Quantitative Study Of Liver Iron Deposition With Dual-Energy CT

Part 1 Quantitative Study of Severe Liver Iron Deposition with Dual-Energy CT on A Rabbit ModelObjectives:To explore the feasibility and accuracy of severe liver iron quantification with virtual iron concentration（VIC）imaging based on dual energy CT（DECT）Materials and Methods:One hundred and thirty-six rabbits were randomly divided into 6 groups,i.e.severe iron overloaded liver experimental group（n=32）and validation group（n=16）,underwent a weekly intramuscular injection of iron dextran,100 mg/kg from 1^st to 16^th weeks;severe iron overloaded liver and fatty liver experimental group（n=32）and validation group（n=16）,underwent a weekly intramuscular injection of iron dextran,100 mg/kg from1^st to 16^th weeks and fed with fat diet;fatty liver group（n=32）,fed with fat diet and normal group（n=8）.DECT was performed on 2 rabbits from each experimental group,1 from each validation group and 2 from fatty liver group weekly and 1 from normal group every 2 weeks in order to measure CT values on 80k Vp,120k Vp,140k Vp and VIC imaging.After examination,the rabbits were sacrificed and the liver specimens were collected to measure liver iron concentration（LIC）,liver fat concentration（LFC）,and to perform pathology for hematoxylin and eosin（HE）staining and Prussian blue staining.The VIC values were fitted against LIC using linear regression for the rabbits in the two experimental groups respectively.The rabbits in the two validation groups were used to test the prediction accuracy of the derived models respectively.Results:The mean LIC values of severe iron overloaded liver experimental group and validation group were 34.75±17.86 mg Fe/g dry tissue（4.20～70.30 mg Fe/g dry tissue）and 34.40±16.79 mg Fe/g dry tissue（4.50～67.95mg Fe/g dry tissue）respectively.The mean LIC values of severe iron overloaded liver and fatty liver experimental group and validation group were21.83±11.32 mg Fe/g dry tissue（4.10～47.90 mg Fe/g dry tissue）and 21.12±9.77 mg Fe/g dry tissue（4.00～45.10 mg Fe/g dry tissue）respectively.The mean LIC value of normal group was 0.52±0.13 mg Fe/g dry tissue（0.26～0.68 mg Fe/g dry tissue）.CT values of 80k Vp,120k Vp,140k Vp and VIC in the severe iron overloaded liver group were positively linearly correlated with LIC（r=0.971,0.971,0.944 and 0.979 respectively）;The linear regression equation for LIC calculated from VIC was y=0.33x+0.89（F=793.0,P<0.05）.The accuracy of equation for LIC quantification was validated in a group of 16 rabbits loaded with different levels of iron.CT values of VIC in the validation group were substituted into verification equation to calculate predicted LIC values.Mean difference between predicted LIC and actual LIC was 0.99 mg Fe/g dry tissue,where Bland-Altman analysis showed an excellent consistency.CT values of 80k Vp,120k Vp,140k Vp and VIC in the severe iron overloaded and fatty liver group were positively linearly correlated with LIC（r=0.849,0.806,0.600 and 0.963 respectively）.The linear regression equation for LIC calculated from VIC was y=0.32x+0.71（F=321.2,P<0.05）.Mean difference between predicted LIC and actual LIC was 1.09 mg Fe/g dry tissue,where Bland-Altman analysis showed an excellent consistency.There was no statistically significant difference in the slope and intercept of the linear equations between the two groups（F=0.020,P<0.05;F=0.203,P>0.05）,The new equation y=0.33x+0.63（F=1397.6,P<0.05）was obtained after combining the above two sets of data and ROC was analyzed.At a LIC threshold of 15mg Fe/g dry tissue,the corresponding optimal threshold of VIC was 40.5HU,and diagnostic sensitivity,specificity and AUC were 96.15%,100.00%and 0.994respectively.At a LIC threshold of 43.0 mg Fe/g dry tissue,the corresponding optimal threshold of VIC was 121.6HU,and diagnostic sensitivity,specificity and AUC were 92.86%,98.00%and 0.989 respectively.Conclusion:Virtual iron concentration imaging on DECT shows potential ability to accurately quantify severe liver iron accumulation on the iron overloaded rabbit model,without being affected by fatty liver.Part 2 Quantitative Study of Mild and Moderate Liver Iron Deposition with Dual-Energy CT and MR on A Rabbit ModelObjectives: To explore the feasibility and accuracy of mild and moderate liver iron quantification with VIC imaging based on DECT.Materials and Methods: One hundred and thirty-six rabbits were randomly divided into 6 groups,i.e.mild and moderate liver iron overloaded experimental group（n = 32）and validation group（n = 16）,underwent a weekly intramuscular injection of iron dextran 15 mg / kg from 1st to 16 th weeks;mild and moderate iron overloaded and fatty liver experimental group（n = 32）and validation group（n = 16）,underwent a weekly intramuscular injection of iron dextran 15 mg / kg from 1st to 16 th weeks and fed with fat diet;fatty liver group（n=32）,fed with fat diet and normal group（n = 8）.DECT and MRI were performed on 2 rabbits in experimental groups,1 in validation group and 2 in fatty liver group weekly and 1 in normal group every 2 weeks to measure CT values on 80 k Vp,120 k Vp,140 k Vp and VIC imaging and R2* respectively.After examination the rabbits were sacrificed