Validity of microsphere depositions for regional myocardial flows

Abstract

Due to the particulate nature of microspheres, their deposition in small-tissue regions may not be strictly flow dependent. To evaluate the importance of rheological and geometric factors and random error, their deposition densities in small regions of rabbit hearts were examined in comparison with those of a new "molecular microsphere," 2-iododesmethylimipramine (IDMI), whose high lipid solubility allows it to be delivered into tissue in proportion to flow, and whose binding in tissue prevents rapid washout. 141Ce- and 103Ru-labeled 16.5-micron spheres in one syringe and [125I]- and [131I]DMI in another syringe were injected simultaneously into the left atrium of open-chest rabbits, while obtaining reference blood samples from the femoral artery. Hearts were removed 1 min after injection, cut into approximately 100 pieces averaging 54 mg, and the regional deposition densities calculated for each tracer from the isotopic counts. Correlations between the differently labeled microspheres were r greater than 0.95 and for the two IDMIs were greater than 0.98. Scatter plots of sphere densities vs. IDMI densities showed that differences between microspheres and IDMI had substantial scatter, 0.87 less than r less than 0.96 and were not random. Microsphere depositions tended to be lower than IDMI depositions at low flows and higher at high flows. The tendency for spheres to be deposited preferentially in high-flow regions may be explained by a bias at bifurcations toward entering the branch with higher flow and secondarily toward entering those branches that are straighter. We conclude that microspheres are generally adequate for estimating regional flows but suffer systematic error when the regions of interest are supplied via arteries of diameters only a few times those of the microspheres.

FIG. 1

Intraexperiment paired controls defining methodological error. A: linear scatter plot of [¹²⁵I]DMI vs. [¹³¹I]-DMI deposition densities d_j(¹³¹IDMI) in ventricular myocardium of 1 rabbit; r = 0.993; percent differences averaged 2.1 ± 1.6% (mean ± SD, n = 102). B: linear scatter plot of ¹⁴¹Ce-labeled microspheres d_j(¹⁴¹Ce) vs. ¹⁰³Ru-labeled microspheres deposition densities d_j(¹⁰³Ru) in same animal. For 102 pieces r = 0.976; percent differences averaged 6.4 ± 5.1%. Thus methodological error for microsphere deposition is about 3 times that for IDMI.

FIG. 2

Microsphere deposition densities (d_j) vs. IDMI deposition densities (f_j), which are assumed equivalent to relative regional flow. Each d_j is average of 2 observations in each piece, as is each f_j. A: rabbit 1, mean ventricular flow $({\mathrm{F}}_{\mathrm{H}}^{\prime })=0.99\text{ml}·{\mathrm{g}}^{-1}·{\text{min}}^{-1};$ r = 0.938. B: rabbit 2, ${\mathrm{F}}_{\mathrm{H}}^{\prime }=1.02\text{ml}·{\mathrm{g}}^{-1}·{\text{min}}^{-1};$ r = 0.892. Regressions given in Table 2.

FIG. 3

Microsphere deposition densities d_j vs. IDMI deposition densities f_j in ventricular myocardium of 8 open-chest rabbits. Each ordinate value represents mean of 2 deposition densities of microspheres in a given piece; abscissa values represent mean of two IDMI deposition densities. Best fitting regression line was d_j (spheres) = −0.067 + 1.087 f_j; r = 0.900, n = 691.

FIG. 4

Distributions of relative deposition densities d_i for 2 different IDMIs (A) and 2 different microspheres (B) in ventricular myocardium of 1 open-chest rabbit. Mean for each distribution is, by definition, 1. For clarity of presentation, the histograms are represented by polygons joining midpoints of classes. Standard deviations of distributions for IDMIs were 0.247 and 0.241 and for microspheres were 0.288 and 0.278.

FIG. 5

Distribution of relative flows (from IDMI) in ventricular myocardium of 7 open-chest rabbits. Data are classed within intervals of 0.1 (10% of mean); w_i represents fractions of organ per unit mean flow having flows in specified class. Bars are standard deviations for n = 7. Values for each animal were calculated from mean of 2 IDMIs in each piece. Heterogeneity of flows is indicated by relative dispersion (standard deviation/mean) of 32% for distribution.

FIG. 6

Distribution of relative deposition densities of microspheres in ventricular myocardium of 7 open-chest rabbits. Bars are standard deviations for each class of width Δd = 0.1 (n = 7 hearts), where values in each individual heart were taken from average of 2 microspheres in each piece. Dotted line gives mean IDMI distribution for comparison and is the same as that in Fig. 5. Relative dispersion of distribution is 45%.