Neurocritical Care

, Volume 8, Issue 3, pp 448–455 | Cite as

MRI of the Perihemorrhagic Zone in a Rat ICH Model: Effect of Hematoma Evacuation

  • Berk OrakciogluEmail author
  • Kristina Becker
  • Oliver W. Sakowitz
  • Christian Herweh
  • Martin Köhrmann
  • Hagen B. Huttner
  • Thorsten Steiner
  • Andreas Unterberg
  • Peter D. Schellinger
Translational Research



Perihemorrhagic pathophysiology of spontaneous intracerebral hemorrhages (ICH) remains unclear. Recently, ischemic changes in the perihemorrhagic zone (PHZ) have been discussed as a potential source of secondary damage. In this study, we focussed on diffusion and perfusion characteristics of experimental ICH.


Experimental ICH was induced with a double injection model in rats. In total, 49 animals were examined at three timepoints within 3.5 h after ICH with a 2.35T animal scanner. We investigated perihemorrhagic relative apparent diffusion coefficients (rADC) and relative mean transit time (rMTT). Animals were divided into 2 groups; controls (gr1, n = 27) and facilitated hematoma evacuation with recombinant tissue plasminogen activator (rt-PA) after the first of 3 imaging time points (gr2, n = 22). Diffusion (rADC) and perfusion (rMTT) characteristics were analyzed in 3 regions of interest surrounding the hematoma (ROI1–3).


Overall rADC and rMTT values in ROI3 (normal tissue) did not show any changes. There was mild edema—not ischemia—in ROIs1 and 2 at TP1 with rADC of 1.05–1.18 in both groups indicating vasogenic edema (not ischemia). This did not change with hematoma evacuation. There was mild (non-critical) perfusion reduction in ROIs1 and 2 at TP1, which disappeared after clot evacuation in group 2 (P < 0.05 for TP3). Multifactorial ANOVA showed a solid trend (0.06 < P < 0.1) for clot evacuation associated normalization of perfusion in ROIs 1 and 2 within and in between groups 1 and 2.


We demonstrated vasogenic edema and mild perfusion reduction in the PHZ above the ischemic threshold. The existence of a perihemorrhagic “penumbra” indicating critically ischemic tissue analogous to ischemic stroke is unlikely.


MRI PI DWI Ischemia Rats ICH Evacuation 



This work was funded by a grant from the German Research Council (Dr. Schellinger, SCHE 613/1-1).