and the liver specimens were collected to measure LIC and LFC and to perform pathology for HE and Prussian blue staining.The VIC values were fitted against LIC using linear regression for the rabbits in the two experimental groups respectively.The rabbits in the two validation groups were used to test the prediction accuracy of the derived models respectively.Results: The mean LIC values of liver iron overload experimental group and validation group were 8.60±4.90 mg Fe/g dry tissue（1.10²2.90 mg Fe/g dry tissue）and 8.54±4.97 mg Fe/g dry tissue（1.50¹6.90 mg Fe/g dry tissue）respectively.The mean LIC values of iron overloaded and fatty liver in the experimental group and validation group were 3.99±2.35 mg Fe/g dry tissue（0.30¹0.30 mg Fe/g dry tissue）and 4.01±2.14 mg Fe/g dry tissue（1.10⁹.10 mg Fe/g dry tissue）respectively.The LIC of normal group was 0.52 ± 0.13 mg Fe/g dry tissue（0.26⁰.68 mg Fe/g dry tissue）.CT values of 80 k Vp,120 k Vp,140 k Vp and VIC and R2* in the iron overloaded liver group were positively linearly correlated with LIC（r =0.900,0.837,0.719,0.895 and 0.935 respectively）.The linear regression equation for LIC calculated from VIC was y=0.31x-0.48（F=129.7,P<0.05）.The accuracy of that equation for LIC quantification was validated in a group of 16 rabbits loaded with different levels of iron.CT values of VIC in the validation group were substituted into verification equation to calculate predicted LIC.Mean difference between predicted LIC and actual LIC was 0.21 mg Fe/g dry tissue,where BlandAltman analysis showed an excellent consistency.CT values of 80 k Vp,120 k Vp,140 k Vp and VIC and R2* in the iron overloaded and fatty liver group were linearly correlated with LIC（r=-0.376,-0.531,-0.618,0.924 and 0.942 respectively）.The linear regression equation for LIC calculated from VIC was y=0.30x+0.23（F=265.4,P<0.05）.Mean difference between predicted LIC and actual LIC was 0.19 mg Fe/g dry tissue,where Bland-Altman analysis showed an excellent consistency.There was no statistically significant difference in the slope and intercept of the linear equations between the two groups（F=0.020,P>0.05;F=0.203,P>0.05）.The new equation y=0.33x+0.63（F=1397.6,P<0.05）was obtained after combining the above two sets of data and ROC was analyzed.At a LIC threshold of 2.0 mg Fe / g dry tissue,the corresponding optimal threshold of VIC was 9.2 HU,and diagnostic sensitivity,specificity and AUC were 94.55%,88.89% and 0.937 respectively.At a LIC threshold of 3.2 mg Fe/g dry tissue,the optimal threshold of VIC was 13.7 HU,and diagnostic sensitivity,specificity and AUC were 80.43%,100% and 0.961 respectively.At a LIC threshold of 7.0 mg Fe / g dry tissue,the optimal threshold of VIC was 22.0 HU,and diagnostic sensitivity,specificity and AUC were 95.65%,90.24% and 0.968 respectively.Conclusion: Virtual iron concentration imaging on DECT shows potential ability to accurately quantify mild and moderate liver iron accumulation on the iron overloaded rabbit model,without being affected by fatty liver.Part 3 Clinical Study of Quantification of Liver Iron Deposition in Patients with Thalassemia through Dual-Energy CT and MRObjectives: To explore the feasibility and accuracy of liver iron quantification with VIC imaging based on DECT in patients with thalassemiaMaterials and Methods:A total of 47 patients with severe beta thalassemia confirmed by gene diagnosis were recruited from June 2012 to March in the First Affiliated Hospital of Guangxi Medical University.DECT was perform to measure CT values on 80 kvp,140 k Vp and VIC imaging.1.5T MR was performed according to the Ferriscan standards.All the data were processed by using Ferriscan to obtain LIC.Results: Out of the 47 patients,25 were male and 22 were female,aged 10²8 years old,with a median age of 17 years.The number of patients with normal,mild,moderate and severe hepatic iron deposition were 1,22,11 and 14 respectively.The LIC of 4 patients with a severe liver iron overloaded（LIC>43.0 mg Fe/g dry tissue）could not be measured by MRI.The mean LIC of the other 43 patients were 10.34±9.16 mg Fe/g dry tissue（1.5³3.3 mg Fe/g dry tissue）.The mean of volumetric CT dose index（CTDIvol）was 11.37±1.62 m Gy and the mean of dose length product（DLP）was 240±38.05 m Gycm.CT values of 80 k Vp,140 k Vp and VIC imaging were positively linearly correlated with LIC（r =0.821,0.803 and 0.825 respectively）.The linear regression equation for LIC calculated from VIC was y=0.74x+6.90（F=142.4,P<0.05）.Through ROC analysis,at a LIC threshold of 3.2 mg Fe/g dry tissue,the corresponding optimal threshold of VIC was 0.1 HU,and diagnostic sensitivity,specificity and AUC were79.41%,92.31% and 0.921 respectively.At a LIC threshold of 7.0 mg Fe/g dry tissue,the optimal threshold of VIC was 3.4 HU,and diagnostic sensitivity,specificity and AUC were 76.00%,100.00% and 0.914 respectively.At a LIC threshold of 15.0 mg Fe/g dry tissue,the optimal threshold of VIC was 16.2 HU,and diagnostic sensitivity,specificity and AUC were 85.71%,100.00% and 0.983 respectively.Conclusion: Virtual iron concentration imaging on DECT shows potential ability to accurately quantify liver iron accumulation in patients with thalassemia.