2002 Medical Workshop

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REVIEW OF THE SECOND UIA MEDICAL WORKSHOP by Foster B. Stulen, Ph.D. and Alan A. Winder, M.E.E.

The Second UIA Medical Workshop was held at the Taj Mahal in Atlantic City, NJ, Monday May 20, 2002. It immediately proceeded the four-day Leading Edge Conference on diagnostic ultrasound (US) from May 21-24. The UIA program focused on therapeutic US designed to complement the Leading Edge program. The Workshop had three sessions: Bioeffects and Drug Delivery, Hemodynamics and Devices, and Materials and Transducer Arrays.

The Workshop included three invited speakers: Drs. Terry Matsunaga, Peter Lewin, and Flemming Forsberg. Dr. Terry Matsunaga of ImaRx Therapeutics, Inc discussed their targeted lipid coated microbubble technology. The molecular construct includes a bioconjugate ligand that directs the rest of the molecule to a target, a tether that allows the entropic freedom to seek and align with the receptor, and an anchor moiety to tie the tether to the lipid shell. After they have attached to their targets, US energy is introduced to lyze the microbubbles to deliver their payload of drug or specific gene. Dr. Matsunaga presented data from several in vitro and in vivo experiments that demonstrated the effectiveness of targeted microbubbles binding to their targets, which included microbubbles targeted to the surface of blood clots, with heparin or tissue plasminogen activator (TPA) plus US, and US mediated gene delivery (via microbubbles) to myocardium. He was immediately followed by Dr. Peter Lewin of Drexel University who presented his paper on the "Therapeutic Wonders of Ultrasound," which reviewed the underlying therapeutic ultrasonic mechanisms, including thermal, cavitation, acoustic microstreaming and radiation force. Dr. Lewin ended his thorough overview with a stimulating discussion of current and future applications of therapeutic US, including sonophoresis, pain relief/management, non-invasive stimulation of human neural structures, soft tissue wound and bone fracture healing, lithotripsy, HIFU, and controlled drug and gene delivery. Dr. Forsberg of Thomas Jefferson University described the development of anti-angiogensis agents and the clinical evaluation and monitoring of anti-angiogenic therapy in the treatment of malignant tumors.

MORNING SESSIONS

The presentations by Drs. Matsunaga and Lewin were given in the morning session of Bioeffects and Drug delivery. Three additional presentations were made in the session. Dr. Muratore of the Riverside Research Institute presented Dr. Lizzi's and his work on radiation force elastography. This is an imaging modality that uses correlation between one spatial ultrasonic data set and one obtained after local deformation from radiation force. The technique can be used to differentiate healthy and diseased tissues based on differences in effective Young's modulus. Dr. Everbach of Swarthmore College presented his research on ultrasonically enhanced thrombolysis and shared some potential theories, which he plans to test this summer. Dr. Stulen presented the doctoral research on ultrasonic tissue cutting of Mr. Vaitekunas from Ethicon Endo-Surgery. Dr. Stulen serves as his research advisor at the University of Cincinnati.

AFTERNOON SESSIONS

The afternoon session opened up with Dr. Levon Nazarian of the Thomas Jefferson University Hospital presenting the importance of power Doppler US to distinguish pathologies and acute inflammatory processes in musculoskeletal structures. Dr. Nazarian gave clinical examples where increased power Doppler flow was associated with abnormalities such as chronic tendonitis, tenosynovitis, rotator cuff tears, muscle inflammation, joint effusions (shoulder, elbow, hip, knee and ankle), rheumatoid joints, etc. Increased flow was also seen due to neovascularity from soft tissue tumors. Dr. Nazarian was followed by Roger Talish of Smith & Nephew-Exogen. The first part of Mr. Talish's presentation addressed the extension of the Exogen therapeutic US product to include non-union bone fractures. Utilizing low-intensity pulsed US, the registry database showed that the healing rate for fresh fractures (0-90 days), delayed unions (91-255 days), and nonunions (³256 days) was 94%, 90%, and 83%, respectively. The second half discussed the results of preliminary in vivo studies of low frequency (25-40 Hz) mechanical vibrational stimulation (acceleration 0.2-0.4 g) of the musculoskeletal system for increasing bone mass in animals (turkeys and sheep) and postmenopausal women. Dr. Flemming Forsberg then gave his paper on evaluating angiogenesis with applications in ultrasound.

The second part of the afternoon session focused on materials and transducer development. Dr. Wesley Hackenberger of TRS Ceramics, Inc. presented an overview of ceramic materials for medical applications in the 1-20 MHz range. He primarily focused on single crystal piezoelectric materials which exhibit very high electromechanical coupling coefficients (k33 > 90%) and field induced strains (>1%), with inherently more bandwidth (>120%). Dr. Rajesh Panda of Philips Medical Systems then discussed some practical considerations in utilizing PMN-PT and PZN-PT for fabricating 1-D linear arrays, such as chemical composition within the wafer, curie temperature, orientation cut, and their impact on reliability and reproducibility. An interelement amplitude uniformity of +/- 1 dB was measured for a prototype 50-element linear array operating in the 1-4 MHz band. This was followed by Dr. Bahram Jadidian of J&W Medical LLC who reviewed the design and development of transducers in the 20-200 MHz range. Dr. Jadidian addressed a matrix of ceramic materials, including fine grain lead zirconate titanate (PZT), PVDF, piezo-ceramic/polymer composites, thin film zinc oxide (ZnO), and lead titanate (PT). Finally, Dr. AJ Kahn from Advanced Cerametrics, Inc. discussed the fabrication and characterization of fine-scale piezoelectric fiber composites with 1-3 connectivity. A spinning process produced PZT and PMN-PT fibers with a diameter of the order of 10 microns. The orientation within fiber composites facilitates the elimination or minimization of masking radial modes.

AFTER-THOUGHTS

The overall attendance was lower than desired, but a 40% increase over last year, including speakers. The general feedback is that it was an excellent meeting and is one of the more desirable conferences for biomedical scientists and engineers to attend. The message we are hearing is that it is also desirable to keep the workshop to one day, thereby requiring that we maintain the high quality of the papers. Both the presenters and the audience appreciated the extended 25-minute format with 5 minutes for questions and answers. It allowed a presenter to go into much deeper detail than otherwise, and gave the audience that much more of an understanding. The UIA Medical Workshop, focusing on both the low and high intensity therapeutic fields and their bridges to the diagnostic world, appears to be gaining recognition as a premier source of cutting edge practical and theoretical information.

Workshop Program (PDF)