DYNAMIC AND DIFFUSION MAGNETIC RESONANCE IMAGING IN EVALUATION OF MALIGNANT HEPATIC NEOPLASMS AFTER PERCUTANEOUS RADIOFREQUENCY ABLATION

Document Type : Original Article

Authors

1 Departments of Radiodiagnosis, Faculty of Medicine, Al-Azhar University, New Damietta and Girl Faculty in Cairo

2 Departments of Tropical Medicine, Al-Azhar New Damietta- Egypt

Abstract

Background: Evaluation of hepatic malignancies response after loco-regional treatment is crucial to assess treatment success and to guide future therapy. MRI DWI liver added to conventional unenhanced and contrast enhanced MRI always be used in the follow up of RFA showing promising results in the detection of ablation site recurrence/residual lesions.
Objective: Evaluation of the role of dynamic and diffusion MRI in evaluation of recurrent/residual hepatic neoplasms after radiofrequency ablation.
Patients and methods: This prospective study included 50 patients, 40 males and 10 females. Patients ages ranged between 45 and 80 years with the mean age of 57.02 years, (SD±8.07). Patients were referred from Tropical Medicine Department to MRI unit after the procedure of radiofrequency ablation of complete ablated malignant liver tumors.
Results: Thirty seven patients (74%) had resolved lesions, while 13 patients (26%) had recurrent/residual lesions. The border of resolved lesions were smooth, but in unresolved lesions were nodular in 11 patient out of 13 (84.6%), and irregular in two patients (15.4%). The measured cut off value between the completely ablated lesions and residual/recurrent lesions was 1.05x10-3 mm2/s. The ablation zones can be differentiated from liver parenchyma visually in the DWIs and by means of ADC in all patients. There were no statistical differences in the mean ADC values between the ablation zones of the resolved and unresolved lesions.
Conclusion: Dynamic and DWI showed viable tumor regions, and suspected areas in the periphery of the ablation zone could be identified more easily, and analyzed precisely in conjunction with the conventional T1 and T2 WIs.

Keywords


DYNAMIC AND DIFFUSION MAGNETIC RESONANCE IMAGING IN EVALUATION OF MALIGNANT HEPATIC NEOPLASMS AFTER PERCUTANEOUS RADIOFREQUENCY ABLATION

 

By

 

Mohammad Mostafa, Abdullah Hussein and Farid Atia*

 

Departments of Radiodiagnosis and *Tropical Medicine - Faculty of Medicine, Al-Azhar University

New Damietta and Girl Faculty in Cairo, and *Al-Azhar New Damietta- Egypt

 

ABSTRACT

Background: Evaluation of hepatic malignancies response after loco-regional treatment is crucial to assess treatment success and to guide future therapy. MRI DWI liver added to conventional unenhanced and contrast enhanced MRI always be used in the follow up of RFA showing promising results in the detection of ablation site recurrence/residual lesions.

Objective: Evaluation of the role of dynamic and diffusion MRI in evaluation of recurrent/residual hepatic neoplasms after radiofrequency ablation.

Patients and methods: This prospective study included 50 patients, 40 males and 10 females. Patients ages ranged between 45 and 80 years with the mean age of 57.02 years, (SD±8.07). Patients were referred from Tropical Medicine Department to MRI unit after the procedure of radiofrequency ablation of complete ablated malignant liver tumors.

Results: Thirty seven patients (74%) had resolved lesions, while 13 patients (26%) had recurrent/residual lesions. The border of resolved lesions were smooth, but in unresolved lesions were nodular in 11 patient out of 13 (84.6%), and irregular in two patients (15.4%). The measured cut off value between the completely ablated lesions and residual/recurrent lesions was 1.05x10-3 mm2/s. The ablation zones can be differentiated from liver parenchyma visually in the DWIs and by means of ADC in all patients. There were no statistical differences in the mean ADC values between the ablation zones of the resolved and unresolved lesions.

Conclusion: Dynamic and DWI showed viable tumor regions, and suspected areas in the periphery of the ablation zone could be identified more easily, and analyzed precisely in conjunction with the conventional T1 and T2 WIs.

Key words: Diffusion weighted Image (DWI); Apparent Diffusion Coefficient (ADC) and Radiofrequency ablation (RFA).

  

 

INTRODUCTION

     Liver resection and loco-regional therapies which comprise tissue ablation and chemoembolization techniques are utilized for management of hepatic malignancies (Dodd et al., 2000). Ablative therapies could be classified into either chemical or thermal ablation. Chemical ablation includes the use of acetic acid and ethanol, while thermal ablation is gained by utilizing cold (cryoablation) or heat (radiofrequency ablation, laser ablation, and microwave ablation).  RF ablation is the most widely used for both primary and secondary hepatic malignances, but all therapies produce coagulation necrosis, and exhibit common imaging characters on follow-up. In fact, ablative techniques are a substan-tial choice for individuals with hepatic tumors who are not fit for surgery. These procedures are known to have low mortality and morbidity, as well as being with lower cost than surgical resection with the possibility to use these techniques on outpatient basis (Ozkavukcu et al., 2009). The percutaneous ablation proce-dures has the ability to destroy the tumor, preserving the normal liver parenchyma with low risk of complication accom-panied with the technique and being easily available and relatively inexpensive. There is in addition to the eligibility to easily repeat the procedure in case of recurrent lesions (McWilliams et al., 2011). Evaluation of tumor response after loco-regional treatment is crucial to assess treatment success and to guide future therapy (Vossen et al., 2006). After RFA, the dynamic contrast enhanced MRI for evaluation of the response of the tumor is still difficult. Residual contrast enhance-ment may also be hard to appreciate. Hence, some types of secondary tumors are hypovascular (Tri-Linhet al., 2012). The MRI characters of the ablated zones should be assessed for lesion size after ablation, the signal intensity on unenhanced images, the presence of perilesional enhancement, and for lesion washout. Moreover, focal liver lesions managed by RFA often contain a high signal on T1WIs, corresponding to coagulation necrosis, which makes any residual tumor contrast enhancement difficult to be differentiated (Kierans et al., 2010). DWI is a technique that has been helpful in liver tumor detection, tumor characterization, and monitoring response to treatment (Bruegel & Rummeny 2010, Figueiras et al., 2011 and Lee et al., 2011). ADC value and DWI parameter, has been correlated the presence of necrosis and tumor cell necrosis after successful treatment (Anzidei  et al., 2011 and Padhani & Koh, 2011). Studies have demonstrated a potential to characterize malignant lesions and to differentiate viable tissue from necrosis on the basis of ADC cut-off values, because necrosis has higher ADC values (Wagner  et al., 2012 and Heijmen  et al., 2013).The European Association for the Study of Liver Disease (EASL) has recommended the use of lesion enhancement, rather than change in size, as the standard method to determine treatment response. However, uniform rim enhancement may also result from post-treatment reactive granulation tissue. Hence, a marker that would assess cellularity, such as DWI, may offer additional benefit to accurately assess tumor necrosis (Kamel and Morgan, 2011). DWI in the liver in addition to conventional unenhanced and contrast enhanced MRI always be used in the follow up after RFA shows promising results in the detection of ablation site recurrence/residual lesions (Kele and Van Der Jagt, 2010). ADC is used to assess metabolic tumor response after loco-regional treatment. Additionally, some authors have tried to determine whether the intra-lesion measurement of the lowest ADC might be helpful in monitoring tumor recurrence because this value could reflect the persistence of viable and residual tumor cells (Lu et al., 2010).

