An Innovative Ultrasound Signal Processing Technique to Selectively Detect Nanosized Contrast Agents in Echographic Images

The aim of this paper was to optimize the employment of a novel algorithm for acquisition and processing of medical ultrasound (US) signals to facilitate its clinical translation. The implemented procedure is dedicated to selective enhancement of nanoparticle (NP) contrast agents in echographic images and is based on the differences in US signal backscatter between NP-containing targets and more homogeneous objects. Previous preliminary studies verified the feasibility of this approach on silica nanospheres (SiNSs) dispersed at a constant volume concentration (0.7%) in agarose gel samples. The present extended these evaluations, addressing two issues of direct clinical interest: 1) safety: SiNSs were coated with a biocompatible layer made of polyethylene glycol (PEG) and the adopted NP volume concentration was reduced to 0.2%, which is in the nontoxic range and 2) reproducibility: a different phantom configuration was used, to verify the independence of algorithm performance from a specific target region shape. The obtained results demonstrated that the proposed method can be effectively applied to enhance the presence of PEG-coated SiNSs in the diameter range 160-660 nm at a low and biocompatible volume concentration: the combined employment of a phantom with a different geometry and a lower concentration of PEG-coated NPs, in fact, caused only slight variations in the suppression patterns of noncontrast echoes, without affecting the final diagnostic effectiveness of the investigated contrast detection scheme. This approach also provides specific advantages with respect to the available measurement techniques dedicated to the enhancement of targeted US contrast agents for molecular imaging purposes.

[1]  Raúl Mateos,et al.  A Strict-time Distributed Architecture for Digital Beamforming of Ultrasound Signals , 2007, 2007 IEEE International Symposium on Intelligent Signal Processing.

[2]  Marcantonio Catelani,et al.  Experimental Stress Characterization of a Biomedical Ultrasound Probe Soldered With Innovative Silver Isotropically Conductive Adhesive , 2012, IEEE Transactions on Instrumentation and Measurement.

[3]  Francesco Conversano,et al.  Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging , 2013, Journal of Nanoparticle Research.

[4]  Filippo Attivissimo,et al.  A Suitable Threshold for Speckle Reduction in Ultrasound Images , 2013, IEEE Transactions on Instrumentation and Measurement.

[5]  A. Bouakaz,et al.  Contrast agent response to chirp reversal: simulations, optical observations, and acoustical verification , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[6]  Sergio Casciaro,et al.  Theranostic applications: Non-ionizing cellular and molecular imaging through innovative nanosystems for early diagnosis and therapy. , 2011, World journal of radiology.

[7]  P. Burns,et al.  Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. , 2000, Investigative radiology.

[8]  Enzo Terreno,et al.  Image guided therapy: the advent of theranostic agents. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Wendy Van Moer,et al.  Functional Magnetic Resonance Imaging: An Improved Short Record Signal Model , 2011, IEEE Transactions on Instrumentation and Measurement.

[10]  Enzo Terreno,et al.  Encoding the frequency dependence in MRI contrast media: the emerging class of CEST agents. , 2010, Contrast media & molecular imaging.

[11]  Tobias Schaeffter,et al.  A Novel Receive-Only Liquid Nitrogen ($\hbox{LN}_{2}$ )-Cooled RF Coil for High-Resolution In Vivo Imaging on a 3-Tesla Whole-Body Scanner , 2012, IEEE Transactions on Instrumentation and Measurement.

[12]  Vladimir P. Torchilin,et al.  Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K J Wolf,et al.  Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases. , 2001, AJR. American journal of roentgenology.

[14]  Juan Antonio Hernández Tamames,et al.  Objective Assessment of Olfactory Function Using Functional Magnetic Resonance Imaging (fMRI) , 2010, IEEE Transactions on Instrumentation and Measurement.

[15]  R. Haag,et al.  Dendritic Polyamines: Simple Access to New Materials with Defined Treelike Structures for Application in Nonviral Gene Delivery , 2004, Chembiochem : a European journal of chemical biology.

