Hepatocellular carcinoma (HCC) is one of the foremost common cancers worldwide, and encompasses a poor prognosis if not treated. Cirrhotic patients are at highest risk of developing this malignant disease [1].
Generally, surgical resection and liver transplantation are the most effective treatment decision for HCC But unfortunately; only 10–15% of HCC patients are eligible for resection because of the severity of underlying cirrhosis or the diffuse distribution of the tumor and absence of donor organs hinder both options so several minimally invasive techniques are used as alternatives to surgery for treating the disease and one amongst widely used is percutaneous radio-frequency ablation [2].
Thermal ablation is achieved by using heat (radiofrequency ablation, microwave ablation, laser ablation); or cold (cryoablation). Among all the ablative techniques, RF ablation is that the one most generally used for treatment of carcinoma, but all techniques produce coagulation necrosis, and demonstrate similar imaging features on follow-up studies [3].
Monitoring tumor response to loco-regional therapy is an increasingly important task in oncologic imaging. Early favorable response generally indicates effectiveness of therapy, and will lead to significant survival benefit. Early identification of treatment failure is additionally critical in patient management, since a repeat treatment cycle is performed if liver function is maintained, before disease progression occurs [4].
Recent advances within the development of functional imaging techniques have provided the power to detect microscopic changes in tumor microenvironment and microstructure, thus allowing the assessment of tumor response after locoregional treatment by observing alterations in tumor viability, perfusion or vascularity [5].
Dynamic contrast enhanced MR imaging can assess the change in tumor vascularity and perfusion after ablation. Recently, Subtraction and color mapping were developed to boost the evaluation of the ablated hepatic lesions [6].
Subtraction imaging relies on removing any preexisting signal of T1 unenhanced images causing contrast enhancement within a mass to become more conspicuous on subtracted sequences. This can be helpful when evaluating a lesion with high signal on unenhanced T1-weighted sequences, where visual detection of the enhancement is difficult on conventional MR [7].
Our findings agreed with Kierans et al. [9] who demonstrated that the treated lesions exhibits high signal intensity on T1-weighted images.
In our study, the T2 signal was variable in Treated ( Ablation Zone), Within the treated 76 lesions; 41Leisons (53.9%) showed Intermediate/Iso intense signal, 16 Leisons (21.1%) showed heterogeneous signal and 13 Lesions (17.1%)showed hypointense signal and only 6 Lesions (7.9%) showed hyperintense signal.
These findings agreed with Hussein et al. [10], that also found also variable T2 signal intensity. They explained the high signal by the liquifactive necrosis, which occurs late, and therefore the low signal by the coagulative necrosis which occurs early.
We did a statistical analysis to detect any relationship between the T2 signal and also the tumor viability. We found there's no significant difference within the signal intensity of the whole ablation zone between the resolved and unresolved lesions at the first follow up imaging. These findings agreed with Granata et al. [11] who also didn't detect any significant correlation between the T2 signal and neoplastic activity.
On the opposite hand, Hussein et al. [10] found 86% of RF treated areas to be homogeneous hypo intense signal on T2 weighted images thanks to coagulative necrosis while only 14% showed markedly high heterogeneous signal intensity thanks to liquifactive necrosis. The superior sensitivity of T2-weighted imaging might be explained by a rise in contrast between the coagulated area that features a low signal intensity, and also the viable residual tumor which includes a high signal intensity. Moderate hyperintensity on T2-weighted images corresponded to the presence of residual viable tumor altogether cases. Therefore, T2-weighted imaging is demonstrated to be highly specific. Moreover, the moderately hyperintense area on T2-weighted images related to corresponding enhancement on contrast-enhanced T1-weighted images offers optimal specificity (100%) for residual viable tumor all told cases.
In our study, we found a relation between the pre-contrast T1 signal intensity and therefore the mismatched findings between the primary and second readers where we noticed that the mismatch occurs in cases with high T1 signal intensity in pre-contrast series.
Winters et al. [12] agreed with our study regarding the relation between precontrast signal and interpretation of imaging where they found that the Treated ablated zones show high signal on the unenhanced T1-weighted images secondary to coagulative hemorrhagic necrosis that complicates the interpretation of contrast- enhanced MRI. The contrast-enhanced T1-weighted high signal is also a results of enhancement, pre-existing T1-weighted high signal, or a mix of those and hence the issue in interpretation.
We compared statistical analysis between Conventional Dynamic MRI in addition because the Diffusion WI ends up in respect to added value of Subtraction MRI, as a gold standard, We found that adding diffusion MRI can provide more accuracy to plain conventional Dynamic MRI increased Specificity and Positive Predictive values.
The findings nearly matched with those findings in an exceedingly study performed by Hamed et al. [13] that concluded that Compared to DWI, Subtraction MRI is way more valuable, where it increases radiologists’ confidence in interpreting treatment response following loco-regional therapies for HCC supported a in an exceedingly study on 32 patients with 54 HCC lesion that compared Subtraction MRI versus diffusion weighted imaging in post locoregional treatment of HCC, where Diffusion WI MRI showed Sensitivity 70.6%, Specificity 75%, PPV 82.7% and NPV 60% compared to Added Subtraction Dynamic MRI with Sensitivity 97%, Specificity 100%, PPV 100% and NPV 95%.
In our study and on revising the info collected from both readers we noted that the subtraction technique has an additive value plus the agreement with the dynamic technique. These results revealed a big additive value of the subtraction imaging to the dynamic MRI (P < 0.001) with moderate degree of agreement between the 2 diagnostic tools (Kappa value = 0.491). This implies that Subtraction MRI significantly improves the reader confidence level within the assessment of treatment response following locoregional therapies for HCC.
Our findings agreed with Winters et al. [12] who reached to the identical result about the additive value of Subtraction MRI technique by removing pre-existing T1-weighted high signal from the post-processed images so the remaining high signal is solely because of enhancement which would improve reader confidence in detecting enhancement in targeted zones and thus improving the MRI assessment of the treatment response following loco-regional therapy. Subtraction MRI is reported to boost the conspicuity of enhancement in other imaging applications (Fig. 5).
Newatia et al. [7] agreed with additive value of subtraction and located that subtraction can make subtle enhancement within a tumor more conspicuous and may remove the high T1 signal, which is usually present thanks to coagulative necrosis. It may also help differentiate the graceful, indistinct peritumoral enhancement seen in benign post treatment hyperemia from the discontinuous nodular enhancement of viable tumor (Fig. 6).
Hence, the role of added subtraction imaging being helpful for the assessment of the therapeutic efficacy for post TACE and RF Ablation for HCCs where by accomplishing this operation, any native T1 signal is removed and therefore the remaining signal on the subtracted images is merely because of enhancement. [7] (Fig. 7).