the nodules with ggo that were used in this study were made from material from swine lung tissue . after a pig was sacrificed , the thorax was opened and the main pulmonary artery was ligated . the lungs were inflated with a fixative composed of the following compounds : 50% polyethylene glycol 400 , 25% of 95% ethyl alcohol , 10% of 37% formaldehyde and 15% water by volume . this fluid was instilled into the lungs through the trachea so that the lung would be inflated incompletely . the trachea was then clamped to prevent loss of the fixative , and the specimen was kept in a container of the same fixative for three days . forty nodules were prepared , each with a diameter of approximately , or greater than , 10 mm ( fig . the mean attenuation value of the nodules was approximately from-350 hu to -750 hu . styrofoam matrix material ( with a mean attenuation value of-986 hu ) was used as a phantom of the surrounding pulmonary parenchyma . forty wells , each with a diameter of 10 mm , were drilled into a 5 cm - thick styrofoam plate ( fig . 1b ) . to obtain the reference - standard amount of soft tissue ( stars ) the weight measurement was repeated three times and was averaged to calculate the values used in the analysis . the stars of a nodule was then calculated by dividing the weight by the specific gravity of the fixed pulmonary parenchymal tissue in the same condition as the phantom nodules . after 20 - 30 g of the fixed lung tissue was weighed on a precision scale , the lung tissue was compressed and squeezed vigorously with a stick in a 100 ml cylinder to remove the entrapped air in the tissue , and was soaked overnight in water . then , the mean specific gravity was determined by dividing the weight by the volume . the imaging data on the phantom nodules were acquired with the use of a 16-channel multidetector ct scanner ( mx 8000 ; philips medical system , cleveland , oh ) . the imaging parameters were as follows : spiral mode , 16  0.75 mm collimation , 120 kvp , 200 ma , 1 mm thickness , and 0.75 sec rotation time . the images were reconstructed at 1 mm intervals using a soft tissue algorithm ( reconstruction kernel standard c ) and an 18 cm field of view ( fig . initially , the volume of the nodules was measured with commercially available 3-d software ( rapidia ; infinitt , seoul , korea ) . this program allows a user to segment the nodule and to measure the volume of the nodules at a user - defined attenuation threshold . regions of interest ( roi ) were manually placed on each nodule , and the nodules were segmented automatically on the gray - level threshold . the ct - measured volume of the nodules ( vct ) it was assumed that the mean ct attenuation value of a given nodule volume correlated with the proportion of the gas and tissue within the nodule . considering that the attenuation value of air is -1,000 hu and the attenuation value of water is 0 hu , it is possible to compute the amount of gas and tissue present in the roi using the following equation : volumetissue = volumegas + tissue [ 1 + hu / 1,000 ] . according to previously described analyses ( 13 - 15 ) , this equation was applied for the measurement of the air volume in the lung with acute lung injury . it was assumed that this method could also be used to measure the amount of soft tissue in pulmonary ggo nodules . the amount of soft tissue in each nodule of interest was measured using the following equation : the amount of soft tissue measured by ct ( stact ) = ct - measured volume ( vct )  ( 1 + mean attenuation value / 1,000 ) . the volume of the nodules was measured using the fixed threshold method . three lower thresholds ( -900 hu , -800 hu and -700 hu ) and an upper threshold ( 200 hu ) were used . the accuracy of the lower threshold value was compared , and the most accurate value was selected as the lower threshold . to evaluate the measurement accuracy , the relative percent error ( rpe ) was used ( 16 , 17 ) . the rpe of vct or stact is defined as 100  ( vct or stact - stars ) / stars , in which vct is the ct - measured volume of each nodule and stact and stars are the ct - measured amount of soft tissue and the reference - standard amount of soft tissue , respectively , in each nodule . all of the measurement data sets were tested for normality using the kolmogorov - smirnov test . to assess the difference between the rpes with the use of the two measurement methods and among different lower thresholds , the paired t test and the friedman test ( a non - parametric repeated measure one - way analysis of variance ) were performed . the pearson correlation coefficient ( r ) between the stact of each lower threshold level and the stars was calculated to compare the measurement accuracy of the three lower threshold levels . linear regression analysis was used to assess the association between the stact and the stars of the nodules and between the vct and the stars at the -900 hu lower threshold level as the measurement was most accurate at that threshold level . regression between the