     The aim of the current study was to evaluate the role of dynamic and diffusion weighted magnetic resonance imaging in evaluation of recurrent/residual hepatic neoplasms after radiofrequency ablation, and also aiming to improve the technique and to standardize MR protocol to be used after interventional therapy for malignant hepatic tumors.

PATIENTS AND METHODS

     This prospective study was performed in the period between January 2014 to January 2016 .The study included 50 patients, 40 males and 10 females. Their   ages   ranged   between 45 and 80 years old with the mean age of 57.02 years, (SD±8.07). Forty patients (80%) with hepatocellular carcinoma and 10 patients (20%) with liver metastases detected. This shows a more prevalence of HCC among hepatic malignancies. Patients were refer-red from Tropical Medicine Department as well as from outpatient clinic after the procedure of radiofrequency ablation.

Inclusion criteria:  Patients with hepatic malignancy (HCC) or metastases after radiofrequency ablation.

Exclusion criteria: Contraindications to magnetic resonance imaging, to contrast media and tumors other than HCC or metastases.

All patients were subjected to the following:

A) History and clinical examinations.

B) Laboratory investigations:

1. Complete blood picture (CBC), hepatitis B surface antigen (HBSAg) and hepatitis C virus (HCV).

2. Liver and renal function tests.

3. Tumor markers: Alpha fetoprotein and carcino embryonic antigen.

C) RF ablation system:

     Radiofrequency ablations were perfor-med for less sizable tumors less than 5cm under real time ultrasound guidance using A 5 or 3.5-MHz curvilinear probe. Patients were treated under conscious sedation. The RITA model 1500 RF ablation system provides multiple temperature displays and simple intuitive panel design. Radiofrequency energy was applied from 12 to 15 minute to ensure predictable controllable ablations. The generator also provided automatic temperature control and impending monitoring. Its needle was 15 G, 13 to 25 cm long insulated cannulae that housed 7 solid expandable curved electrodes. This system allowed ablation of 3.5 to 4 cm spherical tumors tissue per cycle at temperature 70°C or higher. Dispersive electrode pads to be applied to the patient's thighs and connected to the generator to close the electric circuit. Patients were discharged the day following the procedure.

D. MRI examination:

     Dynamic MRI of the liver was examined using Resonance Achieva 1.5 Tesla-XR Class IIa 2010, Philips. Technical considerations for dynamic MRI of the liver scanning protocol:

T1 weighted image (T1WIs) gradient echo sequences (GRE) was with and without fat suppression (FS). Repetition time (TR) =100-200 ms, echo time (TE) ≤ 8 ms, number of excitations (NEX) 1-4 , matrix 128-256 x 256 with a field of view as small as possible, slice thickness 5-7 mm, slice gap 0-2 mm, flip angle =90°.

T2 weighted  image  (T2WIs) fast spin echo sequences was with  and  without fat suppression (FS): (TR) ³ 2000 ms, (TE) = 90-120 ms, number of excitations (NEX) 1-4, matrix 192-256 x 256 with a field of view as small as possible, slice thickness 5-7 mm, slice gap 0-2 mm, flip angle = 90°.

Dual echo (in and out of phase): (TR) = 99 ms, (TE) = 4.6 ms in phase and 2.3 ms in out phase WIs, flip angle = 80°.

DWI and ADC map was performed before the dynamic imaging using respiratory triggered fat-suppressed single-shot echoplanar sequence that combined the two diffusion (motion-probing) gradients before and after the 180° pulse along the three directions of section-select, phase-encoding, frequency encoding and data acquisition with an EPI readout were obtained by applying three different b factors of 0, 500, and 1000 s/mm2.

Dynamic study:  It was done after diffusion study to avoid the effect of contrast agents on ADC value.T1 spoiled gradient WIs was used by IV adminis-tration of gadopentetate dimeglumine (Gd-DTPA) (0.1mm l/kg) using pump injector at rate of 2ml/s followed immediately by 20 ml of sterile 0.9% saline solution injection, arterial phase (16-20 sec.), porto-venous phase (45-60sec.) and delayed/equilibrium phase (3-5 min.). All patients were imaged in end expiration to limit the risk of image misregistration.  The used MRI pulse sequences parameters were detailed in Table (1).

 

 

 

Table (1): MRI pulse parameters sequences.

MRI

 

Parameters

sequences  

T1WI

T2WI

In phase

Out of phase

DWI

Dynamic

T1WIs

Repetition time (msec)

100-200

³2000

 

99

 

 

99

 

 

1600-2000

 

 

140

 

Echo time (msc)

≤8ms

90-120

4.6

2.3

70

5

Matrix

128-

256x256

192-

256x256

128-

256x256

128-

256x256

144 X 192

128-

256x256

Field of view

380 mm

300 mm

380mm

380mm

300mm

380 mm

Slice thickness

5-7mm

5-7mm

5-7mm

5-7mm

7-8mm

5-7mm

Interslice gap

0-2mm

0-2mm

0-2mm

0-2mm

1 mm

1 mm

Acquisition time

4 min

4min

4min

4min

4 min

15 sec

Flip angle

90°

90°

80°

80°

180°

90°

 

 

● MR images analysis: Images were sent to the workstation (Phillips Extended MR Workspace) for further image processing.

● ADC map measurement:-

○ ADC maps were generated on the workstation. Calculation of the ADC value was an automated process.

○ ROI at the ablation zone.

○ ROI at the margins of the ablation zone.

○ ROI at segment IV or V of the liver.

● Interpretation of the MR images:

○ Signal of the ablation zone at T1, T2, Dual phase and DWIs.

○ ADC measurement (mean and ADC ratios) of the liver parenchyma, ablation zone, at the margins of the ablation zone and periablation zone.

● Dynamic study interpretation:

○ Pattern of enhancement of ablation zone in arterial, portal and delayed phases.

○ Ill-defined perilesional parenchymal enhancement may relate to post interventional changes. This was defined as early arterial phase enhancement beyond the ablated cavity that persisted in the delayed phase.

○ Well defined enhancement at the margin of the ablation zone which may be either:

a) Granulation tissue persistent on delayed phase enhancement.

b) Nodular or hallow enhancement that suggested tumor recurrence/ residual. 

