TY - JOUR
T1 - Leakage and water exchange characterization of gadofosveset in the myocardium
AU - Bane, Octavia
AU - Lee, Daniel C.
AU - Benefield, Brandon C.
AU - Harris, Kathleen R.
AU - Chatterjee, Neil R.
AU - Carr, James C.
AU - Carroll, Timothy J.
N1 - Funding Information:
The authors would like to thank Marie Wasielewski, MRI technologist, and the cardiovascular imaging staff of the Center for Translational Imaging at Northwestern University, for technical training and clinical assistance with recruiting and imaging the volunteers. The volunteer study was supported by the US National Institute of Healthy grants T32 EB005170, R01 NS0493395, and R01 HL088437. The animal data presented here are part of a study supported by an award from the American Heart Association and the Northwestern Memorial Foundation.
PY - 2014/4
Y1 - 2014/4
N2 - Purpose: To determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV). Methods: Myocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions.fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5. T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization. Results: Simulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent. Conclusions: The distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the interstitium and the myocytes, is appropriate. The ferumoxytol measurements indicate that this USPIO is an intravascular contrast agent that can be used to quantify myocardial blood volume, with the appropriate correction for water exchange using a two-compartment water exchange model.
AB - Purpose: To determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV). Methods: Myocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions.fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5. T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization. Results: Simulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent. Conclusions: The distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the interstitium and the myocytes, is appropriate. The ferumoxytol measurements indicate that this USPIO is an intravascular contrast agent that can be used to quantify myocardial blood volume, with the appropriate correction for water exchange using a two-compartment water exchange model.
KW - Blood pool contrast agent
KW - Extracellular contrast agent
KW - Ferumoxytol
KW - Gadofosveset
KW - Myocardial vascular fraction
KW - Water exchange
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U2 - 10.1016/j.mri.2013.10.014
DO - 10.1016/j.mri.2013.10.014
M3 - Article
C2 - 24418327
AN - SCOPUS:84894229844
VL - 32
SP - 224
EP - 235
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
SN - 0730-725X
IS - 3
ER -
