Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management.

The 10th Global Forum for Liver Magnetic Resonance Imaging (MRI) was held as a virtual 2-day meeting in October 2021, attended by delegates from North and South America, Asia, Australia, and Europe. Most delegates were radiologists with experience in liver MRI, with representation also from specialists in liver surgery, oncology, and hepatology. Presentations, discussions, and working groups at the Forum focused on the following themes: • Gadoxetic acid in clinical practice: Eastern and Western perspectives on current uses and challenges in hepatocellular carcinoma (HCC) screening/surveillance, diagnosis, and management • Economics and outcomes of HCC imaging • Radiomics, artificial intelligence (AI) and deep learning (DL) applications of MRI in HCC. These themes are the subject of the current manuscript. A second manuscript discusses multidisciplinary tumor board perspectives: how to approach early-, mid-, and late-stage HCC management from the perspectives of a liver surgeon, interventional radiologist, and oncologist (Taouli et al, 2023). Delegates voted on consensus statements that were developed by working groups on these meeting themes. A consensus was considered to be reached if at least 80% of the voting delegates agreed on the statements. CLINICAL RELEVANCE STATEMENT: This review highlights the clinical applications of gadoxetic acid-enhanced MRI for liver cancer screening and diagnosis, as well as its cost-effectiveness and the applications of radiomics and AI in patients with liver cancer. KEY POINTS: • Interpretation of gadoxetic acid-enhanced MRI differs slightly between Eastern and Western guidelines, reflecting different regional requirements for sensitivity vs specificity. • Emerging data are encouraging for the cost-effectiveness of gadoxetic acid-enhanced MRI in HCC screening and diagnosis, but more studies are required. • Radiomics and artificial intelligence are likely, in the future, to contribute to the detection, staging, assessment of treatment response and prediction of prognosis of HCC-reducing the burden on radiologists and other specialists and supporting timely and targeted treatment for patients.

Evaluation of health economic impact of initial diagnostic modality selection for colorectal cancer liver metastases in suspected patients in China, Japan and the USA.

AIMS: To compare cost offsets and contributing factors (false-negative rates and confirmatory imaging requirements, potentially leading to longer waiting times for diagnosis) as well as long-term cost effectiveness associated with the diagnostic and treatment pathways for colorectal cancer liver metastases (CRCLM) in the US, Japan, and China according to initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) (the US and China only) and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Decision tree models were developed to simulate the clinical pathway, from first diagnostic test to initial treatment decision, based on local clinical guidelines and validated by experts. Input data were derived from the literature (up to 31st December 2020) as well as from interviews with local experts. A Markov model extension was built to evaluate the number of false-negative patients and associated costs, over a lifetime horizon. RESULTS: The decision-tree models showed that, increasing proportionate use of initial EOB-MRI resulted in a cost-offset per patient (excluding false-negative patients) in all countries (USD 201 for the US, JPY 6,284 for Japan and CNY 446 for China) driven by reductions in follow-on diagnostic procedures and unnecessary treatment. The use of EOB-MRI was also associated with a shorter average waiting time to a final diagnosis and treatment decision compared to MDCT, ECCM-MRI and CEUS. The Markov model showed that with an increase in EOB-MRI use, there are fewer false-negative diagnoses over a lifetime horizon. In all three countries, the incremental cost-effectivenes ratio (ICER) was below standard willingness-to-pay thresholds. CONCLUSION: The findings of these models demonstrate that use of EOB-MRI early in the diagnostic pathway for CRCLM results in short-term cost savings, as well as being cost effective in the long term.

Evaluation of the health economic impact of initial diagnostic modality selection in patients suspected of having HCC in China and the USA.

AIMS: To compare relative costs associated with the diagnostic pathways for hepatocellular carcinoma (HCC) in the US and China according to the initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to contrast-enhanced multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Decision tree models were developed to simulate the clinical pathway, based on local clinical guidelines, and validated by experts. Input data were derived from the literature (up to 31 December 2020) as well as from interviews with local experts. RESULTS: The models showed that compared to alternative initial imaging modalities, EOB-MRI was associated with higher diagnostic accuracy (fewer false-positive and fewer false-negative results). Increasing proportionate use of EOB-MRI resulted in a cost offset per patient (excluding false-negative patients) in both the US (USD 337) and China (CNY 1,443), driven by reductions in scan costs and unnecessary treatment costs. The use of EOB-MRI was also associated with a shorter average waiting time for a final diagnosis and treatment decision for patients compared to MDCT, ECCM-MRI, and CEUS. CONCLUSION: The findings of these models demonstrate that EOB-MRI is the most accurate and rapid imaging modality for the diagnosis of HCC in the US and China, resulting in cost offsets that may benefit the healthcare system.

