TIC Analysis

The TIC analysis was performed using an off‐line personal computer with an image analysis software program (ImageJ; National Institutes of Health, Bethesda, MD). First, we decompressed the cine saved in Audio Video Interleave (AVI) format into uncompressed AVI files. In the uncompressed AVI file, the interval of each frame was 1/15th of a second. A total of 15 frames of the grayscale images were processed per second using the ImageJ software program. We observed the cine image frame by frame and set the time of the first echogenic microbubble observed in the HA at baseline. A circular region of interest (ROI) was established within the HA, PV, HV, and LP, and the intensity values were measured automatically using the ImageJ software program. The ROI with a 5‐mm diameter was set on the HV 3‐5 cm from the inferior vena cava and on the first branch of the HA or PV. Then, the ROI with a 10‐mm diameter was set on the LP area, avoiding vessels, and at the same depth as the other ROIs (Fig. 2A). The intensity value of each pixel was expressed as 0 at minimum and 255 at maximum. After measuring the intensity values in the ROIs, we created a TIC of the arterial phase for 20 seconds from the time the contrast agent arrived at HA, using the Excel software program (Microsoft, Redmond, WA). The time to peak (TTP) and peak intensity (PI) were evaluated according to the TIC. We then calculated the time intervals (TIs) between TTP of HA and PV (TI [HA, PV]), HA and LP (TI [HA, LP]), and PV and LP (TI [PV, LP]). Furthermore, we calculated and recorded the arrival times of HA and HV, and then HA to HV transit time (HA‐HVTT), with reference to previous reports⁽ 29 ⁾ (Fig. 2B‐F). All TIC parameters were measured until recovery or death, from hospital admission, at 7‐day intervals. The investigators (H.K. and T.A.) were blinded to all patient data. All TIC parameters were measured three times for each patient, to investigate the intra‐observer variability. Furthermore, the TI (HA, LP) of all patients was successively evaluated by two investigators to determine interobserver variability.

Intensities of the HA, PV, HV, and LP were measured by setting circular ROIs using ImageJ software. (A) The ROIs were set at a depth of 6‐8 cm (±3 cm from the focus point) from the surface. (B) Schematic TIC describing events after the bolus injection. The TTP indicates the duration from the first appearance of the contrast agent in the HA until maximum enhancement was reached. The PI indicates the maximum enhancement after subtracting the baseline intensity. The TI indicates the duration between two curves of TTP. The transit time (TT) describes the period of arrival time between two curves. TIC of the liver in a survivor (C) and nonsurvivor (D). The orange line is the signal intensity of the HA; the green line is the signal intensity of the PV; the blue line is the signal intensity of the HV; and the gray line is the signal intensity of the LP. In the nonsurvivor, the slope of the HA and LP are steeper, and the TTP is short compared with that observed in the survivor. CEUS perfusion imaging of the liver in a survivor (E) and a nonsurvivor (F). In the liver of the nonsurvivor, the HA and LP were enhanced steeply, whereas the PV was enhanced slowly.