The present manuscript was approved by the local ethics committee of Cairo University Hospital [D-23-2019] and prepared in concordance with the recommendations of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) .
Study design and patients
We conducted a prospective diagnostic test accuracy study that recruited 70 HCC patients who were scheduled to undergo TACE or RFA through the period from January 2019 to December 2020 at the Cairo university hospitals. Adult patients (older than 18 years) were included, with no gender restriction, if they had an established diagnosis of focal or multifocal HCC diagnosed by histopathology or CT findings. Only patients with Child–Pugh class A or B disease were included. We excluded patients with relative or absolute contraindications to CT imaging or intravenous (IV) contrast. Patients were required to sign written informed consent before the study’s initiation.
Data collection and CT perfusion
Eligible patients underwent detailed history and data collection regarding the age, sex, clinical status, stage of liver cirrhosis according to Child–Pugh, etiology of HCC, date of intervention, type of intervention, size, number and location of lesions, laboratory parameters (blood screen, bilirubin, transaminase, urea, creatinine, alfa feto protein level), extrahepatic spread of the disease.
In patients who underwent TACE, we collected selectiveness of TACE, the use of microcatheter, type and size of embolization particles, the dose of chemotherapeutic agent, number of TACE procedures, response to treatment according to mRECIST criteria and survival.
All patients underwent multi-detector CT (MDCT) and CT perfusion examination 3 ± 1.3 months post-intervention.
For MDCT, we utilized a 16-slice MDCT scanner (Alexion, Toshiba Medical Systems, Japan), alongside with injection of 100–120 mL of non-ionic iodinated CM (Ultravist® (brand of iopromide) injection 300; Bayer, Berlin, Germany). The scan passed through an unenhanced phase, followed by a post-contrast triphasic acquisition.
CTP was performed using the same scanner, after the multiphase MDCT study. Before injection of CM, we selected the appropriate transverse level in order to include the maximal diameter of the treated HCC lesion, according to the unenhanced scan of the prior CECT study. Care was taken to ensure that 2 cm of the target lesion was included for the cine acquisition. Both the tumor location and anatomic landmarks (such as portal vein and aorta) were used in the decision. In patients with multiple lesions who underwent TACE, we chose the largest lesion and considered it as the target lesion.
The dynamic image acquisition includes first initial phase study and delayed phase study. The first phase study is composed of images acquired during the initial phase of contrast agent administration within 40–60 s. The second delayed phase study is 2–10 min after the first phase study. The following CT parameters were used to acquire perfusion data: image acquisition for a total duration of 40–60 s with one image every 1 s starting 1 s after injection of 40–50 ml of contrast at a rate of 4–7 ml/s with a tube current of 50–100 mAs, delayed phase involves acquisition of 1 s images acquired every 10 s for 2 min. Every patient was clearly instructed to breathe normally during images acquisition and to avoid a deep breath when experiencing a hot flush sensation, commonly associated with the rapid bolus of iodinated CM. Moreover, to avoid motion artifacts and images mis-registration,
Data were processed at a workstation (Advantage Windows 4.0; GE Medical Systems) with CTP software (GE Perfusion 3.0) by 2 radiologists. The parametric map images were created using the highest spatial resolution pixel-by-pixel calculation technique. Tissue perfusion valuation was based on the maximum slope model and using deconvolutional analysis as the average slope of the tissue enhancement divided by the peak enhancement in the aorta. ROIs were drawn, respectively, within surrounding cirrhotic liver parenchyma, trying to avoid arterial and portal vessels. The resulting temporal changes in contrast enhancement were then analyzed to quantify a range of parameters that reflected the functional status of tissue perfusion. For each dynamic CT scan acquisition, 4 single perfusion CT image maps were generated, including functional maps of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS). To draw region of interest (ROI), the readers manually drew ROI on each CTP map and corresponding CTP parameters (BF, BV, MTT, and PS), values were averaged for all ROIs in each patient. ROI included at least two-thirds of the area of the HCC. Functional maps were represented in a color-coding scheme in rainbow format ranging from blue to red so as to obtain comparable color maps as varying shades of blue, green, yellow, and red in order of increasing perfusion.
Two hepatic imaging experienced readers evaluated CT perfusion data. The readers independently reviewed hepatic focal lesion perfusion parameters. Acquisition date and participant identification were removed from all images. The radiologists were blinded to all clinical information.
The primary outcome in the present study was the diagnostic accuracy of CT perfusion parameters in assessment of responders to TACE and RFA. The secondary outcomes included comparing CT perfusion parameters of TACE/RFA responders and recurrent activity between ablated lesions and cirrhotic parenchyma.
SPSS version 19 (SPSS Inc., Cary, NC) was used for the statistical analysis. We described the central tendency and variation in age and CT perfusion parameters using mean and standard deviation (SD). Frequency tables were used for gender and response to TACE/RFA. The association between response to TACE/RFA and CT perfusion parameters was assessed using an Independent t test. Spearman correlation test was used to test the correlation between CT perfusion parameters and age. The diagnostic performance of CT perfusion parameters to predict TACE/RFA responders was evaluated using Receiver Operating Characteristic (ROC) curve analysis. A P-value of less than 5% was considered statistically significant.