Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography

Physics in Medicine and Biology, vol. 68, pp. 115014

Abstract

Abstract Objectives. As the central organ of the respiratory system, the human lung is responsible for supplying oxygen to the blood, which reaches the erythrocytes by diffusion through the alveolar walls and is then distributed throughout the body. By exploiting the difference in electron density detected by a phase shift in soft tissue, high-resolution x-ray phase-contrast computed tomography (XPCT) can resolve biological structures in a sub- μ m range, shedding new light on the three-dimensional structure of the lungs, physiological functions and pathological mechanisms. Approach. This work presents both synchrotron and laboratory XPCT results of postmortem tissue from autopsies and biopsies embedded with various preparation protocols such as precision-cut lung slices, cryogenically fixed lung tissue, as well as paraffin and alcohol fixed tissue. The selection of pathological abnormalities includes channel of Lambert, bronchus-associated lymphoid tissue and alveolar capillary dysplasia with misalignment of pulmonary veins. Subsequently, quantification and visualization approaches are presented. Main results. The overall high image quality even of in-house XPCT scans for the case of FFPE biopsies can be exploited for a wide range of pulmonary pathologies and translated to dedicated and optimized instrumentation which could be operated in clinical setting. By using synchrotron radiation, contrast can be further increased to resolve sub- μ m sized features down to the sub-cellular level. The results demonstrate that a wide range of preparation protocols including sample mounting in liquids can be used. Significance. With XPCT, poorly understood 3D structures can be identified in larger volume overview and subsequently studied in more detail at higher resolution. With the full 3D structure, the respective physiological functions of airways or vascular networks, and the different pathophysiologic mechanisms can be elucidated or at least underpinned with structural data. Moreover, synchrotron data can be used to validate laboratory protocols and provide ground truth for standardizing the method.

Authors 11

1. Jakob Reichmann

   University of Göttingen

   Affiliation as printed

   Institute for X-ray Physics, University of Göttingen, Friedrich-Hund-Platz 1, D-37077 Göttingen, Germany

2. Stijn E. Verleden

   University of Antwerp

   Affiliation as printed

   Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium

3. Mark Kühnel

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

   Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

4. Jan C. Kamp

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

   Department of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

5. Christopher Werlein

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

   Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

6. Lavinia Neubert

   Medizinische Hochschule Hannover · German Center for Lung Research

   Affiliation as printed

   Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

   Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

7. Jan-Hendrik Müller

   University of Göttingen

   Affiliation as printed

   Institute for X-ray Physics, University of Göttingen, Friedrich-Hund-Platz 1, D-37077 Göttingen, Germany

8. Thanh Quynh Bui

   University of Göttingen

   Affiliation as printed

   Institute for X-ray Physics, University of Göttingen, Friedrich-Hund-Platz 1, D-37077 Göttingen, Germany

9. Maximilian Ackermann

   Witten/Herdecke University · Helios Universitätsklinikum Wuppertal

   Affiliation as printed

   Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Heusnerstraße 40, D-42283 Wuppertal, Germany

10. Danny David Jonigk Aachen Institute of Pathology

    German Center for Lung Research · RWTH Aachen University

    Affiliation as printed

    Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

    Institute of Pathology, RWTH Aachen Medical Faculty, Pauwelsstraße 30, D-52074 Aachen, Germany

11. Tim Salditt

    University of Göttingen

    Affiliation as printed

    Institute for X-ray Physics, University of Göttingen, Friedrich-Hund-Platz 1, D-37077 Göttingen, Germany