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Evaluation of drug candidates: Efficacy readouts during lead optimization

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Imaging in Drug Discovery and Early Clinical Trials

Part of the book series: Progress in Drug Research ((PDR,volume 62))

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References

  1. Wohnsland F, Faller B (2001) High-throughput permeability pH profile and highthroughput alkane/water log P with artificial membranes. J Med Chem 44: 923–930

    Article  PubMed  CAS  Google Scholar 

  2. Phelps ME (2004) PET: molecular imaging and its biological applications. Springer, New York

    Google Scholar 

  3. Rudin M (2005) Molecular imaging — Basic principles and applications to biomedical research. Imperial College Press (London)

    Google Scholar 

  4. Jiang Q, Chopp M, Zhang AG, Knight RA, Jacobs N, Windham JP, Peck D, Ewing JR, Welch KMA (1997) The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat. J Neurol Sci 145: 15–23

    Article  PubMed  CAS  Google Scholar 

  5. Rudin M, Baumann D, Ekatodramis D, Stirnimann R, McAllister KH, Sauter A (2001) MRI analysis of the changes in apparanet water diffusion coefficient, T2 relaxation time, and cerebral blood flow and volume in the temporal evolution o cerebral infarction following permanent middle cerebral artery occlusion in rats. Exp Neurol 169: 56–63

    Article  PubMed  CAS  Google Scholar 

  6. Laurent D, Wasvary J, Yin J, Rudin M, Pellas TC, O’Byrne E (2001) Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging. Magn Reson Imag 19: 1279–1286

    Article  CAS  Google Scholar 

  7. Bashir A, Gray ML, Hartke J, Burstein D (1999) Nondestructive imaging of human cartilage glycosaminoglycan concentration depletion in articular cartilage. Magn Reson Med 41: 857–865

    Article  PubMed  CAS  Google Scholar 

  8. Laurent D, Wasvary J, Rudin M, O’Byrne E, Pellas T (2003) In vivo assessment of proteoglycan content in articular cartilage of the goat knee. Magn Reson Med 49: 1037–1046

    Article  PubMed  CAS  Google Scholar 

  9. Beckmann N, Bruttel K, Joergensen J, Rudin M, Schuurman H (1996) Magnetic resonance imaging for the evaluation of rejection of a kidney allograft in the rat. Transpl Int 9: 175–183

    Article  PubMed  CAS  Google Scholar 

  10. Rudin M, Sauter A (1992) In vivo NMR in pharmaceutical research. Magn Reson Imag 10: 723–731

    Article  CAS  Google Scholar 

  11. Rudin M, Beckmann N, Porszasz R, Reese T, Sauter A (1999) In vivo magnetic resonance in pharmaceutical research: current status and perspectives. NMR Biomed 12: 69–97

    PubMed  CAS  Google Scholar 

  12. Manning, WJ, Wei JY, Fossel ET, Burstein D (1990) Measurement of left ventricular mass in rats using electrocardiogramm-gated magnetic resonance imaging. Am J Physiol 258: H1181–1186

    PubMed  CAS  Google Scholar 

  13. Rudin M, Pedersen B, Umemura K, Zierhut W (1991) Determination of rat heart morphology and function in vivo in two models of cardiac hypertrophy by means of magnetic resonance imaging. Bas Res Cardiol 86: 165–174

    CAS  Google Scholar 

  14. Watson PJ, Carpenter TA, Hall LD, Tyler JA (1996) Cartilage swelling and loss in a spontaneous model of osteoarthritis visualized by magnetic resonance imaging. Osteoarthritis Cartilage 4: 197–207

    Article  PubMed  CAS  Google Scholar 

  15. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6: 371–388

    Article  PubMed  CAS  Google Scholar 

  16. Rudin M, Sauter A (1992) Measurement of reaction rates in vivo using magnetization transfer techniques. In: M Rudin, J Seelig (eds): NMR Basic Principles and Progress, Vol 27: In vivo Magnetic Resonance Spectroscopy II.). Springer-Verlag, Berlin, Heidelberg, 257–293

    Google Scholar 

  17. Podo F (1999) Tumour phospholipids metabolism. NMR Biomed 12: 413–439

    Article  PubMed  CAS  Google Scholar 

  18. Tofts PS (1997) Modeling tracer kinetcis in dynamic GdDTPA MR imaging. J Magn Reson Imag 7: 91–101

    CAS  Google Scholar 

  19. Reivich M, Alavi A, Wolf A, Fowler J, Russel J, Arnett C, MacGregor RR, Shiue CY, Atkins H, Anand A et al (1985) Glucose metabolic kinetic model parameter determination in humans: the lumoed constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cerebr Blood Flow Metab 5: 179.192

    Google Scholar 

  20. Meier P, Zierler KL (1954) On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 6: 731–744

    PubMed  CAS  Google Scholar 

  21. Rausch M, Scheffler K, Rudin, M, Radü E (2000) Analysis of input functions from different arterial branches with gamma variate functions and cluster analysis for quantitative blood volume measurements. Magn Reson Imag 18: 1235–1243

    Article  CAS  Google Scholar 

  22. Detre JA, Leigh JS, Williams DS, Koretsky AP (1992) Perfusion imaging. Magn Reson Med 23: 37–45

    PubMed  CAS  Google Scholar 

  23. Zhang W, Silva AC, Williams DS, Koretsky AP (1992) Measurement of brain perfusion by volume-localized NMR spectroscopy using inversion of arterial water spins: accounting for transit time and cross-relaxation. Magn Reson Med 25: 362–371

    PubMed  CAS  Google Scholar 

  24. Ogawa S, Lee TM, Kay AR, Tank DW. (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Nat Acad Sci USA 87: 9868–9872

    PubMed  CAS  Google Scholar 

  25. Scheffler K, Seifritz E, Haselhorst R, Bilecen D (1999) Titration of the BOLD effect: separation and quantitation of blood volume and oxygenation changes in the human cerebral cortex during neuronal activation and ferumoxide infusion. Magn Reson Med 42: 829–836

    Article  PubMed  CAS  Google Scholar 

  26. Dijkhuizen RM, Singhal AB, Mandeville JB, Wu O, Halpern EF, Finklestein SP, Rosen BR, Lo EH (2003) Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study. J Neurosci 23: 510–517

    PubMed  CAS  Google Scholar 

  27. Sauter A, Reese T, Pórszász R, Baumann D, Rausch M, Rudin M (2002) Recovery of function in cytoprotected cerebral cortex in rat stroke model assessed by functional MRI. Magn Reson Med 47: 759–765

    Article  PubMed  Google Scholar 

  28. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916

    PubMed  CAS  Google Scholar 

  29. Mierisova S, Ala-Korpela M (2001) MR spectroscopy quantitation: a review of frequency domain methods. NMR Biomed 14: 247–259

    PubMed  CAS  Google Scholar 

  30. de Beer R, van Ormondt D (1992) Analysis of NMR data using time domain fitting procedures. In: M Rudin, J Seelig (eds): NMR Basic Principles and Progress, Vol 27: In vivo Magnetic Resonance Spectroscopy II. Springer-Verlag Berlin Heidelberg, 201–248

    Google Scholar 

  31. Rudin M, Sauter A (1992) In vivo phosphorus-31 NMR: Potential and limitations. In: M Rudin, J Seelig (eds): NMR Basic Principles and Progress, Vol 28: In vivo Magnetic Resonance Spectroscopy III. Springer-Verlag, Berlin Heidelberg, 161–188

    Google Scholar 

  32. Bittl JA, Ingwall JS (1985) Reaction rates of creatine kinases and ATP synthesis in the isolated rat heart. J Biol Chem 26: 3512–2517

    Google Scholar 

  33. Rudin M, Sauter A (1989) Dihydropyridine calcium antagonists reduce the consumption of high-energy phosphates in the rat brain. A study using combine 31P/1H magnetic resonance spectroscopy and 31P saturation transfer. J Pharm Exp Ther 251: 700–706

    CAS  Google Scholar 

  34. Sauter A, Rudin M (1993) Determination of creatine kinase kinetic parameters in rat brain by NMR magnetization transfer: Correlation with brain function. J Biol Chem 268: 13166–13171

