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Multimodal MRI of Experimental Stroke

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Abstract

Stroke is the fourth leading cause of death and the leading cause of long-term disability in USA. Brain imaging data from experimental stroke models and stroke patients have shown that there is often a gradual progression of potentially reversible ischemic injury toward infarction. Reestablishing tissue perfusion and/or treating with neuroprotective drugs in a timely fashion are expected to salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic resonance imaging (MRI) in which contrast is based on water motion can detect ischemic injury within minutes after onsets, whereas computed tomography and other imaging modalities fail to detect stroke injury for at least a few hours. Along with quantitative perfusion imaging, the perfusion–diffusion mismatch which approximates the ischemic penumbra could be imaged noninvasively. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study ischemic tissue at risk in experimental stroke in rats.

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References

  1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123:e18–e209.

    Article  PubMed  Google Scholar 

  2. Davis SM, Donnan GA. 4.5 hours: the new time window for tissue plasminogen activator in stroke. Stroke. 2009;40:2266–7.

    Article  PubMed  Google Scholar 

  3. Hoehn-Berlage M, Norris DG, Kohno K, Mies G, Leibfritz D, Hossmann K-A. Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances. J Cereb Blood Flow Metab. 1995;15:1002–11.

    Article  PubMed  CAS  Google Scholar 

  4. Back M. T., Hoehn-Berlage, PhD, M., Kohno, MD, K., Hossmann, PhD, MD, K-A. Diffusion nuclear magnetic resonance imaging in experimental stroke correlation with cerebral metabolites. Stroke. 1994;25:494–500.

    Article  PubMed  CAS  Google Scholar 

  5. Kohno K, Hoehn-Berlage M, Mies G, Back T, Hossmann KA. Relationship between diffusion-weighted MR images, cerebral blood flow, and energy state in experimental brain infarction. Magn Reson Imag. 1995;13:73–80.

    Article  CAS  Google Scholar 

  6. Albers GW. Expanding the window for thrombolytic therapy in acute stroke: the potential role of acute MRI for patient selection. Stroke. 1999;30:2230–7.

    Article  PubMed  CAS  Google Scholar 

  7. Heiss WD, Graf R. The ischemic penumbra. Curr Opin Neurol. 1994;7:11–9.

    Article  PubMed  CAS  Google Scholar 

  8. NINDS. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorder, and Stroke rt-PA Stroke study group. N Engl J Med. 1995;333:1581–7.

    Article  Google Scholar 

  9. Rohl L, Ostergaard L, Simonsen CZ, Vestergaard-Poulsen P, Andersen G, Sakoh M, Le Bihan D, Gyldensted C. Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient. Stroke. 2001;32:1140–6.

    Article  PubMed  CAS  Google Scholar 

  10. Schlaug G, Benfield A, Baird AE, Siewert B, Lovblad KO, Parker RA, Edelman RR, Warach S. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology. 1999;53:1528–37.

    PubMed  CAS  Google Scholar 

  11. Kidwell CS, Alger JR, Saver JL. Beyond mismatch: evolving paradigms in imaging the ischemic penumbra with multimodal magnetic resonance imaging. Stroke. 2003;34:2729–35.

    Article  PubMed  Google Scholar 

  12. Moseley ME, Cohen Y, Mintorovitch J, Chileuitt L, Shimizu H, Kucharczyk J, Wendland MF, Weinstein PR. Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med. 1990;14:330–46.

    Article  PubMed  CAS  Google Scholar 

  13. Duong TQ, Ackerman JJH, Ying HS, Neil JJ. Evaluation of extra- and intracellular apparent diffusion in normal and globally ischemic rat brain via 19 F NMR. Magn Reson Med. 1998;40:1–13.

    Article  PubMed  CAS  Google Scholar 

  14. Barbier EL, Lamalle L, Decorps M. Methodology of brain perfusion imaging. J Magn Reson Imaging. 2001;13:496–520.

    Article  PubMed  CAS  Google Scholar 

  15. Calamante F, Thomas DL, Pell GS, Wiersma J, Turner R. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab. 1999;19:701–35.

    Article  PubMed  CAS  Google Scholar 

  16. Wong EC, Buxton RB, Frank LR. A theoretical and experimental comparison of continuous and pulsed arterial spin labeling techniques for quantitative perfusion imaging. Magn Reson Med. 1998;40:348–55.

    Article  PubMed  CAS  Google Scholar 

  17. Shen Q, Meng X, Fisher M, Sotak CH, Duong TQ. Pixel-by-pixel spatiotemporal progression of focal ischemia derived using quantitative perfusion and diffusion imaging. J Cereb Blood Flow and Metab. 2003;23:1479–88.

