Fig. 1(a). Planar reformatted image. To precisely understand lung function, it is necessary to accurately visualize detailed lung architecture. We used a novel X-ray tomographic technique [1] to study the morphology of human lung at a high resolution. Postmortem lungs were inflated and chemically fixed by Heitzman’s method. Lung samples were sectioned at a 15-mm thickness. Utilizing the p r e s e n t s y n c h r o t r o n r a d i a t i o n c o m p u t e d tomography (CT) system, the entire sample must be contained within the field to enable visualization of multiple viewing angles in a cylinder, 8 mm in diameter. We, therefore, reduced the sample size by carefully removing the edges of the block, yielding a column specimen containing the target site. During this process, we were careful to retain one terminal bronchiole to include the peripheral structure in the column specimen. HIGH RESOLUTION MICROTOMOGRAPHY OF HUMAN LUNG TISSUE SPECIMENS: OBSERVATION OF NORMAL ANATOMY AND THREE-DIMENSIONAL RECONSTRUCTION (b) The CT images were obtained at BL20B2 using a phosphor X-ray detector with a cooled CCD camera at an X-ray energy of 9 keV. Synchrotron radiation CT images effectively captured the alveolar wall, the air spaces, and small airways. Alveolar septa were visualized at an effective spatial resolution of approximately 24 μ m, experimentally determined in the present synchrotron radiation CT system. Detailed correlation between the synchrotron radiation microtomography and histology can be achieved by precise spatial registration [2]. (a) Fig. 1(b). TB = terminal bronchiole RB = respiratory bronchiole AD = alveolar duct AS = alveolar sac V = pulmonary vessel Fig. 2. Three-dimensional reconstruction of the sub-acinus. Using the nearly-parallel, synchrotron radiation beam, comprehensive isotropic volumetric data can b e o b t a i n e d i n m u l t i p l e c r o s s - s e c t i o n a l p l a n e s , throughout the full three-dimensional volume of the t i s s u e . S e r i a l a n a l y s i s o f t h e s e s y n c h r o t r o n r a d i a t i o n C T i m a g e s a l l o w e d u s t o i d e n t i f y t h e terminal bronchiole, the respiratory bronchiole, the alveolar duct, and the alveolar sac. We reformatted t h e p a r a - s a g i t t a l p l a n a r i m a g e f r o m t h e t h r e e - d i m e n s i o n a l i s o t r o p i c v o l u m e t r i c d a t a w i t h a h i g h r e s o l u t i o n ( F i g . 1 a ) t o s y s t e m a t i c a l l y c o n f i r m t h e s t r u c t u r a l s e q u e n c e ; t h e r e s p i r a t o r y b r o n c h i o l e o r i g i n a t e s f r o m t h e t e r m i n a l b r o n c h i o l e ( T B ) , se qu en ti al ly br an ch es of f in to al ve ol ar du ct s (A D) a n d t e r m i n a t e s i n t h e a l v e o l a r d u c t s a b u t t i n g o n either the pleura or the interlobular septum ( F i g . 1 b ) . A n a l v e o l a r d u c t , d i s t a l t o t h e b r o n c h i o l e - alveolar duct junction, communicates with all alveoli in th e ve nt il at or y un it de fi ne d in ou r st ud ie s. Fo r each voxel within the air spaces, we calculated the d i s t a n c e t o t h e n e a r e s t v o x e l o n t h e b o u n d a r y , a s s i g n i n g t h i s v a l u e t o t h e v o x e l a s t h e d e n s i t y value . A subse quent volum e rende ring techn ique a l l o w e d i n t e r a c t i v e v i e w i n g o f t h e s e g m e n t e d s t r u c t u r e i n t h e a p p r o p r i a t e v i e w i n g p e r s p e c t i v e w i t h o u t h i d d e n s t r u c t u r e s ( F i g . 2 ) . T h i s t h r e e - dimensional imaging technique, possessing a high isotropic spatial resolution, offers a new mechanism t o a n a l y z e t h e a c i n a r g e o m e t r y , n e c e s s a r y t o accurately define the physiology of the human lung. Three-dimensional, super-resolution imaging of t h e i n f l a t e d a n d f i x e d h u m a n l u n g , u t i l i z i n g t h e combination of synchrotron radiation and histology, e s t a b l i s h e s a n o v e l , f u n d a m e n t a l a p p r o a c h allowing greater understanding of the human lung. D e e p e r u n d e r s t a n d i n g o f t h e n o r m a l l u n g a r c h i t e c t u r e a n d t h e c o n s e q u e n t m o r p h o l o g i c a l m o d i f i c a t i o n s r e s u l t i n g f r o m p h y s i o p a t h o l o g i c a l c o n d i t i o n s w i l l h o p e f u l l y a l l o w a d v a n c e s i n biomedicine. K e n j i S h i m i z u a , b , J u n p e i I k e z o e a a n d Naoto Yagi c (a) Ehime University School of Medicine (b) Yamaguchi University (c) SPring-8 / JASRI E-mail: simi @ kinchu.hosp.go.jp References [1] K. Uesugi et al. , Proc. SPIE 3772 (1999) 214. [ 2 ] K . S h i m i z u , J . I k e z o e , H . I k u r a , H . E b a r a , T . N a g a r e d a , N . Y a g i , K . U m e t a n i , K . U e s u g i , K . Okada, A. Sugita and M. Tanaka, Proc. SPIE 3977 (2000) 196.
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