AJR:192, April 2009 1037 Findings of dyspnea and lung cysts on CT can precede findings of abnormalities on spirometry [2, 7]. Progressive dyspnea and respiratory fail- ure occur over a highly variable period of time, with an often unpredictable pattern of decline [2]. A number of studies report a high mortality rate, with a 10-year sur- vival rate of approximately 40–80% [8–12], but more recent data suggest a more opti- mistic prognosis, perhaps related to greater awareness and earlier detection [13]. Accu- mulating evidence indicates that LAM is a metastatic process in which histological- ly benign cells of unknown origin infiltrate the lung and promote remodeling [14]. Aber- rant LAM cell proliferation, migration, and infiltration result from mutations in one of two tuberous sclerosis genes, TSC1 or TSC2, both in patients with tuberous sclerosis com- plex (TSC-LAM) and those without germ- line mutations who have sporadic LAM (S- Automated Algorithm for Quantifying the Extent of Cystic Change on Volumetric Chest CT: Initial Results in Lymphangioleiomyomatosis Vincent J. Schmithorst 1 Talissa A. Altes 2, 3 Lisa R. Young 4,5 David N. Franz 6 John J. Bissler 7 Francis X. McCormack 5 Bernard J. Dardzinski 1,8 Alan S. Brody 1 Schmithorst VJ, Altes TA, Young LR, et al. 1 Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. 2 Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, PA. 3 Present address: Department of Radiology, University of Virginia, Box 800170, Chalottesville, VA 22908. Address correspondence to T. A. Altes (taa2c@virginia.edu). 4 Division of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH. 5 Division of Pulmonary and Critical Care Medicine, University of Cincinnati, Cincinnati, OH. 6 Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. 7 Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH. 8 Present address: Merck and Co., Inc., Whitehouse Station, NJ. Cardiopulmonary฀Imaging฀•฀Original฀Research AJR 2009; 192:1037–1044 0361–803X/09/1924–1037 © American Roentgen Ray Society L ymphangioleiomyomatosis (LAM) is a rare disease characterized by smooth muscle cell infiltration and cystic destruction of the lung [1, 2]. Although LAM primarily affects young adult women of childbearing age, it also occurs in women after menopause and has been documented in a few men. The most common presenting symptoms are dyspnea on exertion, pneumothorax, or chylothorax. Pulmonary function testing (PFT) typically shows obstructive physiology, with a dispro- portionate reduction in forced expiratory volume in 1 second (FEV 1 ) percentage pre- dicted, but restrictive patterns are also seen. Additional PFT findings include elevations in residual volume (RV) and total lung ca- pacity (TLC) indicating air-trapping and hy- perinflation, respectively [3]. Chest CT re- veals characteristic findings of thin-walled parenchymal cysts, chylous pleural effu- sions, and recurrent pneumothoraces [4–6]. Keywords: chest CT, cystic lung disease, lymphangio- leiomyomatosis (LAM), quantitative CT DOI:10.2214/AJR.07.3334 Received October 18, 2007; accepted after revision October 27, 2008. D. N. Franz, F. X. McCormack, and J. J. Bissler supported by grants from the Rare Lung Disease Consortium, National Institutes of Health (RR019498); National Cancer Institute (CA103486); LAM Foundation; and Tuberous Sclerosis Alliance. OBJECTIVE. The purpose of our study was to develop a new method for quantifying the severity of cystic lung disease using chest CT and to evaluate this method in patients with lymphangioleiomyomatosis (LAM). SUBJECTS฀AND฀METHODS. Eighteen patients with LAM (all women; mean age, 43.6 years) underwent chest CT and pulmonary function testing including diffusing capacity for car- bon monoxide (DLCO). All patients were at their clinical baseline on the day of imaging. Stan- dard quantitative CT metrics including the percentage of the lung volume < –910 HU and the 15th percentile of Hounsfield units were computed from the histogram of lung voxels. A new histogram analysis method was developed to compute the cyst volume and the volume of the re- maining lung by segmenting the entire lung attenuation histogram into two underlying distribu- tions, one from the cysts and the other from the remaining lung tissue. RESULTS. The mean ± SD for quantitative lung metrics was 21% ± 16% for percentage < –910 HU, –915 ± 47 HU for 15th percentile of Hounsfield units, and 19% ± 13% for cyst vol- ume. The correlation between pulmonary function tests and CT metrics was strongest for the percentage of cyst volume for all pulmonary function testing indexes, with correlations be- tween forced expiratory volume in 1 second (FEV 1 ) percentage predicted and the CT metrics of r = –0.52, r = 0.50, and r = –0.86 for the percentage of lung < –910 HU, the 15th percentile of Hounsfield units, and the percentage of cyst volume, respectively. CONCLUSION. A new method for quantifying cyst volume as a percentage of total lung volume using chest CT correlates with pulmonary function parameters in patients with LAM and may have utility in the assessment of disease severity and progression of cystic lung diseases. Schmithorst et al. CT of Cystic Change in Lymphangioleiomyomatosis Cardiopulmonary Imaging Original Research Downloaded from www.ajronline.org by Univ. of Cincinnati-Serial Dep on 12/24/13 from IP address 129.137.26.178. Copyright ARRS. For personal use only; all rights reserved