rpe of the stact and the mean attenuation value was not analyzed as the stact already included the mean attenuation value , so that a separate regression would have been meaningless . a p value of less than 0.05 was considered statistically significant and was subject to further analysis with multiple posttest comparisons . statistical analyses were performed using spss 12.0 for windows ( spss , chicago , il ) . the nodules with ggo that were used in this study were made from material from swine lung tissue . after a pig was sacrificed , the thorax was opened and the main pulmonary artery was ligated . the lungs were inflated with a fixative composed of the following compounds : 50% polyethylene glycol 400 , 25% of 95% ethyl alcohol , 10% of 37% formaldehyde and 15% water by volume . this fluid was instilled into the lungs through the trachea so that the lung would be inflated incompletely . the trachea was then clamped to prevent loss of the fixative , and the specimen was kept in a container of the same fixative for three days . forty nodules were prepared , each with a diameter of approximately , or greater than , 10 mm ( fig . the mean attenuation value of the nodules was approximately from-350 hu to -750 hu . styrofoam matrix material ( with a mean attenuation value of-986 hu ) was used as a phantom of the surrounding pulmonary parenchyma . forty wells , each with a diameter of 10 mm , were drilled into a 5 cm - thick styrofoam plate ( fig . to obtain the reference - standard amount of soft tissue ( stars ) , the nodules were weighed on a scale with a precision of 0.1 mg . the weight measurement was repeated three times and was averaged to calculate the values used in the analysis . the stars of a nodule was then calculated by dividing the weight by the specific gravity of the fixed pulmonary parenchymal tissue in the same condition as the phantom nodules . after 20 - 30 g of the fixed lung tissue was weighed on a precision scale , the lung tissue was compressed and squeezed vigorously with a stick in a 100 ml cylinder to remove the entrapped air in the tissue , and was soaked overnight in water . then , the mean specific gravity was determined by dividing the weight by the volume . the imaging data on the phantom nodules were acquired with the use of a 16-channel multidetector ct scanner ( mx 8000 ; philips medical system , cleveland , oh ) . the imaging parameters were as follows : spiral mode , 16  0.75 mm collimation , 120 kvp , 200 ma , 1 mm thickness , and 0.75 sec rotation time . the images were reconstructed at 1 mm intervals using a soft tissue algorithm ( reconstruction kernel standard c ) and an 18 cm field of view ( fig . initially , the volume of the nodules was measured with commercially available 3-d software ( rapidia ; infinitt , seoul , korea ) . this program allows a user to segment the nodule and to measure the volume of the nodules at a user - defined attenuation threshold . regions of interest ( roi ) were manually placed on each nodule , and the nodules were segmented automatically on the gray - level threshold . the ct - measured volume of the nodules ( vct ) was defined as the segmented nodule volume with a variety of thresholds . it was assumed that the mean ct attenuation value of a given nodule volume correlated with the proportion of the gas and tissue within the nodule . considering that the attenuation value of air is -1,000 hu and the attenuation value of water is 0 hu , it is possible to compute the amount of gas and tissue present in the roi using the following equation : volumetissue = volumegas + tissue [ 1 + hu / 1,000 ] . according to previously described analyses ( 13 - 15 ) , this equation was applied for the measurement of the air volume in the lung with acute lung injury . it was assumed that this method could also be used to measure the amount of soft tissue in pulmonary ggo nodules . the amount of soft tissue in each nodule of interest was measured using the following equation : the amount of soft tissue measured by ct ( stact ) = ct - measured volume ( vct )  ( 1 + mean attenuation value / 1,000 ) . . three lower thresholds ( -900 hu , -800 hu and -700 hu ) and an upper threshold ( 200 hu ) were used . the accuracy of the lower threshold value was compared , and the most accurate value was selected as the lower threshold . to evaluate the measurement accuracy , the relative percent error ( rpe ) was used ( 16 , 17 ) . the rpe of vct or stact is defined as 100  ( vct or stact - stars ) / stars , in which vct is the ct - measured volume of each nodule and stact and stars are the ct - measured amount of soft tissue and the reference - standard amount of soft tissue , respectively , in each nodule . all of the measurement data sets were tested for normality using the kolmogorov - smirnov test . to assess the difference between the rpes with the use of the two measurement methods and among different lower thresholds , the paired t test and the friedman test ( a non - parametric repeated measure one - way analysis of variance ) were performed . the pearson correlation coefficient ( r ) between the stact of each lower threshold level and the stars was calculated to compare the measurement accuracy of the three lower threshold levels . linear regression analysis was used to assess the association between the stact and the stars of the nodules and between the vct and the stars at the -900 hu lower threshold level as the measurement was most accurate at that threshold level . regression between the rpe of the stact and the mean attenuation value was not analyzed as the stact already included the mean attenuation value , so that a separate regression would have been meaningless . a p value of less than 0.05 was considered statistically significant and was subject to further analysis with multiple posttest comparisons . statistical analyses were performed using spss 12.0 for windows ( spss , chicago , il ) . the mean rpe of the stact was -7.79  1.88% at the lower threshold level of -900 hu , -13.4 5.04% at -800 hu and -22.1  11.46% at -700 hu ( table 1 ) . the rpe of the stact at the lower threshold level of -900 hu was significantly smaller than that at -800 hu and at -700 hu ( p < 0.01 ) . the stact was much more accurate than the vct ( p < 0.01 ) ( table 1 ) . the pearson correlation coefficients determined between the stact and the stars were 0.998 for the -900 hu threshold level , 0.996 for -800 hu and 0.990 for -700 hu ( table 1 ) . linear regression of the stars on the stact of the nodules showed the strongest correlation at the -900 hu threshold level ( r = 0.996 , p < 0.01 ) ( fig . the resulting linear equation was as follows : stars = 1.036  stact + 21.199 . regression of the stars on the vct of the nodules at the -900 hu lower threshold level showed a poor correlation ( r = 0.294 , p < 0.01 ) ( fig . 3b ) . regression of the rpe of the vct at the -900 hu threshold level on the mean attenuation value showed a strong negative correlation ( r = 0.941 , p < 0.01 ) ( fig . the mean rpe of the stact was -7.79  1.88% at the lower threshold level of -900 hu , -13.4 5.04% at -800 hu and -22.1  11.46% at -700 hu ( table 1 ) . the rpe of the stact at the lower threshold level of -900 hu was significantly smaller than that at -800 hu and at -700 hu ( p < 0.01 ) . the stact was much more accurate than the vct ( p < 0.01 ) ( table 1 ) . the pearson correlation coefficients determined between the stact and the stars were 0.998 for the -900 hu threshold level , 0.996 for -800 hu and 0.990 for -700 hu ( table 1 ) . linear regression of the stars on the stact of the nodules showed the strongest correlation at the -900 hu threshold level ( r = 0.996 , p < 0.01 ) ( fig . the resulting linear equation was as follows : stars = 1.036  stact + 21.199 . regression of the stars on the vct of the nodules at the -900 hu lower threshold level showed a poor correlation ( r = 0.294 , p < 0.01 ) ( fig . 3b ) . regression of the rpe of the vct at the -900 hu threshold level on the mean attenuation value showed a strong negative correlation ( r = 0.941 , p < 0.01 ) ( fig . volumetric assessment of small pulmonary nodules to estimate tumor growth is gaining increased attention in radiological practice , particularly in conjunction with ongoing lung cancer screening trials ( 18 ) . recent advances in imaging technology enable precise 3-d volumetric measurement of tumors , and the use of advanced technology allows more accurate assessments of tumor burden than the use of traditional unidimensional or bidimensional measurement methods ( 3 , 16 , 19 , 20 ) . ko et al . ( 11 ) reported that a higher precision in volume measurement is associated with the use of a partial volume method and a predetermined pure - nodule - attenuation high - frequency algorithm . the investigators used simulated ggo nodules with approximately -360 hu , which were composed of a plastic created by blending epoxy resins and urethanes . the absolute errors of the ggo nodules were observed as higher than the absolute errors of the solid - attenuation nodules . the investigators suggested that any difference between methods of measuring ggo nodule volume was related to the reduced contrast between the ggo nodules and the lung parenchyma . however , the investigators did not consider the effect of the mean attenuation of the nodules on the measured volume . the amount of soft tissue in a attenuation of -300 hu is different from the amount in a nodule with a mean attenuation of -700 hu . if two nodules have the same diameter , the measured volume of the ggo nodule with a mean attenuation of -300 hu would be the same as that of the nodule with a mean attenuation of -700 hu using current volumetric measurement methods . the amount of tissue in a ggo nodule should increase based on the mean attenuation value of the nodules . therefore , the mean attenuation value of a nodule should be considered when measuring the volume or amount of tissue in nodules . in this study , there was a tendency towards improved accuracy with an increase in the mean attenuation