O(Nlog(N)), readily scaling to reconstruction of whole-body 3D data sets in real time.We then develop the x-Space theory of MPI. In x-Space theory, we no longer consider signal excitation and reception as a frequency space process, but instead as occurring in real space. We derive the one-dimensional MPI signal, resolution, bandwidth requirements, SNR, specific absorption rate, and slew rate limitations. We follow with experimental data measuring the point spread function for commercially available SPIO nanoparticles and a demonstration of the principles behind one-d imaging using a static offset field. We conclude by generalizing x-Space MPI to multiple dimensions, where we discover that MPI imaging occurs on a reference frame aligned with the FFP velocity vector. We briefly discuss pulse sequences, and finish by presenting experimental results demonstrating the three-dimensional point spread function of the MPI experiment