Abdominal Imaging

, Volume 30, Issue 3, pp 343–355

MR and optical approaches to molecular imaging

Invited update


With an increasing understanding of the molecular basis of disease, various new imaging targets have recently been defined that potentially allow for an early, sensitive, and specific diagnosis of disease or monitoring of treatment response. Different approaches to depict these molecular structures in vivo are currently being explored by the molecular imaging community. We briefly review methodologies for molecular imaging by magnetic resonance imaging and optical methods. Special emphasis is put on different contrast agent designs (e.g., targeted and smart probes). New technical developments in optical imaging are briefly discussed. In addition, current research results are put into a clinical perspective to elucidate the potential merits one might expect from this new research field.


Molecular imaging Magnetic resonance imaging Optical imaging Contrast media Amplification strategy Smart probes Abdominal imaging Review 


  1. 1.
    Weissleder, R, Mahmood, U 2001Molecular imagingRadiology219316333PubMedGoogle Scholar
  2. 2.
    Bremer, C, Ntziachristos, V, Weissleder, R 2003Optical-based molecular imaging: contrast agents and potential medical applicationsEur Radiol13231243PubMedGoogle Scholar
  3. 3.
    Brasch, RC, Li, KC, Husband, JE,  et al. 2000In vivo monitoring of tumor angiogenesis with MR imagingAcad Radiol7812823PubMedGoogle Scholar
  4. 4.
    Bremer, C, Mustafa, M, Bogdanov, A,Jr,  et al. 2003Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in miceRadiology226214220PubMedGoogle Scholar
  5. 5.
    Johnson, GA, Benveniste, H, Black, RD,  et al. 1993Histology by magnetic resonance microscopyMagn Reson Q9130PubMedGoogle Scholar
  6. 6.
    Smith, BR, Johnson, GA, Groman, EV, Linney, E 1994Magnetic resonance microscopy of mouse embryosProc Natl Acad Sci USA9135303533PubMedGoogle Scholar
  7. 7.
    Bogdanov, A, Matuszewski, L, Bremer, C,  et al. 2002Oligomerization of paramagnetic substrates results in signal amplification and can be used for MR imaging of molecular targetsMol Imaging11623CrossRefPubMedGoogle Scholar
  8. 8.
    Wickline, SA, Lanza, GM 2002Molecular imaging, targeted therapeutics, and nanoscienceJ Cell Biochem399097CrossRefGoogle Scholar
  9. 9.
    Lanza, GM, Yu, X, Winter, PM,  et al. 2002Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosisCirculation10628422847CrossRefPubMedGoogle Scholar
  10. 10.
    Brasch, RC, Gossmann, A, Helbich, TH,  et al. 2002Can a small-molecular gadolinium contrast agent be applied successfully with dynamic MRI to quantitatively define brain tumor microvascular responses to angiogenesis inhibition? Acad Radiol2S326S327CrossRefGoogle Scholar
  11. 11.
    Daldrup, H, Shames, DM, Wendland, M,  et al. 1998Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast mediaAJR171941949PubMedGoogle Scholar
  12. 12.
    Brasch, R, Turetschek, K 2000MRI characterization of tumors and grading angiogenesis using macromolecular contrast media: status reportEur J Radiol34148155CrossRefPubMedGoogle Scholar
  13. 13.
    Brasch, RC, Daldrup, H, Shames, D,  et al. 1998Macromolecular contrast media-enhanced MRI estimates of microvascular permeability correlate with histopathologic tumor gradeAcad Radiol1S2S5Google Scholar
  14. 14.
    Turetschek, K, Huber, S, Floyd, E,  et al. 2001MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlationRadiology218562569PubMedGoogle Scholar
  15. 15.
    Helbich, TH, Roberts, TP, Rollins, MD,  et al. 2002Noninvasive assessment of wound-healing angiogenesis with contrast-enhanced MRIAcad Radiol1 S145S147CrossRefGoogle Scholar
  16. 16.
    Roberts, TP, Turetschek, K, Preda, A,  et al. 2002Tumor microvascular changes to anti-angiogenic treatment assessed by MR contrast media of different molecular weightsAcad Radiol2S511S513CrossRefGoogle Scholar
  17. 17.
    Turetschek, K, Preda, A, Floyd, E,  et al. 2002MRI monitoring of tumor response to a novel VEGF tyrosine kinase inhibitor in an experimental breast cancer modelAcad Radiol2S519S520CrossRefGoogle Scholar
  18. 18.
