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Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF-transgenic mice.

Abstract Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is a debilitating condition with poor survival prognosis. High resolution computed tomography (CT) is a common clinical tool to diagnose RA-ILD, and is increasingly being adopted in pre-clinical studies. However, murine models recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease have yet to be formally validated. To address this, we validate μCT outcomes for ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA.
PMID
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Publication Year Start




PMID- 29320550
OWN - NLM
STAT- In-Data-Review
LR  - 20180110
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 1
DP  - 2018
TI  - Longitudinal micro-CT as an outcome measure of interstitial lung disease in
      TNF-transgenic mice.
PG  - e0190678
LID - 10.1371/journal.pone.0190678 [doi]
AB  - INTRODUCTION: Rheumatoid arthritis associated interstitial lung disease (RA-ILD) 
      is a debilitating condition with poor survival prognosis. High resolution
      computed tomography (CT) is a common clinical tool to diagnose RA-ILD, and is
      increasingly being adopted in pre-clinical studies. However, murine models
      recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease 
      have yet to be formally validated. To address this, we validate muCT outcomes for
      ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA. METHODS: 
      Cross sectional muCT was performed on cohorts of male TNF-Tg mice and their WT
      littermates at 3, 4, 5.5 and 12 months of age (n = 4-6). Lung muCT outcomes
      measures were determined by segmentation of the muCT datasets to generate Aerated
      and Tissue volumes. After each scan, lungs were obtained for histopathology and 3
      sections stained with hematoxylin and eosin. Automated histomorphometry was
      performed to quantify the tissue area (nuclei, cytoplasm, and extracellular
      matrix) and aerated area (white space) within the tissue sections. Spearman's
      correlation coefficients were used to evaluate the extent of association between 
      muCT imaging and histopathology endpoints. RESULTS: TNF-Tg mice had significantly
      greater tissue volume, total lung volume and mean intensity at all timepoints
      compared to age matched WT littermates. Histomorphometry also demonstrated a
      significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg
      mice. Lung tissue volume was correlated with lung tissue area (rho = 0.81,
      p<0.0001), and normalize lung aerated volume was correlated with normalized lung 
      air area (rho = 0.73, p<0.0001). CONCLUSIONS: We have validated in vivo muCT as a
      quantitative biomarker of ILD in mice. Further, development of longitudinal
      measures is critical for dissecting pathologic progression of ILD, and muCT is a 
      useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.
FAU - Bell, Richard D
AU  - Bell RD
AUID- ORCID: http://orcid.org/0000-0002-8327-0676
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine
      and Dentistry, Rochester, New York, United States of America.
AD  - Department of Pathology and Laboratory Medicine, University of Rochester School
      of Medicine and Dentistry, Rochester, New York, United States of America.
FAU - Rudmann, Christopher
AU  - Rudmann C
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine
      and Dentistry, Rochester, New York, United States of America.
FAU - Wood, Ronald W
AU  - Wood RW
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine
      and Dentistry, Rochester, New York, United States of America.
AD  - Department of Obstetrics and Gynecology, University of Rochester School of
      Medicine and Dentistry, Rochester, New York, United States of America.
AD  - Department of Urology, University of Rochester School of Medicine and Dentistry, 
      Rochester, New York, United States of America.
AD  - Department of Neuroscience, University of Rochester School of Medicine and
      Dentistry, Rochester, New York, United States of America.
FAU - Schwarz, Edward M
AU  - Schwarz EM
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine
      and Dentistry, Rochester, New York, United States of America.
AD  - Department of Pathology and Laboratory Medicine, University of Rochester School
      of Medicine and Dentistry, Rochester, New York, United States of America.
AD  - Department of Urology, University of Rochester School of Medicine and Dentistry, 
      Rochester, New York, United States of America.
AD  - Department of Orthopaedics, University of Rochester School of Medicine and
      Dentistry, Rochester, New York, United States of America.
FAU - Rahimi, Homaira
AU  - Rahimi H
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine
      and Dentistry, Rochester, New York, United States of America.
AD  - Department of Pediatrics, University of Rochester School of Medicine and
      Dentistry, Rochester, New York, United States of America.
LA  - eng
PT  - Journal Article
DEP - 20180110
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
EDAT- 2018/01/11 06:00
MHDA- 2018/01/11 06:00
CRDT- 2018/01/11 06:00
PHST- 2017/08/04 00:00 [received]
PHST- 2017/12/19 00:00 [accepted]
PHST- 2018/01/11 06:00 [entrez]
PHST- 2018/01/11 06:00 [pubmed]
PHST- 2018/01/11 06:00 [medline]
AID - 10.1371/journal.pone.0190678 [doi]
AID - PONE-D-17-29024 [pii]
PST - epublish
SO  - PLoS One. 2018 Jan 10;13(1):e0190678. doi: 10.1371/journal.pone.0190678.
      eCollection 2018.