● Result of ablation of the tumor: The border of resolved lesions were smooth but in unresolved lesions were nodular and irregular.

● Standard of reference:

○ It was difficult to obtain pathologic confirmation in patients who underwent ablation because most of these patients did not undergo surgery. In addition, biopsy may result in sampling error as recurrent lesions were mostly small nodules. So, resolved lesions were considered if the finding become regressed or disappeared in the follow up studies.

○ Unresolved lesions were considered if the findings showed:

Enlargement of the ablation zone.

Focal changes at the margin of the ablation zone with:

a) Diffusion hyperintensity (restric-tion) and low ADC value <1.05x10-3 mm2/s.

b) Early arterial phase enhancement of the ablation zone which became hypointense relative to the liver parenchyma in the delayed phase.

c) The general observation period included clinical, LAB and imaging follow up within first three months after the RFA then every 3 months for 1 year, and every 6 months for 2 years.

Statistical analysis of data: The collected data were organized, tabulated and statistically analyzed using statistical package for social science (SPSS) version 19 (SPSS Inc, Chicago, USA). Mean, standard deviation, frequency and percentage were used as descriptive. Examining the difference in ADC values was performed using unpaired t test. P value less or equal to 0.05 was considered significant  

Ethical consideration:

     Institutional review board (IRB) approval:  The protocol was discussed by the ethical scientific committee for approving the study and informed consent was obtained before participation.

Consent procedure:

     The Investigator made certain that an appropriate informed consent process was in place to ensure that potential research subjects, or their authorized representa-tives, were fully informed about the nature and objectives of the clinical study, the potential risks and benefits of study participation, and their rights as research subjects. The Investigator obtained the written, signed informed consent of each subject, or the subject’s authorized representative, prior to performing any study-specific procedures on the subject. The Investigator retained the original signed informed consent form.

Subject Confidentiality: 

     All laboratory specimens, evaluation forms, reports, video recordings, and other records that lift the site did not include unique personal data to maintain subject confidentiality.

RESULTS

In our study there were 37 patients (74%) have resolved lesions while 13 patients (26%) have recurrent/residual lesions. 

The signal intensity of the ablation zone in the T1,  T2 WIs, DWIs and in dynamic study was  67%  of the patients imaged within the 1st. month after ablation showing heterogeneous high T1 and low T2, 20% showed homogenous high T1 and low T2 signal and 13.3% showed homogenous low T1 and high T2 signal. In the 4-12 months imaging, most of the ablation zones elicited homogenous high T1 and low T2 signal, (Fig. 1 & 2) 77% of patients imaged within 4-6 months and 85% of patients imaged within 9-12 months. DWIs showed high signal (restricted) and low signal in ADC map. In dynamic study revealed non enhancing ablation zones.

The border ofresolved lesions were smooth but in unresolved lesions were nodular in 11 patient out of 13 (84.6%) (Fig. 3 & 4), and irregular in two patient (15.4%).

The signal intensity of the recurrent/ residual lesions in the T1, T2, DWIs and in dynamic study were classified into intermediate, high or low signal (relative to the ablation zone). 31% of the recurrent/residual lesions elicited low T1 and 77% elicited high T2 signal, but in DWIs appeared hyperintense (restricted) whereas necrotic regions appeared hypointense and low signal in ADC map. Dynamic study showed early arterial enhancement and rapidly washing out in delayed images. 

We used b values 0, 500 and 1000 s/mm2 to avoid intravoxel perfusion effect which resulted from low b values (less than 50 s/mm2) as well as image degradation from high b values (more than 1000 s/mm2).Table (2) showed mean ADC values of liver parenchyma, ablation zones, residual/recurrent lesions and periablation tissue changes.

 


Table (2): Mean ADC values of liver parenchyma, ablation zones, residual/recurrent lesions and periablation tissue changes.

Category

No.

Mean ADC

SD

Liver parenchyma

50

1.18 x 10-3 mm2/s

0.07

Ablation zones

50

1.38 x 10-3 mm2/s

0.19

Residual/recurrent lesions

13

0.91 x 10-3 mm2/s

0.09

Periablation tissue changes

30

1.29 x 10-3 mm2/s

0.12

 

 

  • The measured cut off value between the completely ablated lesions and residual/ recurrent lesions was 1.05x10-3 mm2/s. Our study showed that ablation zones can be differentiated from liver parenchyma visually in the DWIs and by means of ADC in all patients.  There were no statistical difference in the mean ADC values between the ablation zones of the resolved 1.37 x 10-3 mm2/s and unresolved lesions 1.39 x 10-3 mm2/s (P value 0.7). ADC ratios between the recurrent/residual lesions and the liver parenchyma were 0.77. The mean ADC value within segment VI or V of the liver was 1.18×10-3 mm2/s denoting parenchymatous liver disease.  

We studied the presence of periablation thin and regular enhancement area surrounding the ablation zone in all phases of dynamic study. These areas had low signal in T1 and high signal in T2 WIs with mild hypointensity in the DWIs. This was present in 99% of patients imaged within the 1st. month after ablation. This persists in 11% of patients imaged at 4-6 months and only in 7% after   9-12 months. The benign finding (based on the follow up study) represented reactive inflammatory and vascular changes of the liver parenchyma adjacent to the ablation zones (Table 3).


 

Table (3): Comparison between the mean ADC values.

Ablation zones in all patients (n= 50)

SD

Liver parenchyma in all patients

(n= 50)

SD

ADC Ratio

P value

1.38 x 10-3 mm2/s

±0.17

1.18 x 10-3 mm2/s

±0.06

1.15

0.0001

Residual/recurrent lesions (n=13)

 

 

Ablation zones in all patients

(n=50)

 

 

ADC Ratio

P value

0.91 x 10-3 mm2/s

±0.08

1.38 x 10-3 mm2/s

±0.17

0.66

0.0001

Residual/recurrent lesions (n=13)

 

 

Liver parenchyma in all patients

 (n=50)

 

 

ADC Ratio

P value

0.91 x 10-3 mm2/s

±0.08

1.18 x 10-3 mm2/s

±0.06

0.77

0.0001

Ablation zones in the resolved lesion

(n=37)

 

 

 

Ablation zones in the

residual/recurrent lesions

(n=13)

 

 

P value

1.37 x 10-3 mm2/s

±0.19

1.39 x 10-3 mm2/s

±0.08

0.7

Residual/recurrent lesions (n= 13)

 

 

Periablation tissue changes

 (n=30)

 

 

ADC Ratio

P value

0.91 x 10-3 mm2/s

±0.08

1.29 x 10-3 mm2/s

±0.11

0.70

0.0001

A  B

 

C  D E

 

 

F      G

 

Figure (1): Radiofrequency ablation for HCC at segment V after 1 month. (A) and (B). Precontrast axial T1 and T2 WIs. The ablation zone appeared of high signal in T1 and low signal in T2 WIs. Dynamic MRI examination (C). Arterial, (D)- Portal and (E) Equilibrium phases. The ablation zone revealed no contrast enhancement, while the surrounding parenchyma showed inhomogeneous contrast enhancement during the arterial phase that showed delayed washout in the portal and delayed phases. (F). DWI and (G). ADC map. The ablation zone appeared of low signal in the DWIs and high signal in the ADC map (average ADC value = 1.330 x 10-3 mm2/s). The surrounding hepatic parenchyma showing low T1 and intermediate signal in T2 WIs appeared hyperintense in the DWI and low signal intensity in ADC map, representing perfusion changes secondary to portal vein thrombosis.

