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DOI: 10.1148/radiol.2292030409
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(Radiology 2003;229:608-610.)

Letters to the Editor

Proper Handling of Research with Invalid Conclusions [letter]

Yicheng Ni, MD, PhD, Steven Dymarkowski, MD, Feng Chen, MD, Jan Bogaert, MD, PhD and Guy Marchal, MD, PhD

Biomedical Imaging and Magnetopharmaceutical Research, Department of Radiology, University Hospitals K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium. e-mail: yicheng.ni@med.kuleuven.ac.be

Editor:

For the past decade, we have pioneered the research on necrosis-avid contrast agents, including bis-gadolinium mesoporphyrin (Gadophrin-2; Schering, Berlin, Germany), especially with regard to potential applications for myocardial viability assessment with cardiac magnetic resonance (MR) imaging (1–15). Despite a variety of other experimental findings published later by many other groups, our initially defined extraordinary necrosis avidity of these contrast agents has consistently been proved to be a reliable standard for differentiation between viable and nonviable myocardium (16–25).

By performing an experiment with some inappropriate methods, however—namely, an exceptionally low intravenous dose at 0.01 mmol per kilogram of body weight administered too early at 90 minutes postischemically, Dr Choi and colleagues (26) concluded that occlusive myocardial infarction could not be detected accurately at Gadophrin-2–enhanced MR imaging, a finding contradictory to that in other studies (3,8,24). This work (26) with overlooked defects was published in a previous issue of Radiology.

Accordingly, in a letter to the editor, we pointed out these defects with detailed reasoning and obtained a serious response from the original authors (27). By conducting an extra experiment as we suggested, the authors appeared to be convinced that the above-mentioned conclusion in their article (26) indeed seems to be invalid (27). Surprisingly, in an article by the same group published in a more recent issue of Radiology (25), it is stated on page 744 that "our previous results also demonstrated that occluded infarcted myocardium did not show contrast enhancement and could not be distinguished from normal myocardium with this contrast agent" (28). These authors still cited this misleading finding without acknowledging the defects we indicated and with which they agreed. In our opinion, this statement should not have been made in this article. Therefore, it is important for us to write again to raise the issue because we believe this to be essential for making accurate scientific progress.

