Quantification of Pulmonary Emphysema from Lung Computed Tomography Images

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1 Quantification of Pulmonary Emphysema from Lung Computed Tomography Images RENUKA UPPALURI, THEOPHANO MITSA, MILAN SONKA, ERIC A. HOFFMAN, and GEOFFREY MCLENNAN Departments of Electrical and Computer Engineering, Radiology, Biomedical Engineering, and Internal Medicine, The University of Iowa, Iowa City, Iowa A texture-based adaptive multiple feature method (AMFM) for evaluating pulmonary parenchyma from computed tomography (CT) images is described. This method incorporates multiple statistical and fractal texture features. The AMFM was compared to two previously published methods, namely, mean lung density (MLD) and the lowest fifth percentile of the histogram (HIST). First, the ability of these methods to detect subtle differences in ventral dorsal lung density gradient in the prone normal lung was studied. Second, their abilities to differentiate between normal and emphysematous whole lung slices were compared. Finally, regional analyses comparing normal and emphysematous regions were performed by dividing the lungs in the CT slices into six equal regions, ventral to dorsal, and analyzing each region separately. The results demonstrated that the AMFM could separate the ventral from the dorsal one-third of the normal prone lung with 89.8% accuracy, compared to an accuracy of 74.6% with the MLD and 64.4% with the HIST methods. The normal and emphysematous slices were separated on a global basis with 100.0% accuracy using the AMFM as compared to an accuracy of 94.7% and 97.4% using the MLD and HIST methods, respectively. The regional normal and emphysematous tissues were discriminated with an average accuracy of 97.9%, 89.9%, and 99.1% with the AMFM, MLD, and HIST methods, respectively. The three methods and the pulmonary function tests in the normal and emphysema groups were poorly correlated. Quantitative texture analysis using adaptive multiple features holds promise for the objective noninvasive evaluation of the pulmonary parenchyma. Uppaluri R, Mitsa T, Sonka M, Hoffman EA, McLennan G. Quantification of pulmonary emphysema from lung computed tomography images. AM J RESPIR CRIT CARE MED 1997;156: Pulmonary emphysema is defined as a lung disease characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls (1). These lung parenchymal changes are pathognomonic for emphysema. Detection of such changes during life, however, is difficult. Early and accurate diagnosis of emphysema is important for smoking cessation advice, evaluating the natural history of the disease, and disease phenotyping as we improve our understanding of disease processes and therapeutic interventions. Generally, the diagnosis of emphysema is based on indirect features, such as clinical examination, pulmonary function tests, and subjective visual evaluation of computed tomography (CT) scans. These tests are of limited value in assessing mild to moderate emphysema. (Received in original form June 24, 1996 and in revised form March 14, 1997) The work was supported in part by an award from the Whitaker Foundation, a contract from the National Library of Medicine (N01-LM US PHS), and a Career Investigator Award from the American Lung Association. Correspondence and requests for reprints should be addressed to Geoffrey McLennan, Department of Internal Medicine, The University of Iowa, Iowa City, IA, Am J Respir Crit Care Med Vol pp , 1997 Computed tomography demonstrates pathological changes in the lung parenchyma and has shown to be more sensitive than the chest radiograph in detecting alterations in lung parenchyma, including changes due to emphysema (2 5). Two basic approaches to detecting and quantifying emphysema from CT scans have been used. One approach involves assigning a grade or a rating to assess the presence of emphysema by visual examination of the hard copy scans (2, 3, 6, 7). In this approach, the visual assessments are compared with the subsequent pathological examination for emphysema, and the results have demonstrated a good correlation. However, such visual evaluations are time-consuming and limited by a wide range of interobserver variability and lack of sensitivity to early disease. The second approach directly analyzes digital data obtained from the CT scan (4, 5, 8 11). This approach is objective and, therefore, not subject to interpreter bias. There are at least two computerized methods of identifying emphysema currently in use. One technique identifies areas of low attenuation (a characteristic of emphysema) based on a single density index threshold or a range of density indices (X-ray attenuation coefficients reported as Hounsfield Units [HU] or electromagnetic imaging [EMI] units). Here, all areas having densities lower than the threshold (e.g., 910 HU or the lowest fifth percentile of the histogram) or falling within a given range of densities are considered to be emphysematous. Addi-