Diagnosis: Complete ablated lesion with portal vein thrombosis and secondary perfusion changes.

 

 

       
   
     
 

 

 

 

 

 

 

 

 

 

 

 


A                                                                B

 

 

 

 

C                                                      D

 

Figure (2): Radiofrequency ablation for solitary hepatic metastases from cancer colon in segment V1 after 12 months. (A). Precontrast axial T1WI the ablated zone showed high signal intensity with pyramidal shape interior low signal intensity. (B) Dynamic study: Late arterial phase showed faint marginal enhancement of the ablated area. (C) DWI: The ablated zone showed interior low signal and marginal high signal intensity.(D).ADC map: The ablated zone appeared isointense to liver parenchyma (average ADC value = 1.380 x10-3 mm2/s).

Diagnosis: Completely ablated lesion.  

 

 

 

 

 

 

 

 

 

 

 

     A                                      B

 

 

C                                            D

 

 

 

                                                                    E                                                         

 

Figure (3): Radiofrequency ablation for HCC at segment V after 3 months (A). Precontrast coronal T1WI, the ablated zone showed peripheral high signal intensity. (B) Dynamic study: Late arterial phase the ablated zone showed  marginal contrast enhancement. (C). Portal phase the ablated zone showed early washout of the lesion enhancement. (D) DWI the lesion showed Inhomogeneous bright signal (restrict diffusion).  (E) ADC map: The lesion showed superior and anterior subcapsular eccentric and elliptical shape small area of low signal intensity, with heterogeneous low signal of the rest parenchymal lesion (average ADC value = 1 x10-3 mm2/s).

Diagnosis: Incomplete ablated lesion with eccentric residual area revealed low ADC value.

                            A                                               B                                               C

 

 

 

 

 

 

 

 

 

 

                          

                                                  D                                                E

 

Figure (4): Radiofrequency ablation for metastatic lesions from breast cancer at segment V11 after 9 months. (A) and (B). Precontrast axial T1 and T2 WIs. The ablated zone showed central area of high T1 and low T2 signal intensity and superior crescent margin and small posterior spherical nodule of low T1 and high T2 signal intensity. (C). Dynamic study: Late arterial phase showed enhancement of the nodule and the crescentic superior margin and poor contrast enhancement of the central interior zone. (D). DWIs showed restricted diffusion of the superior margin and the small posterior nodule in contrast to the center of the lesion (low signal intensity). (E). ADC map showed reversible of the signal intensity where low signal superior margin and the nodule with high signal intensity of the interior lesion (average ADC value = 1.001x10-3 mm2/s).                                                    

Diagnosis: Incomplete ablated lesion with anterior marginal and posterior residual lesions revealed low ADC value.                                                                                                                                                                                                                   

 


DISCUSSION

     In the current study, DWI was done by using respiratory triggered fat suppressed single shot echoplanar sequence. Kandpal et al. (2009) reported high concordance of results of ADC evaluation  by used both  breath hold and respiratory triggering examination techniques considering the fact that respiratory triggering imaging require longer acquisition time. Kim et al. (2011) mentioned that the dynamic contrast enhanced MRI can assesses the change in tumor vascularity and perfusion local ablation therapy.

     In the present study, the signal intensity of the ablation zone in the T1, T2 WIs, DWIs and in dynamic study  was  67%  of the patients imaged within the 1st month after ablation showing hetero-geneous high T1 and low T2. 20% showed homogenous high T1 and low T2 signal and 13.3% show homogenous low T1 and high T2 signal. In the 4-12 months imaging most of the ablation zones elicited homogenous high T1 and low T2 signal (77% of patients imaged within 4-6 months and 85% of patients imaged within 9-12 months). In DWIs appeared high signal (restricted) and low signal in ADC map. In dynamic study revealed non enhancing ablation zones. Kierans et al. (2010)  found that 87.8% of the ablation zones imaged within the first 4 months after ablation show high T1 signal with persistence of the high signal in about 84.1% in patients imaged >9months after ablation. Braga et al. (2010) stated that the treated lesion exhibits increased signal on T1 and decreased signal intensity on T2 WIs. The heterogeneous appearance of the ablation zone reflecting the different post treatment tissue changes that can be found after RFA is mainly due to necrosis, hemorrhage  and dehydration. In the study performed by Batra and Tripathi (2004) necrosis and microhemorrhage are the cause of hyperintensity in DWIs in post therapeutic necrosis of malignant lesions. Nisha and Sainani (2013) reported in dynamic study that the ablation zone is well demarcated and no enhancement suggests a lack of viable tumor.

    We reported that the borders of resolved lesions were smooth but in unresolved  lesions were nodular in (84.6%) and irregular in two patients (15.4%). This agreed with another study byDromain et al. (2002) who reported that (77.5%) of the recurrent lesions showed small nodules at the ablation zone margins and (22.5%) of the lesions showed thick irregular rim at the ablation zone margins. Also, Koda et al. (2012) and Minami et al. (2014) found that the recurrent or residual rate tends to be lower in HCC patients with an adequate ablation margin.

    Our finding demonstrated that 31% of the recurrent/residual lesions elicit low T1 and 77% eliciting high T2 signal but in DWIs appeared hyperintense, whereas necrotic regions appear hypointense. Nisha et al. (2013) found that the recurrence lesions appeared isointense to hypointense on T1, and is isointense to moderately hyperintense on T2. Schraml et al. (2009) mentioned that viable tumor regions appear hyperintense on DWIs, whereas necrotic regions appear hypoin-tense.

     Our study had  b values 0, 500 and 1000 s/mm2 to avoid intravoxel perfusion effect which resuldte from low b values (less than 50 s/ mm2) as well as image degradation from high b values (more than 1000 s/ mm2). Jiang et al. (2008) stated that the signal intensity on DWI is a mixture of diffusion and perfusion. Also they stated that the image quality diminished greatly with increasing b value especially on b 2000 DWI.

