TY - JOUR
T1 - Multifocused Ultrasound Therapy for Controlled Microvascular Permeabilization and Improved Drug Delivery
AU - Basavarajappa, Lokesh
AU - Rijal, Girdhari
AU - Hoyt, Kenneth
N1 - Funding Information:
Manuscript received May 27, 2020; accepted September 21, 2020. Date of publication September 25, 2020; date of current version March 26, 2021. This work was supported in part by the National Institutes of Health (NIH) under Grant R01EB025841, in part by the Cancer Prevention and Research Institute of Texas (CPRIT) under Grant RP180670, and in part by Lan-theus Medical Imaging who generously provided the microbub-ble (MB) contrast agent (Definity) for all the experimental studies. (Corresponding author: Kenneth Hoyt.) Lokesh Basavarajappa and Kenneth Hoyt are with the Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080 USA (e-mail: lokesh.basavarajappa.@.utdallas.edu; kenneth.hoyt.@.utdallas.edu).
Publisher Copyright:
© 1986-2012 IEEE.
PY - 2021/4
Y1 - 2021/4
N2 - Focused ultrasound (FUS) exposure of micro-bubble (MB) contrast agents can transiently increase microvascular permeability allowing anticancer drugs to extravasate into a targeted tumor tissue. Either fixed or mechanically steered in space, most studies to date have used a single element focused transducer to deliver the ultrasound (US) energy. The goal of this study was to investigate various multi-FUS strategies implemented on a programmable US scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). The multi-FUS strategies include multi-FUS with sequential excitation (multi-FUS-SE) and multi-FUS with temporal sequential excitation (multi-FUS-TSE) and were compared to single-FUS and sham treatment. This study was performed using athymic mice implanted with breast cancer cells ( {N} = 20 ). FUS therapy experiments were performed for 10 min after a solution containing MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared (NIR, surrogate drug) dye were injected via the tail vein. The fluorescent signal was monitored using an in vivo optical imaging system (Pearl Trilogy, LI-COR) to quantify intratumoral dye accumulation at baseline and again at 0.1, 24, and 48 h after receiving US therapy. Animals were then euthanized for ex vivo dye extraction analysis. At 48 h, fluorescent tracer accumulation within the tumor space for the multi-FUS-TSE therapy group animals was found to be 67.3%, 50.3%, and 36.2% higher when compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. Also, dye extraction and fluorescence measurements from excised tumor tissue found increases of 243.2%, 163.1%, and 68.1% for the multi-FUS-TSE group compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. In summary, experimental results revealed that for a multi-FUS sequence, increased microvascular permeability was considerably influenced by both the spatial and temporal aspects of the applied US therapy.
AB - Focused ultrasound (FUS) exposure of micro-bubble (MB) contrast agents can transiently increase microvascular permeability allowing anticancer drugs to extravasate into a targeted tumor tissue. Either fixed or mechanically steered in space, most studies to date have used a single element focused transducer to deliver the ultrasound (US) energy. The goal of this study was to investigate various multi-FUS strategies implemented on a programmable US scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). The multi-FUS strategies include multi-FUS with sequential excitation (multi-FUS-SE) and multi-FUS with temporal sequential excitation (multi-FUS-TSE) and were compared to single-FUS and sham treatment. This study was performed using athymic mice implanted with breast cancer cells ( {N} = 20 ). FUS therapy experiments were performed for 10 min after a solution containing MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared (NIR, surrogate drug) dye were injected via the tail vein. The fluorescent signal was monitored using an in vivo optical imaging system (Pearl Trilogy, LI-COR) to quantify intratumoral dye accumulation at baseline and again at 0.1, 24, and 48 h after receiving US therapy. Animals were then euthanized for ex vivo dye extraction analysis. At 48 h, fluorescent tracer accumulation within the tumor space for the multi-FUS-TSE therapy group animals was found to be 67.3%, 50.3%, and 36.2% higher when compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. Also, dye extraction and fluorescence measurements from excised tumor tissue found increases of 243.2%, 163.1%, and 68.1% for the multi-FUS-TSE group compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. In summary, experimental results revealed that for a multi-FUS sequence, increased microvascular permeability was considerably influenced by both the spatial and temporal aspects of the applied US therapy.
KW - Cancer
KW - drug delivery
KW - image-guided therapy
KW - microbubbles (MBs)
KW - ultrasound (US)
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U2 - 10.1109/TUFFC.2020.3026697
DO - 10.1109/TUFFC.2020.3026697
M3 - Article
C2 - 32976098
AN - SCOPUS:85103431895
VL - 68
SP - 961
EP - 968
JO - IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
JF - IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
SN - 0885-3010
IS - 4
M1 - 9205916
ER -