    Turetschek, K, Preda, A, Floyd, E,  et al. 2003MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer modelEur J Nucl Med Mol Imaging30448455PubMedGoogle Scholar
  19. 19.
    Daldrup-Link, HE, Brasch, RC 2003Macromolecular contrast agents for MR mammography: current statusEur Radiol13354365PubMedGoogle Scholar
  20. 20.
    Padhani, AR 2002Dynamic contrast-enhanced MRI in clinical oncology: current status and future directionsJ Magn Reson Imaging16407422Google Scholar
  21. 21.
    Padhani, AR, Neeman, M 2001Challenges for imaging angiogenesisBr J Radiol74886890PubMedGoogle Scholar
  22. 22.
    Schellenberger, EA, Bogdanov, A,Jr, Hogemann, D,  et al. 2002Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRIMol Imaging1102107CrossRefPubMedGoogle Scholar
  23. 23.
    Kang, HW, Josephson, L, Petrovsky, A,  et al. 2002Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell cultureBioconjug Chem13122127CrossRefPubMedGoogle Scholar
  24. 24.
    Flacke, S, Fischer, S, Scott, MJ,  et al. 2001Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaquesCirculation10412801285PubMedGoogle Scholar
  25. 25.
    Winter, PM, Caruthers, SD, Kassner, A,  et al. 2003Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imagingCancer Res6358385843PubMedGoogle Scholar
  26. 26.
    Lanza, GM, Abendschein, DR, Yu, X,  et al. 2002Molecular imaging and targeted drug delivery with a novel, ligand-directed paramagnetic nanoparticle technologyAcad Radiol2 S330S331CrossRefGoogle Scholar
  27. 27.
    Winter, PM, Caruthers, SD, Yu, X,  et al. 2003Improved molecular imaging contrast agent for detection of human thrombusMagn Reson Med50411416CrossRefPubMedGoogle Scholar
  28. 28.
    Winter, PM, Morawski, AM, Caruthers, SD,  et al. 2003Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticlesCirculation10822702274CrossRefPubMedGoogle Scholar
  29. 29.
    Sipkins, DA, Cheresh, DA, Kazemi, MR,  et al. 1998Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imagingNat Med4623626CrossRefPubMedGoogle Scholar
  30. 30.
    Artemov, D, Mori, N, Ravi, R, Bhujwalla, ZM 2003Magnetic resonance molecular imaging of the HER-2/neu receptorCancer Res6327232727PubMedGoogle Scholar
  31. 31.
    Artemov, D, Mori, N, Okollie, B, Bhujwalla, ZM 2003MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticlesMagn Reson Med49403408CrossRefPubMedGoogle Scholar
  32. 32.
    Louie, AY, Huber, MM, Ahrens, ET,  et al. 2000In vivo visualization of gene expression using magnetic resonance imagingNat Biotechnol18321325CrossRefPubMedGoogle Scholar
  33. 33.
    Josephson, PJ, Weissleder, R 2001Magnetic nanosensors for the detection of oligonucleotide sequencesAngew Chem In Ed4032043206CrossRefGoogle Scholar
  34. 34.
    Perez, JM, Josephson, L, O’Loughlin, T,  et al. 2002Magnetic relaxation switches capable of sensing molecular interactionsNat Biotechnol20816820PubMedGoogle Scholar
  35. 35.
    Perez, JM, O’Loughin, T, Simeone, FJ,  et al. 2002DNA-based magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agentsJ Am Chem Soc12428562857CrossRefPubMedGoogle Scholar
  36. 36.
    Grimm, J, Perez, JM, Josephson, L, Weissleder, R 2004Novel nanosensors for rapid analysis of telomerase activityCancer Res64639643PubMedGoogle Scholar
  37. 37.
    Kircher, MF, Allport, JR, Graves, EE,  et al. 2003In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumorsCancer Res6368386846PubMedGoogle Scholar
  38. 38.
    Moore, A, Sun, PZ, Cory, D,  et al. 2002MRI of insulitis in autoimmune diabetesMagn Reson Med47751758CrossRefPubMedGoogle Scholar
  39. 39.
    Beckmann, N, Cannet, C, Fringeli-Tanner, M,  et al. 2003Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantationMagn Reson Med49459467CrossRefPubMedGoogle Scholar
  40. 40.
    Beckmann, N, Falk, R, Zurbrugg, S,  et al. 2003Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritisMagn Reson Med4910471055CrossRefPubMedGoogle Scholar
  41. 41.