     We found that the mean ADC value of the liver parenchyma was (1.18 x 10-3 mm2/s), ablation zones in all patients were (1.38 x 10-3 mm2/s), recurrent/residual lesions were (0.91 x 10-3 mm2/s) for ablation zones in the resolved lesions were (1.37 x 10-3 mm2/s), while for ablation zones in the residual/recurrent lesions were (1.39 x 10-3 mm2/s) and for periablation tissue changes was (1.29 x 10-3 mm2/s). This agreed with Schraml et al. (2009) who found that mean ADC values of the liver parenchyma was (1.06 ±0.21 x 10-3 mm2/s ) while for the ablation zones were (1.19±0.30 x 10-3 mm2/s). They Also foundthat  the mean ADC values of the whole ablation zones do not significantly differ between the resolved lesions and the unresolved lesions also the mean ADC value of the recurrent lesions differ significantly from the mean ADC value of the perilesional tissue changes (P value 0.0124). Different studies by Miller et al. (2010), Vergara et al. (2010) andOnura et al. (2012) worldwide were established to determine the value of DWI in evaluation of hepatic focal lesions and in assessment of malignant lesions response after loco-regional therapy. They reported that ADC values of benign hepatic lesions were significantly higher than that of malignant hepatic tumors  Szurowska et al. (2013) stated that quantitative measurements of diffusion showed that malignant lesions present lower ADC values than benign ones and surrounding liver parenchyma.

      Our study revealed that the ablation zones can be differentiated from liver parenchyma visually in the DWIs and by means of ADC in all patients. This finding was also stated by (Schraml et al. (2009).          

     We also calculated the ADC ratios between the recurrent/residual lesions and the liver parenchyma was 0.77 ±0.12. This agreed with Schraml et al. (2009) who found that ADC ratio between the recurrent/residual lesions and the liver parenchyma was 0.90 ±0.21.

     In the present study mean ADC value within segment VI or V of the liver was (1.18×10-3 mm2/s) denoting parenchy-matous liver disease. Similar results were also obtained by Bittencourt et al. (2011) who mentioned that mean ADC value in parenchymatous disease was (1.12 × 10-3 mm2/s), while in normal liver was ( 1.47 × 10-3 mm2/s).

      The present work showed presence of periablation thin and regular enhancement area surrounding the ablation zone in all phases of dynamic study. These areas had low signal in T1 and high signal in T2 WIs with mild hypointensity in the DWIs, in 99 % of patients imaged within the 1st month after ablation. This persisted in 11% of patients imaged at 4-6 months and only in 7% after 9-12 months. The benign finding (based on the follow up study) represented reactive inflammatory and vascular changes of the liver parenchyma adjacent to the ablation zones. This was in line with results of Kierans et al. (2010) who found the perilesional enhancement in 53.7% of cases imaged < 4 months after RFA, that persists in 25.6% at 4-9 months and only in 12.2% in cases imaged >9 months after RFA. These areas exhibit mild hyperintensity in DWIs in the 20% of the patients imaged within the first 6 months after the ablation, persist in 10% in the next follow up study at 6-9 months and only in 5% of patients at 9-12 months. Also, Schraml et al. (2009) reported perilesional ill-defined area of diffusion hyperintensity in 22.5% of the patients imaged within the first 6 months after the ablation, persist in 19.5% in the next follow up study at 6-9 months and only in 6.5% of patients at 9-12 months. Goldberg et al. (2009) stated that benign periablational enhancement surrounding the ablation zone is frequently found to show moderate to intense peripheral rim like enhancement on the arterial phase of  contrast enhanced MRI which may persist on the delayed  phase. This rim has low signal on T1 and high signal intensity on T2WIs. Nisha et al. (2013) mentioned that the signal alterations in the periphery of the ablation one due to the fact that therapeutically induced nontumoral tissue changes show low cellularity and therefore present with less signal in DWI and high ADC, respectively, and can thereby be distinguished from tumoral tissue that presents with high signal in DWI and low ADC value, respectively. Also, Kim et al. (2011) found that ADC could be helpful for analyzing unclear hyperintense areas adjacent to the ablation zone. where differentiation between tumor tissue and post treatment changes is unambiguous.

      Our finding demonstrated that DWI showed viable tumor regions and suspected areas in the periphery of the ablation zone could be identified more easily, and analyzed precisely in conjunction with the conventional T1, T2, and dynamic contrast enhanced images. Hayashida et al. (2006) demonstrated that, in different organs , DWIs has been used to predict and monitor the effect of several treatment options and to differentiate between viable and necrotic tumor tissues. Close and careful follow up is needed in patients who underwent treatment by RFA to detect recurrence at an early stage. Ajaykumar et al. (2013) mentioned that  radiologists must interpret DWI in conjunction with other MRI pulse sequences, especially keeping in mind the pretest probability of an abnormality. Overall, the limitation of the DWI sequence is predominantly lesion characterization rather than lesion detection.

CONCLUSION

     Dynamic contrast enhanced images and DWI showed viable tumor regions and suspected areas in the periphery of the ablation zone could be identified more easily, and analyzed precisely in conjunction with the conventional T1 and T2WIs. Recognition of abnormal post RFA imaging findings and differentiation of abnormal findings from normal post-procedural changes are important for diagnostic and interventional radiologists. Early identification of residual or recurrent disease can facilitate timely retreatment, management, and follow up care. 

REFERENCES

1. Morani AC1, Elsayes KMLiu PSWeadock WJSzklaruk J, Dillman JR, Khan A, Chenevert TL and Hussain HK. (2013): Abdominal Applications of Diffusion Weighted Magnetic Resonance Imaging: Where do we stand. World J Radiol., 5(3): 68-80.

2. Anzidei M, Napoli A , Zaccagna F, Cartocci G, Saba  L and Menichini   G. (2011): Liver me­tastases from colorectal cancer treated with conven­tional and anti-angiogenetic chemo-therapy: evalua­tion with liver computed tomography perfusion and magnetic resonance diffusion weighted imaging. J Comput Assist Tomogr., 35(6):690–696.

3. Batra A and Tripathi RP (2004): Atypical diffusion-weighted magnetic resonance findings in glioblastoma multiforme,  Australas Radiol., 48,388-391.

4. Bittencourt LK, Matos C and Coutinho AC. (2011): Diffusion-weighted magnetic resonance imaging in the upper abdomen: technical issues and clinical applications. Magn Reson Imaging Clin N Am., 19: 111-131.

5. Bruegel M and Rummeny EJ. (2010): Hepatic metastases: use of diffusion weighted echo-planar imaging. Abdom Imaging, 35(4):454-61.

6. Chiu FY, Jao JC, Chen CY, Liu GC, Jaw TS, Chiou YY, Hsu FO and Hsu JS. (2005): Effect of intravenous  gadolinium   DTPA    on    diffusion weighted magnetic resonance images for evaluation of focal hepatic lesions. J Comput Assist Tomogr. , 29(2):176-80.

7. Dodd GD 3rd, Soulen MC, Kane RA, Livraghi T, Lees WR, Yamashita Y, Gillams AR, Karahan OI and Rhim H. (2000): Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough. Radiographics, 20:9-27.

