Abstract
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Objectives The goal is to evaluate corrective methods for image-derived (IFi) and arterial blood sampled (IFa) input functions in a PET angiotensin II subtype 1 receptor (AT1R) kinetic study in swine renal artery stenosis.
Methods We studied 12 pigs including 3 in control group, 6 in chronic stenosis group, 3 in acute stenosis group injected with [11C]KR31173 that targets the AT1R in the kidneys. The IFi for each pig was derived from a narrow and long 2D ROI placed along the abdominal aorta of the coronal PET images. It was then corrected for partial volume effect (PVE) and the recovery coefficient was estimated from a simulation study with the known PET resolution and aorta size obtained from MRI images of the same pig. It was also corrected for plasma tracer concentration using estimated tracer concentration ratio of plasma to whole blood. The IFa was corrected for delay determined by cross correlation with the IFi of the same pig which was assumed to have more accurate timing. Both IFi and IFa were corrected for the un-metabolized concentration based on measured metabolite rate. A three-compartment kinetic model for the kidney was used and the rate constants of compartments of plasma to specific binding, K1, specific binding to plasma, k2, plasma to non-specific binding, k3, and non-specific binding to plasma, k4, were determined.
Results The corrected IFi and IFa curves agreed well in terms of shape and amplitude. The estimated parameters obtained using the corrected IFi and IFa agreed with <20% difference except for certain parameters. The relative errors of the estimated parameters using the corrected IFi with respect to corrected IFa have great improvement comparing to those without correction.
Conclusions Our preliminary results show that IFi with careful correction for PVE can provide accurate kinetic parameters relative to those determined using the corrected IFa. The use of IFi is important in the application of the PET kinetic study protocol to patients where the use of IFa has proven difficult.
Research Support NIH R01DK05018