Applications Of Magnetic Resonance Diffusion-weighted Imaging In Evaluation Of Therapeutic Effects In Hepatic Malignancies

1 Reproducibility and characteristics of the apparent diffusion coefficient (ADC) values of primary and metastatic liver cancers by MR diffusion-weighted imaging (DWI)Objective To study the apparent diffusion coefficient (ADC) values of primary and metastatic liver cancers and their evolvement characteristics by MR diffusion-weighted imaging (DWI) under the condition of different b values; and to evaluate the intra-and inter-observer consistency, short-term repeatability and reproducibility of the measurement of ADC values of hepatic malignant lesions.Materials and Methods This research program was approved by the Hospital Ethics Committee and the informed consents were obtained from the patients. Seventy four cases of 40 patients (male 31 cases, female 9 cases, age range 32-77 yrs, average age 58.7 yrs) with primary and metastatic liver cancers (including 31 hepatocellular carcinomas,15 colorectal cancer liver metastasis,9 pancreatic cancer liver metastasis. 8 pancreatic neuroendocrine carcinoma liver metastasis,7 gastric cancer liver metastasis and 4 lung cancer liver metastasis) were included. MR DWI (b= 0,50,150, 500,800 s/mm2) was performed and the ADC values of the lesions were obtained. The differences among the ADC values of different liver metastasis were analyzed, and the trend of the ADC values in accordance to the increasing of b values was evaluated: Fifteen patients (male 11 cases, female 3 cases, age range 49-77 yrs, average age 62 yrs) underwent DWI scans for three times with different intervals and repeated measurements were performed on 30 lesions (including 8 hepatocellular carcinomas,8 colorectal cancer liver metastasis,6 pancreatic cancer liver metastasis,4 gastric cancer liver metastasis and 4 lung cancer liver metastasis). The intra-and interobserver consistency, short-term repeatability and reproducibility of the measurement of ADC values of hepatic malignant lesions were evaluated by using paired t test, Pearson's correlation analysis, reliability test and Bland-Altman analysis in SPSS 13.0 software.Results When b was set as 500 s/mm, there was no significant difference between the ADC value (×10-3 mm2/s) of the surrounding liver tissue (1.84) and the pancreatic endocrine liver metastasis (1.90). The ADC values of the surrounding liver tissue and pancreatic endocrine liver metastasis were significantly higher than those of pancreatic cancer liver metastasis (1.42), gastric cancer liver metastasis (1.39), hepatocellular carcinoma (1.36), lung cancer liver metastasis (1.30) and colorectal cancer liver metastasis (1.23). And there were no significant differences between the ADC values of the latter five kinds of liver metastasis. There were significant differences between the ADC values (b= 800 s/mm2) of the surrounding liver tissue and all the primary and metastatic liver lesions except pancreatic cancer liver metastasis. All the ADC values of the lesions decreased when the b value increased with a common and somewhat unique trend of each kind of the lesion. No significant differences of ADC values of malignant liver lesions could be found by using paired t test in the intra-and inter-observer consistency, the repeatability (two sequences both with a b of 500 s/mm2 lesion in the same session) and the reproducibility(two sequences both with a b of 500 s/mm2 in two sessions) evaluation. Pearson's correlation coefficients were 0.994,0.983, 0.753 and 0.712, intraclass correlation coefficient of the reliability test was 0.997, 0.991,0.857 and 0.827, and the average coefficient of variation was 1.75%,2.86%, 9.88% and 9.55%, respectively. Bland-Altman analysis showed that all the data points from the intra-and inter-observer consistency, as well as repeatability tests were located within the limits of consistency, while 6.7%(2/30) points of reproducibility analysis located beyond the reference lines.Conclusion MR DWI can characterize different ADC values of primary and metastatic liver cancers. Intra-and inter-observer consistency and the short-term repeatability of the ADC values measurement are satisfied. A variation rate of the ADC value less than 18.72% may be due to measurement error and attention should be paid to control the measurement error involving reproducibility.2 Assessment of the efficacy of molecular targeted therapy in patients with advanced hepatocellular carcinoma with MR Diffusion-weighted imaging (DWI)Objective To explore the findings on CT and MR scans in patients with advanced hepatocellular carcinoma (HCC) during molecular targeted therapy (Sorafenib), with a focus on the regular pattern and clinical sense of apparent diffusion coefficient (ADC) values obtained from MR diffusion-weighted imaging (DWI), and to provide an early assessment tool for such an evolving therapy strategy. Materials andMethods This research program was approved by the Hospital Ethics Committee and informed consents were obtained from the patients. From Dec.2008 to Jan.2010,10 patients with advanced hepatocellular carcinoma (all male; age range 39-77 years old, with an average age of 60) were included. Upper abdominal MR-diffusion weighted imaging (DWI) scans (b=500,800 s/mm") were performed within 1 week