8. Dromain C, de Baere T, Elias D, Kuoch V, Ducreux M, Boige V, Petrow P, Roche A and Sigal RV. (2002): Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow up. Radiology, 223:255-262.

9. Figueiras RG, Padhani AR, Goh VJ, Vilanova JC, González SB, Martín CV, Caamano AG, Naveira AB and Choyke PL. (2011): Novel oncologic drugs: what they do and how they affect images. Radiographics, 31(7):2059-2091.

10. Goldberg SN, Grassi CJ, Cardella JF, Charboneau JW, Dodd GD 3rd, Dupuy DE, Gervais DA, Gillams AR, Kane RA, Lee FT Jr, Livraghi T, McGahan J, Phillips DA, Rhim H, Silverman SG, Solbiati L, Vogl TJ, Wood BJ, Vedantham S and Sacks D. (2009):  Image guided tumor ablation: standardization of terminology and reporting criteria. J Vasc Interv Radiol., 20(7):S377–90.

11. Goshima S, Kanematsu M, Kondo H, Yokoyama R, Kajita K, Tsuge Y, Watanabe H, Shiratori Y, Onozuka M and Moriyama N. (2008): Diffusion weighted imaging of the liver: optimizing b value for the detection and characterization of benign and malignant hepatic lesions. J Magn. Reson. Imaging, 28(3):691-7.

12.Hayashida Y, Yakushiji T, Awai K, Katahira K, Nakayama Y, Shimomura O, Kitajima M, Hirai T, Yamashita Y and Mizuta H. (2006): Monitoring therapeutic responses of primary bone tumors by diffusion weighted image: Initial results. Eur Radiol., 16:(12) 2637-2643

13. Heijmen L, Ter Voert EE, Nagtegaal ID, Span P, Bussink J, Punt CJ, de Wilt JH, Sweep FC, Heerschap A and Van Laarhoven HW. (2013): Diffusion weighted MR imaging in liver metastases of colorectal cancer: reproducibility and biological validation. Eur Radiol., 23(3):748–756.

14.Kandpal H, Sharma R, Madhusudhan KS and Kapoor KS. (2009): Respiratory triggered versus breath hold diffusion weighted MRI of liver lesions: comparison of image quality and apparent diffusion coefficient values. AJR, 192(4):915-22.

15. Kele PG and Van Der Jagt EJ. (2010): Diffusion weighted imaging in the liver. World J Gastroenterol. ,16(13): 1567–1576.

16. Kierans AS, Elazzazi M and Braga L,  Polytimi Leonardou1, David A. Gerber, Charles Burke, Waqas Qureshi1, Masayuki Kanematsu and Richard C. Semelka. (2010): Thermoablative treatments for malignant liver lesions: 10 year experience of MRI appearances of treatment response. AJR, 194:523–529.

17. Kim KW, Lee JM and Choi BI. (2011): Assessment of the treatment response of HCC. Abdom Imaging, 36:300–314.

18. Koda M, Tokunaga S, Miyoshi K, Kishina M, Fujise Y, Kato J, Matono T, Okamoto K, Murawaki Y and Kakite S. (2012): Assessment of ablative margin by unenhanced magnetic resonance imaging after radio-frequency ablation for hepatocellular carcinoma. Eur J Radiol., 81(10):2730–6.

19. Koh DM and Collins DJ. (2007): Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol., 188(6): 1622–1635.

20. Braga L., Armao D, Azzazi M and Semelka R.C. (2010):  Liver  R.C. Semelka (Ed.), Abdominal-Pelvic MRI (third ed.), pbl. Wiley Blackwell, Hoboken, NJ, pp.445-454.

21. Lee CH, Braga L, de Campos R.O. and Semelka R.C. (2011): Hepatic tumor response evaluation by MRI. NMR Biomedicine, 24(6):721–733.

22. Lu TL, Meuli RA, Marques-Vidal PM, Bize P, Denys A and Schmidt S. (2010): Inter-observer and intra-observer variability of the apparent diffusion coefficient in treated malignant hepatic lesions on a (3.0) T machine: measurements in the whole lesion versus in the area with the most restricted diffusion. Journal of Magnetic Resonance Imaging. 32(3):647–653.

23. Mc Williams JP, Kee  ST, Loh  CT, Lee   EW and Liu  DM. (2011): Prophylactic embolization of the cystic artery before radio-embolization: feasibility, safety, and outcomes. Cardiovascular Intervent Radiol., 34:786-792.

24. Miller FH, Hammond N, Siddiqi AJ, Shroff S, Khatri G, Wang Y, Merrick LB and Nikolaidis P. (2010): Utility of diffusion weighted MRI in distinguishing benign and malignant hepatic lesions., J Magn Reson Imaging.,32(1):138-47.

25. Minami Y, Nishida N and Kudo M. (2014): Therapeutic response assessment of RFA for HCC: Contrast enhanced US, CT and MRI. World J Gastroenterol., 20(15): 4160–4166.

26. Nisha I., Debra A., Peter R. and Ronald S. (2013): Imaging after percutaneous radio-frequency ablation of hepatic tumors: Part 2, abnormal findings. AJR, 200 (1):194-204 31-Onur MR, Cicekci M ,Kayali A, Poyraz AK and Kocakoc E. (2012): The role of ADC measurement in differential diagnosis of focal hepatic lesions. European Journal of Radiology, 81(3): 171-6.

27. Ozkavukcu E., Haliloglu N. and Erden A. (2009): Post-treatment MRI findings of hepatocellular carcinoma. Diagn. Interv. Radiol., 15:111–120.

28. Padhani AR and Koh DM. (2011): Diffusion MR imaging for monitoring of treatment response. Magn. Reson. Im­aging. Clin N Am, 19(1):181-209.

29. Park HJ, Kim SH and Jang KM, Lim S, Kang TW, Park HC and Choi D. (2014): Added value of diffusion weighted MRI for evaluating viable tumor of hepatocellular carcinomas treated with radiotherapy in patients with chronic liver disease. AJR, 202(1):92-101.

30. Schraml C, Schwenzer N and Clasen S, Rempp HJ, Martirosian P, Claussen CD and Pereira PL. (2009): Navigator respiratory triggered diffusion weighted imaging in the follow up after hepatic radiofrequency ablation initial results. Journal of Magnetic Resonance Imaging. 29:1308-1316.

31. Szurowska E, Nowicki TK and Swieszewska EI, Dariusz Z, Karolina M. and Michal S. (2013): Predictive value of apparent diffusion coefficient in evaluation of colorectal carcinoma hepatic metastases response to radiofrequency ablation. Journal of Magnetic Resonance Imaging, 38, (5): 991-1297.

