SPECT Imaging of Teboroxime during Myocardial Blood Flow Changes

Abstract

Kinetic parameters and static images from dynamic SPECT imaging of (99m)Tc-teboroxime have been shown to reflect blood flow in dogs and in humans at rest and during adenosine stress. When compartment modeling is used, steady-state physiological conditions are assumed. With standard adenosine stress protocols, imaging of teboroxime would likely involve significant changes in flow, even if performed only for five minutes. These flow changes may significantly bias the kinetic parameter estimates. On the other hand, when static imaging is performed, large flow changes during acquisition may improve contrast between normal and occluded regions. Computer simulations were performed to determine the effect of changing flows on kinetic parameter estimation and on static (average tissue uptake) images. Two canine studies were also performed in which adenosine was given with a standard protocol, and then imaging was repeated with adenosine infusion held constant. The simulations predicted biases on the order of 7% for kinetic washin parameter estimation and 18% for the washout parameter. Contrast for static studies was found to depend critically on the time-activity behavior of the distribution as well as on the stress protocol. The differences in washin contrast from the standard and continous adenosine dog studies was slightly larger than predicted from the simulations. Optimal imaging of teboroxime with adenosine using compartment modeling will require non-standard adenosine stress protocols, although sub-optimal imaging may still be useful clinically.

Figure 1

(a) Average blood input time-activity curves for teboroxime at stress and at rest, from regions of interest drawn on the images of six dog studies. (b) Plasma time-activity curves from one dog study. The input functions are similar at stress and at rest, justifying the use of a single blood input in the simulation.

Figure 2

Simulated time-activity curves. The dip seen in the transition period for the 6 minute curves arises because washin and washout are changing at different rates. That is, the distribution volume (k₂₁/k₁₂) is decreasing (see Table 1).

Figure 3

Simulated time-activity curves with noise added.

Figure 4

k₂₁ parameters from simulated data. The lighter symbols marked with * are from 25 noise realizations of continuous stress. The ‘o’ symbols are from the 6 minute stress protocol. The error bars show ± one standard deviation. All of the continuous stress results are not significantly different from the true washin (p>0.05). All of the 6 minute results are significantly different from truth (p<0.05), except when 990 seconds of occluded data is used.

Figure 5

Washout (k₁₂) parameters from simulated data. Symbols are the same as described in Figure 4. Differences between continuous stress and truth were not significant (p>0.05); 6 min. stress results were all significantly different from truth (p<0.05).

Figure 6

Washin parameter O/N ratios. Only the 990 sec. acquisition for the 6 min. stress case was significantly different (p<0.05) from the true O/N ratio of 0.34.

Figure 7

Washout (k₁₂) O/N ratios. Only the 990 sec. acquisition for the 6 min. stress case was significantly different (p<0.05) from the true O/N ratio of 0.57.

Figure 8

O/N ratios for summed data. With the model and parameters used in this paper, it was not possible to improve contrast by switching to rest during image acquisition. All of the ratios were significantly different (p<0.05) from the true O/N ratio of 0.34.

Figure 9

Top row: short axis slices from standard 6 min. adenosine protocol (5.5 minutes total scan time, started 147 seconds post-injection of teboroxime). Bottom row: slices from continuous infusion (same scan time and delay).

Figure 10

O/N ratios for the categories labeled on the x-axis for two dog studies. Static 1 and 2 refer to time delays of 22 and 147 seconds post-injection, respectively.