Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease

Benjamin Pulli, Gregory Wojtkiewicz, Yoshiko Iwamoto, Muhammad Ali, Matthias W. Zeller, Lionel Bure, Cuihua Wang, Yuri Choi, Ricard Masia, Alexander Guimaraes, Kathleen E. Corey, John W. Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods: In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results: With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion: MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples.

Original languageEnglish (US)
Pages (from-to)390-400
Number of pages11
JournalRadiology
Volume284
Issue number2
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Fingerprint

Fatty Liver
Peroxidase
Magnetic Resonance Imaging
Noise
Confidence Intervals
Biopsy
Liver
Diet
Endotoxins
Non-alcoholic Fatty Liver Disease
Leptin Receptors
Gadolinium DTPA
Nonparametric Statistics
Choline
Knockout Mice
Methionine
Lipopolysaccharides
Students

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Pulli, B., Wojtkiewicz, G., Iwamoto, Y., Ali, M., Zeller, M. W., Bure, L., ... Chen, J. W. (2017). Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease. Radiology, 284(2), 390-400. https://doi.org/10.1148/radiol.2017160588

Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease. / Pulli, Benjamin; Wojtkiewicz, Gregory; Iwamoto, Yoshiko; Ali, Muhammad; Zeller, Matthias W.; Bure, Lionel; Wang, Cuihua; Choi, Yuri; Masia, Ricard; Guimaraes, Alexander; Corey, Kathleen E.; Chen, John W.

In: Radiology, Vol. 284, No. 2, 01.08.2017, p. 390-400.

Research output: Contribution to journalArticle

Pulli, B, Wojtkiewicz, G, Iwamoto, Y, Ali, M, Zeller, MW, Bure, L, Wang, C, Choi, Y, Masia, R, Guimaraes, A, Corey, KE & Chen, JW 2017, 'Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease', Radiology, vol. 284, no. 2, pp. 390-400. https://doi.org/10.1148/radiol.2017160588
Pulli, Benjamin ; Wojtkiewicz, Gregory ; Iwamoto, Yoshiko ; Ali, Muhammad ; Zeller, Matthias W. ; Bure, Lionel ; Wang, Cuihua ; Choi, Yuri ; Masia, Ricard ; Guimaraes, Alexander ; Corey, Kathleen E. ; Chen, John W. / Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease. In: Radiology. 2017 ; Vol. 284, No. 2. pp. 390-400.
@article{739c33f9fe0e4f589e92778f2f55829b,
title = "Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease",
abstract = "Purpose: To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods: In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results: With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95{\%} confidence interval {CI}: 1.53, 2.10] vs 1.02 [95{\%} CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95{\%} CI: 1.27, 1.40] vs 0.98 [95{\%} CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95{\%} CI: 1.48, 3.74] vs 1.29 [95{\%} CI: 1.06, 1.52]; P = .004). Conclusion: MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples.",
author = "Benjamin Pulli and Gregory Wojtkiewicz and Yoshiko Iwamoto and Muhammad Ali and Zeller, {Matthias W.} and Lionel Bure and Cuihua Wang and Yuri Choi and Ricard Masia and Alexander Guimaraes and Corey, {Kathleen E.} and Chen, {John W.}",
year = "2017",
month = "8",
day = "1",
doi = "10.1148/radiol.2017160588",
language = "English (US)",
volume = "284",
pages = "390--400",
journal = "Radiology",
issn = "0033-8419",
publisher = "Radiological Society of North America Inc.",
number = "2",

}

TY - JOUR

T1 - Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease

AU - Pulli, Benjamin

AU - Wojtkiewicz, Gregory

AU - Iwamoto, Yoshiko

AU - Ali, Muhammad

AU - Zeller, Matthias W.

AU - Bure, Lionel

AU - Wang, Cuihua

AU - Choi, Yuri

AU - Masia, Ricard

AU - Guimaraes, Alexander

AU - Corey, Kathleen E.

AU - Chen, John W.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Purpose: To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods: In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results: With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion: MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples.

AB - Purpose: To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods: In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results: With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion: MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples.

UR - http://www.scopus.com/inward/record.url?scp=85025094077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025094077&partnerID=8YFLogxK

U2 - 10.1148/radiol.2017160588

DO - 10.1148/radiol.2017160588

M3 - Article

C2 - 28358240

AN - SCOPUS:85025094077

VL - 284

SP - 390

EP - 400

JO - Radiology

JF - Radiology

SN - 0033-8419

IS - 2

ER -