    PubMed  CAS  Google Scholar 

  35. Shields AF, Grierson JR, Kozawa SM, Zheng M (1996) Development of labelled thymidine analogues for imaging tumor proliferation. Nucl Med Biol 23: 17–22

    PubMed  CAS  Google Scholar 

  36. Laverman P, Boerman OC, Corstens FHM, Oyen WJG (2002) Fluorinated amino acids for tumour imaging with positron emission tomography. Eur J Nucl Med 29: 681–690

    Article  CAS  Google Scholar 

  37. Hara T, Kosaka N, Shinoura N, Kondo T (1998) PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 39: 990–995

    PubMed  CAS  Google Scholar 

  38. DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN, Polascik TJ, Price DT (2000) Synthesis and evaluation of 18F labeled choline as an oncologic tracer for positron emission tomography: initial findings with prostate cancer. Cancer Res 61: 110–117

    Google Scholar 

  39. Hacke W, Brott T, Caplan L, Meier D, Fieschi C, von Kummer R, Donnan G, Heiss WD, Wahlgren NG, Spranger M et al (1999) Thrombolysis in acute ischemic stroke: controlled trials and clinical experience. Neurology 53Suppl 4: S3–14

    PubMed  CAS  Google Scholar 

  40. Leira EC, Adams HP (1999) Management of acute ischemic stroke. Clin Geriatr Med 15: 701–720

    PubMed  CAS  Google Scholar 

  41. Siesjö BK (1978) Brain energy metabolism. John Wiley & Sons, New York

    Google Scholar 

  42. Hossman KA (1982) Treatment of experimental cerebral ischemia. J Cerebr Blood Flow Metabl 2: 275–297

    Google Scholar 

  43. Rother J, deCrespigny AJ, D’Arcueil H, Moseley ME (1996) MR detection of cortical spreading depression immediately after focal ischemia in the rat. J Cerebr Blood Flow Metab 16: 214–220

    CAS  Google Scholar 

  44. Busch E, Gyngell ML, Eis M, Hoehn-Berlage M, Hossman KA (1996) Potassium-induced spreading depressions during focal cerebral ischemia in rats: contribution to lesion growth assessed by diffusion — weighted NMR and biochemical imaging. J Cerebr Blood Flow Metab 16: 1090–1099

    CAS  Google Scholar 

  45. Banasiak KJ, Xia Y, Haddad GG (2000) Mechanisms underlying hypoxia-induced neuronal apoptosis. Progr Neurobiol 16: 202–213

    Google Scholar 

  46. Del Zoppo GJ, Ginis I, Hallenbrck JM, Iadecola C, Wang X, Feuerstein GZ (2000) Inflammation in stroke: putative role of cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol 10: 95–112

    PubMed  Google Scholar 

  47. Schellinger PD, Warrach S (2004) Therapeutic time window of thrombolytic therapy following stroke. Curr Atheroscler Rep 6: 288–294

    PubMed  Google Scholar 

  48. Sauter A, Rudin M (1986) Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging. Stroke 17: 1228–1234

    PubMed  CAS  Google Scholar 

  49. Germano IM, Bartkowsky HM, Berry I, Moseley M, Brant-Zawadski M, Pitts LH (1986) Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia. Acta Radiol Suppl Stockh 369: 49–52

    PubMed  CAS  Google Scholar 

  50. Sauter A, Rudin M (1995) Strain-dependent drug effects in rat middle cerebral artery occlusion model of stroke. J Pharm Exp Ther 274: 1008–1013

    CAS  Google Scholar 

  51. Sauer D, Martin P, Allegrini PR, Bernasconi R, Amacker H, Fagg GE (1992) Differing effects of alpha-difluormethylornithin and CGP40116 on polyamine levels and infarct volume in a rat model of focal cerebral ischemia. Neurosci Lett 141: 131–135

    Article  PubMed  CAS  Google Scholar 

  52. Urwyler S, Campbell E, Fricker G, Jenner P, Lemaire M, McAllister K, Neijt HC, Park CK, Perkins M, Rudin M et al (1996) Biphenyl-derivatives of 2-amino-7-phophono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists. II. Pharmacological characterization in vivo. Neuropharmacol 35: 655–669

    CAS  Google Scholar 

  53. Qiu H, Hedlund LW, Gewalt SL, Benveniste H, Bare TM, Johnson GA (1997) Progression of a focal ischemic lesion in rat brain during treatment with a novel glycine/NMDA antagonist: an in vivo three-dimensional diffusion-weighted MR microscopy study. J Magn Reson Imaging 7: 739–744

    PubMed  CAS  Google Scholar 

  54. Petty MA, Neumann-Haefelin C, Kalisch J, Sarhan S, Wettstein JG, Juretschke HP (2003) in vivo neuroprotective effects of ACEA 1021 confirmed by magnetic resonance imaging in ischemic stroke. Eur J Pharmacol 474: 53–62

    Article  PubMed  CAS  Google Scholar 

  55. Buchan AM, Li HS, Cho S, Pulsinelli WA (1991) Blockade of AMPA receptors prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats. Neurosci Lett 132: 1358–1362

    Article  Google Scholar 

  56. Nellgard B, Wieloch T (1992) Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following transient severe cerebral ischemia. J Cereb Blood Flow Metab 12: 2–11

    PubMed  CAS  Google Scholar 

  57. Muller TB, Haraldseth O, Jones RA, Sebastiani G, Lindboe CF, Unsgard G, Oksendal AN (1995) Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model. Stroke 26: 1453–1458

    PubMed  CAS  Google Scholar 

  58. Wiessner C, Sauer D, Alaimo D, Allegrini PR (2000) Protective effects of casapase inhibitors in models for cerebral ischemia in vitro and in vivo. Cell Mol Biol 46: 53–62

    PubMed  CAS  Google Scholar 

  59. Deckwerth TL, Adams LM, Wiessner C, Allegrini PR, Rudin M, Sauter A, Hengerer B, Sayers RO, Rovelli G, Aja T et al (2001) Longterm protection of brain tissue from cerebral ischemia by peripherally administered peptidomimetic caspase inhibitors. Drug Dev Res 52: 579–586

    Article  CAS  Google Scholar 

  60. Li PA, Uchino H, Elmer E, Siesjö BK (1997) Amelioration by cyclosorine A of brain damage following 5 or 10 min of ischemia in rats subjected to preischemic hyperglycemia. Brain Res 753: 133–140

    Article  PubMed  CAS  Google Scholar 

  61. Sharkey J, Crawford JH, Butcher SP, Marston HG (1996) Tacrolimus (FK506) ameliorates skilled motor deficits produced by middle cerebral artery occlusion in trats. Stroke 27: 2282–2286

    PubMed  CAS  Google Scholar 

  62. Bochelen D, Rudin M, Sauter A (1999) Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic/reperfusion injury. J Pharm Exp Ther 288: 653–659

    CAS  Google Scholar 

  63. Hughes PM, Allegrini PR, Rudin M, Perry VH, Mir AK, Wiessner C (2002) Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab 22: 308–317

    PubMed  CAS  Google Scholar 

  64. Modo M, Stroemer RP, Tang E, Patel S, Hodges H (2002) Effects of implantation site of stem cell grafts on behavioral recovery from stroke damage. Stroke 33: 2270–2278

    Article  PubMed  Google Scholar 

  65. Mattsson B, Sorensen JC, Zimmer J, Johansson BB (1997) Neuronal grafting to experimental neocortical infracts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments. Stroke 28: 1225–1231

    PubMed  CAS  Google Scholar 

  66. Reese T, Bochelen D, Sauter A, Beckmann N, Rudin M (1999) Magnetic resonance angiography of the rat cerebrovascular system without the use of contrast agents. NMR Biomed 12: 189–196

    Article  PubMed  CAS  Google Scholar 

  67. Villringer A, Rosen BR, Belliveau JW, Ackerman JR, Lauffer RB, Buxton RD, Chao YS, Wedeen VJ, Brady TJ (1988) Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects. Magn Reson Med 6: 164–174

    PubMed  CAS  Google Scholar 

  68. Rudin M, Sauter A (1991) Noninvasive determination of regional cerebral blood flow in rats using dynamic imaging with Gd(DTPA). Magn Reson Med 22: 32–46