    Article  Google Scholar 

  18. Meng X, Shen Q, Li F, Ratan M, Fisher M, Sotak CH, Duong TQ. Quantitative assessment of temporal changes in the “perfusion/diffusion mismatch” following focal cerebral ischema in the rat brain. 2003; Toronto, Canada. p 303.

  19. Shen Q, Fisher M, Sotak CH, Duong TQ. Effects of reperfusion on ADC and CBF pixel-by-pixel dynamics in stroke: characterizing tissue fates using quantitative diffusion and perfusion imaging. J Cereb Blood Flow Metab. 2004;24:280–90.

    Article  PubMed  Google Scholar 

  20. Shen Q, Ren H, Cheng H, Fisher M, Duong TQ. Functional, perfusion and diffusion MRI of acute focal ischemic brain injury. J Cereb Blood Flow and Metab. 2005;25:1265–79.

    Article  Google Scholar 

  21. Tagaris GA, Richter W, Kim SG, Pellizzer G, Andersen P, Ugurbil K, Georgopoulos AP. Functional magnetic resonance imaging of mental rotation and memory scanning: a multidimensional scaling analysis of brain activation patterns. Brain Res Brain Res Rev. 1998;26:106–12.

    Article  PubMed  CAS  Google Scholar 

  22. Bardutsky J, Meng X, Bouley J, Duong TQ, Ratan R, Fisher M. Effects of IV dimethyl sulfoxide on ischemia evolution in permanently occluded rats. J Cereb Blood Flow and Metab. 2005;25:968–77.

    Article  Google Scholar 

  23. Shen Q, Ren H, Bouley J, Fisher M, Duong TQ. Dynamic tracking of acute ischemic tissue fates using improved unsupervised ISODATA analysis of high-resolution quantitative perfusion and diffusion data. J Cereb Blood Flow and Metab. 2004;24:887–97.

    Article  Google Scholar 

  24. Sicard KM, Henninger N, Fisher M, Duong TQ, Ferris CF. Long-term changes of functional MRI-based brain function, behavioral status, and histopathology after transient focal cerebral ischemia in rats. Stroke. 2006;37:2593–600.

    Article  PubMed  Google Scholar 

  25. Sicard KM, Henninger N, Fisher M, Duong TQ, Ferris CF. Differential recovery of multimodal MRI and behavior after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2006;26:1451–62.

    Article  PubMed  Google Scholar 

  26. Ren H, Shen Q, Bardutzky J, Fisher M, Duong TQ. Partial-volume effect on ischemic tissue-fate delineation using quantitative perfusion and diffusion imaging on a rat stroke model. Magn Reson Med. 2004;52:1328–35.

    Article  PubMed  Google Scholar 

  27. Bardutzky J, Shen Q, Bouley J, Sotak CH, Duong TQ, Fisher M. Perfusion and diffusion imaging in acute focal cerebral ischemia: temporal vs. spatial resolution. Brain Res. 2005;1043:155–62.

    Article  PubMed  CAS  Google Scholar 

  28. Ogawa S, Tank DW, Menon R, Ellermann JM, Kim S-G, Merkle H, Ugurbil K. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA. 1992;89:5951–5.

    Article  PubMed  CAS  Google Scholar 

  29. Roy CS, Sherrington CS. On the regulation of blood supply of the brain. J Physiol. 1890;1:85–108.

    Google Scholar 

  30. Liu ZM, Schmidt KF, Sicard KM, Duong TQ. Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia. Magn Reson Med. 2004;52:277–85.

    Article  PubMed  Google Scholar 

  31. Sicard KM, Duong TQ. Effects of hypoxia, hyperoxia and hypercapnia on baseline and stimulus-evoked BOLD, CBF and CMRO2 in spontaneously breathing animals. NeuroImage. 2005;25:850–8.

    Article  PubMed  Google Scholar 

  32. Silva A, Lee S-P, Yang C, Iadecola C, Kim S-G. Simultaneous BOLD and perfusion functional MRI during forepaw stimulation in rats. J Cereb Blood Flow Metab. 1999;19:871–9.

    Article  PubMed  CAS  Google Scholar 

  33. Duong TQ, Silva AC, Lee S-P, Kim S-G. Comparison of spatial localization between synaptic activity and hemodynamic responses following somatosensory stimulation: an MRI study at 9.4 Tesla. Proc of the ISMRM 7th Scientific Meeting, Philadelphia, 1999. p 378.

  34. Wu O, Sumii T, Asahi M, Sasamata M, Ostergaard L, Rosen BR, Lo EH, Dijkhuizen RM. Infarct prediction and treatment assessment with MRI-based algorithms in experimental stroke models. J Cereb Blood Flow and Metab. 2007;27:196–204.

