HCC is considered as the fifth most common cancer worldwide and the most common liver malignancy . It is one of the leading causes of morbidity and mortality, with an estimated incidence of more than 500,000 new cases per year .
In Egypt, almost two and half fold increase in the HCC incidence was noticed between 1993 and 2009 among the hepatic patients. HCC is expected to continue rising in the upcoming years forming major health problem this could be explained by the highest prevalence of hepatitis C worldwide, increasing urbanization, environmental exposures and aging .
The assessment of the treatment response after TACE by cross-sectional imaging is crucial to assess the patient’s prognosis, determine whether an additional procedures is needed or not or to select another therapeutic option. Recently, enhancement approaches, such as Liver Imaging Reporting and Data System (LiRADS), mRECIST, and European Association for the Study of the Liver (EASL) are better criteria for categorizing distinct tumor responses following TACE rather than the criteria depending on the change in the lesion’s size [11, 12].
HCCs underwent coagulative necrosis after locoregional therapy. The treatment zone exhibits hyperintense T1 signal on pre-contrast images, which makes the assessment of tumor enhancement difficult on the dynamic contrast-enhanced T1WI . Subtraction imaging is an available technique whereby an unenhanced T1-weighted image is digitally subtracted from the identical image performed after contrast administration aiming to remove any native T1 signal from the images and the remaining signal on the subtracted images is solely due to enhancement .
An important technical principle in dynamic subtraction imaging is to keep all acquisition parameters of the unenhanced and dynamic contrast-enhanced images constant throughout the different dynamic phases. Also, the patient’s position should not be changed during the acquisition of the unenhanced and corresponding dynamic sequences. The patient should be able to maintain a breath-hold throughout the acquisition, the images should be done at end expiration, and the breath-hold should be reproducible from sequence to sequence .
Misregistration artifact and image degradation will result in cases not fulfilling one or more of the forementioned criteria . A hyperintense nonenhancing lesion on unenhanced images could erroneously be designated as an enhancing lesion and yield a false impression of a hypervascular tumor. A hypointense lesions on unenhanced images subtracted by hepatic parenchyma on contrast-enhanced images can yield hyperintense pseudolesions on subtraction images . If this occurs, subtracting individual images rather than entire data sets can be useful .
In this study, we aimed to evaluate the role of dynamic subtraction MRI technique in the assessment of the treatment response of HCC after TACE procedure. This study included 38 patients (after exclusion of five patients due to misregistration artifact at the subtraction images).
In a previous study , it was found that the subtraction has a sensitivity of 97.06%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 95.24% by two readers which agreed with our results. Our results were also comparable with another study  who found that both subtraction and dynamic techniques showed excellent diagnostic performance with AUC ≥ 0.90 (P < 0.001). With the subtraction has sensitivity 83.3%, specificity 90.9%, PPV 76.9%, and NPV 93.8% compared to 63.9%, 86.9%, 63.9%, and 86.9% respectively for the dynamic technique.
For DWI, reader 1 found that it had sensitivity of 80%, specificity of 80%, PPV of 75%, and NPV of 78% Compared to sensitivity of 80%, specificity of 96%, PPV of 95.2%, and NPV of 82.7% for reader 2 and sensitivity of 80%, specificity of 80%, PPV of 81.8%, and NPV of 75% for reader 3. Our results were comparable with previous study  who found that the DWI imaging had an overall sensitivity of 83.9%, a specificity of 64.3%, PPV of 72.2%, and a NPV of 78.3% and accuracy of 74.5% and with another study  who found that reader 1 evaluation of DWI yielded sensitivity of 70.59%, specificity of 75%, PPV of 82.76%, and a NPV of 60% compared to 76.47%, 90%, 92.86%, and 69.23% respectively with reader 2.
As a conclusion, we found that the subtraction images had higher sensitivity, specificity, PPV, and NPV values compared to the dynamic images and DWI images as found by previous studies  and .
The readers results to standard of reference agreement
Using kappa analysis, our study showed a stronger reader to standard of reference (SOR) agreement for the subtraction MRI images compared to the dynamic MRI images. For the subtraction MRI images, the k values were 1, 0.96, and 0.96 (high significant agreement) for the three readers respectively, compared to k values of 0.88, 0.88, and 0.48 for the dynamic MRI images. These results agreed with some previous studies [13, 16,17,18].
Correlation between the precontrast T1 signal intensity and the mismatched finding between the SOR and the dynamic MRI images that resulted in the false positive and false negative results were occurred in lesions having high signal intensity at the precontrast T1 images. This finding agreed with previous study 
Our study also showed that DWI images have kappa value 0.56, 0.76, and 0.56 for the three readers respectively. That was in agreement with a previous study  who found that the DWI results were disappointing and ADC was not a significant predictor of complete tumor necrosis.
Interobserver agreement analysis
It was noted that a high level of agreement between the three readers through all of the studied sequences with the higher agreement value with the subtraction imaging which is comparable with recent studies [2, 18].
Dynamic significant agreement of (kappa = 0.601) and P < 0.001.
Subtraction significant agreement of (kappa = 0.947) with P < 0.001.
DWI significant agreement of (kappa = 0.728) and P < 0.001.
Reader confidence level
The mean reader confidence level for the dynamic MRI protocols was 3.46, 3.34, and 2.88 for the three readers respectively. On the other hand, mean reader confidence level for the subtraction MRI protocols was 4.86, 4.90, and 4.84 for the three readers respectively. Denoting significantly higher reader confidence levels were found for all three readers when using the subtraction MRI protocol as compared to the dynamic MRI protocol.
Limitations of the study were as follows
The study design is a retrospective study which is subjected to the limitations inherent to such study design. Another limitation is a relatively small sample size reducing the power of the statistical analysis. The small sample size could be related to the strict selection criteria adopted for this highly specialized indication. However, a statistically significant higher confidence level was proven for the subtraction MRI over the dynamic MRI protocol which is an important finding not sufficiently published in the literature. Also, the reference slandered was not based on histopathological results to confirm whether there is complete treatment or residual disease. However, as discussed before, this point is related to clinical practice. False negative results are commonly seen as the residual/recurrent neoplastic lesions are mostly small sized and difficult to be properly identified on the non-contrast image-guided biopsy. In fact, the only true reference standard is the liver explant. This will be done only if patients are scheduled for hepatic transplantation. One of the limitations is the misregistration artifact that could be seen in many of HCC patients especially when the patient is unable to hold his breath properly during the scan time and thus interfering with proper image assessment. However, in such cases, we depend on the T1 and T2 signal of the lesion as well as the diffusion images and ADC analysis. The size of the lesion was not included in our assessment criteria; however, we depend on other criteria as done in previous studies.