    PubMed  CAS  Google Scholar 

  69. Roussel SA, van Bruggen N, King MD, Houseman J, Williams SR, Gadian DG (1994) Monitoring the initial expansion of focal ischaemic changes by diffusion-weighted MRI using a remote controlled method of occlusion. NMR Biomed 7: 21–28

    PubMed  CAS  Google Scholar 

  70. Moseley ME, Vendland MF, Kucharczyk J.(1991) Magnetic resonance imaging of diffusion and perfusion. Top Mag Reson Imag 3: 50–67

    CAS  Google Scholar 

  71. Mintorovitch J, Moseley ME, Chileuitt L, Shimizu H, Cohen Y, Weinstein, PR (1991) Comparison of diffusion-and T2-weighted MRI for the early detection of cerebral ischemia and reperfusion in rats. Magn Reson Med 18: 39–50

    PubMed  CAS  Google Scholar 

  72. van Dorsten FA, Hata R, Maeda K, Franke C, Eis M, Hossmann KA, Hoehn M (1999) Diffusion-and perfusion-weighted MR imaging of transient focal cerebral ischaemia in mice. NMR Biomed 12: 525–534

    Article  PubMed  Google Scholar 

  73. van Lookeren Campagne M, Verheul JB, Nicolay K, Balazs R. (1994) Early evolution and recovery from excitotoxic injury in the neonatal rat brain: a study combining magnetic resonance imaging, electrical impedance, and histology. J Cereb Blood Flow Metab 14: 1011–1023

    PubMed  Google Scholar 

  74. Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ (1990) Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 175: 494–498

    PubMed  CAS  Google Scholar 

  75. Rausch M, Sauter A, Fröhlich J, Neubacher U, Radü EW, Rudin M (2001) Dynamic pattern of USPIO enhancement can be observed in macrophages after ischemic brain damage. Magn Reson Med 46: 1018–1022

    Article  PubMed  CAS  Google Scholar 

  76. Rausch M, Baumann D, Neubacher U, Rudin M (2002) In-vivo visualization of phagocytotic cells in rat brains after transient ischemia by USPIO. NMR Biomed 15: 278–283

    Article  PubMed  CAS  Google Scholar 

  77. Sauter A, Rudin M (1987) Effects of calcium antagonists on high-energy phosphates in ischemic rat brain measured by 31P NMR spectroscopy. Magn Reson Med 4: 1–8

    PubMed  CAS  Google Scholar 

  78. Delpy DT, Gordon RE, Hope PL, Parker D, Reynolds EOR, Shaw D, Whitehead MD (1982) Noninvasive investigation of cerebral ischemia by phosphorus magnetic resonance. Pediatrics 70: 310–313

    PubMed  CAS  Google Scholar 

  79. Prichard JW, Alger JR, Behar KL, Petroff OAC, Shulman RG (1983) Cerebral metabolic studies in vivo by 31P NMR. Proc Natl Acad Sci USA 80: 2748–2751

    PubMed  CAS  Google Scholar 

  80. Forsen S, Hoffman RA (1963) Study of moderately rapid chemical exchange reaction by means of nuclear magnetic double resonance. J Chem Phys 40: 1189–1196

    Google Scholar 

  81. Koretsky AP, Wang S, Klein MP, James TL, Weiner MW (1986) 31P NMR saturation transfer measurements of phosphorus exchange reactions in rat heart and kidney in situ. Biochemistry 25: 77–84

    Article  PubMed  CAS  Google Scholar 

  82. Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 3: 123–131

    Google Scholar 

  83. Buonanno FS, Pykett IL, Brady TJ, Vielma J, Burt CT, Goldman MR, Hinshaw WS, Pohost GM, Kistler JP (1983) Proton NMR imaging in experimental ischemic infarction. Stroke 14: 173–177

    PubMed  Google Scholar 

  84. Allegrini PR, Sauer D (1992) Application of magnetic resonance imaging to the measurement of neurodegeneration in rat brain: MRI data correlate strongly with histology and enzymatic analysis. Magn Reson Imag 10: 773–778

    Article  CAS  Google Scholar 

  85. van der Toorn A, Sykova E, Dijkhurzen RM, Vorisek I, Vargova L, Skobisova E, van Lookeren-Campagne M, Reese T, Nicolay K (1996) Dynamic changes in water ADC, energy metabolism Magn Reson Med 36: 52–60

    PubMed  Google Scholar 

  86. Davis D, Ulatowski J, Eleff S, Izuta M, Mori S, Shungu D, van Zijl PC (1994) Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain. Magn Reson Med 31: 454–460

    PubMed  CAS  Google Scholar 

  87. Hasegawa Y, Fisher M, Latour LL, Dardzinski BJ, Sotak CH (1994) MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia. Neurology 44: 1484–1490

    PubMed  CAS  Google Scholar 

  88. Neumann-Haefelin T, Wittsack HJ, Wenserski F, Siebler M, Seity RJ, Mödder U, Freund HL (1999) Diffusion-and perfusion-weighted MRI: the DWI/PWI mismatch region in acute stroke. Stroke 30: 1591–1597

    PubMed  CAS  Google Scholar 

  89. Reese T, Porszasz R, Baumann D, Bochelen D, Boumezbeur F, McAllister KH, Sauter A, Bjelke B, Rudin B (2000) Cytoprotection does not preserve brain functionality in rats during acute post-stroke phase despite evidence of non-infarction provided by MRI. NMR Biomed 13: 361–370

    PubMed  CAS  Google Scholar 

  90. Rausch M, Hiestand P, Foster CA, Baumann D, Cannet C, Rudin M (2004) Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: clinical implications for ultrasmall superparamagnetic iron oxideenhanced magnetic resonance imaging. J Magn Reson Imag 20: 16–24

    Article  Google Scholar 

  91. Hoehn M, Küstermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Föcking M, Heinz A, Hescheler J, Fleischmann BK et al (2002) Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci USA 99: 16267–16272

    Article  PubMed  CAS  Google Scholar 

  92. Kim DE, Schellingerhout D, Ishii K, Shah K, Weissleder R (2004) Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke 35: 952–957

    PubMed  Google Scholar 

  93. Benveniste H, Einstein G, Kim KR, Hulette C, Johnson GA (1999) Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy. Proc Natl Acad Sci USA 96: 14079–14084

    Article  PubMed  CAS  Google Scholar 

  94. Rudin M, Mueggler T, Allegrini P.R, Baumann D, Rausch M. (2003b) Characterization of CNS disorders and evaluation of therapy using structural and functional MRI. Anal Bioanal Chem 377: 973–981

    PubMed  CAS  Google Scholar 

  95. Zhang J, Yarowsky P, Gordon MN, Di Carlo G, Munireddy S, van Zijl PC, Mori S. (2004) Detection of amyloid plaques in mouse models of Alzheimer’s disease by magnetic resonance imaging. Magn Reson Med 51: 452–457

    PubMed  Google Scholar 

  96. Jack CR Jr, Petersen RC, Xu YC, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Waring SC, Tangalos EG, Kokmen E (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52: 1397–1403

    PubMed  Google Scholar 

  97. Wadghiri YZ, Sigurdsson EM, Sadowski M, Elliott JI, Li Y, Scholtzova H, Tang CY, Aguinaldo G, Pappolla M, Duff K et al (2003) Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med 50: 293–302

    Article  PubMed  CAS  Google Scholar 

  98. Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, Cole GM, Small GW, Huang SC, Barrio JR (2001) Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci 21: RC189

    PubMed  CAS  Google Scholar 

  99. Hintersteiner M, Frey P, Kinzy W, Kneuer R, Neumann U, Rudin M, Staufenbiel M, Wiederhold KH, Gremlich HU (2005) In vivo detection of amyloid deposits by nearinfrared fluorescence imaging using a novel oxazine derivative as contrast agent. Nature Biotechnolog 23: 577–583

    CAS  Google Scholar 

  100. Parvathy S, Davies P, Haroutunian V, Purohit DP, Davis KL, Mohs RC, Park H, Moran TM, Chan JY, Buxbaum JD (2001) Correlation between Aßx-40-, Aßx-42-, and Aßx-43-containing amyloid plaques and cognitive decline. Arch Neuro 58: 2025–2032