2 Uppaluri, Mitsa, Sonka, et al.: Quantification of Emphysema 249 Figure 1. Flow chart explaining the steps involved in the AMFM. tionally, the lowest fifth percentile of the histograms of emphysematous subjects has been shown to correlate well with the surface area of walls of distal air spaces per unit lung volume, or AWUV (4). The second method computes the mean lung density as a defining characteristic of emphysema. These studies have reported good correlation with some pulmonary function tests, such as DL CO and lung pathology. Because of partial volume effects, when lung parenchymal regions affected by the pathologic process are smaller and more dispersed amongst normal parenchyma, simple densitybased features become insensitive. Thus, while the use of these lung density masks (5) has moved CT evaluation into an objective, quantitative arena, the utility of such approaches is limited. Improved methodology based upon the underlying pattern of disease is one possible way of improving quantitative CT evaluation. In this study, we examined the use of an automated texture-based adaptive multiple feature method (AMFM) and compared it to two previously published measures of emphysema, namely mean lung density (MLD) and the lowest fifth percentile of the density histogram (HIST). METHODS Subjects We studied nine normal volunteers and ten patients with emphysema. The normal volunteers had no history of pulmonary disease, were lifelong nonsmokers, were taking no medications, and had no evidence of lung disease. Normal data were acquired as part of a previous study to evaluate interstitial pulmonary fibrosis. The subjects with emphysema were from a group of patients who were being evaluated for potential lung reduction surgery. These subjects had severe emphysema, and the CT scans were performed as part of their preoperative evaluation for lung reduction. All subjects had a CT scan and pulmonary function tests in close temporal proximity. Computed Tomography Data Acquisition Computed tomography scans were acquired with an electron beam CT scanner (Imatron Fastrac C-150 XL, South San Francisco, CA) at the University of Iowa Hospitals and Clinics. Scans of the normal subjects were acquired in the prone position, and the scans of the subjects with emphysema were acquired in the supine position. It has long been recognized that the lung is more uniformly expanded in the prone posture, and thus this posture would be expected to allow for better characterization of the lung field. In the subjects with severe emphysema, however, it was considered too difficult to perform prone scans. All subjects were scanned during breath-holding at maximal inspiration. A standardized protocol of the same slice thickness and a similar field of view was used. The field of view was mm, and collimation was 3 mm. The images were reconstructed to pixels. The grey level resolution of the images was 11 bit. Pulmonary Function Tests The pulmonary function tests (PFT) consisted of standard spirometry using the Medical Graphics 1070 system (Medical Graphics, St. Paul, MN) and lung volumes via plethysmography using a Medical Graphics 1085 system. Single-breath diffusing capacity (DL CO ) was tested using the Medical Graphics 1070 system. The measurements of lung function were performed using standard protocols, and the American Thoracic Society guidelines were used to determine acceptability (12). The predicted normal values used were those of Morris and co-workers (13) for spirometry, Goldman and Becklake (14) for lung volumes, and Van Ganse and colleagues (15) for the diffusing capacity. Computed Tomography Data Analysis The AMFM for examining the lung parenchyma from CT scans uses a combination of statistical (16) and fractal approaches. The combination of all these features provides a description of the texture as well as structure in the regions of interest (ROI). This method was compared with the MLD and the HIST methods for evaluating the normal lung as well as differentiating between the normal and emphysematous parenchyma. Three experiments were designed for this purpose. Figure 2. Electron beam computed tomography image of a human normal lung scanned in prone position. (A) Original image of a 3-mm thick slice from a 3-D scan. (B) The same image after automatic lung segmentation. Figure 3. Electron beam computed tomography image of a human normal lung scanned in prone position. (A) Original image of a 3-mm thick slice from a 3-D scan. (B) The same image after edgmentation, an edge-based region-growing technique.