    Article  Google Scholar 

  35. Wu O, Koroshetz WJ, Ostergard L, Buonanno FS, Copen W, Gonzales G, Rordorf G, Rosen BR, Schwamm LH, Weisskoff RM, Sorensen AG. Predicting tissue outcome in acute human cerebral ischemia using combined diffusion-and perfusion-weighted MR imaging. Stroke. 2001;32:933–42.

    Article  PubMed  CAS  Google Scholar 

  36. Shen Q, Ren H, Fisher M, Duong TQ. Statistical prediction of tissue fates in acute ischemic brain injury. J Cereb Blood Flow and Metab. 2005;25:1336–45.

    Article  Google Scholar 

  37. Shen Q, Duong TQ. Quantitative prediction of ischemic stroke tissue fate. NMR Biomed. 2008;21:839–48.

    Article  PubMed  Google Scholar 

  38. Huang S, Shen Q, Duong TQ. Artificial neural-network prediction of ischemic tissue fate in acute stroke imaging. J Cereb Blood Flow Metab. 2010;30:1661–70.

    Article  PubMed  Google Scholar 

  39. Huang S, Shen Q, Duong TQ. Quantitative prediction of acute ischemic tissue fate using support vector machine. Brain Res. 2011;1405:77–84.

    Article  PubMed  CAS  Google Scholar 

  40. Lassen NA. The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localised within the brain. Lancet. 1966;2:1113–5.

    Article  PubMed  CAS  Google Scholar 

  41. Heiss W-D, Graf R, Lottgen J, Ohta K, Fujita T, Wagner R, Grond M, Weinhard K. Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats. Journ of cereb blood flow and metab. 1997;17:388–400.

    Article  CAS  Google Scholar 

  42. Kastrup A, Engelhorn T, Beaulieu C, de Crespigny A, Moseley ME. Dynamics of cerebral injury, perfusion, and blood–brain barrier changes after temporary and permanent middle cerebral artery occlusion in the rat. J Neurol Sci. 1999;166:91–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kidwell CS, Saver JL, Mattiello J, Starkman S, Vinuela F, Duckwiller G, Gobin YP, Jahan R, Vespa JP, Villablanca JP, Liebeskind DS, Woods RP, Alger JR. Diffusion–perfusion MRI characterization of post-recanalization hyperperfusion in humans. Neurology. 2001;57:2015–21.

    PubMed  CAS  Google Scholar 

  44. Marchal G, Beaudouin V, Rioux P, de la Sayette V, Le Doze F, Viader F, Derlon JM, Baron JC. Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: a correlative PET-CT study with voxel-based data analysis. Stroke. 1996;27:599–606.

    Article  PubMed  CAS  Google Scholar 

  45. Sundt Jr TM, Grant WC, Garcia JH. Restoration of middle cerebral artery flow in experimental infarction. J Neurosurg. 1969;31:311–21.

    Article  PubMed  Google Scholar 

  46. Tasdemiroglu E, Macfarlane R, Wei EP, Kontos HA, Moskowitz MA. Pial vessel caliber and cerebral blood flow become dissociated during ischemia–reperfusion in cats. Am J Physiol. 1992;263:H533–536.

    PubMed  CAS  Google Scholar 

  47. Marchal G, Furlan M, Beaudouin V, Rioux P, Hauttement JL, Serrati C, de la Sayette V, Le Doze F, Viader F, Derlon JM, Baron JC. Early spontaneous hyperperfusion after stroke. A marker of favourable tissue outcome? Brain. 1996;119(2):409–19.

    Article  PubMed  Google Scholar 

  48. Schaller B, Graf R. Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab. 2004;24:351–71.

    Article  PubMed  Google Scholar 

  49. Pan J, Konstas AA, Bateman B, Ortolano GA, Pile-Spellman J. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology. 2007;49:93–102.

    Article  PubMed  Google Scholar 

  50. Ackerman RH, Correia JA, Alpert NM, Baron JC, Gouliamos A, Grotta JC, Brownell GL, Taveras JM. Positron imaging in ischemic stroke disease using compounds labeled with oxygen 15. Initial results of clinicophysiologic correlations. Arch Neurol. 1981;38:537–43.

    Article  PubMed  CAS  Google Scholar 

  51. Baron JC, Bousser MG, Comar D, Soussaline F, Castaigne P. Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo. Potentials, limitations, and clinical applications in cerebral ischemic disorders. Eur Neurol. 1981;20:273–84.

    Article  PubMed  CAS  Google Scholar 

  52. Baron JC, Delattre JY, Bories J, Chiras J, Cabanis EA, Blas C, Bousser MG, Comar D. Comparison study of CT and positron emission tomographic data in recent cerebral infarction. AJNR Am J Neuroradiol. 1983;4:536–40.