32. Tri-Linh Lu., Fabio B, Pierre B, Alban D, Reto M and Sabine S. (2012): Assessment of liver tumor response by high field (3.0T) MRI after radiofrequency ablation: Short  and midterm evolution of diffusion parameters within the ablation zone. European Journal of Radiology, 81: 944– 950.

33. Vandecaveye V, De Keyzer F , Nuyts S, Deraedt K, Dirix P, Hamaekers P, Vander Poorten V, Delaere P and Hermans R. (2007): Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after (chemo) radiotherapy: correlation between radiologic and histopathologic findings. Int J Radiat Oncol Biol Phys. ,67(4):960-71.

34. Vergara ML, Fernandez M and Pereira R. (2010): Diffusion weighted MRI characteriza-tion of solid liver lesions. Revista Chilena De Radiología, 16 (1): 510.

35. Vossen JA, Buijs M and Kamel IR. (2006): Assessment of tumor response on MR imaging after loco-regional therapy. Techniques in Vascular and Interventional Radiology, 9:125-132.

36. Wagner M, Doblas S and Daire JL, Paradis V, Haddad N and Leitao H. (2012): Diffusion weighted MR imaging for the regional character­ization of liver tumors. Radiology, 264(2): 464–472.

37. Yu JS, Kim JH, JJ Chung and KW Kim. (2009): Added Value of diffusion weighted imaging in the MRI assessment of perilesional tumor recurrence after chemoembolization of hepatocellular carcinomas. Journal of Magnetic Resonance Imaging, 30(1):153-160.

 


دور التصویر بالرنین المغناطیسى الدینامیکى والتصویر الإنتشاری فى تقیم أورام الکبد الخبیثة بعد علاجها  بالتردد الحراری

 

محمد مصطفى-   عبد الله حسین - فرید عطیة*

 

قسمى الأشعة التشخیصیة - کلیة طب الأزهر بنین دمیاط- کلیه بنات الأزهر القاهرة والمتوطنة* کلیة طب بنین دمیاط

 

خلفیة البحث: یعتبر من الأهمیة تقییم إستجابة الأورام الخبیثة فی الکبد بعد علاجها بالتردد الحراری حیث أن التصویر بالرنین المغناطیسی الدینامیکى بالصبغة والتصویر الإنتشاری بعد علاج أورام الکبد الخبیثة بالتردد الحراری یستخدم فی متابعة الکشف عن علاج أو وجود بقایا للأورام.

الغرض من البحث: تقییم دور التصویر بالرنین المغناطیسی الدینامیکى بالصبغة والتصویر الإنتشاری بعد علاج أورام الکبد الخبیثة بالترددالحراری.

المرضى و طرق البحث: تم  عمل  هذه  الدارسة   فی  الفترة   من  ینایر  2014 م إلى دیسمبر 2015 م  وشملت 50  مریضا بأورام الکبد الخبیثة بعد علاجها  بالتردد الحراری  40 ذکور (80٪) و10 إناث (20٪ ) وتراوحت  أعمارهم  بین 45-80 سنة من العمر.

وقد خضع جمیع المرضی للتالی:

1- التاریخ المرضی والفحص السریری.  

2- الفحوص المعملیة.

3-التصویر بالرنین المغناطیسی الدینامیکى بالصبغة والتصویر الإنتشاری.

النتائج:وجد أن 40 مریضا مصابون بسرطان الکبد الأولى, بینما 10 مرضى مصابون بثانویات سرطان الکبد. وقد تم علاج 37  حالة منها بنجاح بالتردد الحراری.  ووجد  فی 13 حالة بقایا من الورم بعد علاجها بالتردد الحراری.

وأظهرت نتائج البحث إرتفاع الأنتشار الظاهرى للحالات ناجحة العلاج بالتردد الحراری بالمقارنة بالحالات التى وجد فیها بقایا الأورام الخبیثة.

الخلاصة: التصویر بالرنین المغناطیسی الدینامیکى بالصبغة والتصویر الإنتشاری یستخدمان معا فى متابعة مرضى الأورام الخبیثة للکبد بعد علاجها بالتردد الحراری حیث یعتبر الأخیر إضافة هامة وفعالة للتشخیص.

