|ECR 2018 / C-3043|
|Imaging features of hepatic malignancies during and after interventional radiological procedures: a practical guide for radiologists|
Findings and procedure details
Interventional radiology procedures need accurate staging of disease before treatment: radiologists should carefully report number, size and location of lesions; in addition, vascular patency or infiltration should be evaluated.
It is very important to recognise abnormal post-interventional radiology procedures imaging findings and differentiation of abnormal findings from normal postprocedural changes.
Ultrasound is generally used in screening and is not recommended for follow up of patients with treated hepatic lesions. However, there is increasing interest in using contrast-enhanced ultrasound (CEUS) to assess response to locoregional therapy, because of its ease of use during or immediately after treatment. In addition the iodized oils used during TACE do not represent a limit for CEUS interpretation, as can be the case with CT. 
Computed Tomography (CT) and Magnetic Resonance (MRI) are widely used in the post-treatment follow-up of these patients, for the detection of residual or recurrent tumors after treatment, as well as for the depiction of post-treatment complications. 
After locoregional therapies, the goal of follow up imaging is to detect residual or recurrent disease that requires additional treatment; however, currently no established guidelines for ideal surveillance time intervals exist. Since recurrence occurs more often in the first year after therapy, most guidelines suggest 3 monthly interval imaging with MRI or CT in the first year. Fig. 2
- Imaging after ablative techniques
Currently, RF and Microwave ablation are the most widely used ablative techniques for both primary and secondary malignancies of the liver; the common effect caused by all ablative techniques is the development of coagulation necrosis, so on follow up studies we can find similar imaging features. 
Ethanol ablation (PEI) is now rarely used because of inhomogeneous injection and high recurrence rate in tumors with a diameter of greater than 3 cm. 
It’s important to remember that, when local recurrence occurs, is almost always depicted at the periphery of the necrotic area, where heat development and accumulation is less because of the distance from the needle electrode and, in addition, of the cooling effect, even more markedly in tissues in contact with large vessels (heat sink phenomenon). 
According to previous studies, unenhanced US doesn’t play a role in the evaluation of RFA efficacy, since necrotic and viable tumor tissue show similar appearance on US images.
Tumor necrosis is considered complete when no foci of enhancement are seen within the tumor or at its periphery on CT scans obtained at least 5 months after treatment.
In the majority of cases, on portal phase of contrast enhancement CT scan obtained right after RFA, treated lesions show a rim of hyperattenuation surrounding the region of coagulated tumor: this can be explained by reactive hyperemia, not by residual viable tumor and disappears progressively on subsequent follow-up studies. 
On MRI, in the early post-ablation period (up to one week after ablation), it’s difficult to detect residual tumor since the necrotic cavity shows variable signal intensity changes on T1- and T2-weighted sequences and contrast-enhanced MRI must be performed for accurate analysis.
After RFA or MWA a treated liver lesion could show an enlargement due to intratumoral edema, haemorrhage, or necrosis; therefore imaging response criteria based only on size changes cannot be applied. Fig. 4
Currently the modified RECIST are the most appropriate criteria for the imaging assessment of malignant hepatic lesions treated with locoregional therapies. 
Some complications of ablative techniques, such as arterioportal shunts, can result in perfusion abnormality: in these cases a wedge-shaped enhancement of liver parenchyma adjacent to the ablation zone can be observed on arterial phase images. These abnormalities usually vanish within 30 days after the procedure. 
In the early period around the necrotic cavity, also a thin (usually 1 mm) and regular rim, with a low signal intensity on T1-, high signal intensity on T2-weighted images and moderate to intense enhancement on arterial phase, can be seen and can be referred to vascularized inflammatory reaction, haemorrhage, and granulation tissue. Fig. 5
The thickness and enhancement of this rim regress progressively, and it generally disappears by six months after ablation. In order to differentiate this enhancing rim from a tumor regrowth, it must be stressed that in the latter case the area of contrast enhancement is irregular and thicker.
On MRI, the role of subtraction images in order to differentiate coagulative necrosis from partial response or recurrence disease is crucial. Subtraction MRI is a technique whereby corresponding contrast-enhanced and unenhanced T1-weighted sequences are digitally subtracted image-by-image using post-processing MRI software. The objective of this process is to remove pre-existing T1-weighted high signal (due to coagulative necrosis) from the post-processed images so that the remaining high signal is only due to enhancement. Fig. 6 Fig. 7 Fig. 8
After 4-6 months, MRI imaging assessment is generally easier because of the resolution of inflammation; at this point the ablation area should show homogeneous T1-hyperintense and T2-hypointense signals. 
