Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging
Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/8/775 |
| _version_ | 1797558015712296960 |
|---|---|
| author | Per Mose Nielsen Christian Østergaard Mariager Daniel Guldager Kring Rasmussen Marie Mølmer Federica Genovese Morten Asser Karsdal Christoffer Laustsen Rikke Nørregaard |
| author_facet | Per Mose Nielsen Christian Østergaard Mariager Daniel Guldager Kring Rasmussen Marie Mølmer Federica Genovese Morten Asser Karsdal Christoffer Laustsen Rikke Nørregaard |
| author_sort | Per Mose Nielsen |
| collection | DOAJ |
| description | Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression following renal ischemia-reperfusion injury (IRI): magnetic resonance imaging (MRI) and noninvasive extracellular matrix (ECM) biomarkers. MRI was used to evaluate fibrosis in bilateral IRI in rats after reperfusion at 7, 14, and 21 days. This was performed with <sup>1</sup>HT<sub>1</sub> and T<sub>2</sub>* mapping, dynamic contrast-enhanced (DCE)-MRI, and chemical shift imaging (CSI)-<sup>23</sup>Na. The degradation of laminin gamma-1 chain (LG1M) and type III collagen (C3M) was measured in urine and plasma. Fibrosis was analyzed in tissue using fibronectin (FN) and alpha-smooth muscle actin (α-SMA) using quantitative polymerase chain reaction qPCR and western blotting. We found increased fibrosis 7 days after reperfusion, which dropped to sham levels after 21 days. Single kidney glomerular filtration rate (skGFR), perfusion (DCE-MRI), and total <sup>23</sup>Na kidney content correlated positively with fibrotic markers FN and α-SMA as well as noninvasive LG1M and C3M. We showed that novel MRI protocols and ECM markers could track fibrogenic development. This could give rise to a multi-parametric practice to diagnose and assess fibrosis whilst treating kidney disease without using invasive methods. |
| first_indexed | 2024-03-10T17:24:27Z |
| format | Article |
| id | doaj.art-80c6f9ff803849348e3b4d9137cac687 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:24:27Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-80c6f9ff803849348e3b4d9137cac6872023-11-20T10:13:55ZengMDPI AGPharmaceutics1999-49232020-08-0112877510.3390/pharmaceutics12080775Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance ImagingPer Mose Nielsen0Christian Østergaard Mariager1Daniel Guldager Kring Rasmussen2Marie Mølmer3Federica Genovese4Morten Asser Karsdal5Christoffer Laustsen6Rikke Nørregaard7Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, DenmarkMR Research Centre, Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, DenmarkNordic Bioscience A/S, 2730 Herlev, DenmarkDepartment of Clinical Medicine, Aarhus University, 8200 Aarhus N, DenmarkNordic Bioscience A/S, 2730 Herlev, DenmarkNordic Bioscience A/S, 2730 Herlev, DenmarkMR Research Centre, Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, DenmarkDepartment of Clinical Medicine, Aarhus University, 8200 Aarhus N, DenmarkFibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression following renal ischemia-reperfusion injury (IRI): magnetic resonance imaging (MRI) and noninvasive extracellular matrix (ECM) biomarkers. MRI was used to evaluate fibrosis in bilateral IRI in rats after reperfusion at 7, 14, and 21 days. This was performed with <sup>1</sup>HT<sub>1</sub> and T<sub>2</sub>* mapping, dynamic contrast-enhanced (DCE)-MRI, and chemical shift imaging (CSI)-<sup>23</sup>Na. The degradation of laminin gamma-1 chain (LG1M) and type III collagen (C3M) was measured in urine and plasma. Fibrosis was analyzed in tissue using fibronectin (FN) and alpha-smooth muscle actin (α-SMA) using quantitative polymerase chain reaction qPCR and western blotting. We found increased fibrosis 7 days after reperfusion, which dropped to sham levels after 21 days. Single kidney glomerular filtration rate (skGFR), perfusion (DCE-MRI), and total <sup>23</sup>Na kidney content correlated positively with fibrotic markers FN and α-SMA as well as noninvasive LG1M and C3M. We showed that novel MRI protocols and ECM markers could track fibrogenic development. This could give rise to a multi-parametric practice to diagnose and assess fibrosis whilst treating kidney disease without using invasive methods.https://www.mdpi.com/1999-4923/12/8/775renal IRIMRIrat modelsinterstitial fibrosisnoninvasive ECM markers |
| spellingShingle | Per Mose Nielsen Christian Østergaard Mariager Daniel Guldager Kring Rasmussen Marie Mølmer Federica Genovese Morten Asser Karsdal Christoffer Laustsen Rikke Nørregaard Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging Pharmaceutics renal IRI MRI rat models interstitial fibrosis noninvasive ECM markers |
| title | Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging |
| title_full | Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging |
| title_fullStr | Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging |
| title_full_unstemmed | Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging |
| title_short | Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging |
| title_sort | noninvasive assessment of fibrosis following ischemia reperfusion injury in rodents utilizing na magnetic resonance imaging |
| topic | renal IRI MRI rat models interstitial fibrosis noninvasive ECM markers |
| url | https://www.mdpi.com/1999-4923/12/8/775 |
| work_keys_str_mv | AT permosenielsen noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT christianøstergaardmariager noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT danielguldagerkringrasmussen noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT mariemølmer noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT federicagenovese noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT mortenasserkarsdal noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT christofferlaustsen noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging AT rikkenørregaard noninvasiveassessmentoffibrosisfollowingischemiareperfusioninjuryinrodentsutilizingnamagneticresonanceimaging |