[16]  S. Sahoo,et al.  Nanotech approaches to drug delivery and imaging. , 2003, Drug discovery today.

[17]  Antonino S. Fiorillo,et al.  Low-Frequency Ultrasound in Medicine: An In Vivo Evaluation , 2012, IEEE Transactions on Instrumentation and Measurement.

[18]  Tapas Nandy,et al.  In vitro measurement of attenuation and nonlinear scattering from echogenic liposomes. , 2012, Ultrasonics.

[19]  Aimé Lay-Ekuakille,et al.  Multi-frequency differential image enhancement of nanosized ultrasound contrast agents , 2014, 2014 IEEE International Symposium on Medical Measurements and Applications (MeMeA).

[20]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[21]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .

[22]  V L Newhouse,et al.  Second harmonic ultrasonic blood perfusion measurement. , 1993, Ultrasound in medicine & biology.

[23]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[24]  Francesco Conversano,et al.  In Vitro Evaluation and Theoretical Modeling of the Dissolution Behavior of a Microbubble Contrast Agent for Ultrasound Imaging , 2012, IEEE Sensors Journal.

[25]  E. Picano Sustainability of medical imaging , 2004, BMJ : British Medical Journal.

[26]  John E. Johnson,et al.  Hybrid virus-polymer materials. 1. Synthesis and properties of PEG-decorated cowpea mosaic virus. , 2003 .

[27]  Francesco Conversano,et al.  Optimal Enhancement Configuration of Silica Nanoparticles for Ultrasound Imaging and Automatic Detection at Conventional Diagnostic Frequencies , 2010, Investigative radiology.

[28]  Aimé Lay-Ekuakille,et al.  Harmonic Ultrasound Imaging of Nanosized Contrast Agents for Multimodal Molecular Diagnoses , 2012, IEEE Transactions on Instrumentation and Measurement.

[29]  Enzo Terreno,et al.  Gadolinium-doped LipoCEST agents: a potential novel class of dual 1H-MRI probes. , 2011, Chemical communications.

[30]  R. Y. Chiao,et al.  Subharmonic Imaging with Microbubble Contrast Agents: Initial Results , 1999, Ultrasonic imaging.

[31]  D. May,et al.  Nondestructive subharmonic imaging , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[32]  Sunil Unnikrishnan,et al.  Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application. , 2012, AJR. American journal of roentgenology.

[33]  Andrea Trucco,et al.  Interpolation of Medical Ultrasound Images From Coherent and Noncoherent Signals , 2009, IEEE Transactions on Instrumentation and Measurement.

[34]  POLITECNICO DI TORINO Hypothesis Validation of Far-Wall Brightness in Carotid-Artery Ultrasound for Feature-Based IMT Measurement Using a Combination of Level-Set Segmentation and Registration , .

[35]  R. J. Lee,et al.  Targeted drug delivery via the folate receptor. , 2000, Advanced drug delivery reviews.

[36]  Francesco Conversano,et al.  Magnetic/Silica Nanocomposites as Dual‐Mode Contrast Agents for Combined Magnetic Resonance Imaging and Ultrasonography , 2011 .

[37]  Aimé Lay-Ekuakille,et al.  Multiparametric Evaluation of the Acoustic Behavior of Halloysite Nanotubes for Medical Echographic Image Enhancement , 2014, IEEE Transactions on Instrumentation and Measurement.

[38]  Isabelle Tardy,et al.  BR55: A Lipopeptide-Based VEGFR2-Targeted Ultrasound Contrast Agent for Molecular Imaging of Angiogenesis , 2010, Investigative radiology.

[39]  Fabian Kiessling,et al.  Ultrasound Microbubbles for Molecular Diagnosis, Therapy, and Theranostics , 2012, The Journal of Nuclear Medicine.

[40]  Fabian Kiessling,et al.  Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38) , 2011, European Radiology.

[41]  Francesco Conversano,et al.  A novel dual-frequency method for selective ultrasound imaging of targeted nanoparticles , 2011, 2011 IEEE SENSORS Proceedings.