REFERENCES
1. Morani AC1, Elsayes KMLiu PSWeadock WJSzklaruk J, Dillman JR, Khan A, Chenevert TL and Hussain HK. (2013): Abdominal Applications of Diffusion Weighted Magnetic Resonance Imaging: Where do we stand. World J Radiol., 5(3): 68-80.
2. Anzidei M, Napoli A , Zaccagna F, Cartocci G, Saba  L and Menichini   G. (2011): Liver me­tastases from colorectal cancer treated with conven­tional and anti-angiogenetic chemo-therapy: evalua­tion with liver computed tomography perfusion and magnetic resonance diffusion weighted imaging. J Comput Assist Tomogr., 35(6):690–696.
3. Batra A and Tripathi RP (2004): Atypical diffusion-weighted magnetic resonance findings in glioblastoma multiforme,  Australas Radiol., 48,388-391.
4. Bittencourt LK, Matos C and Coutinho AC. (2011): Diffusion-weighted magnetic resonance imaging in the upper abdomen: technical issues and clinical applications. Magn Reson Imaging Clin N Am., 19: 111-131.
5. Bruegel M and Rummeny EJ. (2010): Hepatic metastases: use of diffusion weighted echo-planar imaging. Abdom Imaging, 35(4):454-61.
6. Chiu FY, Jao JC, Chen CY, Liu GC, Jaw TS, Chiou YY, Hsu FO and Hsu JS. (2005): Effect of intravenous  gadolinium   DTPA    on    diffusion weighted magnetic resonance images for evaluation of focal hepatic lesions. J Comput Assist Tomogr. , 29(2):176-80.
7. Dodd GD 3rd, Soulen MC, Kane RA, Livraghi T, Lees WR, Yamashita Y, Gillams AR, Karahan OI and Rhim H. (2000): Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough. Radiographics, 20:9-27.
8. Dromain C, de Baere T, Elias D, Kuoch V, Ducreux M, Boige V, Petrow P, Roche A and Sigal RV. (2002): Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow up. Radiology, 223:255-262.
9. Figueiras RG, Padhani AR, Goh VJ, Vilanova JC, González SB, Martín CV, Caamano AG, Naveira AB and Choyke PL. (2011): Novel oncologic drugs: what they do and how they affect images. Radiographics, 31(7):2059-2091.
10. Goldberg SN, Grassi CJ, Cardella JF, Charboneau JW, Dodd GD 3rd, Dupuy DE, Gervais DA, Gillams AR, Kane RA, Lee FT Jr, Livraghi T, McGahan J, Phillips DA, Rhim H, Silverman SG, Solbiati L, Vogl TJ, Wood BJ, Vedantham S and Sacks D. (2009):  Image guided tumor ablation: standardization of terminology and reporting criteria. J Vasc Interv Radiol., 20(7):S377–90.
12.Hayashida Y, Yakushiji T, Awai K, Katahira K, Nakayama Y, Shimomura O, Kitajima M, Hirai T, Yamashita Y and Mizuta H. (2006): Monitoring therapeutic responses of primary bone tumors by diffusion weighted image: Initial results. Eur Radiol., 16:(12) 2637-2643
13. Heijmen L, Ter Voert EE, Nagtegaal ID, Span P, Bussink J, Punt CJ, de Wilt JH, Sweep FC, Heerschap A and Van Laarhoven HW. (2013): Diffusion weighted MR imaging in liver metastases of colorectal cancer: reproducibility and biological validation. Eur Radiol., 23(3):748–756.
14.Kandpal H, Sharma R, Madhusudhan KS and Kapoor KS. (2009): Respiratory triggered versus breath hold diffusion weighted MRI of liver lesions: comparison of image quality and apparent diffusion coefficient values. AJR, 192(4):915-22.
15. Kele PG and Van Der Jagt EJ. (2010): Diffusion weighted imaging in the liver. World J Gastroenterol. ,16(13): 1567–1576.
16. Kierans AS, Elazzazi M and Braga L,  Polytimi Leonardou1, David A. Gerber, Charles Burke, Waqas Qureshi1, Masayuki Kanematsu and Richard C. Semelka. (2010): Thermoablative treatments for malignant liver lesions: 10 year experience of MRI appearances of treatment response. AJR, 194:523–529.
17. Kim KW, Lee JM and Choi BI. (2011): Assessment of the treatment response of HCC. Abdom Imaging, 36:300–314.
18. Koda M, Tokunaga S, Miyoshi K, Kishina M, Fujise Y, Kato J, Matono T, Okamoto K, Murawaki Y and Kakite S. (2012): Assessment of ablative margin by unenhanced magnetic resonance imaging after radio-frequency ablation for hepatocellular carcinoma. Eur J Radiol., 81(10):2730–6.
19. Koh DM and Collins DJ. (2007): Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol., 188(6): 1622–1635.
20. Braga L., Armao D, Azzazi M and Semelka R.C. (2010):  Liver  R.C. Semelka (Ed.), Abdominal-Pelvic MRI (third ed.), pbl. Wiley Blackwell, Hoboken, NJ, pp.445-454.
21. Lee CH, Braga L, de Campos R.O. and Semelka R.C. (2011): Hepatic tumor response evaluation by MRI. NMR Biomedicine, 24(6):721–733.
22. Lu TL, Meuli RA, Marques-Vidal PM, Bize P, Denys A and Schmidt S. (2010): Inter-observer and intra-observer variability of the apparent diffusion coefficient in treated malignant hepatic lesions on a (3.0) T machine: measurements in the whole lesion versus in the area with the most restricted diffusion. Journal of Magnetic Resonance Imaging. 32(3):647–653.
23. Mc Williams JP, Kee  ST, Loh  CT, Lee   EW and Liu  DM. (2011): Prophylactic embolization of the cystic artery before radio-embolization: feasibility, safety, and outcomes. Cardiovascular Intervent Radiol., 34:786-792.
24. Miller FH, Hammond N, Siddiqi AJ, Shroff S, Khatri G, Wang Y, Merrick LB and Nikolaidis P. (2010): Utility of diffusion weighted MRI in distinguishing benign and malignant hepatic lesions., J Magn Reson Imaging.,32(1):138-47.
25. Minami Y, Nishida N and Kudo M. (2014): Therapeutic response assessment of RFA for HCC: Contrast enhanced US, CT and MRI. World J Gastroenterol., 20(15): 4160–4166.
26. Nisha I., Debra A., Peter R. and Ronald S. (2013): Imaging after percutaneous radio-frequency ablation of hepatic tumors: Part 2, abnormal findings. AJR, 200 (1):194-204 31-Onur MR, Cicekci M ,Kayali A, Poyraz AK and Kocakoc E. (2012): The role of ADC measurement in differential diagnosis of focal hepatic lesions. European Journal of Radiology, 81(3): 171-6.
27. Ozkavukcu E., Haliloglu N. and Erden A. (2009): Post-treatment MRI findings of hepatocellular carcinoma. Diagn. Interv. Radiol., 15:111–120.
28. Padhani AR and Koh DM. (2011): Diffusion MR imaging for monitoring of treatment response. Magn. Reson. Im­aging. Clin N Am, 19(1):181-209.
29. Park HJ, Kim SH and Jang KM, Lim S, Kang TW, Park HC and Choi D. (2014): Added value of diffusion weighted MRI for evaluating viable tumor of hepatocellular carcinomas treated with radiotherapy in patients with chronic liver disease. AJR, 202(1):92-101.
30. Schraml C, Schwenzer N and Clasen S, Rempp HJ, Martirosian P, Claussen CD and Pereira PL. (2009): Navigator respiratory triggered diffusion weighted imaging in the follow up after hepatic radiofrequency ablation initial results. Journal of Magnetic Resonance Imaging. 29:1308-1316.
31. Szurowska E, Nowicki TK and Swieszewska EI, Dariusz Z, Karolina M. and Michal S. (2013): Predictive value of apparent diffusion coefficient in evaluation of colorectal carcinoma hepatic metastases response to radiofrequency ablation. Journal of Magnetic Resonance Imaging, 38, (5): 991-1297.
32. Tri-Linh Lu., Fabio B, Pierre B, Alban D, Reto M and Sabine S. (2012): Assessment of liver tumor response by high field (3.0T) MRI after radiofrequency ablation: Short  and midterm evolution of diffusion parameters within the ablation zone. European Journal of Radiology, 81: 944– 950.
33. Vandecaveye V, De Keyzer F , Nuyts S, Deraedt K, Dirix P, Hamaekers P, Vander Poorten V, Delaere P and Hermans R. (2007): Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after (chemo) radiotherapy: correlation between radiologic and histopathologic findings. Int J Radiat Oncol Biol Phys. ,67(4):960-71.
34. Vergara ML, Fernandez M and Pereira R. (2010): Diffusion weighted MRI characteriza-tion of solid liver lesions. Revista Chilena De Radiología, 16 (1): 510.
35. Vossen JA, Buijs M and Kamel IR. (2006): Assessment of tumor response on MR imaging after loco-regional therapy. Techniques in Vascular and Interventional Radiology, 9:125-132.
36. Wagner M, Doblas S and Daire JL, Paradis V, Haddad N and Leitao H. (2012): Diffusion weighted MR imaging for the regional character­ization of liver tumors. Radiology, 264(2): 464–472.
37. Yu JS, Kim JH, JJ Chung and KW Kim. (2009): Added Value of diffusion weighted imaging in the MRI assessment of perilesional tumor recurrence after chemoembolization of hepatocellular carcinomas. Journal of Magnetic Resonance Imaging, 30(1):153-160.