Publications by authors named "Kyle P Morrison"

4 Publications

  • Page 1 of 1

Dual-Use Transducer for Ultrasound Imaging and Pulsed Focused Ultrasound Therapy.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2930-2941. Epub 2021 Aug 27.

Pulsed focused ultrasound (pFUS) uses short acoustic pulses delivered at low duty cycle and moderate intensity to noninvasively apply mechanical stress or introduce disruption to tissue. Ultrasound-guided pFUS has primarily been used for inducing cavitation at the focus, with or without contrast agents, to promote drug delivery to tumors. When applied in tandem with contrast agents, pFUS is often administered using an ultrasound imaging probe, which has a small footprint and does not require a large acoustic window. The use of nonlinear pFUS without contrast agents was recently shown to be beneficial for localized tissue disruption, but required higher ultrasound pressure levels than a conventional ultrasound imaging probe could produce. In this work, we present the design of a compact dual-use 1-MHz transducer for ultrasound-guided pFUS without contrast agents. Nonlinear pressure fields that could be generated by the probe, under realistic power input, were simulated using the Westervelt equation. In water, fully developed shocks of 42-MPa amplitude and peak negative pressure of 8 MPa were predicted to form at the focus at 458-W acoustic power or 35% of the maximum reachable power of the transducer. In absorptive soft tissue, fully developed shocks formed at higher power (760 W or 58% of the maximum reachable power) with the shock amplitude of 33 MPa and peak negative pressure of 7.5 MPa. The electronic focus-steering capabilities of the array were evaluated and found to be sufficient to cover a target with dimensions of 19 mm in axial direction and 44 mm in transversal direction.
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http://dx.doi.org/10.1109/TUFFC.2021.3070528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443157PMC
September 2021

Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model.

Mol Ther Methods Clin Dev 2019 Sep 26;14:275-284. Epub 2019 Jul 26.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA.

Ultrasound (US)-mediated gene delivery (UMGD) of nonviral vectors was demonstrated in this study to be an effective method to transfer genes into the livers of large animals via a minimally invasive approach. We developed a transhepatic venous nonviral gene delivery protocol in combination with transcutaneous, therapeutic US (tUS) to facilitate significant gene transfer in pig livers. A balloon catheter was inserted into the pig hepatic veins of the target liver lobes via jugular vein access under fluoroscopic guidance. tUS exposure was continuously applied to the lobe with simultaneous infusion of pGL4 plasmid (encoding a luciferase reporter gene) and microbubbles. tUS was delivered via an unfocused, two-element disc transducer (H105) or a novel focused, single-element transducer (H114). We found applying transcutaneous US using H114 and H105 with longer pulses and reduced acoustic pressures resulted in an over 100-fold increase in luciferase activity relative to untreated lobes. We also showed effective UMGD by achieving focal regions of >10 relative light units (RLUs)/mg protein with minimal tissue damage, demonstrating the feasibility for clinical translation of this technique to treat patients with genetic diseases.
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http://dx.doi.org/10.1016/j.omtm.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718807PMC
September 2019

Ultrasound-Mediated Gene Therapy in Swine Livers Using Single-Element, Multi-lensed, High-Intensity Ultrasound Transducers.

Mol Ther Methods Clin Dev 2018 Sep 5;10:179-188. Epub 2018 Jul 5.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA.

We have achieved significant enhancement of gene delivery into livers of large animals using ultrasound (US)-targeted microbubble (MB) destruction methods. An infusion of pGL4 (encoding a reporter gene) plasmid DNA (pDNA) and MBs into a portal-vein segmental branch of a porcine liver was exposed to US for 4 min. Therapeutic US induced cavitation of MBs to temporarily permeabilize the vascular endothelium and cell membranes, allowing entry of pDNA. We obtained a 64-fold enhancement in expression in pig livers compared to control without US using an unfocused, dual-element transducer (H105, center frequency [f] = 1.10 MHz) at 2.7 MPa peak negative pressure (PNP). However, input electrical energy was limited, and modified transducers were designed to have spherical (H185A, f = 1.10 MHz) or cylindrical foci (H185B, f = 1.10 MHz; H185D, f = 1.05 MHz) to enhance PNP output. The revised transducers required less electrical input to achieve 2.7 MPa PNP compared to H105, thereby allowing PNP outputs of up to 6.2 MPa without surpassing the piezo-material limitations. Subsequently, expression significantly improved up to 9,000-fold compared to controls with minor liver damage. These advancements will allow us to modify our current protocols toward minimally invasive US gene therapy.
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http://dx.doi.org/10.1016/j.omtm.2018.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077835PMC
September 2018

Ultrasound-targeted microbubble destruction-mediated gene delivery into canine livers.

Mol Ther 2013 Sep 4;21(9):1687-94. Epub 2013 Jun 4.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington 98101, USA.

Ultrasound (US) was applied to a targeted canine liver lobe simultaneously with injection of plasmid DNA (pDNA)/microbubble (MB) complexes into a portal vein (PV) segmental branch and occlusion of the inferior vena cava (IVC) to facilitate DNA uptake. By using a 1.1 MHz, 13 mm diameter transducer, a fivefold increase in luciferase activity was obtained at 3.3 MPa peak negative pressure (PNP) in the treated lobe. For more effective treatment of large tissue volumes in canines, a planar unfocused transducer with a large effective beam diameter (52 mm) was specifically constructed. Its apodized dual element configuration greatly reduced the near-field transaxial pressure variations, resulting in a remarkably uniform field of US exposure for the treated tissues. Together with a 15 kW capacity US amplifier, a 692-fold increase of gene expression was achieved at 2.7 MPa. Transaminase and histology analysis indicated minimal tissue damage. These experiments represent an important developmental step toward US-mediated gene delivery in large animals and clinics.
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http://dx.doi.org/10.1038/mt.2013.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776626PMC
September 2013
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