View More View Less
  • 1 Center of Integrated Magnetic Resonance and Applied Research, National High Magnetic Field Laboratory, Tallahassee, FL, 32304, USA
  • | 2 Center of Nanomagnetics and Biotechnology, Florida State University, Tallahassee, Florida, 32304, USA
  • | 3 Amity Institute of Nanotechnology, Amity University UP, Noida, India, 201303
Restricted access

Abstract

Gadolinium-based magnetic resonance imaging (MRI) contrast agents cause undefined fibrosis in kidneys and skin damage. Magnetic resonance microimaging of rat skin and kidney was used first time to identify the physical factors modulating the gadolinium Omniscan®-induced fibrosis by protein targeting. A 500-MHz MR imaging was done to visualize fibrosis in gadolinium-treated animals. Cationic superparamagnetic iron oxide magnetoferritin (SPIOM) was injected in rat to target basement membrane (in rat kidney and different skin structures including epidermis glycolipids and dermis proteins. After MR imaging, excised rat skin and kidneys tissues were imaged by ex vivo 900 MHz MR microimaging to confirm renal fibrosis and skin epidermis thickening. The proton density-weighted images visualized micro details of skin structures and nephron territories while T2-weighted images showed better contrast of tissue structures in both skin and kidney. The gadolinium further enhanced the image contrast and targeted the proteins in renal basement membrane and viable proteins in epidermis. SPIOM enhanced the tissue contrast due to dephasing effect caused by SPIOM on structural changes in nephron and epidermis. Conclusion: Tissue membrane protein and chelate ligand group binding with gadolinium biophysical interaction at molecular level may develop fibrosis. SPIOM injection improved the dephased image contrast of different structures in both skin and nephrons. The epidermis thickening and nephrofibrosis changes may be associated with nephrogenic systemic fibrosis or fibrosing dermatopathy.

  • 1. M.A. Sieber P. Hubertus J. Walter W. Haider T. Frenzel H.J. Weinmann 2008 A preclinical study to investigate the development of nephrogenic systemic fibrosis: a possible role for gadolinium based contrast media Invest Radiol 43 65 75.

    • Search Google Scholar
    • Export Citation
  • 2. P. Yerram G. Saab P.R. Karuparthi M.R. Hayden R. Khanna 2007 Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure — role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate Clin J Am Soc Nephrol 2 258 263.

    • Search Google Scholar
    • Export Citation
  • 3. T. Grobner 2006 Gadolinium — a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21 1104 1108.

    • Search Google Scholar
    • Export Citation
  • 4. S. Piera-Velazquez N. Louneva J. Fertala P.J. Wermuth F.D. Galdo S.A. Jimenez 2010 Persistent activation of dermal fibroblasts from pateinets with gadolinium associated nephrogenic systemic fibrosis Ann Rheum Dis 69 2017 2023.

    • Search Google Scholar
    • Export Citation
  • 5. S. Becker S. Walter O. Witzke B. Wilde U. Hillen D. Napieralski A. Kreuter P. Altmeyer G. Scieren A. Dual L.C. Rump A. Kribben 2010 The German registry for nephrogenic systemic fibrosis: findings from 23 patients Clin Nephrol 73 6 426 430.

    • Search Google Scholar
    • Export Citation
  • 6. A. Kribben O. Witzke U. Hillen J. Barkhausen A.E. Daul R. Erbel 2009 Nephrogenic systemic fibrosis: pathogenesis, diagnosis and therapy J Am Coll Cardiol 53 1621 1628.

    • Search Google Scholar
    • Export Citation
  • 7. D.R. Martin S.K. Krishnamoorthy B. Kalb K.N. Salman P. Sharma J.D. Carew P.A. Martin A.B. Chapman G.L. Ray C.P. Larsen T.C. Pearson 2010 Decreased incidence of NSF in patients on dialysis after changing gadolinium contrast-enhanced MRI protocols J Magn Reson Imaging 31 2 440 446.

    • Search Google Scholar
    • Export Citation
  • 8. A.S. Boyd J.A. Zic J.L. Abraham 2007 Gadolinium deposition in nephrogenic fibrosing dermopathy J Am Acad Dermatol 56 1 27 30.

  • 9. P. Marckmann L. Skov K. Rossen et al.2006 Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrastenhanced magnetic resonance imaging J Am Soc Nephrol 17 2359 2362.

    • Search Google Scholar
    • Export Citation
  • 10. D.R. Broome M.S. Girguis P.W. Baron A.C. Cottrell I. Kjellin G.A. Kirk 2007 Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned AJR Am J Roentgenol 188 2 586 592.

