European Radiology

, Volume 27, Issue 10, pp 4209–4217 | Cite as

Co-registration of pre-operative CT with ex vivo surgically excised ground glass nodules to define spatial extent of invasive adenocarcinoma on in vivo imaging: a proof-of-concept study

  • Mirabela RusuEmail author
  • Prabhakar Rajiah
  • Robert Gilkeson
  • Michael Yang
  • Christopher Donatelli
  • Rajat Thawani
  • Frank J. Jacono
  • Philip Linden
  • Anant MadabhushiEmail author
Computer Applications



To develop an approach for radiology-pathology fusion of ex vivo histology of surgically excised pulmonary nodules with pre-operative CT, to radiologically map spatial extent of the invasive adenocarcinomatous component of the nodule.


Six subjects (age: 75 ± 11 years) with pre-operative CT and surgically excised ground-glass nodules (size: 22.5 ± 5.1 mm) with a significant invasive adenocarcinomatous component (>5 mm) were included. The pathologist outlined disease extent on digitized histology specimens; two radiologists and a pulmonary critical care physician delineated the entire nodule on CT (in-plane resolution: <0.8 mm, inter-slice distance: 1–5 mm). We introduced a novel reconstruction approach to localize histology slices in 3D relative to each other while using CT scan as spatial constraint. This enabled the spatial mapping of the extent of tumour invasion from histology onto CT.


Good overlap of the 3D reconstructed histology and the nodule outlined on CT was observed (65.9 ± 5.2%). Reduction in 3D misalignment of corresponding anatomical landmarks on histology and CT was observed (1.97 ± 0.42 mm). Moreover, the CT attenuation (HU) distributions were different when comparing invasive and in situ regions.


This proof-of-concept study suggests that our fusion method can enable the spatial mapping of the invasive adenocarcinomatous component from 2D histology slices onto in vivo CT.

Key Points

3D reconstructions are generated from 2D histology specimens of ground glass nodules.

The reconstruction methodology used pre-operative in vivo CT as 3D spatial constraint.

The methodology maps adenocarcinoma extent from digitized histology onto in vivo CT.

The methodology potentially facilitates the discovery of CT signature of invasive adenocarcinoma.


Lung adenocarcinoma Computed tomography Pathology Computer-assisted image processing Multimodal imaging 



Two dimensional


Three dimensional


Hounsfield units








Miliampere second




Compliance with ethical standards


The scientific guarantor of this publication is Mirabela Rusu.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: GE Global Research, Elucid Bioimaging and Inspirata Inc.


This study has received funding from the US Department of Defense (W81XWH-13-1-0487), US National Institutes of Health (R01CA202752-01A1, R01CA208236-01A1, R21CA179327-01, R21CA19515201, U24CA199374-01), the US National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098503-02), the US Department of Defense Prostate Cancer Synergistic Idea Development Award (PC120857); the US Department of Defense Lung Cancer Idea Development Award (LC130463); the US Department of Defense Prostate Cancer Idea Development Award; US Department of Defense Peer Reviewed Medical Research Program (W81XWH-16-1-0329); the Case Comprehensive Cancer Center Pilot Grant, the VelaSano Grant from the Cleveland Clinic, Ohio, US the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering at Case Western Reserve University, Ohio, US. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Statistics and biometry

One of the authors has significant statistical expertise.

Ethical approval

Institutional Review Board approval was obtained.

Informed consent

Written informed consent was waived by the Institutional Review Board.


• retrospective

• experimental

• performed at one institution

Supplementary material

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Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringCase Western Reserve UniversityClevelandUSA
  2. 2.GE Global ResearchNiskayunaUSA
  3. 3.UT Southwestern Medical CenterDallasUSA
  4. 4.University HospitalsCleveland Medical Center and Case Western Reserve UniversityClevelandUSA
  5. 5.Louis Stokes Cleveland VA Medical CenterClevelandUSA

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