3 250 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL Figure 4. Electron beam computed tomography image of human emphysematous lung scanned in supine position. (A) Original image of a 3-mm thick slice from a 3-D scan. (B) The same image after edgmentation, an edge-based region-growing technique. 1. Adaptive Multiple Feature Method The steps involved in this method are outlined in Figure 1. Each CT slice was first segmented (17) to remove nonlung structures (Figure 2). Preprocessing on the original image was performed using edgmentation (18, 19) for computing some of the texture features. Edgmentation is a region-growing technique that merges adjacent pixels to form regions where the difference between the grey levels of the adjacent pixels is small. The grey level assigned to a merged region is the average of the grey levels of the pixels forming the region. Figures 3 and 4 show examples of the edgmented image of a normal and an emphysematous CT slice, respectively. The ROI was then defined on the original image as well as on the preprocessed image. Feature extraction was performed on the ROIs. Five first-order texture features adapted from Ferdeghini and colleagues (20) and the geometric fractal dimension (21) were computed on the ROI of the original image. The firstorder features were mean, variance, skewness, kurtosis, and grey-level entropy. Eleven second-order features adapted from Fleagle and colleagues (22) were computed on the ROI from the preprocessed image. Five of the second-order features were run-length features: shortrun emphasis, long-run emphasis, grey-level nonuniformity, run-length nonuniformity, and run percentage. The remaining six features were based on the co-occurrence matrix: angular second moment, entropy, inertia, contrast, correlation, and inverse difference moment. All the features were normalized for pixel sizes and for the size of the lung in the CT image. The available ROIs from the CT slices were then split randomly into two distinct sets the training set and the test set. The training set provided example regions for the available classes, and the classes were chosen differently for each experiment. The optimal set of features was selected using the divergence measure along with correlation analysis (23). Optimal feature selection was performed using the ROIs in the training set. Finally, classification was performed using the Bayesian classifier (24). There are two phases to the classification process. In the training phase, classifier parameters are determined from the optimal features extracted on the ROIs in the training set. Finally, in the testing phase, the ROIs in the test set are classified based on the parameters determined in the training phase. Figure 5. Flow chart explaining the steps involved in the MLD method. 2. Mean Lung Density Method The mean lung density extracted from the ROI of the original image, as a feature by itself, was used to study parenchymal changes in normal and emphysematous subjects. The MLD is equivalent to the mean extracted as a first-order feature. Figure 5 shows the steps involved in the MLD method. The classification step was similar to that in the AMFM. 3. Histogram Analysis The lowest fifth percentile of the histogram of the original image ROI was computed. This percentile was used to classify the test ROIs (Figure 6). Again, the classification step was similar to that in the AMFM. These three methods were compared in three different experiments. Four slices from each CT scan were included in the experiments. By an arbitrary convention, two of these slices were from the region at the carina and the remaining two were from the region halfway between the carina and the base of the lung. The first experiment involved the evaluation of the lung parenchyma in nine normal subjects. It has long been recognized that there is lung density variation from dependent to nondependent regions of the lung (25). To examine this dependence, each lung in the CT image slice was divided into three equal parts, anterior to posterior (Figure 7A). The posterior one-third and the anterior one-third regions were defined as the ROIs and served as the available classes. Regions of interest passing directly through the horizontal fissure line or blurry due to movement were removed from the analysis. Classifier training used samples of ROIs from these two regions. The classifier was then applied to the test set and each test sample was identified as being either anterior one-third or posterior one-third. The rate of correct classification (percentage of samples correctly classified in each class) and accuracy (percentage of correctly classified samples in both classes) were calculated. In the second experiment, we compared the normal lung images with the images obtained from subjects with emphysema. Global analysis to assess the overall normality and emphysema in the lung was performed with the entire image slice as the ROI to extract the texture features. Nine normal subjects and ten patients with emphysema were used in this experiment. The available samples were split randomly into the training set and test set. Training was performed on ROIs of normal and emphysematous lungs from the training set. Figure 6. Flow chart explaining the steps involved in the HIST method.