    CAS  Google Scholar 

  101. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA et al (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 94: 13287–13292

    Article  PubMed  CAS  Google Scholar 

  102. Sturchler-Pierrat C, Staufenbiel M (2000) Pathogenic mechanisms of Alzheimer’s disease analyzed in the APP23 transgenic mouse model. Ann NY Acad Sci 920: 134–139

    PubMed  CAS  Google Scholar 

  103. Kelly PH, Bondolfi L, Hunziker D, Schlecht HP, Carver K, Maguire E, Abramowski D, Wiederhold KH, Sturchler-Pierrat C, Jucker M et al (2003) Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging 24: 365–378

    Article  PubMed  CAS  Google Scholar 

  104. Van Dam D, D’Hooge R, Staufenbiel M, Van Ginneken C, Van Meir F, De Deyn PP (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 17: 388–396

    PubMed  Google Scholar 

  105. Helpern JA, Lee SP, Falangola MF, Dyakin VV, Bogart A, Ardekani B, Duff K, Branch C, Wisniewski T, de Leon MJ et al (2004) MRI assessment of neuropathology in a transgenic mouse model of Alzheimer’s disease. Magn Reson Med 51: 794–798

    Article  PubMed  Google Scholar 

  106. Müggler T, Meyer-Luehmann M, Rausch M, Staufenbiel M, Jucker M, Rudin M (2004) Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis. Eur J Neurosci 20: 811–817

    Google Scholar 

  107. Beckmann N, Schuler A, Mueggler T, Meyer EP, Wiederhold KH, Staufenbiel M, Krucker T (2003) Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer’s disease. J Neurosci 23: 8453–8459

    PubMed  CAS  Google Scholar 

  108. Müggler T, Sturchler-Pierrat C, Baumann D, Rausch M, Staufenbiel M, Rudin M (2002) Dynamic CBV imaging in amyloid precursor protein transgenic mice. J Neuroscience 22: 7218–7224

    Google Scholar 

  109. Müggler T, Baumann D, Rausch M, Staufenbiel M, Rudin M (2003) Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer’s disease. J Neurosci 23: 8231–8236

    Google Scholar 

  110. Burgermeister P, Calhoun ME, Winkler DT, Jucker M (2000) Mechanisms of cerebrovascular amyloid deposition. Lessons from mouse models. Ann NY Acad Sci 903: 307–316

    PubMed  CAS  Google Scholar 

  111. Winkler DT, Bondolfi L, Herzig MC, Jann L, Calhoun ME, Wiederhold KH, Tolnay M, Staufenbiel M, Jucker M (2001) Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. J Neurosci 21: 1619–1627

    PubMed  CAS  Google Scholar 

  112. Graves EE, Ripoll J, Weissleder R, Ntziachristos V (2003) A submillimeter resolution fluorescence molecular imaging system for small animal imaging. Med Phys 30: 901–911

    Article  PubMed  CAS  Google Scholar 

  113. Dawson J, Miltz W, Mir AK, Wiessner C (2003) Targeting monocyte chemoattractant protein-1 signalling in disease. Expert Opin Ther Targets 7: 35–48

    Article  PubMed  CAS  Google Scholar 

  114. Lehrmann E, Christensen T, Zimmer J, Diemer NH, Finsen B (1997)Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion. J Comp Neurol 386: 461–476

    Article  PubMed  CAS  Google Scholar 

  115. Feuerstein G, Wang X, Barone F (1998) The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation 5:143–149

    Article  PubMed  CAS  Google Scholar 

  116. Hemmer B, Archelos JJ, Hartung HP (2002) New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci 3: 291–301

    Article  PubMed  CAS  Google Scholar 

  117. Barkhof F, van Walderveen M (1999) Characterization of tissue damage in multiple sclerosis by nuclear magnetic resonance. Philos Trans R Soc Lond B Biol Sci 354: 1675–1686

    PubMed  CAS  Google Scholar 

  118. Boneschi FM, Rovaris M, Comi G, Filippi M (2004) The use of magnetic resonance imaging in multiple sclerosis: lessons learned from clinical trials. Mult Scler 10: 341–347

    Article  PubMed  Google Scholar 

  119. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M (2001) Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 70: 311–317

    Article  PubMed  CAS  Google Scholar 

  120. Gold R, Hartung HP, Toyka KV (2000) Animal models for autoimmune demyelinating disorders of the nervous system. Mol Med Today 6: 88–91

    PubMed  CAS  Google Scholar 

  121. Hawkins CP, Munro PM, MacKenzie F, Kesselring J, Tofts PS, du Boulay EP, Landon DN, McDonald WI (1990) Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. Brain 113 (Pt 2): 365–378

    PubMed  Google Scholar 

  122. Tofts PS, Kermode AG (1991) Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17: 357–367

    PubMed  CAS  Google Scholar 

  123. Veldhuis WB, Floris S, van der Meide PH, Vos IM, de Vries HE, Dijkstra CD, Bar PR, Nicolay K (2003) Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption. J Cereb Blood Flow Metab 23: 1060–1069

    PubMed  CAS  Google Scholar 

  124. Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14: 57–64

    Article  PubMed  CAS  Google Scholar 

  125. Graham SJ, Henkelman RM (1997) Understanding pulsed magnetization transfer. J Magn Reson Imaging 7: 903–912

    PubMed  CAS  Google Scholar 

  126. ’t Hart BA, Vogels J, Bauer J, Brok HP, Blezer E (2004) Non-invasive measurement of brain damage in a primate model of multiple sclerosis. Trends Mol Med 2004 10: 85–91

    PubMed  Google Scholar 

  127. Rausch M, Hiestand P, Baumann D, Cannet C, Rudin M (2003) MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE. Magn Reson Med 50: 309–314

    Article  PubMed  CAS  Google Scholar 

  128. Dousset V, Delalande C, Ballarino L, Quesson B, Seilhan D, Coussemacq M, Thiaudiere E, Brochet B, Canioni P, Caille JM (1999) In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance. Magn Reson Med 41: 329–333

    Article  PubMed  CAS  Google Scholar 

  129. Dousset V, Doche B, Petry KG, Brochet B, Delalande C, Caille JM (2002) Correlation between clinical status and macrophage activity imaging in the central nervous system of rats. Acad Radiol 9Suppl 1: S156–S159

    PubMed  Google Scholar 

  130. Dousset V, Gomez C, Petry KG, Delalande C, Caille JM (1999) Dose and scanning delay using USPIO for central nervous system macrophage imaging. MAGMA 8: 185–189

    PubMed  CAS  Google Scholar 

  131. Barber PA, Foniok T, Kirk D, Buchan AM, Laurent S, Boutry S, Muller RN, Hoyte L, Tomanek B, Tuor UI (2004) MR molecular imaging of early endothelial activation in focal ischemia. Ann Neurol 56: 116–120

    Article  PubMed  CAS  Google Scholar 

  132. Sipkins DA, Gijbels K, Tropper FD, Bednarski M, Li KC, Steinman L (2000) ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging. J Neuroimmunol 104: 1–9

    Article  PubMed  CAS  Google Scholar 

  133. Damadian R. (1971) Tumor detection by nuclear magnetic resonance. Science 171: 1151–1153

    PubMed  CAS  Google Scholar 

  134. Siegel R, Tolesvai L, Rudin M (1988) Partial inhibition of the growth of transplanted Dunning rat prostate tumors with the longacting somatostatin analogue sandostatin (SMS 201–995) Cancer Res. 48: 4651–4655

    PubMed  CAS  Google Scholar 

  135. Furr BJ (1996) The development of Casodex (bicalutamide): preclinical studies. Eur Urol 29(Suppl 2): 83–95

    PubMed  Google Scholar 

  136. Rudin M, Briner U, Doepfner W (1988) Quantitative magnetic resonance imaging of estradiol-induced pituitary hyperplasia in rats. Magn Reson Med 7: 285–291

    PubMed  CAS  Google Scholar 

  137. Qin Y, Van Cauteren M, Osteaux M, Schally, AV, Willems G (1992) Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. Cancer Res 51: 6025–6030