  1. 1.
    Altumbabic M, Peeling J, Del Bigio MR. Intracerebral hemorrhage in the rat: effects of hematoma aspiration. Stroke 1998;29:1917–22; discussion 1922–3.PubMedGoogle Scholar
  2. 2.
    Auer LM, Deinsberger W, Niederkorn K, et al. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study. J Neurosurg 1989;70:530–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Belayev L, Saul I, Curbelo K, et al. Experimental intracerebral hemorrhage in the mouse: histological, behavioral, and hemodynamic characterization of a double-injection model. Stroke 2003;34:2221–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Deinsberger W, Hartmann M, Vogel J, et al. Local fibrinolysis and aspiration of intracerebral hematomas in rats. An experimental study using MR monitoring. Neurol Res 1998;20:349–52.PubMedGoogle Scholar
  5. 5.
    Deinsberger W, Vogel J, Fuchs C, et al. Fibrinolysis and aspiration of experimental intracerebral hematoma reduces the volume of ischemic brain in rats. Neurol Res 1999;21:517–23.PubMedGoogle Scholar
  6. 6.
    Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365:387–97.PubMedGoogle Scholar
  7. 7.
    Wagner KR, Xi G, Hua Y, et al. Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood–brain barrier protection. J Neurosurg 1999;90:491–8.PubMedGoogle Scholar
  8. 8.
    Wagner KR, Dwyer BE. Hematoma removal, heme, and heme oxygenase following hemorrhagic stroke. Ann N Y Acad Sci 2004;1012:237–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Orakcioglu B, Fiebach JB, Steiner T, et al. Evolution of early perihemorrhagic changes—ischemia vs. edema: an MRI study in rats. Exp Neurol 2005;193:369–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Butcher KS, Baird T, MacGregor L, et al. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke 2004;35:1879–85.PubMedCrossRefGoogle Scholar
  11. 11.
    Schellinger PD, Fiebach JB, Hoffmann K, et al. Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke 2003;34:1674–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Pascual AM, Lopez-Mut JV, Benlloch V, et al. Perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage at baseline and during the 1st and 2nd week: a longitudinal study. Cerebrovasc Dis 2007;23:6–13.PubMedCrossRefGoogle Scholar
  13. 13.
    Kidwell CS, Saver JL, Mattiello J, et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage. Neurology 2001;57:1611–7.PubMedGoogle Scholar
  14. 14.
    Herweh C, Juttler E, Schellinger PD, et al. Evidence against a perihemorrhagic penumbra provided by perfusion computed tomography. Stroke 2007;38:2941–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Deinsberger W, Vogel J, Kuschinsky W, Auer LM, Boker DK. Experimental intracerebral hemorrhage: description of a double injection model in rats. Neurol Res 1996;18:475–7.PubMedGoogle Scholar
  16. 16.
    Benveniste H, Hedlund LW, Johnson GA. Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy. Stroke 1992;23:746–54.PubMedGoogle Scholar
  17. 17.
    Fisher M. The new magnetic resonance techniques of diffusion and perfusion imaging. Adm Radiol J 1997;16:29–30, 35–6.PubMedGoogle Scholar
  18. 18.
    Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging. Stroke 2004;35:502–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Qureshi AI, Wilson DA, Hanley DF, Traystman RJ. No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage. Neurology 1999;52:266–72.PubMedGoogle Scholar
  20. 20.
    Bullock R, Brock Utne J, van Dellen J, Blake G. Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow. Surg Neurol 1988;29:101–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Carhuapoma JR, Wang PY, Beauchamp NJ, et al. Diffusion-weighted MRI and proton MR spectroscopic imaging in the study of secondary neuronal injury after intracerebral hemorrhage. Stroke 2000;31:726–32.PubMedGoogle Scholar
  22. 22.
    Videen TO, Dunford-Shore JE, Diringer MN, Powers WJ. Correction for partial volume effects in regional blood flow measurements adjacent to hematomas in humans with intracerebral hemorrhage: implementation and validation. J Comput Assist Tomogr 1999;23:248–56.PubMedCrossRefGoogle Scholar
  23. 23.
    Hirano T, Read SJ, Abbott DF, et al. No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage. Neurology 1999;53:2179–82.PubMedGoogle Scholar
  24. 24.
    Belayev L, Saul I, Busto R, et al. Albumin treatment reduces neurological deficit and protects blood–brain barrier integrity after acute intracortical hematoma in the rat. Stroke 2005;36:326–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab 2001;21:804–10.PubMedCrossRefGoogle Scholar
  26. 26.
    Rosand J, Eskey C, Chang Y, et al. Dynamic single-section CT demonstrates reduced cerebral blood flow in acute intracerebral hemorrhage. Cerebrovasc Dis 2002;14:214–20.PubMedCrossRefGoogle Scholar
  27. 27.
    Mayer SA, Lignelli A, Fink ME, et al. Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study. Stroke 1998;29:1791–8.PubMedGoogle Scholar
  28. 28.
    Nilsson OG, Polito A, Saveland H, Ungerstedt U, Nordstrom CH. Are primary supratentorial intracerebral hemorrhages surrounded by a biochemical penumbra? A microdialysis study. Neurosurgery 2006;59:521–8; discussion 521–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Lee ST, Chu K, Jung KH, et al. Memantine reduces hematoma expansion in experimental intracerebral hemorrhage, resulting in functional improvement. J Cereb Blood Flow Metab 2006;26:536–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Park HK, Chu K, Lee ST, et al. Granulocyte colony-stimulating factor induces sensorimotor recovery in intracerebral hemorrhage. Brain Res 2005;1041:125–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Strbian D, Tatlisumak T, Ramadan UA, Lindsberg PJ. Mast cell blocking reduces brain edema and hematoma volume and improves outcome after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 2007;27:795–802.PubMedGoogle Scholar
  32. 32.
    Qureshi AI, Ali Z, Suri MF, et al. Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: an in vivo microdialysis study. Crit Care Med 2003;31:1482–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Hemphill JC III, Morabito D, Farrant M, Manley GT. Brain tissue oxygen monitoring in intracerebral hemorrhage. Neurocrit Care 2005;3:260–70.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Berk Orakcioglu
    • 1
    Email author
  • Kristina Becker
    • 2
  • Oliver W. Sakowitz
    • 1
  • Christian Herweh
    • 3
  • Martin Köhrmann
    • 4
  • Hagen B. Huttner
    • 4
  • Thorsten Steiner
    • 2
  • Andreas Unterberg
    • 1
  • Peter D. Schellinger
    • 4
  1. 1.Department of NeurosurgeryUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Department of NeurologyUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of NeuroradiologyUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of NeurologyUniversity Hospital ErlangenErlangenGermany

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