Sensitivity of quantitative relaxometry and susceptibility mapping to microscopic iron distribution.

PURPOSE: Determine the impact of the microscopic spatial distribution of iron on relaxometry and susceptibility-based estimates of iron concentration. METHODS: Monte Carlo simulations and in vitro experiments of erythrocytes were used to create different microscopic distributions of iron. Measuring iron with intact erythrocyte cells created a heterogeneous distribution of iron, whereas lysing erythrocytes was used to create a homogeneous distribution of iron. Multi-echo spin echo and spoiled gradient echo acquisitions were then used to estimate relaxation parameters ( R2 and R2* ) and susceptibility. RESULTS: Simulations demonstrate that R2 and R2* measurements depend on the spatial distribution of iron even for the same iron concentration and volume susceptibility. Similarly, in vitro experiments demonstrate that R2 and R2* measurements depend on the microscopic spatial distribution of iron whereas the quantitative susceptibility mapping (QSM) susceptibility estimates reflect iron concentration without sensitivity to spatial distribution. CONCLUSIONS: R2 and R2* for iron quantification depend on the spatial distribution or iron. QSM-based estimation of iron concentration is insensitive to the microscopic spatial distribution of iron, potentially providing a distribution independent measure of iron concentration.

Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial.

OBJECTIVES: To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. METHODS: In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64-detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. RESULTS: Per-patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [-8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. CONCLUSIONS: With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. KEY POINTS: • Iodine concentration is an important parameter for image quality in coronary CTA. • Contrast enhancement must be balanced against the amount of iodine injected. • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. • Higher attenuation with higher iodine concentrations, but no SNR or CNR differences.

Segment-by-segment assessment of left ventricular myocardial affection in Anderson-Fabry disease by non-enhanced T1-mapping.

Background Anderson-Fabry disease (AFD) is an X-linked lysosomal enzyme disorder associated with an intracellular accumulation of sphingolipids, which shorten myocardial T1 relaxation times. Myocardial affection, however, varies between different segments. Purpose To evaluate the specific segmental distribution and degree of segmental affection in AFD patients. Material and Methods Twenty-five patients with AFD, 14 patients with hypertrophic cardiomyopathy (HCM), and 21 controls were included. A Modified Look-Locker Inversion Recovery sequence (MOLLI) was used for non-enhanced T1 mapping at 1.5 T in addition to standard cardiac imaging in 10-12 short axis views. T1 values were evaluated with a mixed model ANOVA and regression analysis to determine the best diagnostic cutoff values for T1 for each myocardial segment. Results Regression analysis showed the best diagnostic cutoff compared to controls in cardiac segments 1-4, 8-9, and 14. Mean differences between T1 for AFD versus HCM were greatest in segment 3, 4, and 9 (99 ms, 103 ms, 86 ms, respectively). Overall T1 times were 888 ± 70 ms and 903 ± 14 ms (AFD with and without LVH); 1014 ± 17 ms and 1001 ± 22 ms (HCM and controls, P < 0.05). Conclusion Myocardial segments are affected by a varying degree of T1 shortening in AFD patients. Segment-specific cutoff values allow the most specific detection and quantification of the extent of myocardial affection.

Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT.

OBJECTIVES: The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. METHODS: A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). RESULTS: The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. CONCLUSIONS: DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. KEY POINTS: • Regorafenib treatment response was evaluated by CT in a rat tumour model. • Dual-energy contrast-enhanced CT allows early treatment monitoring of targeted anti-tumour therapies. • Dual-energy CT showed higher diagnostic potential than conventional contrast enhanced single-energy CT. • Dual-energy CT showed diagnostic potential comparable to dynamic contrast-enhanced CT. • Dual-energy CT is a promising method for efficient clinical treatment response evaluation.