Ethics and study design
The study was approved by regional ethics committee of the Faculty of Health Sciences, Linköping University (dnr. 2016-43/31 and dnr. 2019-05855). Informed consent was obtained from all patients. Patients from the consecutive hepatocellular carcinoma study [31] were included for a retrospective analysis of CT scans. The CT scans were performed between October 2016 to March 2019. All patients had hepatocellular carcinoma and were planned for transarterial chemoembolisation treatment. All patients first underwent a CTPI examination of the upper body (28 scans in total), and, after a waiting period of 10 min, a full 4-phase CT examination (four scans in total) of the abdomen was performed (Fig. 1). The HU units in the aorta and the portal vein were measured approximately in the height of vertebra L1. The time curves of the aorta and portal vein were considered as a reference for the contrast media behaviour in different blood phases.
CTPI
CTPI examinations were undertaken on a Somatom Force scanner (Siemens Healthcare, Forchheim, Germany). The scanning parameters were as follows: tube voltage 70 kVp, tube current of 150 mAs with a collimation of 48 × 1.2 or 192 × 0.6 mm. The total scanning time was 62.5 s, with the first 20 scans made every 1.5 s, the following 5 scans every 3 s, and the last 3 scans (venous phase) after a waiting time of 6 s were undertaken every 3 s (Fig. 1). The first CTPI scan was taken 7 s after contrast injection, leaving the first scans with no contrast enhancement in vertebral tissue. The anatomical scan length for the first 25 scans was 22.4 cm including the upper border of the liver and including L1–L3 in most patients. The anatomical scan length for last three scans (venous phase) was 48 cm and included the whole abdomen (from the diaphragm to the symphysis). The scans were obtained with the patient moving back-and-forth through the gantry in a “pendulum” movement. Patients were instructed to take shallow breaths during imaging. A fixed dose of 50 mL of iopromide 370 mg I/kg (Ultravist™, Bayer Healthcare, Leverkusen, Germany) was injected at 6 mL/s followed by a flush of physiologic (0.9%) saline (50 mL) at 6 mL/s with a dual-head power injector (Ulrich Medical, Ulm, Germany) with a maximum inflow time of 8 s. Compression to the upper abdomen was not applied. The mean contrast to weight ratio for the CT perfusion examination was 0.62 ± 0.14 (mean ± standard deviation), ranging from 0.38 to 0.83, with a fixed amount of 50 mL of contrast agent applied.
Four-phase CT
The same CT scanner as for the CT perfusion protocol was used to perform a 4-phase CT scan with a tube voltage of 120 kVp and a tube current of 130 mAs. The examination included an unenhanced scan and three contrast-enhanced phases, i.e., arterial (30 + 2 s after contrast-injection), venous (63 + 2 s after contrast-injection), and late venous phase (4 min after contrast-injection). Low-osmolarity nonionic contrast medium iopromide 370 mg I/kg (Ultravist™, Bayer Healthcare, Leverkusen, Germany) was injected at a maximum volume of 118 mL and injection rate of 5–6 mL/s. The contrast dose per patient was calculated regarding our clinical routine with a software program called OmniVis©, version 5.1, GE Healthcare Sverige AB, Danderyd, Sweden). The iodine dose per kilogram is set to 450 mg I/kg. The mean contrast ratio for the 4-phase CT examination was 1.18 ± 0.11 (mean ± standard deviation, ranging from 0.86 to 1.29, with a mean contrast load of 97.7 mL and a mean weight of 84 kg ± 19.8, ranging from 60 to 130 kg.
Bone mineral density assessment
For the vBMD analysis, Mindways qCT PRO software, version 2 (Mindways, Austin, TX, USA) was used as described in detail earlier [28]. In brief, preceding the study, calibration scans with Mindways dedicated phantom were performed, repeated monthly during the study period. After inclusion of patients, all scans were exported from the clinical picture archiving and communication system to a dedicated analysis computer. For the CTPI, we used every second scan for the vBMD analysis, resulting in a time resolution of 3 s for all time points (16 scans in the first phases and 3 scans in the later phase). The Mindways qCT PRO software uses semi-automatically placed regions of interest (ROIs) in the trabecular part of the lumbar vertebrae (middle part), which, if needed, could be manually adjusted before the vBMD values were calculated. The ROIs were made as large as possible, including as much trabecular bone material as possible, but carefully avoiding cortical, sclerotic, and cystic structures (Fig. 2). None of the patients had bone metastases, vertebral fractures or artefacts affecting bone analysis. The thickness of the ROI was 9 mm and vertebrae L1–L3 were included in the analysis, except for 2 patients in whom L3 was anatomically outside the scan length of the CTPI examination. The measurements were performed by an experienced osteoporosis physician (A.S.) with an over 15-year clinical experience. A vBMD < 80 mg/cm3 was considered as osteoporotic, a vBMD of 80–119 cm3 as osteopenic, and a vBMD > 120 mg/cm3 as normal regarding to the definition by the American College of Radiology [32].
Radiation dose
The effective radiation dose was 20.9 mSv ± 3.6 (mean ± standard deviation), ranging from 16.0 to 30.4 mSv for CTPI and 22.5 mSv ± 7.9, ranging from 11.8 to 38.0 mSv for the 4-phase CT.
Statistical analysis
SPSS Statistics (version 25.0, IBM Corp., Armonk, NY, USA) was used for the statistical analysis. As data showed normal distribution (tested with the Kolmogorov-Smirnov test and the Shapiro-Wilks test), parametric t test was used. Data is reported as mean ± standard deviation. For correlation analysis, Pearson correlation was used. A p value < 0.05 was considered significant.