    PubMed  CAS  Google Scholar 

  53. Tran Dinh YR, Ille O, Guichard JP, Haguenau M, Seylaz J. Cerebral postischemic hyperperfusion assessed by Xenon-133 SPECT. J Nucl Med. 1997;38:602–7.

    PubMed  CAS  Google Scholar 

  54. Kontos HA, Wei EP. Oxygen-dependent mechanisms in cerebral autoregulation. Ann Biomed Eng. 1985;13:329–34.

    Article  PubMed  CAS  Google Scholar 

  55. Berne RM, Rubio R. Regulation of coronary blood flow. Adv Cardiol. 1974;12:303–17.

    PubMed  CAS  Google Scholar 

  56. Joo F. The blood-brain barrier. New aspects to the function of the cerebral endothelium. Nature. 1986;321:197–8.

    Article  PubMed  CAS  Google Scholar 

  57. Macfarlane R, Moskowitz MA, Sakas DE, Tasdemiroglu E, Wei EP, Kontos HA. The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes. Journal of neurosurgery. 1991;75:845–55.

    Article  PubMed  CAS  Google Scholar 

  58. Yamaguchi T. Regional cerebral blood flow in experimental cerebral infarction, with special reference to hyperemia in the ischemic cerebral hemisphere. Int J Neurol. 1977;11:162–78.

    PubMed  CAS  Google Scholar 

  59. Shen Q, Du F, Huang S, Duong TQ. Spatiotemporal characteristics of postischemic hyperperfusion with respect to changes in T1, T2, diffusion, angiography, and blood–brain barrier permeability. J Cereb Blood Flow Metab. 2011;31:2076–85.

    Article  PubMed  Google Scholar 

  60. Dani KA, Santosh C, Brennan D, McCabe C, Holmes WM, Condon B, Hadley DM, Macrae IM, Shaw M, Muir KW. T2*-weighted magnetic resonance imaging with hyperoxia in acute ischemic stroke. Ann Neurol. 2010;68:37–47.

    Article  PubMed  Google Scholar 

  61. Santosh C, Brennan D, McCabe C, Macrae IM, Holmes WM, Graham DI, Gallagher L, Condon B, Hadley DM, Muir KW, Gsell W. Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra. J Cereb Blood Flow Metab. 2008;28:1742–53.

    Article  PubMed  CAS  Google Scholar 

  62. Ogawa S, Lee TM. Magnetic resonance imaging of blood vessels at high fields: in vivo and in vitro measurements and image simulation. Magn Reson Med. 1990;16:9–18.

    Article  PubMed  CAS  Google Scholar 

  63. Ogawa S, Menon RS, Tank DW, Kim S-G, Merkle H, Ellermann JM, Ugurbil K. Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. Biophys J. 1993;64:800–12.

    Article  Google Scholar 

  64. Shen Q, Huang S, Du F, Duong TQ. Probing ischemic tissue fate with BOLD fMRI of brief oxygen challenge. Brain Res. 2011;1425:132–41.

    Article  PubMed  CAS  Google Scholar 

  65. Wey HY, Wang DJ, Duong TQ. Baseline CBF, and BOLD, CBF, and CMRO2 fMRI of visual and vibrotactile stimulations in baboons. J Cereb Blood Flow Metab. 2010;31:715–24.

    Article  PubMed  Google Scholar 

  66. De Crespigny A, D'Arceuil HE, Maynard KL, He J, McAuliffe D, Norbash A, Sahgal PK, Hamberg LM, Hunter GJ, Budzik RF, Putman CM, Gonzalez RG. Acute studies of a new primate model of reversible middle cerebral artery occlusion. J Stroke and Cerebrovas Dis. 2006;14:80–8.

    Article  Google Scholar 

  67. Tanaka Y, Nagaoka T, Nair G, Ohno K, Duong TQ. Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection. J Cereb Blood Flow Metab 2011;31:1403–1411.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Imaging Institute, Departments of Ophthalmology, Radiology and Physiology, University of Texas Health Science Center, 8403 Floyd Curl Dr, San Antonio, TX, 78229, USA

    Timothy Q. Duong

  2. South Texas Veterans Health Care System, Department of Veterans Affairs, San Antonio, TX, USA

    Timothy Q. Duong

  3. Southwest National Primate Research Center, Southwest Foundation, San Antonio, TX, USA

    Timothy Q. Duong

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Duong, T.Q. Multimodal MRI of Experimental Stroke. Transl. Stroke Res. 3, 8–15 (2012). https://doi.org/10.1007/s12975-011-0140-y

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