4 Uppaluri, Mitsa, Sonka, et al.: Quantification of Emphysema 251 TABLE 2 GLOBAL CLASSIFICATION RESULTS OF NORMAL AND EMPHYSEMATOUS LUNG SCANS Method Sensitivity Specificity Accuracy AMFM 100.0% 100.0% 100.0% MLD 95.0% 94.4% 94.7% HIST 95.0% 100.0% 97.4% Figure 7. Divisions of the lung. (A) Regions 1 and 3 were used for gradient analysis in normal scans. (B) Regions 1 to 6 were used for regional analysis of normal and emphysema scans. Therefore, the two possible outputs of the classifier when analyzing the test set were normal and emphysematous. The sensitivity, specificity (26) and accuracy of the results were calculated. Sensitivity was defined as the percentage of regions with disease correctly classified. Specificity was defined as the percentage of normal samples correctly classified. Accuracy was defined as the percentage of correctly classified samples, taking both the classes into consideration. Finally, in our third experiment, regional comparisons of normal and emphysematous lungs were performed. Each lung in the CT slice was split into six equal parts, anterior to posterior (Figure 7B). The samples were blindly reviewed by a trained pulmonologist experienced in CT scan assessment of parenchymal lung disease and only those CT regions being definitely normal from normal subjects and having definite emphysema from subjects with emphysema were retained. On two blinded readings, 4 mo apart, the accuracy of the pulmonologist in selecting or removing regions in normal and emphysematous lungs was 90.0% and 76.4%, respectively. In each of the six parts, the classifier was trained using samples from normal and emphysematous lungs. The classifier was then asked to identify samples from the test set as being normal or emphysematous. This process was repeated for all six regions. The sensitivity, specificity, and accuracy were calculated in each of the six regions. Statistical Analysis To compare with the PFTs, features obtained from the entire CT slice were used. Regression analysis was performed between the average features obtained from the four CT slices (global analysis) and the PFTs, in the normal and emphysema groups separately. All three methods AMFM, MLD, and HIST were analyzed. Multiple regression analysis was performed between the best features chosen by the AMFM for the global analysis and the PFT parameters. Simple regression analysis was used when comparing the PFT parameters with the MLD and HIST methods. StatView 4.1 (Abacus Concepts, Inc., Berkeley, CA) was used for the regression analyses. Analysis of variance (ANOVA) was used to test the significance of the linear regression using the same package. Multiple comparisons were not accounted for in ANOVA. RESULTS In the first experiment, normal subjects were studied by evaluating the anterior and posterior thirds using the AMFM, TABLE 1 CLASSIFICATION RESULTS OF ANTERIOR AND POSTERIOR ONE-THIRD OF LUNG IN NORMAL SCANS Rate of Correct Classification Method Posterior One-Third Anterior One-Third Accuracy AMFM 82.1% 96.8% 89.8% MLD 96.4% 54.8% 74.6% HIST 82.1% 48.4% 64.4% MLD, and HIST methods. The optimal set of features for the AMFM were contrast, variance, geometric fractal dimension, mean, skewness, correlation, and grey level nonuniformity. Table 1 summarizes the ability of each of the three methods to detect differences in density between the anterior and posterior portions of the normal lung. In the second experiment, global analysis was performed to discriminate entire CT slices obtained from normal and emphysematous lungs. The best combination of features selected automatically for the AMFM were short-run emphasis, mean, and grey level nonuniformity. Again, MLD and HIST methods were also applied and compared with AMFM. Table 2 shows the results of classification obtained using all three methods for global analysis. In the last experiment, the scans obtained from the normal and emphysematous lungs were split into six regions anterior to posterior. In each of the six regions, normal and emphysematous regions were discriminated. As before, AMFM, MLD, and HIST methods were applied and compared. Table 3 summarizes the results of regional classification obtained for the classes, normal and emphysematous, for each of the six regions. The best combination of features that were automatically selected for each of the six regions for the AMFM are summarized in Table 4. The means and one standard deviation of the PFT parameters are presented in Table 5. These PFT results (total lung capacity, or TLC [actual and percent predicted], FEV 1 [actual and percent predicted], FEV 1 /FVC, Pa O2 [actual], DL CO [actual and percent predicted], and residual volume, or RV [actual and percent predicted]) and the AMFM, MLD, and HIST methods were compared using regression analysis. The regres- TABLE 3 REGIONAL CLASSIFICATION RESULTS FOR DISCRIMINATION OF NORMAL AND EMPHYSEMATOUS REGIONS Region Method Sensitivity Specificity Accuracy 1 AMFM 100.0% 100.0% 100.0% MLD 94.1% 100.0% 98.0% 2 AMFM 95.8% 100.0% 98.2% MLD 100.0% 93.9% 96.5% 3 AMFM 95.8% 100.0% 98.2% MLD 95.8% 90.9% 93.0% 4 AMFM 90.0% 100.0% 96.0% MLD 85.0% 83.9% 84.3% HIST 95.0% 100.0% 98.0% 5 AMFM 96.1% 100.0% 98.1% MLD 84.6% 88.9% 86.8% 6 AMFM 91.3% 100.0% 96.5% MLD 73.9% 85.7% 81.0% HIST 91.3% 100.0% 96.5%