    Google Scholar 

  138. Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263: 8350–8358

    PubMed  CAS  Google Scholar 

  139. van Eijkeren ME, Thierens H, Seuntjens J, Goethals P, Lemahieu I, Strijckmans K (1996) Kinetics of [methyl-11C]thymidine in patients with squamous cell carcinoma of the head an neck. Acta Oncol 35: 737–741

    Article  PubMed  Google Scholar 

  140. Van der Borght T, Labar D, Pauwels S, Lambotte L (1991) Production of [2-11C]thymidine for quantification of cellular proliferation with PET. Appl Radiat Isot 42: 103–104

    Google Scholar 

  141. Mankoff DA, Shields AF, Link JM, Graham MM, Muzi M, Peterson LM, Eary JF, Krohn KA (1999) Kinetic analysis of 2-[11C]thymidine PET imaging studies: validation studies. J Nucl Med 40: 614–624

    PubMed  CAS  Google Scholar 

  142. Shields AF, Grierson JR, Kozawa SM, Zheng M (1996) Development of labeled thymidine analogs for imaging tumor proliferation. Nucl Med Biol 23: 17–22

    PubMed  CAS  Google Scholar 

  143. Carnochan P, Brooks R (1999) Radiolabelled 5’-iodo’2’deoxyuridine: a promising alternative to [18F]-2-fluoro-deoxy-D-glucose for PET studies of early response to anticancer treatment. Nucl Med Biol 26: 667–672

    PubMed  CAS  Google Scholar 

  144. Sato K, Kameyama M, Ishiwata K, Katakura R, Yoshimoto T (1992) Metabolic changes of glioma following chemotherapy: An experimental study using four PET tracers. J Neuro-Oncol 14: 81–89

    Article  CAS  Google Scholar 

  145. Miyagawa T, Oku T, Uehara H, Desay R, Beattie B, Tjuvajew j. Blasberg R (1998) ‘Facilitated’ amino acid transport is upregulated in brain tumors. J Cerebr Blood Flow Metab 18: 500–509

    CAS  Google Scholar 

  146. Busch H, Davis JR, Honig GR, Anderson DC, Nair PV, Nyhan WL (1995) The uptake of a variety of amino acids into nuclear proteins of tumors and other tissues. Cancer Res 19: 1030–1039

    Google Scholar 

  147. Coenen HH, Kling P, Stocklin G (1989) Cerebral metabolism of L-[2-18F]fluorotyrosine. J Nucl Med 30: 1867–1372

    Google Scholar 

  148. Negendank WG (1992) Studie of human tumors by MRS: a review. NMR Biomed 5: 303–324

    PubMed  CAS  Google Scholar 

  149. Hara T, Kosaka N, Kishi H (1998) PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 39: 990–995

    PubMed  CAS  Google Scholar 

  150. Price DT, Coleman RE, Liao RP, Robertson CN, Polscik TJ, DeGrado TR (2002) Comparison of [18F]fluorocholine and [18F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urology 168: 273–280

    Google Scholar 

  151. Warburg O, Wind F, Negalein E (1927) The metabolism of tumours in the body. J Physiol 8: 519–530

    CAS  Google Scholar 

  152. Semenza GL (1999) Regulation of mammalian O2 homeostatsis by hypoxia-inducible factor 1. Ann Rev Cell Dev Biol 15: 551–578

    CAS  Google Scholar 

  153. Dang CV, Semenza GL (1999) Oncogenic alterations in metabolism. Trend Biochem Sci 24: 68–72

    PubMed  CAS  Google Scholar 

  154. Wahl RL, Zasadny K, Helvie M, Hutchins GD, Weber B, Cody R (1993) Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 11: 2101–2111

    PubMed  CAS  Google Scholar 

  155. Schelling M, Avril N, Nahrig J, Kuhn W, Römer W, Sattler D, Werner M, Dose J, Jänicke F, Graeff H, Schwaiger M (2000) Positron emission tomography using fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 18: 1689–1695

    PubMed  CAS  Google Scholar 

  156. Stroobants S, Goeminne J, Seegers M, Dimitrijevic S, Dupont P, Nuyts J, Martens M, van der Borne B, Cole P, Sciot R et al (2003) 18f Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Gleevec ®). Eur J Cancer 39: 2012–2020

    Article  PubMed  CAS  Google Scholar 

  157. Kaiser WA (1883) MR mammography. Radiologie 33: 292–299

    Google Scholar 

  158. Tofts PS and Kermode AG (1991) Measurement of the blood-brain barrier permeability and leakage space using dynamic MR Imaging: 1. Fundamental concepts. Magn Reson Med 17: 357–367

    PubMed  CAS  Google Scholar 

  159. Rudin M, Beckmann N, Sauter A (1997) Analysis of tracer transit in rat brain after carotid artery and femoral vein administration using linear system theory. Magn Reson Imag 15: 551–558

    Article  CAS  Google Scholar 

  160. Drevs J, Müller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt H, Konerding MA, Allegrini PR, Wood J, Hennig J et al (2002) PTK787/ZK 222584, a specific vascular endothelial growth factor receptor tyrosine kinases inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res 62: 4015–4022

    PubMed  CAS  Google Scholar 

  161. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF (1993) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53: 4727–4735

    PubMed  CAS  Google Scholar 

  162. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380: 435–439

    Article  PubMed  CAS  Google Scholar 

  163. Brasch R, Pham C, Shames D, Roberts T, van Dijke K, van Bruggen N, Mann J, Ostrowitzki S, Melnyk O (1997) Assessment of tumor angiogenesis using macromolecular MRE imaging contrast media. J Magn Reson Imag 7: 68–74

    CAS  Google Scholar 

  164. Rudin M, McSheehy PMJ, Allegrini PR, Kindler-Baumann D, Bequet M, Brecht K, Brueggen J, Ferretti S, Schaeffer F, Schnell C, Wood J (2005) PTK787 / ZK222584, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, reduces uptake of the contrast agent GdDOTA by murine orthotopic B16/BL6 melanoma tumours and inhibits their growth in vivo. NMR Biomed 18: 308–321

    Article  PubMed  CAS  Google Scholar 

  165. Morgan B, Thomas AL, Drevs J, Hennig J, Buchert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L et al (2003) Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol 21: 3955–3964

    Article  PubMed  CAS  Google Scholar 

  166. Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, Green DR (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182: 1545–1556

    Article  PubMed  CAS  Google Scholar 

  167. Fadok VA, de Cathelineau A, Daleke DL, Henson PM, Bratton DL (2001) Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts. J Biol Chem, 276: 1071–1077

    Article  PubMed  CAS  Google Scholar 

  168. Koopman G, Reutelingsperger CPM, Kuijten GAM, Keehnen RMJ, Pals ST, van Oers MHJ (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84: 1415–1420

    PubMed  CAS  Google Scholar 

  169. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, Kopiwoda S, Abrams MJ, Darkes M, Robbins RC et al (1998) In vivo detection and imaging of phosphatidylserin expression during programmed cell death. Proc Natl Acad Sci USA 95: 6349–6354

    Article  PubMed  CAS  Google Scholar 

  170. Zhao M, Beauregard DA, Loizou L, Davletov B, Brindle KM (2001) Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 7: 1241–1244

    Article  PubMed  CAS  Google Scholar 

  171. Dumont EA, Reutelingsperger CP, Smits JF, Daemen MJ, Doevendans PA, Wellens HJ, Hofstra L (2001) Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart. Nat Med 7: 1352–1355

    Article  PubMed  CAS  Google Scholar 

  172. Petrovsky A, Schellenberger E, Josephson L, Weissleder R, Bogdanov A (2003) Near-infrared gluorescent imaging of tumor apoptosis. Cancer Res 63: 1936–1942

    PubMed  CAS  Google Scholar 

  173. Schellenberger EA, Bogdanov A Jr, Petrovsky A, Ntziachristos N, Weissleder R, Josephson L (2003) Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy. Neoplasia 5: 187–192

    PubMed  CAS  Google Scholar 

  174. Hammill AK, Uhr JW, Scheuermann RH (1999) Annexin V staining due to loss of membrane asymmetry can be reversible and precede commitment to apoptotic cell death. Exp Cell Res 251: 16–21

