The DynEQ-CT protocol consisted of three steps (Fig. 1 for flow chart): first, a CT scan to obtain baseline pre-contrast blood and myocardial attenuation in Hounsfield units (HU); second, contrast administration and delay so the contrast distributes into a blood:myocardial dynamic equilibration; third, a repeat scan to re-measure blood and myocardial attenuation. The ratio of the change in blood and myocardial attenuation (ΔHU) represents the contrast agent partition coefficient. If the blood volume of distribution is substituted in (1 minus venous hematocrit; obtained prior to imaging), the myocardial extracellular volume, ECVCT, is obtained, reflecting the myocardial interstitium: ECVCT = (1−Hematocrit) × (ΔHUtissue/ΔHUblood).
CT examinations were performed on a 64–detector row CT scanner (Somatom Sensation 64; Siemens Medical Solutions, Erlangen, Germany). A topogram was used to plan CT volumes from the level of the aortic valve to the inferior aspect of the heart, typically a 10 cm slab. Cardiac scans (tube voltage, 120 kV; tube current–time product, 160 mAs; section collimation, 64 detector rows, 1.2-mm section thickness; gantry rotation time, 330 msec) were acquired with prospective gating (65%–75% of R-R interval), and reconstructed into 3-mm-thick axial sections with a B20f kernel.
To establish the best timing, post contrast imaging was performed at both 5- and 15-minutes following a bolus of Iodixanol (652 mg/mL) at a standard dose of 1 mL/kg and injection rate of 3 ml/sec without a saline chaser. An additional single 3 mm slice acquisition at 1-minute (other parameters as previously described) was introduced in the amyloid cohort to aid blood:myocardial boundary detection for segmentation of the myocardium during analysis.
CT image analysis was performed using a free and open-source Digital Imaging and Communications in Medicine viewer (OsiriX v4.1.2; Pixmeo, Bernex, Switzerland) independently by two experienced readers blinded to all other study data; this was repeated by the second reader to establish inter- and intra-observer agreement. Regions of interest (ROIs) were drawn in the contrast-enhanced 1-minute acquisition in axial sections and propagated to the pre-contrast, 5-minute and 15-minute acquisitions. For myocardium, polygonal ROIs were drawn in an axial slice containing the greatest area of myocardial septum; for the blood pool, circular ROIs were drawn in the LV blood pool away from papillary muscles and the myocardial septum to avoid the endocardial edge and therefore partial voluming (Fig. 2). Myocardial and blood attenuation values were used to calculate the ECV fraction as described.
Signal-to-noise ratios (SNR) were measured in five myocardial ROIs per time point from the ratio of the average HU attenuation value to the standard deviation of the HU attenuation. Radiation exposure was quantified using the dose-length product multiplied by a chest conversion coefficient (κ = 0.014 mSv/mGy cm).20 (link)
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