5 252 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL Region TABLE 4 OPTIMAL FEATURE SET FOR REGIONAL CLASSIFICATION OF NORMAL AND EMPHYSEMATOUS REGIONS USING AMFM sion analyses were performed separately for the normal group and the group with emphysema. Multiple regression analysis was used to compare the PFT parameters with the optimal combination of features determined by the AMFM, i.e., shortrun emphasis, mean, and grey level nonuniformity. Simple regression analysis was used to compare PFT parameters with MLD and HIST. The results are tabulated in Table 6. Total lung capacity (actual) and RV (actual) significantly correlated with the AMFM in the group with emphysema. The FEV 1 / FVC ratio significantly correlated with MLD in the group with emphysema. None of the actual PFT parameters correlated with HIST in either group. In addition, AMFM and MLD did not show significant correlations with any of the actual PFT parameters in the normal group. For the percent-predicted PFT parameters, AMFM, MLD and HIST showed significant correlations with TLC in the normal group. No other significant correlations were observed. DISCUSSION No. of Features Used Features 1 4 Contrast, mean, geometric fractal dimension, run-length nonuniformity 2 5 Mean, short-run emphasis, geometric fractal dimension, grey level nonuniformity, run percentage 3 7 Short-run emphasis, mean, run percentage, grey level nonuniformity, geometric fractal dimension, correlation, contrast 4 7 Short-run emphasis, mean, run-length nonuniformity, grey level nonuniformity, correlation, skew, variance 5 3 Short-run emphasis, mean, grey-level entropy 6 8 Short-run emphasis, inertia, mean, run percentage, grey level nonuniformity, grey-level entropy, kurtosis, variance TABLE 5 PULMONARY FUNCTION VALUES FOR ALL SUBJECTS PFT Parameter Normal (n 9) Emphysema (n 10) TLC, L * TLC, % predicted * FEV 1, L FEV 1, % predicted FEV 1 /FVC Pa O, mm Hg DL CO, ml/mm/mm Hg * DL CO, % predicted * RV, L * RV, % predicted * All data are mean SD. * n 9. TABLE 6 CORRELATION COEFFICIENTS BETWEEN PFT PARAMETERS AND FEATURES FROM AMFM, MLD, AND HIST METHODS PFT Parameter Class AMFM MLD HIST TLC, L Emphysema 0.88* NS NS FEV 1 /FVC Emphysema NS 0.68* NS RV, L Emphysema 0.99 NS NS TLC, % predicted Normal 0.91* 0.72* 0.70* * p p NS not significant. This study is a part of our long-term project of developing a generalizable, completely automated method that can identify specific regions of pulmonary parenchymal abnormality and objectively assess the severity of disease in different locations within the lung. The AMFM incorporates first-order and second-order statistical texture features and the geometric fractal dimension. The first-order features are derived from the greyscale frequency histograms. The second-order features describe the relationships between pixels and their grey levels. In addition to statistical features, a feature to quantify texture is used: the fractal dimension. It has been shown previously (27) that images of natural surfaces can be modeled using the fractional Brownian motion model, and the fractal dimension can provide a feature of a surface s roughness or smoothness. The use of fractals to describe medical images is increasing (28 30). The MLD has been previously shown to be significantly lower in subjects with emphysema than in normal volunteers (31). It also has been previously demonstrated that the histograms of emphysematous lungs are skewed more toward low densities than are normal lungs (4, 32). In this study, the utility of the AMFM is tested against these older methods for detecting emphysema. As a step in validating our approach, particularly in view of difficulty in finding gold standards, we evaluated nine normal subjects and ten subjects with well-defined emphysema. Initially, to apply and understand the AMFM, we examined the lung textural changes associated with position in normal subjects. It has been shown previously that lung density changes due to gravity are minimized when the scanning is performed with the subject in prone position (25). We demonstrated that the AMFM can detect ventral dorsal differences using an automatically selected set of seven features. The AMFM separated the ventral and dorsal regions with 89.8% accuracy. This suggests that, despite the fact that the lung is more uniformly expanded in the prone position (25), subtle gravity-oriented changes still occur, and the AMFM is able to discriminate this. The ventral-dorsal texture differences are not as well detected by MLD and HIST methods, which have accuracies of 74.6% and 64.4%, respectively. This finding indicates that the AMFM is better than single-feature methods in detecting this type of textural difference in the lung. We next studied a group of subjects with emphysema, examining the texture of the entire CT slice to determine the presence or absence of emphysema. In this study, the AMFM was capable of this assessment with an accuracy of 100.0%, using an optimal set of three features. The sensitivity and specificity of AMFM were both found to be 100%. Using MLD alone, the detection of normal and emphysematous scans yielded an accuracy of 94.7%. The sensitivity of the MLD method was 95.0% and the specificity was 94.4%. The HIST method demonstrated an accuracy of 97.4% in determining the presence of emphysema, with sensitivity of 95.0% and specificity of 100.0%. The AMFM, therefore, compares very well to previous methods of discriminating normal from emphysematous lungs. It should be noted that the results of the AMFM are dependent only on the initial grouping of the subjects as normal or emphysematous. They are not dependent in any way on the CT scan assessment by the observer. The analysis includes all of the CT slice information.