    Article  PubMed  CAS  Google Scholar 

  175. Laxman B, Hall DE, Bhojani MS, Hamstra DA, Chevenert TL, Ross BD, Rehemtulla A (2002) Noninvasive real-time imaging of apoptosis. Proc Natl Acad Sci USA 99: 16551–16555

    Article  PubMed  CAS  Google Scholar 

  176. Williams SNO, Anthony ML, Brindle KM (1998) Induction of apoptosis in two mammalian cell lines results in increased levels of fructose-1,6-bisphosphate and CDP-choline as determined by 31P MRS. Magn Reson Med 40: 411–420

    PubMed  CAS  Google Scholar 

  177. Hakumäki JM, Brindle KM (2003) Techniques: Visualizing apoptosis using nuclear magnetic resonance. Trends Pharm Sci 24: 146–149

    PubMed  Google Scholar 

  178. Chevenert TL, McKeever PE, Ross BD (1997) Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging. Clin Cancer Res 3: 1467–1466

    Google Scholar 

  179. Chevenert TL, Stegman LD, Taylor JMG, Robertson PL, Greenberg HS, Rehemtulla A, Ross BD (2000) Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J Natl Cancer Inst 92: 2029–2036

    Google Scholar 

  180. Tung CH, Mahmood U, Bredow S, Weissleder R (2000) In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. Cancer Res 60: 4953–4958

    PubMed  CAS  Google Scholar 

  181. Mahmood U, Tung CH, Bogdanov A, Weissleder R (1999) Near-infrared optical imaging of protease activity for tumor detection. Radiology 213: 866–870

    PubMed  CAS  Google Scholar 

  182. Bremer C, Tung CH, Weissleder R (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 7: 743–748

    Article  PubMed  CAS  Google Scholar 

  183. Bouvet M, Wang J, Nardin SR, Nassirpour N, Yang M, Baranov E, Jiang P, Moossa AR, Hoffman RM (2000) Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model. Cancer Res 62: 1534–1540

    Google Scholar 

  184. Rehemtulla A, Stegman LD, Cardozo SJ, Gupta S, Hall DE, Contag CH, Ross BD (2000) Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2: 491–495

    Article  PubMed  CAS  Google Scholar 

  185. Gambhir SS, Hershman HR, Cherry SR, Barrio JR, Satyamurthy N, Toyokuni T, Phelps ME, Larson SM, Balatoni J, Finn R et al (2000) Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2: 118–138

    Article  PubMed  CAS  Google Scholar 

  186. Barck KH, Lee WP, Diehl LJ, Ross J, Gribling P, Zhang Y, Nguyen K, van Bruggen N, Hurst S, Carano RA (2004), Quantification of cortical bone loss and repair for therapeutic evaluation in collagen-induced arthritis, by micro-computed tomography and automated image analysis. Arthritis Rheum 50: 3377–3386

    Article  PubMed  Google Scholar 

  187. Morenko BJ, Bove SE, Chen L, Guzman RE, Juneau P, Bocan TM, Peter GK, Arora R, Kilgore KS (2004) In vivo micro computed tomography of subchondral bone in the rat after intra-articular administration of monosodium iodoacetate. Contemp Top Lab Anim Sci 43: 39–43

    PubMed  CAS  Google Scholar 

  188. Ford NL, Thornton MM, Holdsworth DW (2003) Fundamental image quality limits for microcomputed tomography in small animals. Med Phys 30: 2869–2877

    PubMed  CAS  Google Scholar 

  189. Beckmann N, Bruttel K, Mir AK, Rudin M (1995) Noninvasive 3D MR microscopy as a tool in pharmacological research: application to a model of rheumatoid arthritis. Magn Reson Imaging 13: 1013–1317

    PubMed  CAS  Google Scholar 

  190. Dawson J, Gustard S, Beckmann N (1999) High-resolution three-dimensional magnetic resonance imaging for the investigation of knee joint damage during the time course of antigen-induced arthritis in rabbits. Arthritis Rheum 42: 119–128

    Article  PubMed  CAS  Google Scholar 

  191. Jacobson PB, Morgan SJ, Wilcox DM, Nguyen P, Ratajczak CA, Carlson RP, Harris RR, Nuss M (1999) A new spin on an old model: in vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat. Arthritis Rheum 42: 2060–2073

    Article  PubMed  CAS  Google Scholar 

  192. Faure P, Doan BT, Beloeil JC (2003) In-vivo high resolution three-dimensional MRI studies of rat joints at 7 T. NMR Biomed 16: 484–493

    Article  PubMed  CAS  Google Scholar 

  193. Harris RR, Black L, Surapaneni S, Kolasa T, Majest S, Namovic MT, Grayson G, Komater V, Wilcox D, King L, Marsh K, Jarvis MF, Nuss M, Nellans H, Pruesser L, Reinhart GA, Cox B, Jacobson P, Stewart A, Coghlan M, Carter G, Bell RL (2004) ABT-963 [2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one], a highly potent and selective disubstituted pyridazinone cyclooxgenase-2 inhibitor. J Pharmacol Exp Ther 311: 904–12

    Article  PubMed  CAS  Google Scholar 

  194. Badger AM, Griswold DE, Kapadia R, Blake S, Swift BA, Hoffman SJ, Stroup GB, Webb E, Rieman DJ, Gowen M et al (2000) Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis. Arthritis Rheum 43: 175–183

    Article  PubMed  CAS  Google Scholar 

  195. Badger AM, Blake S, Kapadia R, Sarkar S, Levin J, Swift BA, Hoffman SJ, Stroup GB, Miller WH, Gowen M, Lark MW (2001) Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvantinduced arthritis. Arthritis Rheum 44: 128–137

    Article  PubMed  CAS  Google Scholar 

  196. Beckmann N, Bruttel K, Schuurman H, Mir AK (1998) Effects of Sandimmune neoral on collagen-induced arthritis in DA rats: characterization by high resolution three-dimensional magnetic resonance imaging and by histology. J Magn Reson 131: 8–16

    Article  PubMed  CAS  Google Scholar 

  197. Calvo E, Palacios I, Delgado E, Ruiz-Cabello J, Hernandez P, Sanchez-Pernaute O, Egido J, Herrero-Beaumont G (2001) High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis. Osteoarthritis Cartilage 9: 463–472

    Article  PubMed  CAS  Google Scholar 

  198. Tessier JJ, Bowyer J, Brownrigg NJ, Peers IS, Westwood FR, Waterton JC, Maciewicz RA (2003) Characterization of the guinea pig model of osteoarthritis by in vivo three-dimensional magnetic resonance imaging. Osteoarthritis Cartilage 11: 841–853

    Article  Google Scholar 

  199. Lohmander LS (1994) Articular cartilage and osteoarthritis. The role of molecular markers to monitor breakdown, repair and disease. J Anat 184: 477–492

    PubMed  CAS  Google Scholar 

  200. Donahue KM, Burstein D, Manning WJ, Gray ML (1994) Studies of Gd-DTPA relaxivity and proton exchange rates in tissue, Magn Reson Med 32: 66–76

    PubMed  CAS  Google Scholar 

  201. Laurent D, Wasvary J, O’Byrne E, Rudin M (2003) In vivo qualitative assessments of articular cartilage in the rabbit knee with high-resolution MRI at 3 T. Magn Reson Med 50: 541–549

    Article  PubMed  Google Scholar 

  202. Kim DK, Ceckler TL, Hascall VC, Calabro A, Balaban RS (1993) Analysis of water-macromolecule proton magnetization transfer in articular cartilage. Magn Reson Med 29: 211–215

    PubMed  CAS  Google Scholar 

  203. Vahlensieck M, Dombrowski F, Leutner C, Wagner U, Reiser M (1994)Magnetization transfer contrast (MTC) and MTC-substraction: enhancement of cartilage lesions and intra-cartilaginous degeneration in vitro. Skeletal Radiol 23: 535–539

    Article  PubMed  CAS  Google Scholar 

  204. Gray ML, Burstein D, Lesperance LM, Gehrke L (1995) Magnetization transfer in cartilage and its constituent macromolecules. Magn Reson Med 34: 319–325

