Top

Published in:

01-04-2015 | Research Article

Measuring Extracellular pH in a Lung Fibrosis Model with acidoCEST MRI

Authors: Kyle M. Jones, Edward A. Randtke, Christine M. Howison, Julio Cárdenas-Rodríguez, Patricia J. Sime, Matthew R. Kottmann, Mark D. Pagel

Published in: Molecular Imaging and Biology | Issue 2/2015

Abstract

Purpose

A feed-forward loop involving lactic acid production may potentially occur during the formation of idiopathic pulmonary fibrosis. To provide evidence for this feed-forward loop, we used acidoCEST MRI to measure the extracellular pH (pHe), while also measuring percent uptake of the contrast agent, lesion size, and the apparent diffusion coefficient (ADC).

Procedures

We developed a respiration-gated version of acidoCEST MRI to improve the measurement of pHe and percent uptake in lesions. We also used T₂-weighted MRI to measure lesion volumes and diffusion-weighted MRI to measure ADC.

Results

The longitudinal changes in average pHe and % uptake of the contrast agent were inversely related to reduction in lung lesion volume. The average ADC did not change during the time frame of the study.

Conclusions

The increase in pHe during the reduction in lesion volume indicates a role for lactic acid in the proposed feed-forward loop of IPF

Nathan SD, Shlobin OA, Weir N et al (2011) Long-term course and prognosis of idiopathic pulmonary fibrosis in the new millennium. Chest 140:221–229CrossRefPubMed

Richeldi L (2012) Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis. Eur Respir Rev 21:147–151CrossRefPubMed

Ley B, Collard HR, King TE Jr (2011) Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183:431–440CrossRefPubMed

Sime PJ, Samstrand B, Xing Z et al (1997) Adenovirus-mediated gene transfer of the proteoglycan biglycan induces fibroblastic responses in the lung. Chest 111:137SCrossRefPubMed

Tarantal AF, Chen H, Shi TT et al (2010) Overexpression of transforming growth factor-beta1 in fetal monkey lung results in pulmonary fibrosis. Eur Respir J 36:907–914CrossRefPubMedCentralPubMed

Kottmann RM, Kulkami AA, Smolnycki KA et al (2012) Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med 186:740–751CrossRefPubMedCentralPubMed

Chen LQ, Howison CM, Jeffery JJ, et al. (2013) Evaluations of extracellular pH within In Vivo Tumors Using acidoCEST MRI. Magn Reson Med, doi:10.1002/mrm.25053

Aime S, Calabi L, Biondi L et al (2005) Iopamidol: exploring the potential use of a well-established x ray contrast agent for MRI. Magn Reson Imaging 53:830–834

Aime S, Barge A, Delli Castelli D et al (2002) Paramagnetic Lanthanide (III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications. Magn Reson Med 47:639–48CrossRefPubMed

10.

Ward KM, Balaban RS (2000) Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST). Magn Reson Med 44:799–802CrossRefPubMed

11.

Liu G, Li Y, Sheth VR, Pagel MD (2012) Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. Mol Imaging 11:47–57PubMed

12.

Ward KM, Aletras AH, Balaban RS (2000) A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). Magn Reson Imaging 143:79–87CrossRef

13.

Grad J, Bryant RG (1990) Nuclear magnetic cross-relaxation spectroscopy. JMR 90:1–8

14.

Liepinsh E, Otting G (1996) Proton exchange rates from amino acid side chains—implications for image contrast. Magn Reson Med 35:30–42CrossRefPubMed

15.

Sheth VR, Li Y, Chen LQ et al (2012) Measuring in vivo tumor pHe with CEST-FISP MRI. Magn Reson Med 67:760–768CrossRefPubMedCentralPubMed

16.

Longo DL, Busato A, Lanzardo S et al (2013) Imaging the pH evolution of an acute kidney injury model by means of iopamidol, a MRI-CEST pH-responsive contrast agent. Magn Reson Med 70:859–864CrossRefPubMed

17.

Sheth VR, van Heeckeren RC, Wilson AG et al (2008) Monitoring infection and inflammation in murine models of cystic fibrosis with magnetic resonance imaging. Magn Reson Imaging 28:527–532CrossRef

18.

Sheth VR, Liu G, Li Y, Pagel MD (2012) Improved pH measurements with a single PARACEST MRI contrast agent. Contrast Media Mol Imaging 7:26–34CrossRefPubMed

19.

Garbow J, Dugas JP, Conradi MS (2003) Respiratory gating for MRI and MRS in rodents. Third IEEE Symp Bioinform Bioeng 126–129

20.

Heijman E, de Graaf W, Niessen P et al (2007) Comparison between prospective and retrospective triggering for mouse cardiac MRI. NBR 20:439–447

21.

Lakatos HF, Burgess HA, Thatcher TH et al (2006) Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation. Exp Lung Res 32:181–99CrossRefPubMed

22.

Kulkarni AA, Thatcher TH, Hsiao HM et al (2013) The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis. PLoS One 8:e63798CrossRefPubMedCentralPubMed

23.

Woessner DE, Zhang S, Merritt ME, Sherry AD (2005) Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 53:790–799CrossRefPubMed

24.

Randtke EA, Chen LQ, Corrales LR, Pagel MD (2013) The Hanes-Woolf linear QUESP method improves measurements of fast chemical exchange rates with CEST MRI. Magn Reson Med. doi:10.1002/mrm.24792

25.

Gregory RB, Crabo L, Percy AJ, Rosenburg A (1983) Water catalysis of peptide hydrogen isotope exchange. Biochemistry 22:910–917CrossRefPubMed

26.

Haacke EM, Brown RW, Thompson MR, Venkatesan R (1999) Magnetic resonance imaging physical principles and sequence design. Wiley-Liss, New York, NY, p 349

27.

Schnieder CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675CrossRef

28.

Caravan P, Yang Y, Zachariah R et al (2013) Molecular magnetic resonance imaging of pulmonary fibrosis in mice. Am J Respir Cell Mol Biol 49:1120–6CrossRefPubMedCentralPubMed

29.

Shaghaghi H, Kadlecek S, Deshpande C et al (2014) Metabolic spectroscopy of inflammation in a bleomycin-induced lung injury model using hyperpolarized 1-¹³C pyruvate. NBM 27:929–947

Title: Measuring Extracellular pH in a Lung Fibrosis Model with acidoCEST MRI
Authors: Kyle M. Jones
Edward A. Randtke
Christine M. Howison
Julio Cárdenas-Rodríguez
Patricia J. Sime
Matthew R. Kottmann
Mark D. Pagel
Publication date: 01-04-2015
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2015
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-014-0784-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Measuring Extracellular pH in a Lung Fibrosis Model with acidoCEST MRI

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2015

Clinical Assessment of MR-Guided 3-Class and 4-Class Attenuation Correction in PET/MR

Hyperpolarized and Inert Gas MRI: The Future

Deglycosylation of mAb by EndoS for Improved Molecular Imaging

Comparison of [11C]Choline ([11C]CHO) and S(+)-β-Methyl-[11C]Choline ([11C]SMC) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model

Evaluation of [111In]-Labeled Zinc–Dipicolylamine Tracers for SPECT Imaging of Bacterial Infection

Reproducibility and Reliability of Anti-3-[18F]FACBC Uptake Measurements in Background Structures and Malignant Lesions on Follow-Up PET-CT in Prostate Carcinoma: an Exploratory Analysis