This is a retrospective study, conducted from January 2017 to September 2021 on 32 patients known to have HCC on top of liver cirrhosis presented for radiological follow-up after therapeutic interventions to search for residual/recurrent neoplasia or metastasis. The study received the approval of the institutional ethical committee, and written or informed consents from all patients were taken after explaining the aim of the study.
Patients under regular follow-up post-therapy and patients with elevated tumor marker (AFP) post-therapy, other imaging modalities findings are not conclusive, patients with portal vein thrombosis (for assessment of the type of thrombosis, benign or malignant), and patients planned to perform hepatic transplantation to exclude extrahepatic metastatic disease.
Patients known to have contraindications for MRI (e.g., metal implants as cochlear implants, implanted magnetic device, cardiac defibrillators and pacemakers or claustrophobia), patients with bad general condition needing life support and patients with severe hepato-renal disease, high serum creatinine > 2 mg/dl, patients known to have severe allergy to contrast material. Also, patients with blood glucose level > 200 mg/dl at time of the study and first trimester pregnancy.
All patients were asked to fast at least 6 h prior to scan with good hydration. All metallic items were removed including pants with zipper, bra, belts, bracelets, etc., and the patients were given gown to wear. Serum glucose was routinely measured prior to 18F-FDG injection, and it should be below 200 mg/dl (including diabetic patients who were advised to properly control their blood glucose level before examination). An intravenous (I.V) cannula was inserted in the patient’s arm for administration of 18F-FDG. The patients were instructed to avoid any kind of strenuous activity prior to the examination (for a minimum of 24 h) and following injection of the radiotracer to avoid physiologic muscle uptake of FDG. To reduce brown fat uptake, a controlled temperature (warm) environment was provided for patients before 18F-FDG injection and low carbohydrate, high fat, protein-permitted diet before the examination. Before MRI scanning, detailed explanation of imaging procedure, including practicing of breath holds, was done.
Technique of 18F-FDG PET/CT scan
The radioactive tracer (18F-FDG) was injected intravenously in a dose of 0.1 mCi/kg body weight. All patients were kept in a warm temperature quiet room and asked to rest without vigorous activity keeping their movements, including talking, at an absolute minimum and void just before imaging. Scanning by a hybrid PET/CT scanner (GE Discovery and Philips Gemini TF (Time-of-Flight) PET/CT machines) was performed 60 min after injection. The patient was positioned supine on the table with a comfortable head fixation position and their arms raised above their heads. We performed low-dose non-enhanced CT scan first and then whole-body PET scan. Triphasic contrast-enhanced CT scan was then performed. The whole study took approximately 20–30 min. Typical whole-body PET/CT scanning began from the skull base and extended caudally to the level of the mid-thighs, the arterial phase CT covering the region of the abdomen from the base of the lungs down to the iliac bones, the venous phase covering from the skull bases down to the mid-thighs and the delayed phase covering the same region as the arterial phase. The total length of CT coverage was an integral number of bed positions scanned during acquisition of PET data. (Approximately 6–7 bed positions are planned in 3D acquisition mode for scanning the entire patient with 3–5-min acquisition at each bed position.) The study was performed with the patient breathing quietly. The scanning parameters for low-dose attenuation correction CT were 120 kV, 100MA, collimator width of (64 × 0.625 mm), pitch of 0.8, gantry rotation time of 0.5 s, and field of view of 50 cm. The scanning parameters for high-dose diagnostic CT were 120 kV, 300MA, collimator width of (64 × 0.625 mm), pitch of 0.8, gantry rotation time of 0.5 s, and field of view of 50 cm. The helical data were retrospectively reconstructed at 1-mm interval. The patient was injected about 100 ml of non-ionic iodinated contrast material using dual syringe Medrad (Stellant) automated injector with injection rate about 2.5 ml/sec; then, liver was scanned in arterial (15–30 s scanning delay), portal (60–90 s scanning delay) and equilibrium/delayed (2–5 min scanning delay) phases. Hundreds of trans-axial PET and CT images were transferred to a dedicated workstation to be reconstructed and then reformatted into coronal and sagittal images to facilitate image interpretation. For each of these sets of PET and CT images, corresponding “fusion” images, combining the two types of data, also were generated.