REFERENCES

  1. Ni Y, Marchal G, Petré C, et al. Metalloporphyrin enhanced magnetic resonance imaging of acute myocardial infarction (abstr). Circulation 1994; 90:I-468.
  2. Ni Y, Marchal G, Yu J, et al. Localization of metalloporphyrin induced "specific" enhancement in experimental liver tumors: a comparison between MRI, microangiographic and histologic findings. Acad Radiol 1995; 2:687-699.[CrossRef][Medline]
  3. Marchal G, Ni Y, Herijgers P, et al. Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by magnetic resonance imaging. Eur Radiol 1996; 6:2-8.[CrossRef][Medline]
  4. Ni Y, Marchal G, Herijgers P, et al. Paramagnetic metalloporphyrins: from enhancers for malignant tumors to markers of myocardial infarcts. Acad Radiol 1996; 3:S395-S397.
  5. Ni Y, Petré C, Miao Y, et al. Magnetic resonance imaging–histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis. Invest Radiol 1997; 32:770-779.[CrossRef][Medline]
  6. Ni Y, Miao Y, Bosmans H, et al. Evaluation of interventional liver tumor ablation with Gd-mesoporphyrin enhanced magnetic resonance imaging (abstr). Radiology 1997; 205(P):319.[Free Full Text]
  7. Marchal G, Ni Y.. Use of porphyrin-complex or expanded porphyrin-complex as an infarction localization diagnosticum. US patent 6 013 241 January 11, 2000.
  8. Herijgers P, Laycock SK, Ni Y, et al. Localization and determination of infarct size by Gd-mesoporphyrin enhanced MRI in dogs. Int J Cardiac Imaging 1997; 13:499-507.[CrossRef][Medline]
  9. Ni Y, Pislaru C, Bosmans H, et al. Validation of intracoronary delivery of metalloporphyrin as an in vivo "histochemical staining" for myocardial infarction with MR imaging. Acad Radiol 1998; 5(suppl 1):S37-S41.
  10. Ni Y. Myocardial viability. In: Bogaert J, Duerinckx AL, Rademakers FE, eds. Magnetic resonance of the heart and great vessels: clinical applications. Berlin, Germany: Springer, 1998; 113-132.
  11. Pislaru S, Ni Y, Pislaru C, et al. Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent. Circulation 1999; 99:690-696.[Abstract/Free Full Text]
  12. Ni Y, Pislaru C, Bosmans H, et al. Intracoronary delivery of Gd-DTPA and Gadophrin-2 for determination of myocardial viability with MR imaging. Eur Radiol 2001; 11:876-883.[CrossRef][Medline]
  13. Ni Y, Adzamli K, Miao Y, et al. MRI contrast enhancement of necrosis by MP-2269 and Gadophrin-2 in a rat model of liver infarction. Invest Radiol 2001; 36:97-103.[CrossRef][Medline]
  14. Ni Y, Cresens E, Adriaens P, et al. Necrosis avid contrast agents: introducing nonporphyrin species. Acad Radiol 2002; 9(suppl 1):S98-S101.
  15. Ni Y, Cresens E, Adriaens P, et al. Exploring multifunctional features of necrosis avid contrast agents. Acad Radiol 2002; 9(suppl 2):S488-S490.
  16. Stillman AE, Wilke N, Jerosch-Herold M. Myocardial viability. Radiol Clin North Am 1999; 37:361-378.[CrossRef][Medline]
  17. Saeed M, Bremerich J, Wendland MF, et al. Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats. Radiology 1999; 213:247-257.[Abstract/Free Full Text]
  18. Lim TH, Choi SII. MRI of myocardial infarction. J Magn Reson Imaging 1999; 10:686-693.[CrossRef][Medline]
  19. Wendland MF, Saeed M, Lund G, Higgins CB. Contrast-enhanced MRI for quantification of myocardial viability. J Magn Reson Imaging 1999; 10:694-702.[CrossRef][Medline]
  20. Choi SI, Choi SH, Kim ST, et al. Irreversibly damaged myocardium at MR imaging with a necrotic tissue-specific contrast agent in a cat model. Radiology 2000; 215:863-868.[Abstract/Free Full Text]
  21. Saeed M, Lund G, Wendland MF, Bremerich J, Weinmann H, Higgins CB. Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation 2001; 103:871-876.[Abstract/Free Full Text]
  22. Jeong AK, Choi SI, Kim DH, et al. Evaluation by contrast-enhanced MR imaging of the lateral border zone in reperfused myocardial infarction in a cat model. Korean J Radiol 2001; 2:21-27.[Medline]
  23. Lund GK, Higgins CB, Wendland MF, Watzinger N, Weinmann HJ, Saeed M. Assessment of Nicorandil therapy in ischemic myocardial injury by using contrast-enhanced and functional MR imaging. Radiology 2001; 221:676-682.[Abstract/Free Full Text]
  24. Barkhausen J, Ebert W, Heyer C, Debatin JF, Weinmann HJ. Acute and chronic myocardial infarction: definition of enhancement profiles based on Magnevist and necrosis-specific Gadophrin-III (abstr). Radiology 2001; 221(P):587.[Abstract/Free Full Text]
  25. Lee SS, Goo HW, Park SB, et al. MR imaging of reperfused myocardial infarction: comparison of necrosis-specific and intravascular contrast agents in a cat model. Radiology 2003; 226:739-747.[Abstract/Free Full Text]
  26. Choi SH, Lee SS, Choi SII, et al. Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model. Radiology 2001; 220:436-440.[Abstract/Free Full Text]
  27. Ni Y, Dymarkowski S, Chen F, et al. Occlusive myocardial infarction enhanced or not enhanced with necrosis-avid contrast agents at MR imaging (letter). Radiology 2002; 225:603-605.[Free Full Text]

Drs Lim and Lee respond:

Tae-Hwan Lim, MD and Seung Soo Lee, MD

Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, West Wing 2, Room 279, 1611 North West 12th Avenue, Miami, FL 33136. e-mail: thlim@amc.seoul.kr

Regarding the question of whether occluded myocardial infarction can be detected with necrosis-avid contrast agent (bis-gadolinium mesoporphyrin, Gadophyrin-2; Schering)–enhanced MR imaging, we already presented our opinion in the response to the letter to the editor submitted by Dr Ni and colleagues (1): "bis-gadolinium mesoporphyrins–enhanced MR imaging delineated infarcted myocardium as a rimlike pattern in a cat model of occlusive MI [myocardial infarction] in which enough ischemic time for evolution of myocardial necrosis was allowed and the proper amount of the contrast medium was used."

We mistakenly included the sentence, "Furthermore, our previous results also demonstrated that occluded infarcted myocardium did not show contrast enhancement and could not be distinguished from normal myocardium with this contrast agent" in the discussion section of our recent publication (2).

REFERENCES

  1. Ni Y, Dymarkowski S, Chen F, et al. Occlusive myocardial infarction enhanced or not enhanced with necrosis-avid contrast agents at MR imaging (letter). Radiology 2002; 225:603-605.
  2. Lee SS, Goo HW, Park SB, et al. MR imaging of reperfused myocardial infarction: comparison of necrosis-specific and intravascular contrast agents in a cat model. Radiology 2003; 226:739-747.




This Article
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