Lars Hoff

Bio: Lars Hoff is an academic researcher from Sewanee: The University of the South. The author has contributed to research in topics: Transducer & Ultrasonic sensor. The author has an hindex of 21, co-authored 115 publications receiving 2700 citations. Previous affiliations of Lars Hoff include Buskerud and Vestfold University College & Norwegian University of Science and Technology.

Oscillations of polymeric microbubbles: Effect of the encapsulating shell

Abstract: A model for the oscillation of gas bubbles encapsulated in a thin shell has been developed. The model depends on viscous and elastic properties of the shell, described by thickness, shear modulus, and shear viscosity. This theory was used to describe an experimental ultrasound contrast agent from Nycomed, composed of air bubbles encapsulated in a polymer shell. Theoretical calculations were compared with measurements of acoustic attenuation at amplitudes where bubble oscillations are linear. A good fit between measured and calculated results was obtained. The results were used to estimate the viscoelastic properties of the shell material. The shell shear modulus was estimated to between 10.6 and 12.9 MPa, the shell viscosity was estimated to between 0.39 and 0.49 Pas. The shell thickness was 5% of the particle radius. These results imply that the particles are around 20 times more rigid than free air bubbles, and that the oscillations are heavily damped, corresponding to Q-values around 1. We conclude that the shell strongly alters the acoustic behavior of the bubbles: The stiffness and viscosity of the particles are mainly determined by the encapsulating shell, not by the air inside.

Acoustic characterization of contrast agents for medical ultrasound imaging

Abstract: Nycomed’s ultrasound contrast agent NC100100 has been investigated by in vitro acoustic measurements. Acoustic attenuation spectra were used to determine resonance frequencies of the particles. The spectra were correlated with size distributions, and it was found that the shell‐encapsulated gas bubbles can be described as viscoelastic particles with bulk modulus 700 kPa. When exposed to hydrostatic overpressures mimicking those found in vivo during the systolic heart cycle, the resonance frequency increased, as expected by the particles’ increased stiffness. This effect was reversible: After the pressure was released, the particles went back to giving the original attenuation spectrum. This shows that the particles are not destroyed or otherwise changed by the pressure. Acoustic backscatter measured as a function of distance through a contrast agent was used to estimate the backscatter efficiency of the particles, that is, the ratio between scattered and absorbed ultrasound. Results from these measurements agree with theoretical estimates based on the attenuation spectra. Measurements on NC100100 were compared with earlier results from measurements on Albunex® and measurements on an experimental polymer‐encapsulated contrast agent, showing how different shell materials cause differences in particle stability and stiffness.

Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors

Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, having reporters comprising gas-filled microbubbles stabilised by monolayers of film-forming surfactants, the reporter being coupled or linked to at least one vector.

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Self-assembly and mineralization of peptide-amphiphile nanofibers

Abstract: We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.

Coated implantable medical device

Abstract: A coated implantable medical device 10 includes a structure 12 adapted for introduction into the vascular system, esophagus, trachea, colon, biliary tract, or urinary tract; at least one layer 18 of a bioactive material positioned over the structure 12; and at least one porous layer 20 positioned over the bioactive material layer 18. Preferably, the structure 12 is a coronary stent, and the bioactive material is at least one of heparin, dexamethasone or a dexamethasone derivative. The device 10 includes layers 18 and 22 of heparin and dexamethasone, the layer 22 of dexamethasone being positioned above the layer 18 of heparin. The layers of bioactive material also can be individual materials or a combination of different materials. Unexpectedly, the more soluble heparin markedly promotes the release of the less soluble dexamethasone above it. The porous layer 20 is composed of a polymer applied by vapor or plasma deposition and provides a controlled release of the bioactive material. It is particularly preferred that the polymer is a polyimide, parylene or a parylene derivative, which is deposited without solvents, heat or catalysts, merely by condensation of a monomer vapor.

Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery.

Abstract: This review offers a critical analysis of the state of the art of medical microbubbles and their application in therapeutic delivery and monitoring. When driven by an ultrasonic pulse, these small gas bubbles oscillate with a wall velocity on the order of tens to hundreds of meters per second and can be deflected to a vessel wall or fragmented into particles on the order of nanometers. While single-session molecular imaging of multiple targets is difficult with affinity-based strategies employed in some other imaging modalities, microbubble fragmentation facilitates such studies. Similarly, a focused ultrasound beam can be used to disrupt delivery vehicles and blood vessel walls, offering the opportunity to locally deliver a drug or gene. Clinical translation of these vehicles will require that current challenges be overcome, where these challenges include rapid clearance and low payload. The technology, early successes with drug and gene delivery, and potential clinical applications are reviewed.