    • Search Google Scholar
    • Export Citation
  • 11. E.A. Sadowshi L.K. Bennett M.R. Chan A.L. Wentland A.L. Garrett R.W. Garrett A. Djamali 2007 Nephrogenic systemic fibrosis: Risk factors and incidence estimation Radiol 243 143 157.

    • Search Google Scholar
    • Export Citation
  • 12. A. Deo M. Fogel S.E. Cowper 2007 Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure Clin J Am Soc Nephrol 2 2 264 267.

    • Search Google Scholar
    • Export Citation
  • 13. A. Khurana V.M. Runge M. Narayanan J.F. Greene A.E. Nickel 2007 Nephrogenic Systemic Fibrosis: A review of 6 cases temporally related to gadodiamide injection (Omniscan) Invest Radiol 42 2 139 145.

    • Search Google Scholar
    • Export Citation
  • 14. W.A. High R.A. Ayers J. Chandler G. Zito S.E. Cowper 2007 Gadolinium is detectable within tissue of patients with nephrogenic systemic fibrosis J Am Acad Dermatol 56 21 26.

    • Search Google Scholar
    • Export Citation
  • 15. Y.L. Lim H.Y. Lee S.C. Low L.P. Chan N.S. Goh S.M. Pang 2007 Possible role of gadolinium in nephrogenic systemic fibrosis: report of two cases and review of the literature Clin Exp Dermatol 32 4 353 358.

    • Search Google Scholar
    • Export Citation
  • 16. J.J. Nikken G.P. Krestin 2007 MRI of kidney-state of art Eur Radiol 17 2780 2793.

  • 17. R. Sharma 2010 Gadolinium toxicity: epidermis thickness measurement by magnetic resonance imaging at 500 MHz Skin Res Tech 16 3 339 353.

    • Search Google Scholar
    • Export Citation
  • 18. P. Caravan 2009 Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action Acc Chem Res 42 7 851 862.

    • Search Google Scholar
    • Export Citation
  • 19. P. Caravan B. Das S. Dumas F.H. Epstein P.A. Helm V. Jacques S. Koerner et al.2007 Collagen targeted MRI contrast agent for molecular imaging of fibrosis Angew Chem Int Ed 46 8171 8173.

    • Search Google Scholar
    • Export Citation
  • 20. P. Caravan 2006 Strategies for increasing the sensitivity of gadolinium based MRI contrast agents Chem Soc Rev 35 512 523.

  • 21. P. Caravan C.T. Farrar L. Frullano R. Uppal 2009 Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium and manganese based T1 contrast agents Contrast Media Mol Imaging 4 89 100.

    • Search Google Scholar
    • Export Citation
  • 22. S.A. Jimenez C.M. Artlett N. Sandorfi et al.2004 Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin Arthritis Rheum 50 2660 2666.

    • Search Google Scholar
    • Export Citation
  • 23. T. Matsuoka S. Aiyama K.I. Kikuchi K. Koike 2000 Uptake of cationized ferritin by the epithelium of the main excretory duct of the rat submandibular gland Anat Rec 258 10 113.

    • Search Google Scholar
    • Export Citation
  • 24. C.S. Geninatti A. Barge E. Battistini C. Cabella S. Coluccia D. Longo V. Mainero G. Tarone S. Aime 2005 Magnetic resonance imaging visualization of targeted cells by the internalization of supramolecular adducts formed between avidin and biotinylated Gd3+ chelates J Inorg Chem 10 78 86.

    • Search Google Scholar
    • Export Citation
  • 25. R. Sharma 2009 Microimaging of hairless rat skin by magnetic resonance at 900 MHz Magn Reson Imaging 27 2 240 255.

  • 26. R. Sharma 2011 Gadolinium induced fibrosis testing by protein targeting assay and nanoparticles: magnetic resonance microimaging of skin and kidneys J. Walker Methods in Molecular Biology Humana Press USA.

    • Search Google Scholar
    • Export Citation
  • 27. K.M. Bennett H. Zhou J.P. Sumner S.J. Dodd N. Bouraoud K. Doi R.A. Star A.P. Koretsky 2008 MRI of the basement membrane using charged nanoparticles as contrast agents Magn Reson Med 60 564 574.

    • Search Google Scholar
    • Export Citation
  • 28. R.A. Brooks R.B. Goldfarb J.W.M. Bulte P. Aisen 1998 Relaxometry and magnetometry of ferritin Magn Reson Med 40 227 235.

