TY - GEN
T1 - Monitoring early tumor response to vascular targeted therapy using super-resolution ultrasound imaging
AU - Ghosh, Debabrata
AU - Xiong, Fangyuan
AU - Sirsi, Shashank R.
AU - Mattrey, Robert
AU - Brekken, Rolf
AU - Kim, Jung Whan
AU - Hoyt, Kenneth
N1 - Funding Information:
This research was supported in part by NIH grants K25EB017222 and R21CA212851 and Texas CPRIT award RR150010.
Publisher Copyright:
© 2017 IEEE.
PY - 2017/10/31
Y1 - 2017/10/31
N2 - The current standard for evaluating breast tumor response to neoadjuvant treatment remains the assessment of a tumor size change several weeks after therapy begins. However, the tumor microenvironment (including microvasculature) is known to change drastically before any detectable change in physical size manifests. To that end, we have developed a new high-resolution ultrasound (US) imaging modality in our laboratory, termed super-resolution ultrasound (SR-US), for improved visualization of the tumor angiogenic network. A clinical US scanner (Acuson Sequoia 512, Siemens Healthcare) equipped with a 15L8-S linear array transducer was used for our study. Operation of this system was done using a nonlinear harmonic imaging. A low transmit power (mechanical index < 0.2) was used to minimize any MB destruction during imaging. After a slow injection of a MB contrast via a tail vein catheter placed in breast cancer-bearing mice (N = 10), each tumor was US imaged for 10 min at baseline and again at 1 and 2 h after dosing with an antiangiogenic drug (bevacizumab, Genentech Inc) or sham control drug. After collecting a stack of US images, images corrupted by respiratory motion were removed using curve fit-based filtering. A singular value decomposition (SVD)-based spatiotemporal filter was then used to localize individual MBs. Subsequently, a SR-US image (i.e., MB density map) was generated by mapping the cumulative MB localizations. SR-US images were reviewed and longitudinal changes in the tumor microvascular network in response to treatment were evaluated. Overall, an acute microvascular response to bevacizumab was found within 2 h of drug dosing. This observation was consistent with immunohistologic findings and suggests that in vivo SR-US imaging has enormous potential in monitoring the early tumor response to drug treatment.
AB - The current standard for evaluating breast tumor response to neoadjuvant treatment remains the assessment of a tumor size change several weeks after therapy begins. However, the tumor microenvironment (including microvasculature) is known to change drastically before any detectable change in physical size manifests. To that end, we have developed a new high-resolution ultrasound (US) imaging modality in our laboratory, termed super-resolution ultrasound (SR-US), for improved visualization of the tumor angiogenic network. A clinical US scanner (Acuson Sequoia 512, Siemens Healthcare) equipped with a 15L8-S linear array transducer was used for our study. Operation of this system was done using a nonlinear harmonic imaging. A low transmit power (mechanical index < 0.2) was used to minimize any MB destruction during imaging. After a slow injection of a MB contrast via a tail vein catheter placed in breast cancer-bearing mice (N = 10), each tumor was US imaged for 10 min at baseline and again at 1 and 2 h after dosing with an antiangiogenic drug (bevacizumab, Genentech Inc) or sham control drug. After collecting a stack of US images, images corrupted by respiratory motion were removed using curve fit-based filtering. A singular value decomposition (SVD)-based spatiotemporal filter was then used to localize individual MBs. Subsequently, a SR-US image (i.e., MB density map) was generated by mapping the cumulative MB localizations. SR-US images were reviewed and longitudinal changes in the tumor microvascular network in response to treatment were evaluated. Overall, an acute microvascular response to bevacizumab was found within 2 h of drug dosing. This observation was consistent with immunohistologic findings and suggests that in vivo SR-US imaging has enormous potential in monitoring the early tumor response to drug treatment.
KW - Angiogenesis
KW - Bevacizumab
KW - Contrast Agents
KW - Microbubbles
KW - Microvascular Imaging
KW - Super-Resolution Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85039452370&partnerID=8YFLogxK
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U2 - 10.1109/ULTSYM.2017.8092944
DO - 10.1109/ULTSYM.2017.8092944
M3 - Conference contribution
AN - SCOPUS:85039452370
T3 - IEEE International Ultrasonics Symposium, IUS
BT - 2017 IEEE International Ultrasonics Symposium, IUS 2017
PB - IEEE Computer Society
T2 - 2017 IEEE International Ultrasonics Symposium, IUS 2017
Y2 - 6 September 2017 through 9 September 2017
ER -