    Daldrup-Link, HE, Rudelius, M, Oostendorp, RA,  et al. 2003Targeting of hematopoietic progenitor cells with MR contrast agentsRadiology228760767PubMedGoogle Scholar
  42. 42.
    Bulte, JW, Douglas, T, Witwer, B,  et al. 2002Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of cellular MR contrast agentsAcad Radiol2S332S335CrossRefGoogle Scholar
  43. 43.
    Lewin, M, Carlesso, N, Tung, CH,  et al. 2000Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cellsNat Biotechnol18410414CrossRefPubMedGoogle Scholar
  44. 44.
    Hill, JM, Dick, AJ, Raman, VK,  et al. 2003Serial cardiac magnetic resonance imaging of injected mesenchymal stem cellsCirculation10810091014CrossRefPubMedGoogle Scholar
  45. 45.
    Bulte, JW, Duncan, ID, Frank, JA 2002In vivo magnetic resonance tracking of magnetically labeled cells after transplantationJ Cereb Blood Flow Metab22899907CrossRefPubMedGoogle Scholar
  46. 46.
    Bulte, JW, Zhang, S, Gelderen, P,  et al. 1999Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelinationProc Natl Acad Sci USA961525615261CrossRefPubMedGoogle Scholar
  47. 47.
    Ntziachristos, V, Tung, CH, Bremer, C, Weissleder, R 2002Fluorescence molecular tomography resolves protease activity in vivoNat Med8756760CrossRefGoogle Scholar
  48. 48.
    Ntziachristos, V, Bremer, C, Graves, EE, Ripoll, J, Weissleder, R 2002In vivo tomographic imaging of near-infrared fluorescent probesMol Imaging18288CrossRefPubMedGoogle Scholar
  49. 49.
    Ntziachristos, V, Bremer, C, Weissleder, R 2003Fluorescence imaging with near-infrared light: new technological advances that enable in-vivo molecular imagingEur Radiol13195208PubMedGoogle Scholar
  50. 50.
    Nztiachristos, V, Tung, C, Bremer, C, Weissleder, R 2001Fluorescence-mediated tomography resolves protease activity in vivoNat Med8757760CrossRefGoogle Scholar
  51. 51.
    Ntziachristos, V, Yodh, AG, Schnall, M, Chance, B 2000Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancementProc Natl Acad Sci USA9727672772CrossRefPubMedGoogle Scholar
  52. 52.
    Weissleder, R, Ntziachristos, V 2003Shedding light onto live molecular targetsNat Med9123128CrossRefPubMedGoogle Scholar
  53. 53.
    Gao, X, Chan, WC, Nie, S 2002Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encodingJ Biomed Opt7532537CrossRefPubMedGoogle Scholar
  54. 54.
    Kim, S, Lim, YT, Soltesz, EG,  et al. 2004Near-infrared fluorescent type II quantum dots for sentinel lymph node mappingNat Biotechnol229397CrossRefPubMedGoogle Scholar
  55. 55.
    Lim, YT, Kim, S, Nakayama, A,  et al. 2003Selection of quantum dot wavelengths for biomedical assays and imagingMol Imaging25064CrossRefPubMedGoogle Scholar
  56. 56.
    Intes, X, Ripoll, J, Chen, Y,  et al. 2003In vivo continuous-wave optical breast imaging enhanced with Indocyanine GreenMed Phys3010391047CrossRefPubMedGoogle Scholar
  57. 57.
    Perlitz, CLK, Hauff, P, Wisniewski, S, Schirner, M 2002Molecular imaging of tumors using fluorescent dyes [abstract]Mol Imaging1184Google Scholar
  58. 58.
    Achilefu, S, Jimenez, HN, Dorshow, RB,  et al. 2002Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agentsJ Med Chem4520032015CrossRefPubMedGoogle Scholar
  59. 59.
    Becker, A, Hessenius, C, Licha, K,  et al. 2001Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligandsNat Biotechnol9327331CrossRefGoogle Scholar
  60. 60.
    Becker, A, Hessenius, C, Bhargava, S,  et al. 2000Cyanine dye labeled vasoactive intestinal peptide and somatostatin analog for optical detection of gastroenteropancreatic tumorsAnn NY Acad Sci921275278PubMedGoogle Scholar
  61. 61.
    Moon, LY, O’Loughlin, T, Tang, Y,  et al. 2003Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugateBioconjug Chem14539545CrossRefPubMedGoogle Scholar
  62. 62.