  • 29. E.H. Kim Y. Ahn H.S. Lee 2007 Biomedical applications of superparamagnetic iron oxide nanoparticles encapsulated within chitosan J Alloy Comp 434–435 633 636.

    • Search Google Scholar
    • Export Citation
  • 30. J.F. Bertram 1995 Analyzing renal glomeruli with the new stereology Int Rev Cytol 161 111 172.

  • 31. C. Kucher X. Xu T. Oasha et al.2005 Histopathologic comparison of naphrogenic fibrosing dermatopathy and scleromyxedema J Cutan Pathol 32 484 490.

    • Search Google Scholar
    • Export Citation
  • 32. N. Serkova T.F. Fuller J. Klawitter C.E. Freise C.U. Niemann 2005 1HNMR based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants Kidney International 67 1142 1151.

    • Search Google Scholar
    • Export Citation
  • 33. N. Ortonne D. Lipsker F. Chantrel et al.2004 Presence of CD45RO+ CD34+ cells with collagen synthesis activity in nephrogenic fibrosing dermopathy: a new pathogenic hypothesis Br J Dermatol 150 1050 1052.

    • Search Google Scholar
    • Export Citation
  • 34. L. Knesplova G.P. Krestin 1998 Magnetic resonance in the assessment of renal function Eur Radiol 8 201 211.

  • 35. E.R. Nirendorf T.M. Grist F.T. Lee Jr. P.C. Bazy G.E. Santyr 1998 Rapid in vivo measurement of single kidney extraction fraction and glomerular filtration rate with MR imaging Radiol 206 791 798.

    • Search Google Scholar
    • Export Citation
  • 36. A.J. Huang V.S. Lee H. Rusinek 2004 Functional renal MR imaging Magn Reson Imaging Clin N Am 12 469 486.

  • 37. R.J. Chalifour R.W. McLaughlin L. Lavoie C. Morissette N. Tremblay M. Boulé P. Sarazin D. Stéa D. Lacombe P. Tremblay F. Gervais 2003 Stereoselective interactions of peptide inhibitors with the betaamyloid peptide J Biol Chem 278 37 34874 34881.

    • Search Google Scholar
    • Export Citation
  • 38. Y.Z. Wadghiri E.M. Sigurdsson M. Sadowski J.I. Elliott Y. Li H. Scholtzova C.Y. Tang G. Aguinaldo et al.2003 Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging Magn Reson Med 50 2 293 302.

    • Search Google Scholar
    • Export Citation
  • 39. M.P. Lowe 2004 Activated MR contrast agents Curr Pharm Biotechnol 5 6 519 528.

  • 40. J.L. Bridot A.C. Faure S. Laurent C. Riviere C. Billotey B. Hiba M. Janier V. Josserand et al.2007 Hybrid gadolinium oxide nanoparticles: multicontrast agents for in vivo imaging J Am Chem Soc 129 5076 5084.

    • Search Google Scholar
    • Export Citation
  • 41. F.K. Kalman M. Woods P. Caravan P. Jurek M. Spiller G. Tircso R. Kiraly E. Brucher A.D. Sherry 2007 Potentiometric and relaxometric properties of a gadolinium based MRI contrast agent for sensing tissue pH Inorg Chem 46 13 5260 5270.

    • Search Google Scholar
    • Export Citation
  • 42. A.L. Nivorozhkin A.F. Kolodziej P. Caravan M.T. Greenfield R.B. Lauffer T.J. McMurry 2001 Enzyme activated Gd3+ magnetic resonance imaging contrast agents with a prominent receptorinduced magnetization enhancement Angew Chem Int Ed 40 15 2903 2906.

    • Search Google Scholar
    • Export Citation
  • 43. Y. Fukuda I. Ohashi K. Hanafusa et al.2000 Anisotropic diffusion in kidney: apparent diffusion coefficient measurement for clinical use JMRI 11 156 160.

    • Search Google Scholar
    • Export Citation
  • 44. J.H.M. Chan E.Y.K. Tsui S.H. Luk et al.2001 MR diffusion weighted imaging of kidney: differentiation between hydronephrosis and pyonephrosis Clin Imaging 25 110 113.

    • Search Google Scholar
    • Export Citation
  • 45. J.W. Bulte T. Douglas S. Mann R.B. Frankel B.M. Moskowitz R.A. Brooks et al.1994 Magnetoferritin: characterization of novel superparamagnetic MR contrast agent JMRI 4 497 505.