Technique of DW MRI
The MRI studies were done using 1.5 T MR machines (MR Systems Achieva release 126.96.36.199 2016-6-27 SRN: 35073 and GE HEALTH CARE 1.5-T MRI scanner, USA). The patient is positioned supine on the MRI table. All patients were subjected to MRI study with the basic sequences including T1, T2, and diffusion study with ADC map. The study took about 10–20 min: Axial T1 WIs (with TR 550 ms and TE 24 ms) and axial and coronal T2 WIs (with TR 7300 ms and TE 115 ms). All these sequences are single-shot spin echo with flip angle 90°. Slice thickness = 5 mm; spacing = 1 mm; acquisition matrix = 256 × 224; number of averages = 1; acquisition type = 2D. Axial diffusion-weighted images were acquired with EP technique; images obtained with b = 0, b = 200 and b = 800 were included in the evaluation and in the comparison with the other sequences. TR = 2300 ms, TE = 63 ms, EPI factor = 80, slice thickness = 5 mm, gap = 1 mm, flip angle = 90, acceleration factor = 2, FOV 32–44 cm, number of signal averages (NSA) = 2, acquisition time 39 s, half scan factor = 2, bandwidth = 250 kHz, acquisition matrix 192 × 160, reconstruction matrix = 256 × 256.
The FDG PET/CT images were evaluated by two radiologists of 12 and 8 years of experience in nuclear imaging, while the MRI images were evaluated blindly and independently by 2 radiologists of 15 and 10 years of experience in abdominal imaging.
The findings were correlated with the findings derived from triphasic contrast-enhanced CT images according to the American Association for the Study of Liver Diseases (AASLD) and LI-RADS v2018 lexicon [13, 14]: LR-TR non-viable for a non-enhancing lesion. LR-TR viable for residual or recurrent tissue within or along the treated HCC or de novo lesions associated with one or more of the following features: 1—arterial phase hyper-enhancement (APHE), 2—washout appearance, 3—enhancement similar to pretreated HCC. Also, the findings were correlated with alpha-fetoprotein (AFP) serum level and histopathologic results (specially in cases with negative CT and elevated AFP).
The main followed lesion was assessed qualitatively in the PET/CT images according to the 18F-FDG accumulation within the main followed lesion or operative bed in surgically treated lesions and any de novo lesions in comparison with the surrounding normal liver tissue, whether visually increased or not. Adequate intervention is considered when the intervention bed appears completely photopenic with no detectable FDG uptake seen within. Recurrent and residual disease defined when the intervention bed margin shows one or more nodular/focal areas of increased FDG uptake, not to be mistaken with reactive hyperemia that appears as uniform low-grade metabolic activity. Satellite/new lesions were defined as the presence of single or multiple hepatic nodules demonstrating focal FDG uptake higher than the surrounding liver parenchyma. Also, metastasis sites were defined by correlating the tracer abnormally high uptake sites and the underlying pathology within the diagnostic body contrast CT images.
Quantitative assessment in the PET/CT images of the suspicious lesions is done by identifying areas of pathologically increased FDG uptake avoiding physiologic uptake. Standardized uptake value (SUV) was independently measured by using region of interest (ROI) drawn on the area of maximal metabolic activity on every axial slice of tumor-related increased FDG uptake; SUVmax was defined as the highest pixel value related to the neoplasm burden in each study.
Qualitative evaluation of the suspected lesions whether the main followed hepatic lesion, new hepatic lesions or suspected metastasis was done by DW-MRI as follows: Malignant lesions were defined as lesions with visually restricted diffusion, measured as increased signal intensity in the DWI, and corresponding decreased signal intensity in the ADC map in comparison with the surrounding normal liver tissue. Benign lesions were defined as lesions with visually facilitated diffusion, has no increased signal intensity in the DWI in comparison with the surrounding normal liver tissue, either similar to the normal liver intensity or decreased and also no decreased signal intensity in the ADC map in comparison with the surrounding normal liver tissue.
While qualitative DWI (signal intensity) was used to predict the nature of the lesion (benign or malignant), quantification of water diffusion was done by obtaining DWIs with multiple b values, which is referred to the ADC value. It is measured in the ADC map by drawing a spherical volume of interest (VOI) on the suspected area to be measured. The area with the more diffusion restriction will show bright signal on DWI and a lower ADC value than that of the area with the less diffusion restriction. The apparent diffusion coefficient (ADC) value was applied for the main followed lesion only, and the mean ADC value was documented as mm2/s.
Two cases were treated surgically with clear operative bed and no evidence of local recurrence/residual neoplasia within the surrounding normal hepatic tissue. In these two cases, no quantitative assessment was done by either the PET/CT SUV, or the DW MRI ADC value.
Results were tabulated and statistically analyzed. All tests were two-sided and were performed at the 5% level of significance by using SPSS for Windows, version 18.0 (SPSS Inc., Chicago, IL). Descriptive statistics included median (IQR), mean (x) and standard deviation (SD) and analytic statistics included chi-square test (χ2), Student's t test, Mann–Whitney test (U), Spearman correlation and ROC curve analysis (cutoff values, sensitivity and specificity). P value < 0.05 was considered statistically significant.