    PubMed  CAS  Google Scholar 

  205. Gaffney K, Cookson J, Blades S, Coumbe A, Blake D (1998) Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging. Ann Rheum Dis 57: 152–157

    Article  PubMed  CAS  Google Scholar 

  206. Cutolo M (1999) Macrophages as effectors of the immunoendocrinologic interactions in autoimmune rheumatic diseases. Ann NY Acad Sci 876: 32–41

    PubMed  CAS  Google Scholar 

  207. Dardzinski BJ, Schmithorst VJ, Holland SK, Boivin GP, Imagawa T, Watanabe S, Lewis JM, Hirsch R (2001) MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles. Magn Reson Imaging 19: 1209–1216

    PubMed  CAS  Google Scholar 

  208. Beckmann N, Falk R, Zurbrugg S, Dawson J, Engelhardt P (2003) Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis. Magn Reson Med 49: 1047–1055

    PubMed  Google Scholar 

  209. Lutz AM, Seemayer C, Corot C, Gay RE, Goepfert K, Michel BA, Marincek B, Gay S, Weishaupt D (2004) Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging. Radiology 233: 149–157

    PubMed  Google Scholar 

  210. Hansch A, Frey O, Sauner D, Hilger I, Haas M, Malich A, Brauer R, Kaiser WA (2004) In vivo imaging of experimental arthritis with near-infrared fluorescence. Arthritis Rheum 50: 961–967

    Article  PubMed  Google Scholar 

  211. Lai WF, Chang CH, Tang Y, Bronson R, Tung CH (2004) Early diagnosis of osteoarthritis zusing cathepsin B sensitive near-infrared fluorescent probes. Osteoarthritis Cartilage 12: 239–244

    Article  PubMed  Google Scholar 

  212. Wunder A, Tung CH, Muller-Ladner U, Weissleder R, Mahmood U (2004) In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatment response. Arthritis Rheum 50: 2459–2465

    Article  PubMed  CAS  Google Scholar 

  213. Cavanaugh D, Johnson E, Price RE, Kurie J, Travis EL, Cody DD (2004) In vivo respiratory-gated micro-CT imaging in small-animal oncology models. Mol Imaging 3: 55–62

    Article  PubMed  Google Scholar 

  214. Hu J, Hawort, ST, Molthen RC, Dawson CA (2004) Dynamic small animal lung imaging via a postacquisition respiratory gating technique using micro-cone beam computed tomography. Acad Radiol 11: 961–970

    Article  PubMed  Google Scholar 

  215. Langheinrich AC, Leithauser B, Greschus S, Von Gerlach S, Breithecker A, Matthias FR, Rau WS, Bohle RM (2004) Acute rat lung injury: feasibility of assessment with micro-CT. Radiology 233: 165–171

    PubMed  Google Scholar 

  216. Bergin CJ, Pauly JM, Macovski A (1991) Lung parenchyma: projection reconstruction MR imaging. Radiology 179: 777–781

    PubMed  CAS  Google Scholar 

  217. Beckmann N, Tigani B, Mazzoni L, Fozard JR (2003) Magnetic resonance imaging of the lung provides potential for non-invasive preclinical evaluation of drugs. Trends Pharmacol Sci 24: 550–554

    Article  PubMed  CAS  Google Scholar 

  218. Gewalt SL, Glover GH, Hedlund LW, Cofer GP, MacFall JR, Johnson GA (1993) MR microscopy of the rat lung using projection reconstruction. Magn Reson Med 29: 99–106

    PubMed  CAS  Google Scholar 

  219. Hedlund LW, Cofer GP, Owen SJ, Allan Johnson G (2000) MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging. Magn Reson Imaging 18: 753–759

    PubMed  CAS  Google Scholar 

  220. Beckmann N, Tigani, B, Mazzoni, L, Fozard JR (2001) MRI of lung parenchyma in rats and mice using a gradient-echo sequence. NMR Biomed 14: 297–306

    PubMed  CAS  Google Scholar 

  221. Beckmann N, Tigani B, Ekatodramis D, Borer R, Mazzoni L, Fozard JR (2001) Pulmonary edema induced by allergen challenge in the rat: noninvasive assessment by magnetic resonance imaging. Magn Reson Med 45: 88–95

    Article  PubMed  CAS  Google Scholar 

  222. Renzi PM, Olivenstein R, Martin JG (1993) Inflammatory cell populations in the airways and parenchyma after antigen challenge in the rat. Am Rev Resp Dis 147: 967–974

    PubMed  CAS  Google Scholar 

  223. Hannon JP, Tigani B, Williams I, Mazzoni L, Fozard JR (2001) Mechanism of airway hyperresponsiveness to adenoside induced by allergen challenge in actively sensitized Brown Norway rats. Br J Pharmacol 132: 1509–1523

    Article  PubMed  CAS  Google Scholar 

  224. Tigani B, Schaeublin E, Sugar R, Jackson AD, Fozard JR, Beckmann N (2002) Pulmonary inflammation monitored non-invasively by MRI in freely breathing rats. Biochem Biophys Res Commun 292: 216–221

    Article  PubMed  CAS  Google Scholar 

  225. Tigani B, Cannet C, Zurbrugg S, Schaeublin E, Mazzoni L, Fozard JR, Beckmann N (2003) Resolution of the oedema associated with allergic pulmonary inflammation in rats. Br J Pharmacol 140: 239–246

    Article  PubMed  CAS  Google Scholar 

  226. Tigani B, Di Padova F, Zurbrugg S, Schaeublin E, Revesz L, Fozard JR, Beckmann N (2003) Effects of a mitogen-activated protein kinase inhibitor on allergic airways inflammation in the rat studied by magnetic resonance imaging. Eur J Pharmacol 482: 319–324

    Article  PubMed  CAS  Google Scholar 

  227. Watson, RW, Redmond HP, Bouchier-Hayes D (1994) Role of endotoxin in mononuclear phagocyte-mediated inflammatory responses. J Leukoc Biol 56: 95–103

    PubMed  CAS  Google Scholar 

  228. Yang RB, Mark MR, Gray A, Huang H, Xie MH, Zhang M, Goddard A, Wood WI, Gurney AL, Godowski PJ (1998) Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395: 284–288

    PubMed  CAS  Google Scholar 

  229. Albelda SM, Smith CW, Ward PA. (1994) Adhesion molecules and inflammatory injury. FASEB J 8: 504–512

    PubMed  CAS  Google Scholar 

  230. Tesfaigzi Y, Fischer MJ, Martin AJ, Seagrave J (2000) Bcl-2 in LPS-and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats. Am J Physiol Lung Cell Mol Physiol 279: L1210–L1217

    PubMed  CAS  Google Scholar 

  231. Harkema JR, Hotchkiss JA (2000) In vivo effects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways. Quantitative histochemistry. Am J Pathol 141: 307–317

    Google Scholar 

  232. Beckmann N, Tigani B, Sugar R, Jackson AD, Jones G, Mazzoni L, Fozard JR (2002) Noninvasive detection of endotoxin induced mucus hypersecretion in rat lung by magnetic resonance imaging. Am J Physiol Lung Cell Mol Physiol 283: L22

    PubMed  CAS  Google Scholar 

  233. Martin JG, Duguet A, Eidelman DH (2000) The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease. Eur Respir J 16: 349–354

    PubMed  CAS  Google Scholar 

  234. Halayko AJ, Amrani Y (2003) Mechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma. Respir Physiol Neurobiol 137: 209–222

    Article  PubMed  CAS  Google Scholar 

  235. Beckmann N, Cannet C, Zurbruegg S, Rudin M, Tigani B (2004) Proton MRI of lung parenchyma reflects allergen-induced airway remodeling and endotoxin-aroused hyporesponsiveness: a step towards ventilation studies in spontaneously breathing rats. Magn Reson Med 52: 258–268

    Article  PubMed  Google Scholar 

  236. Edelman RR, Hatabu H, Tadamura E, Li W, Prasad PV (1996) Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging. Nature Med 2: 1236–1239