The depiction of residual tumor becomes easier on T2-weighed images by means of the distinction between the moderately hyperintense nodule and the hypointense background of the necrotic cavity. Moderately hyperintense areas on T2-weighed images correspond to the presence of residual viable tumour in all cases. Therefore, T2-weighed imaging was shown to be highly specific. Moreover, the moderately hyperintense areas on T2-weighed imaging associated with corresponding enhancement on contrast enhanced T1-weighed imaging, associated with irregular thickening of one margin of the treated area, could offer an optimal specificity (100%) for residual viable tumours. 
- Imaging after embolization
TACE is used in intermediated stage of BCLC classification, when a patient with multiple liver masses or a large tumor is not amenable to percutaneous ablation therapy. It is useful in local tumor control, preventing tumor progression, prolonging survival, and controlling symptoms. Following selective catheterization, chemotherapeutic agents (usually doxorubicin or cisplatin) suspended in Lipiodol (iodized oil), are injected into the feeding hepatic arteries of the tumor.
After TACE, Computed Tomography (CT) is a reliable method for the assessment of therapeutic efficacy. An HCC treated with TACE is to be considered as viable if showing hyperattenuation or isoattenuation on hepatic arterial phase and hypoattenuation on unenhanced and portal/venous phases. Since retained iodized oil of high attenuation may conceal arterial enhancement, the use of unenhanced phase is essential because the homogeneous and complete deposition of Lipiodol within the lesions would indicate the high degree necrosis of the tumors. It is generally agreed that the areas with retained iodized oil after a certain period (e.g. >4 wk) could be considered indicative of necrosis. 
According some studies, the analysis of enhancement pattern at the arterial phase of the first follow-up CT after TACE, is helpful for predicting disease progression. Three types of enhancement patterns can be observed: no enhancement, peripheral ring enhancement and nodule-like enhancement. Peripheral ring enhancements and no enhancements imply initial complete response status; peripheral nodulelike enhancements indicate progression of treated HCC, although it’s required further follow-up.  Fig. 9 Fig. 10
In contrast to CT imaging, the iodized oil that is used during TACE does not affect MR signal intensity. Conventionally, response is evaluated by magnetic resonance imaging (MRI) at 1-3 months after TACE. Fig. 11
TransArterial RadioEmbolization (TARE) is an emerging transarterial therapy for the treatment of hepatic malignancies, involving the administration of micron-sized radioactive particles featuring yttrium90(90Y), with a very local intense local radiotherapeutic effect.
As with the other ablative therapies, TARE induces an area of coagulative necrosis and relative avascularity. Fig. 12 Follow-up imaging is usually performed with multiphase CT 30 days after treatment and at regular 3-month intervals thereafter. On unenhanced CT images, coagulative necrosis generally results in a homogeneously hypoattenuating area. Common post treatment findings on CT and MRI are peritumoral edema and hemorrhage, due to inflammatory reaction and apparent lesion enlargement. Contralateral liver hypertrophy has also been demonstrated in patients receiving TARE, with no alteration of normal liver function. Others findings after TARE are capsular retraction, hepatic fibrosis, and portal hypertension. 
Since in the early post-treatment period, a reduction in tumor size often does not correlate with the degree of tumor necrosis, gadolinium-enhanced MRI might not discern therapy-induced inflammation and granulation tissue from viable tumor.
Alternative MRI techniques, such as diffusion-weighted imaging (DWI), can better evaluate tumor response. Tumor necrosis is associated with an increase in ADC value, which makes it easier to differentiate viable from necrotic portions of tumor. Additionally, DWI can determine treatment response several weeks earlier than anatomical imaging. According to some studies, patients whose ADC increased or decreased from baseline by > 15% immediately after TACE had a 100% rate in predicting a positive EASL response at 1 month. Statistically significant ADC increases have also been observed following yttrium-90 radioembolization.
Use of DWI and ADC mapping in conjunction with traditional anatomical imaging evaluation could further improve tumor response interpretation and subsequent treatment planning. [18,19]
A number of studies have provided prognostic evidence for DWI-based functional response assessment in liver-dominant metastatic disease for entities such as CRC, breast cancer, and neuroendocrine tumors
There was a close correlation between the early post-therapeutic increase in ADC and tumor-size reduction after 90Y-RE, even before significant tumor-size changes could be detected on standard imaging. 
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