    • Search Google Scholar
    • Export Citation
  • 46. S. Geninatti Chric B. Bussolati L. Tei C. Grange G. Esposito S. Lanzardo G. Camussi et al.2006 Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe Cancer Res 66 9196 9201.

    • Search Google Scholar
    • Export Citation
  • 47. D. Baumann M. Rudin 2000 Quantitative assessment of rat kidney function by measuring the clearance of the contrast agent Gd(DOTA) using dynamic MRI MRI 18 587 595.

    • Search Google Scholar
    • Export Citation
  • 48. H. Kobayashi S. Kawamoto H. Yasuda X. Hu M.V. Knopp M.W. Brechbiel O.L. Choyke et al.2004 Polyamine dendrimer based MRI contrast agents for functional kidney imaging to diagnose acute renal failure J Magn Reson Imaging 20 512 518.

    • Search Google Scholar
    • Export Citation
  • 49. Sharma R : Nanoparticles that facilitate imaging of biological tissue and methods of forming the same. US Patent Issue No. 0220434 (2009).

    • Search Google Scholar
    • Export Citation
  • 50. D. Yang Q. Ye M. Williams Y. Sun C.-C. Hu Tom D.S. William J.M.F. Moura C. Ho 2001 USPIO enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys Magn Reson Med 46 1152 1163.

    • Search Google Scholar
    • Export Citation
  • 51. D.L. Buckley A.E. Shurrab C.M. Cheung A.P. Jones H. Mamtora P.A. Kalra 2006 Measurement of single kidney function using dynamic contrast-enhanced MRI: comparison of two models in human subjects J Magn Reson Imaging 24 1117 1123.

    • Search Google Scholar
    • Export Citation
  • 52. C.C. Notle-Ernsting J. Tacke G.B. Adam et al.2001 Diuretic enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echoplanar imaging Eur Radiol 11 18 27.

    • Search Google Scholar
    • Export Citation
  • 53. M. Ritt R. Janka M.P. Schneider P. Martirosian J. Hornegger W. Bautz M.R. Uder E. Schmieder 2010 Measurement of kidney perfusion by magnetic resonance imaging: comparison of MRI with arterial spin labeling to para-aminohippuric acid plasma clearance in male subjects with metabolic syndrome Nephrology Dialysis Transplantation 25 4 1126 1133.

    • Search Google Scholar
    • Export Citation
  • 54. A.C. Parsons Y. Gil D.J. Sheehan O.P. Sangüeza C.S. Greenberg D.C. Sane 2007 Transglutaminases: The Missing Link in Nephrogenic Systemic Fibrosis Am J Dermatopathol 29 5 433 526.

    • Search Google Scholar
    • Export Citation
  • 55. H. Ersoy F.J. Rybicki 2007 Biochemical safety profiles of gadoliniumbased extracellular contrast agents and nephrogenic systemic fibrosis J Magn Reson Imaging 26 1190 1197.

    • Search Google Scholar
    • Export Citation
  • 56. Macqueen DB : Gadolinium exchanged carboxylate alumoxanes as MRI contrast agents. WO 113556 (2006) and PCT/US 014291 (2006).

  • 57. J.L. Zhang E.E. Sigmund H. Chandarana H. Rusinek Q. Chen H. Vivier B. Taouli V.S. Lee 2010 Variability of renal apparent diffusion coefficients: Limitations of monoexponential model for diffusion quantification Radiol 254 3 783 792.

    • Search Google Scholar
    • Export Citation
  • 58. F. Artunc S. Yildiz C. Rossi A. Boss H. Dittmann H.P. Schlemmer T. Risler N. Heyne 2010 Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging Nephrol Dial Transplant 25 6 1986 1991.

    • Search Google Scholar
    • Export Citation

2019  
Scimago
H-index
11
Scimago
Journal Rank
0,220
Scimago
Quartile Score
Medicine (miscellaneous) Q3
Scopus
Cite Score
155/133=1,2
Scopus
Cite Score Rank
General Medicine 199/529 (Q2)
Scopus
SNIP
0,343
Scopus
Cites
206
Scopus
Documents
23

 

Interventional Medicine and Applied Science
Language English
Size  
Year of
Foundation
2009
Publication
Programme
changed title
Volumes
per Year
 
Issues
per Year
 
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2061-1617 (Print)
ISSN 2061-5094 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2021 0 0 0
Jul 2021 2 0 0
Aug 2021 4 0 0
Sep 2021 10 0 0
Oct 2021 11 0 0
Nov 2021 3 0 0
Dec 2021 1 0 0