    Schellenberger, EA, Bogdanov, A,Jr, Petrovsky, A,  et al. 2003Optical imaging of apoptosis as a biomarker of tumor response to chemotherapyNeoplasia5187192PubMedGoogle Scholar
  63. 63.
    Kang, HW, Weissleder, R, Bogdanov, A,Jr 2002Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitroAmino Acids23301308CrossRefPubMedGoogle Scholar
  64. 64.
    Zaheer, A, Lenkinski, RE, Mahmood, A,  et al. 2001In vivo near-infrared fluorescence imaging of osteoblastic activityNat Biotechnol1911481154CrossRefPubMedGoogle Scholar
  65. 65.
    Ke, S, Wen, X, Gurfinkel, M,  et al. 2003Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenograftsCancer Res6378707875PubMedGoogle Scholar
  66. 66.
    Weissleder, R, Tung, CH, Mahmood, U, Bogdanov, A,Jr 1999In vivo imaging of tumors with protease-activated near-infrared fluorescent probesNat Biotechnol17375378CrossRefPubMedGoogle Scholar
  67. 67.
    Bremer, C, Bredow, S, Mahmood, U,  et al. 2001Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse modelRadiology221523529PubMedGoogle Scholar
  68. 68.
    Bremer, C, Tung, CH, Weissleder, R 2001In vivo molecular target assessment of matrix metalloproteinase inhibitionNat Med7743748CrossRefPubMedGoogle Scholar
  69. 69.
    Marten, K, Bremer, C, Khazaie, K,  et al. 2002Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in miceGastroenterology122406414PubMedGoogle Scholar
  70. 70.
    Bremer, C, Tung, C-H, Bogdanov, A, Weissleder, R 2002Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypesRadiology222814818PubMedGoogle Scholar
  71. 71.
    Weissleder, R, Moore, A, Mahmood, U,  et al. 2000In vivo magnetic resonance imaging of transgene expressionNat Med6351355CrossRefPubMedGoogle Scholar
  72. 72.
    Weissleder, R 1999Molecular imaging: exploring the next frontierRadiology212609614PubMedGoogle Scholar
  73. 73.
    Day, RN, Periasamy, A, Schaufele, F 2001Fluorescence resonance energy transfer microscopy of localized protein interactions in the living cell nucleusMethods25418CrossRefPubMedGoogle Scholar
  74. 74.
    Chalfie, M, Tu, Y, Euskirchen, G,  et al. 1994Green fluorescent protein as a marker for gene expressionScience263802805PubMedGoogle Scholar
  75. 75.
    Yang, M, Baranov, E, Jiang, P,  et al. 2000Whole-body optical imaging of green fluorescent protein-expressing tumors and metastasesProc Natl Acad Sci USA9712061211CrossRefPubMedGoogle Scholar
  76. 76.
    Moore, A, Marecos, E, Simonova, M,  et al. 1998Novel gliosarcoma cell line expressing green fluorescent protein: A model for quantitative assessment of angiogenesisMicrovasc Res56145153CrossRefPubMedGoogle Scholar
  77. 77.
    Moore, A, Sergeyev, N, Bredow, S, Weissleder, R 1998A model system to quantitate tumor burden in locoregional lymph nodes during cancer spreadInvasion Metastasis18192197CrossRefPubMedGoogle Scholar
  78. 78.
    Wang, W, Wyckoff, JB, Frohlich, VC,  et al. 2002Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profilingCancer Res6262786288Google Scholar
  79. 79.
    Hastings, JW 1996Chemistries and colors of bioluminescent reactions: a reviewGene173511CrossRefPubMedGoogle Scholar
  80. 80.
    Bhaumik, S, Gambhir, SS 2002Optical imaging of Renilla luciferase reporter gene expression in living miceProc Natl Acad Sci USA99377382CrossRefPubMedGoogle Scholar
  81. 81.
    Funovics, MA, Alencar, H, Su, HS,  et al. 2003Miniaturized multichannel near infrared endoscope for mouse imagingMol Imaging2350357CrossRefPubMedGoogle Scholar
  82. 82.
    Josephson, L, Kircher, MF, Mahmood, U,  et al. 2002Near-infrared fluorescent nanoparticles as combined MR/optical imaging probesBioconjug Chem13554560CrossRefPubMedGoogle Scholar
  83. 83.