value of the nodules . however , the discrepancy among the nodules with different mean attenuation values was not significant . the volume of a ggo nodule , measured with commercially available 3-d software using the threshold method was much greater than the stars . the rpe of the vct showed a very strong negative correlation with the mean attenuation value . this study showed that for a lower mean attenuation value of a nodule , a greater rpe of the vct will be found . this finding is explained by the smaller amount of tissue in a nodule with a lower mean attenuation value . the stact represents the amount of soft tissue in ggo nodules much more accurately than the vct . in this study , the linear regression equation of the stars on the stact was as follows : stars = 1.036 stact + 21.199 = 1.036  vct  ( 1 + mean attenuation value / 1,000 ) + 21.199 . these results show that the stact has a very strong linear correlation with the stars . based on this result , the stars could be calculated from the stact , which could be obtained from the vct and the mean attenuation value of a nodule . to make artificial ggo nodules , fixed swine lungs were used . artificial nodules made by blending epoxy resins or urethanes could not be utilized to represent true ggo nodules . for the lower threshold in this phantom study , -900 hu was used , as the rpe was smaller in proportion to a decrease in the lower threshold . the rpe of the stact with a -900 hu threshold was significantly smaller than the rpe of an stact with -800 hu and -700 hu thresholds ( p < 0.01 ) . this finding indicates that the volume measured at the -900 hu threshold was the most accurate . when -800 hu or -700 hu was used as the lower threshold , some portions of the nodules were not included in the volume measurement , especially for the nodules with lower mean application of -900 hu as the lower threshold was possible in the phantom study . in this study in addition , the measurement of the volume was not disturbed by a surrounding parenchymal phantom . however , -900 hu could not be used as a lower threshold level in the volumetry of real ggo nodules in patient studies . the vct and the stact measured by two researchers were the same , regardless of the mean attenuation value or diameter of the nodules . ct - measurement of the amount of soft tissue in a nodule is an objective method . the results of prior studies on nodule densitometry in phantom models have demonstrated that the mean attenuation value of a nodule is lower in a tissue phantom or a chest phantom . it is uncertain how different the mean attenuation value of ggo nodules within a tissue phantom or a chest phantom is from mean attenuation value of ggo nodules within styrofoam . the effect of the diameter of the ggo nodules on the accuracy of measurement was not evaluated , which could be another limitation of this study . a further study is needed to evaluate the accuracy of volumetric measurement for smaller ggo nodules with diameters of less than 10 mm . in summary , the amount of soft tissue in ggo nodules measured by ct is well correlated with the reference standard amount of soft tissue in ggo nodules , and is much more accurate than as determined with the use of the previous volumetric measurement method .
objectiveto devise a new method to measure the amount of soft tissue in pulmonary ground - glass opacity nodules , and to compare the use of this method with a previous volumetric measurement method by use of a phantom study.materials and methodsphantom nodules were prepared with material from fixed normal swine lung . 
 forty nodules , each with a diameter of 10 mm , were made with a variable mean attenuation . 
 the reference - standard amount of soft tissue in the nodules was obtained by dividing the weight by the specific gravity . 
 the imaging data on the phantom nodules were acquired with the use of a 16-channel multidetector ct scanner . 
 the ct - measured amount of soft tissue of the nodules was calculated as follows : soft tissue amount = volume  ( 1 + mean attenuation value / 1,000 ) . the relative percentage error ( rpe ) between the ct - measured amount of the soft tissue and the reference - standard amount of the soft tissue 
 was also measured . 
 the rpes determined with use of the new method were compared with the rpes determined with the current volumetric measurement method by the use of the paired t test.resultsthe ct - measured amount of soft tissue showed a strong correlation with the reference - standard amount of soft tissue ( r2 = 0.996 , p < 0.01 ) . 
 the mean rpe of the ct - measured amount of soft tissue in the nodules was -7.79  1.88% . 
 the mean rpe of the ct - measured volume was 114.78  51.02%,which was significantly greater than the rpe of the ct - measured amount of soft tissue ( p < 0.01).conclusionthe amount of soft tissue measured by the use of ct reflects the reference - standard amount of soft tissue in the ground - glass opacity nodules much more accurately than does the use of the ct - measured volume .