    PubMed  CAS  Google Scholar 

  237. Stock KW, Chen Q, Morrin M, Hatabu H, Edelman RR (1999) Oxygen-enhanced magnetic resonance ventilation imaging of the human lung at 0.2 T and 1.5 T. J Magn Reson Imaging 9: 838–841

    PubMed  CAS  Google Scholar 

  238. Pauwels RA, Kips JC, Peleman RA, van der Straeten ME (1990) The effect of endotoxin inhalation on airway responsiveness and cellular influx in rats. Am Rev Respir Dis 141: 540–545

    PubMed  CAS  Google Scholar 

  239. Kips JC, Lefebvre RA, Peleman RA, Joos GF, Pauwels RA (1995) The effect of a nitric oxide synthase inhibitor on the modulation of airway responsiveness in rats. Am J Respir Crit Care Med 151: 1165–1169

    PubMed  CAS  Google Scholar 

  240. Kobzik L, Bredt DS, Lowenstein CJ, Drazen J, Gaston B, Sugarbaker D, Stamler JS (1993) Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol 9: 371–377

    PubMed  CAS  Google Scholar 

  241. Moller HE, Chen XJ, Saam B, Hagspiel KD, Johnson GA, Altes TA, de Lange EE, Kauczor HU (2002) MRI of the lungs using hyperpolarized noble gases. Magn Reson Med 47: 1029–1051

    PubMed  Google Scholar 

  242. Stupar V, Berthezene Y, Canet E, Tournier H, Dupuich D, Cremillieux Y (2003) Helium3 polarization using spin exchange technique: application to simultaneous pulmonary ventilation/perfusion imaging in small animals. Invest Radiol 38: 334–340

    Article  PubMed  Google Scholar 

  243. Viallon M, Cofer GP, Suddarth SA, Moller HE, Chen XJ, Chawla MS, Hedlund LW, Cremillieux Y, Johnson GA (1999) Functional MR microscopy of the lung with hyperpolarized 3He, Magn Reson Med 41: 787–792

    Article  PubMed  CAS  Google Scholar 

  244. Viallon M, Berthezene Y, Callot V, Bourgeois M, Humblot H, Briguet A, Cremillieux Y (2000) Dynamic imaging of hyperpolarized (3)He distribution in rat lungs using interleaved-spiral scans. NMR Biomed 13: 207–213

    Article  PubMed  CAS  Google Scholar 

  245. Chen BT, Brau ACS, Johnson GA (2003) Measurement of regional lung function in rats using hyperpolarized 3Helium dynamic MRI. Magn Reson Med 49: 78–88

    Article  PubMed  Google Scholar 

  246. Chen BT, Johnson GA (2004) Dynamic lung morphology of methacholine-induced heterogeneous bronchoconstriction, Magn Reson Med 52: 1080–1086

    PubMed  Google Scholar 

  247. Dupuich D, Berthezene Y, Clouet PL, Stupar V, Canet E, Cremillieux Y (2003) Dynamic 3He imaging for quantification of regional lung ventilation parameters. Magn Reson Med 50: 777–783

    Article  PubMed  Google Scholar 

  248. Barnes PJ (2002) New treatments for COPD. Nat Rev Drug Discov 1: 437–446

    Article  PubMed  CAS  Google Scholar 

  249. Busch RH, Lauhala KE, Loscutoff SM, McDonald KE (1984) Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: morphogenesis. Environ Res 33: 497–513

    PubMed  CAS  Google Scholar 

  250. Chen XJ, Hedlund LW, Moller HE, Chawla MS, Maronpot RR, Johnson GA (2000) Detection of emphysema in rat lungs by using magnetic resonance measurements of 3He diffusion. Proc Natl Acad Sci USA 97: 11478–11481

    PubMed  CAS  Google Scholar 

  251. Peces-Barba G, Ruiz-Cabello J, Cremillieux Y, Rodriguez I, Dupuich D, Callot V, Ortega M, Rubio Arbo ML, Cortijo M, Gonzalez-Mangado N (2003) Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema. Eur Respir J 22: 14–19

    Article  PubMed  CAS  Google Scholar 

  252. Berthezene Y, Vexler V, Price DC, Wisner-Dupon J, Moseley ME, Aicher KP, Brasch RC (1992) Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40. Invest Radiol 27: 346–351

    PubMed  CAS  Google Scholar 

  253. Richard JC, Factor P, Ferkol T, Ponde DE, Zhou Z, Schuster DP (2003) Repetitive imaging of reporter gene expression in the lung. Mol Imag 2: 342–349

    CAS  Google Scholar 

  254. O’Dell WG, McCulloch AD (2000) Imaging three-dimensional cardiac function. Annu Rev Biomed Eng 2: 431–456

    PubMed  CAS  Google Scholar 

  255. Nahrendorf M, Hiller KH, Hu K, Ertl G, Haase A, Bauer WR (2003) Cardiac magnetic resonance imaging in small animal models of human heart failure. Med Image Anal 7: 369–375

    Article  PubMed  CAS  Google Scholar 

  256. Rudin M, Pedersen B, Umemura K, Zierhut W (1991) Determination of rat heart morphology and function in vivo in two models of cardiac hypertrophy by means of magnetic resonance imaging. Basic Res Cardiol 86: 165–174

    Article  PubMed  CAS  Google Scholar 

  257. Ryf S, Spiegel MA, Gerber M, Boesiger P (2002) Myocardial tagging with 3D-CSPAMM. J Magn Reson Imaging 16: 320–325

    Article  PubMed  Google Scholar 

  258. Masood S, Yang GZ, Pennell DJ, Firmin DN (2000) Investigating intrinsic myocardial mechanics: the role of MR tagging, velocity phase mapping, and diffusion imaging. J Magn Reson Imaging 12: 873–883

    Article  PubMed  CAS  Google Scholar 

  259. Jay TM, Lucignani G, Crane AM, Jehle J, Sokoloff L (1988) Measurement of local cerebral blood flow with [14C]iodoantipyrine in the mouse. J Cereb Blood Flow Metab 8: 121–129

    PubMed  CAS  Google Scholar 

  260. Cook NS, Zerwes HG, Pally C, Rudin M, Hof RP (1993) Spirapril and cilazapril inhibit neointimal lesion development but cause no detectable inhibition of lumen narrowing after carotid artery balloon catheter injury in the rat. Blood Press 2: 322–331

    PubMed  CAS  Google Scholar 

  261. Pruessmann KP (2004) Parallel imaging at high field strength: synergies and joint potential. Top Magn Reson Imaging 15: 237–244

    PubMed  Google Scholar 

  262. Bock NA, Konyer NB, Henkelman RM (2004) Multiple-mouse MRI. Magn Reson Med 49: 158–167

    Google Scholar 

  263. Heiss WD, Graf R, Grond M, Rudolf J (1998) Pathophysiology of the ischemic penumbra— revision of a concept. Cell Mol Neurobiol 18: 621–638

    Google Scholar 

  264. Nicholson JK, Connelly J, Lindon JC, Holmes E (2002) Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 1: 153–161

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute for Biomedical Engineering, University of Zurich/ETH, Zurich, Switzerland

    Markus Rudin

  2. Novartis Institute for Biomedical Research, CH-4002, Basel, Switzerland

    Nicolau Beckmann & Martin Rausch

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  1. Markus Rudin
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  2. Nicolau Beckmann
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  3. Martin Rausch
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Editors and Affiliations

  1. Institute for Biomedical Engineering, University of Zürich/ETH Zürich, Moussonstr. 18, CH - 8092, Zürich, Switzerland

    Markus Rudin

  2. Novartis International AG, CH-4002, Basel, Switzerland

    Paul L. Herrling

  3. Novartis Institute for Tropical Diseases, 10 Biopolis Road, #05-01 Chromos, Singapore, 138670, Singapore

    Alex Matter M.D. (Director) (Director)

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© 2005 Birkhäuser Verlag, Basel (Switzerland)

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Rudin, M., Beckmann, N., Rausch, M. (2005). Evaluation of drug candidates: Efficacy readouts during lead optimization. In: Herrling, P.L., Matter, A., Rudin, M. (eds) Imaging in Drug Discovery and Early Clinical Trials. Progress in Drug Research, vol 62. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7426-8_6

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