prior to, 1-3 weeks.6 weeks and 12 weeks after the start of molecular targeted therapy. Apparent diffusion coefficient (ADC) values of hepatic lesions with the diameter larger than 1 cm were measured. Treatment efficacy judgment was referred to RECIST as well as clinical and laboratory observations. Evolving courses of the ADC values of the lesions during therapy were demonstrated.Results Thirty-one HCC lesions which underwent molecular targeted therapy could be assessed by imaging modality,14 of which were responsive and the other 17 lesions fell into the nonresponsive group. The largest diameters and the ADC values (b= 500 s/mm2) of the responsive lesions at the baseline were significantly higher than those of the non-responsive group. The rate of change of ADC values (b= 800 s/mm2) after the start of treatment in responsive group was significantly higher than that in non-responsive group. The ADC values (b= 800 s/mm2) of the responsive lesions after therapy showed a first rise, then a decrease, and then an increase again at last. Traditional CT and MR imaging showed increased signal intensity on T2WI, suggesting cell lysis and destruction, and increased signal intensity on T1WI indicating bleeding within the tumor. Contrast enhanced CT scans demonstrated a reduction of the degree of enhancement and a increase of the necrosis area of the lesions. Based on these findings, the mechanism of the changes of ADC values could be explored. Signal intensities on T1 and T2 WI as well as the CT findings appeared unchanged in non-responsive lesions. And the ADC values remained stable within 6 weeks after the start of treatment. A significant reduction of the ADC values (b= 800 s/mm2) of those lesions was observed at the 12-week-follow-up, suggesting progression of the disease. No significant change of the largest diameter could be observed at the end of follow-up, in both responsive and non-responsive groups, suggesting a limitation of traditional criteria in evaluation of such an evolving therapy. Additionally, the imaging findings consisted with the changes of tumor marker.Conclusion Combined with traditional CT and MR scans, MR-DWI offering ADC values of the lesions can help to predict and monitor the efficacy of molecular targeted therapy in HCC patients, give real-time evaluation of dynamic changes in the course of treatment, and prompted an early tumor recurrence.3 Assessment of treatment efficacy of systemic chemotherapy in patients with liver metastases by magnetic resonance diffusion-weighted imaging (DWI)Objective To explore the utilization of upper abdominal magnetic resonance diffusion-weighted imaging (DWI) in assessment of treatment efficacy of systemic chemotherapy in patients with liver metastases.Materials and Methods This research program was approved by the Hospital Ethics Committee and informed consents were obtained from the patients. From Dec.2008 to Jan.2010,21 patients with liver metastases (male 12 cases, female 9 cases, age range 33-73 yrs, average age 56.6 yrs) were prospectively enrolled, including 10 cases of colorectal cancer liver metastases,3 gastric cancer,3 lung cancer,2 pancreatic cancer, 1 breast cancer,1 undifferentiated carcinoma and 1 pancreatic neuroendocrine carcinoma. Upper abdominal MR-DWI scans (b=500.800 s/mm2) were performed within 1 week prior to,1-3 weeks after the start of systemic chemotherapy and 1 week after the end the therapy. Apparent diffusion coefficient (ADC) values of the target lesions (the largest 3-4 lesions in the liver of each case) were measured. Totally 80 target lesions were divided into three groups according to RECIST after completion of the therapy:remission group (maximum diameter decrease rate>30%,20 lesions), progression group (maximum diameter increase rate>20%.18 lesions) and stable group (range between remission and progress,42 lesions). ADC values before and after the therapy were compared among three groups, and the correlation between the change rates of ADC values and the maximum diameters was also evaluated. Results The ADC value of remission group was significantly lower than those of stable and progression groups (p＜0.015). The ADC values of remission group significantly increased 1-3 weeks after the start of therapy (without obvious change in maximal diameter of the lesions), and the change rate of ADC values was significantly higher than in remission group (32-33%) than in the stable group (7-8%) and progression group (decreased 11-13%). Both the ADC values pretreatment and the early change rate of ADC values (1-3 weeks after the start of therapy) correlated well with the ultimate change rate of maximum diameter of lesions (1 week after the end of therapy). The correlations were higher when the b value was settled as 800 s/mm2 rather than 500 s/mm2, which suggested that DWI with a b value of 800 s/mm2 be more favorable to predict and monitor the treatment efficiency. After therapy, ADC values increased significantly compared with those on the baseline in remission group. However, no significant differenced were observed between baseline and post-treatment ADC values in stable and progression groups.Conclusion MR-DWI has great potential in prediction, early detection and monitoring the therapeutic efficacy of systemic chemotherapy in patients with hepatic metastases.