    Kircher, MF, Mahmood, U, King, RS,  et al. 2003A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineationCancer Res6381228125PubMedGoogle Scholar
  84. 84.
    Harisinghani, MG, Barentsz, J, Hahn, PF,  et al. 2003Noninvasive detection of clinically occult lymph-node metastases in prostate cancerN Engl J Med34824912499PubMedGoogle Scholar
  85. 85.
    Mahmood, U, Tung, CH, Tang, Y, Weissleder, R 2002Feasibility of in vivo multichannel optical imaging of gene expression: experimental study in miceRadiology224446451PubMedGoogle Scholar
  86. 86.
    Fang, J, Shing, Y, Wiederschain, D,  et al. 2000Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor modelProc Natl Acad Sci USA9738843889PubMedGoogle Scholar
  87. 87.
    Folkman, J 1999Angiogenic zip code [news]Nat Biotechnol17749CrossRefPubMedGoogle Scholar
  88. 88.
    Edwards, DR, Murphy, G 1998Cancer. Proteases—invasion and more [news]Nature394527528CrossRefPubMedGoogle Scholar
  89. 89.
    Aparicio, T, Kermorgant, S, Dessirier, V,  et al. 1999Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in ratsCarcinogenesis2014451451CrossRefPubMedGoogle Scholar
  90. 90.
    Herszenyi, L, Plebani, M, Carraro, P,  et al. 1999The role of cysteine and serine proteases in colorectal carcinomaCancer8611351142CrossRefPubMedGoogle Scholar
  91. 91.
    Koblinski, JE, Ahram, M, Sloane, BF 2000Unraveling the role of proteases in cancerClin Chim Acta291113135CrossRefPubMedGoogle Scholar
  92. 92.
    McCarthy, K, Maguire, T, McGreal, G,  et al. 1999High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancerInt J Cancer844448CrossRefPubMedGoogle Scholar
  93. 93.
    Kanayama, H, Yokota, K, Kurokawa, Y,  et al. 1998Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancerCancer8213591366CrossRefPubMedGoogle Scholar
  94. 94.
    Davidson, B, Goldberg, I, Kopolovic, J,  et al. 1999MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma—a clinicopathologic study using immunohistochemistry and mRNA in situ hybridizationGynecol Oncol73372382CrossRefPubMedGoogle Scholar
  95. 95.
    Campo, E, Munoz, J, Miquel, R,  et al. 1994Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survivalAm J Pathol145301309PubMedGoogle Scholar
  96. 96.
    Emmert-Buck, MR, Roth, MJ, Zhuang, Z,  et al. 1994Increased gelatinase A (MMP-2) and cathepsin B activity in invasive tumor regions of human colon cancer samplesAm J Pathol14512851290PubMedGoogle Scholar
  97. 97.
    Khan, A, Krishna, M, Baker, SP, Banner, BF 1998Cathepsin B and tumor-associated laminin expression in the progression of colorectal adenoma to carcinomaMod Pathol11704708PubMedGoogle Scholar
  98. 98.
    Khan, A, Krishna, M, Baker, SP,  et al. 1998Cathepsin B expression and its correlation with tumor-associated laminin and tumor progression in gastric cancerArch Pathol Lab Med122172177PubMedGoogle Scholar
  99. 99.
    Murray, GI, Duncan, ME, O’Neil, P,  et al. 1996Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancerNat Med2461462CrossRefPubMedGoogle Scholar
  100. 100.
    Kuniyasu, H, Ellis, LM, Evans, DB,  et al. 1999Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinomaClin Cancer Res52533PubMedGoogle Scholar
  101. 101.
    Sakakibara, M, Koizumi, S, Saikawa, Y,  et al. 1999Membrane-type matrix metalloproteinase-1 expression and activation of gelatinase A as prognostic markers in advanced pediatric neuroblastomaCancer85231239CrossRefPubMedGoogle Scholar
  102. 102.
    Tung, CH, Gerszten, RE, Jaffer, FA, Weissleder, R 2002A novel near-infrared fluorescence sensor for detection of thrombin activation in bloodChembiochem3207211CrossRefPubMedGoogle Scholar
  103. 103.
    Chen, J, Tung, CH, Mahmood, U,  et al. 2002In vivo imaging of proteolytic activity in atherosclerosisCirculation10527662771CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Clinical RadiologyUniversity Hospital MuensterMünsterGermany
  2. 2.Interdisciplinary Center for Clinical Research Muenster (IZKF Muenster)MünsterGermany

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