TY - GEN
T1 - Quantification in molecular ultrasound imaging using compartmental modeling
AU - Hoyt, Kenneth
AU - Sirsi, Shashank
AU - Mattrey, Robert
N1 - Publisher Copyright:
© 2016 IEEE.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - The goal of project detailed in this paper was to develop a pharmacokinetic compartmental model for describing the complex activity of targeted microbubble (MB) contrast agents used for molecular ultrasound (US) imaging. This imaging study used renal cell carcinoma (RCC)-bearing mice. Either VEGFRR2-targeted or control MBs were intravenously injected. Each animal was imaged before MB injection and for 5 min after using a low-intensity nonlinear imaging mode implemented on a SONIX RP US system (BK Ultrasound) equipped with a L12-4 transducer. After a 4 h delay to allow MB clearance, a subset of animals that received targeted MBs during the first imaging session were reimaged using control MBs and vice versa. Tumors were manually segmented from the US image sequences and a mean intensity value was computed for each frame. A two compartment kinetic model was developed and fit to time-intensity curve (TIC) data. Input parameters for this model include MB dose, tumor size and vascular volume. Output parameters were then estimated using this model that relate to targeted MB binding and clearance. An estimate of fractional tumor vascularity was computed as the percentage of image pixels above a defined intensity threshold compared to the number of pixels for the tumor space. After euthanasia, immunohistologic analysis was performed on excised tumor tissue. The model was in good agreement with TIC data describing targeted MB flow and binding in the tumor vascularity (R2 > 0.89, p < 0.05). Using VEGFR2-targeted MBs, the binding constant was significantly considerably higher than when using control MBs (p = 0.07) In the targeted MB group, regression analysis revealed a positive correlation between the binding constant and VEGFRR2 expression (R2 = 0.75) that diminished when using control MBs in the same animals (R2 = 0.12). There was no difference in vascular or tumor volume estimates when using either targeted or control MBs (p > 0.77). Overall, the two-compartment model may be useful for describing flow binding kinetics of targeted MBs used during molecular US studies.
AB - The goal of project detailed in this paper was to develop a pharmacokinetic compartmental model for describing the complex activity of targeted microbubble (MB) contrast agents used for molecular ultrasound (US) imaging. This imaging study used renal cell carcinoma (RCC)-bearing mice. Either VEGFRR2-targeted or control MBs were intravenously injected. Each animal was imaged before MB injection and for 5 min after using a low-intensity nonlinear imaging mode implemented on a SONIX RP US system (BK Ultrasound) equipped with a L12-4 transducer. After a 4 h delay to allow MB clearance, a subset of animals that received targeted MBs during the first imaging session were reimaged using control MBs and vice versa. Tumors were manually segmented from the US image sequences and a mean intensity value was computed for each frame. A two compartment kinetic model was developed and fit to time-intensity curve (TIC) data. Input parameters for this model include MB dose, tumor size and vascular volume. Output parameters were then estimated using this model that relate to targeted MB binding and clearance. An estimate of fractional tumor vascularity was computed as the percentage of image pixels above a defined intensity threshold compared to the number of pixels for the tumor space. After euthanasia, immunohistologic analysis was performed on excised tumor tissue. The model was in good agreement with TIC data describing targeted MB flow and binding in the tumor vascularity (R2 > 0.89, p < 0.05). Using VEGFR2-targeted MBs, the binding constant was significantly considerably higher than when using control MBs (p = 0.07) In the targeted MB group, regression analysis revealed a positive correlation between the binding constant and VEGFRR2 expression (R2 = 0.75) that diminished when using control MBs in the same animals (R2 = 0.12). There was no difference in vascular or tumor volume estimates when using either targeted or control MBs (p > 0.77). Overall, the two-compartment model may be useful for describing flow binding kinetics of targeted MBs used during molecular US studies.
KW - compartmental modeling
KW - contrast agents
KW - microbubbles
KW - molecular imaging
KW - ultrasound
UR - http://www.scopus.com/inward/record.url?scp=84996522121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84996522121&partnerID=8YFLogxK
U2 - 10.1109/ULTSYM.2016.7728486
DO - 10.1109/ULTSYM.2016.7728486
M3 - Conference contribution
AN - SCOPUS:84996522121
T3 - IEEE International Ultrasonics Symposium, IUS
BT - 2016 IEEE International Ultrasonics Symposium, IUS 2016
PB - IEEE Computer Society
T2 - 2016 IEEE International Ultrasonics Symposium, IUS 2016
Y2 - 18 September 2016 through 21 September 2016
ER -