Editing Medical ultrasound (section)

=== Molecular ultrasonography (ultrasound molecular imaging) ===
The current future of contrast ultrasonography is in [[molecular imaging]] with potential clinical applications expected in [[cancer screening]] to detect [[malignant tumor]]s at their earliest stage of appearance. Molecular ultrasonography (or ultrasound molecular imaging) uses targeted microbubbles originally designed by Dr [[Alexander Klibanov (biologist)|Alexander Klibanov]] in 1997;<ref>{{cite journal |pmid=9240089 |year=1997|last1=Klibanov|first1=A. L. |last2=Hughes |first2=M. S. |last3=Marsh |first3=J. N. |last4=Hall |first4=C. S. |last5=Miller |first5=J. G. |last6=Wilble |first6=J. H. |last7=Brandenburger |first7=G. H. |title=Targeting of ultrasound contrast material. An in vitro feasibility study |volume=412 |pages=113–120 |journal=Acta Radiologica Supplementum}}</ref><ref>{{cite journal |doi=10.1016/S0169-409X(98)00104-5 |title=Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging |year=1999 |last1=Klibanov |first1=A |journal=Advanced Drug Delivery Reviews |volume=37 |pages=139–157 |pmid=10837732 |issue=1–3}}</ref> such targeted microbubbles specifically bind or adhere to tumoral microvessels by targeting [[biomolecular]] cancer expression (overexpression of certain biomolecules that occurs during [[Angiogenesis|neo-angiogenesis]]<ref>{{cite journal |pmid=20027118 |year=2010 |last1=Pochon |first1=S |last2=Tardy |first2=I |last3=Bussat |first3=P |last4=Bettinger |first4=T |last5=Brochot |first5=J |last6=Von Wronski |first6=M |last7=Passantino |first7=L |last8=Schneider |first8=M |title=BR55: A lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis |volume=45 |issue=2 |pages=89–95 |doi=10.1097/RLI.0b013e3181c5927c |journal=Investigative Radiology|s2cid=24089981 }}</ref><ref>{{cite journal |doi=10.2967/jnumed.109.068007 |title=Targeted Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis with Contrast Microbubbles Conjugated to Integrin-Binding Knottin Peptides |year=2010 |last1=Willmann |first1=J. K. |last2=Kimura |first2=R. H. |last3=Deshpande |first3=N. |last4=Lutz |first4=A. M. |last5=Cochran |first5=J. R. |last6=Gambhir |first6=S. S. |journal=Journal of Nuclear Medicine |volume=51 |issue=3 |pages=433–40 |pmid=20150258 |pmc=4111897}}</ref> or [[inflammation]]<ref>{{cite journal |pmid=15052252 |year=2004 |last1=Lindner |first1=JR |title=Molecular imaging with contrast ultrasound and targeted microbubbles |volume=11 |issue=2 |pages=215–21 |doi=10.1016/j.nuclcard.2004.01.003 |journal=Journal of Nuclear Cardiology|s2cid=36487102 }}</ref> in malignant tumors). As a result, a few minutes after their injection in blood circulation, the targeted microbubbles accumulate in the malignant tumor; facilitating its localization in a unique ultrasound contrast image. In 2013, the very first exploratory [[clinical trial]] in humans for [[prostate cancer]] was completed at [[Amsterdam]] in the [[Netherlands]] by Dr. Hessel Wijkstra.<ref>{{ClinicalTrialsGov|NCT01253213|BR55 in Prostate Cancer: an Exploratory Clinical Trial}}</ref>

In molecular ultrasonography, the technique of [[acoustic radiation force]] (also used for shear wave [[elastography]]) is applied in order to literally push the targeted microbubbles towards microvessels wall; first demonstrated by Dr. Paul Dayton in 1999.<ref>{{cite journal |doi=10.1016/S0301-5629(99)00062-9 |title=Acoustic radiation force in vivo: A mechanism to assist targeting of microbubbles |year=1999 |last1=Dayton |first1=Paul |last2=Klibanov |first2=Alexander |last3=Brandenburger |first3=Gary |author4-link=Ferrara, Kathy |last4=Ferrara, Kathy |journal=Ultrasound in Medicine & Biology |volume=25 |issue=8 |pages=1195–1201 |pmid=10576262}}</ref> This allows maximization of binding to the malignant tumor; the targeted microbubbles being in more direct contact with cancerous biomolecules expressed at the inner surface of tumoral microvessels. At the stage of scientific [[preclinical]] research, the technique of acoustic radiation force was implemented as a prototype in clinical ultrasound systems and validated ''[[in vivo]]'' in 2D<ref>{{cite journal |doi=10.1016/j.ultrasmedbio.2012.03.018 |title=Effects of Acoustic Radiation Force on the Binding Efficiency of BR55, a VEGFR2-Specific Ultrasound Contrast Agent |year=2012 |last1=Frinking |first1=Peter J.A. |last2=Tardy |first2=Isabelle |last3=Théraulaz |first3=Martine |last4=Arditi |first4=Marcel |last5=Powers |first5=Jeffry |last6=Pochon |first6=Sibylle |last7=Tranquart |first7=François |journal=Ultrasound in Medicine & Biology |volume=38 |issue=8 |pages=1460–9 |pmid=22579540}}</ref> and 3D<ref>{{cite journal |doi=10.1016/j.ultrasmedbio.2011.12.005 |title=An In Vivo Validation of the Application of Acoustic Radiation Force to Enhance the Diagnostic Utility of Molecular Imaging Using 3-D Ultrasound |year=2012 |last1=Gessner |first1=Ryan C. |last2=Streeter |first2=Jason E. |last3=Kothadia |first3=Roshni |last4=Feingold |first4=Steven |last5=Dayton |first5=Paul A. |journal=Ultrasound in Medicine & Biology |volume=38 |issue=4 |pages=651–60 |pmid=22341052|pmc=3355521 }}</ref><ref>{{cite journal|last=Rognin N |title=Molecular Ultrasound Imaging Enhancement by Volumic Acoustic Radiation Force (VARF): Pre-clinical in vivo Validation in a Murine Tumor Model |journal=World Molecular Imaging Congress, Savannah, GA, USA |year=2013 |url=http://wmis2013.omnibooksonline.com/data/papers/P380.htm |display-authors=etal |url-status=dead |archive-url=https://web.archive.org/web/20131011213605/http://wmis2013.omnibooksonline.com/data/papers/P380.htm |archive-date=October 11, 2013 }}</ref> imaging modes.