6 Uppaluri, Mitsa, Sonka, et al.: Quantification of Emphysema 253 We then examined focal regions of interest in the lung. Regional analysis of the normal and emphysema scans was performed by splitting each lung in each slice into six regions. This provided a reasonable compromise between too small a region, which would not capture texture, and too large a region. Because the normal subjects were scanned prone and subjects with emphysema were scanned supine, it was necessary to align the scans anatomically before splitting the lung into regions. Some regions were removed from the analysis either because the CT region contained artifacts, such as movement, or was not classifiable as either emphysematous or normal because of other disease processes. The emphysematous and normal samples were successfully discriminated in each of the six regions with an average accuracy of 97.9% using the AMFM. The average sensitivity and average specificity were 94.8% and 100.0%, respectively. The average sensitivity and specificity using the MLD method obtained over the same six regions was 88.9% and 90.5%, respectively. The MLD accuracy was 89.9%. Therefore, the AMFM performed better than the MLD method. Classification results for regional analysis using the HIST method demonstrated an average sensitivity of 97.7% and average specificity of 100.0% over all six regions. The average accuracy of 99.1% for the HIST method shows that is comparable to the AMFM for this kind of classification. In this analysis, three to eight features were selected for classification by the AMFM in each region. Overall, thirteen different features were automatically selected. (The four features that did not contribute to the classification at any time were angular second moment, inverse difference moment, long-run emphasis, and entropy.) This adaptability demonstrates that the AMFM can recognize local textures in different regions of the lung and still retain discriminatory power. Pulmonary function tests are currently used to indicate the severity of emphysema. Regression analysis between the PFT parameters and the AMFM, MLD, and HIST methods showed no correlation for the important PFT markers of emphysema such as DL CO, and FEV 1. One explanation for this is that all three methods detect emphysema by measuring parameters that may be independent of airway function and gas exchange. Also, the lung function tests evaluate all of the lung, whereas the CT analysis is restricted to four slices per subject. Another explanation is that our data set included only normal subjects and patients with advanced emphysema; these may not, as groups, have enough variation to indicate significant correlation within the group. The AMFM compares very favorably with previously used methods MLD and HIST in the detection of emphysema. Several features in the AMFM show significant abnormalities in emphysema when compared to the normal lung. These features may be useful for objectively describing the lung texture associated with emphysema and may, in the future, be shown to vary with time or therapy. It is also important that these features can be measured in regional parts of the lung, as opposed to PFT s evaluation of the whole lung function. The AMFM, with its automatic selection of different features, is better able to discriminate positional changes in a normal lung than either the MLD or the HIST method. This finding is encouraging and suggests that the AMFM is more sensitive to textural changes of increased radiopacity. It also suggests that the AMFM may be more generally applicable for other parenchymal lung diseases. The AMFM automatically picked different features to differentiate the ventral-dorsal lung density gradient, to discriminate normal and emphysematous slices, and to discriminate regions. This implies that the AMFM is adaptable to different lung patterns. We conclude that the AMFM can be used for tissue characterization of the lung. This method provides multiple objective features and therefore allows objective, consistent evaluation of parenchymal lung disease. In the future, a larger number of subjects with varying degrees of emphysema will be investigated. Furthermore, improvements in the classification scheme will be incorporated and this methodology will be applied to study other forms of parenchymal lung disease, such as idiopathic pulmonary fibrosis and sarcoidosis. Acknowledgment : The authors would like to thank Dr. Leon F. Burmeister, Professor, Department of Preventive Medicine and Environmental Health, The University of Iowa, for his help regarding statistical analysis of their results. They would also like to acknowledge the helpful suggestions in manuscript preparation by Dr. Gary W. Hunninghake, Professor, Department of Internal Medicine, The University of Iowa. References 1. 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