Summary: In focal ischemia of rats, the volume of ischemic lesion correlates with the number of peri-infarct depolariza tions, To test the hypothesis that depolarizations accelerate in farct growth, we combined focal ischemia with externally evoked spreading depression (SD) waves, Ischemic brain in farcts were produced in halothane-anaesthetized rats by intra luminal thread occlusion of the middle cerebral artery (MCA), In one group of animals, repeated SDs were evoked at IS-min intervals by microinjections of potassium acetate into the fron tal cortex, In another group, the spread of the potassium-evoked depolarizations was prevented by application of the N-methyl D-aspartate (NMDA) receptor antagonist dizocilpine (MK-80 I), The volume of ischemic lesion was monitored for 2 h by diffusion-weighted imaging (DWI) and correlated with electro physiological recordings and biochemical imaging techniques, In untreated rats, each microinjection produced an SD wave and a stepwise rise of the volume and signal intensity of the In focal cerebral ischemia of rat infarct size correlates with the number of peri-infarct spreading depression (SD)-like depolarizations (Mies et aI., 1993; Chen et aI., 1993). These depolarizations are generated in the border zone of the ischemic lesion and spread into the peri infarct surrounding (Nedergaard and Hansen, 1993; Ne dergaard and Astrup, 1986). Glutamate antagonists such as dizocilpine (MK-801) or 2,3-dihydroxy-6-nitro-7-Received January I L 1996; final received May 3. 1996; accepted May 29, 1996.Address correspondence. and reprint requests to Prof. Dr. K.-A. Hossmann, Max-Planck-Institut fUr neurologische Forschung. Gleuelerstrasse 50, D-50931 Kiiln, FR Germany.Abbreviations used: ADC, apparent diffusion coefficient; ANOY A. analysis of variance; DC, direct current; DWl, diffusion-weighted im aging; MCA, middle carotid artery; MR, magnetic resonance; NBQX, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F)-quinoxaline; NMDA, N methyl-D-aspartate; RF, radiofrequency; ROI, region of interest; SD, spreading depression; TE. spin echo. 1090DWI-visible cortical lesion, The volume of this lesion in creased between IS min and 2 h of MCA occlusion from 19 ± 15% to 66 ± 16% of ipsilateral cortex, In dizocilpine-treated animals, microinjections of potassium did not evoke SDs, nor did the volume and signal intensity of the DWI-visible cortical lesion change, At 15 min after MCA occlusion, the DWI visible lesion was larger than in untreated animals-43 ± 16% of the ipsilateral cortex; however, after 2 h, it increased only slightly further to 49 ± 21 %. Slower lesion growth in the ab sence of SDs was also reflected by the volume of ATP-depleted tissue, which, after 2 h of MCA occlusion, involved 26 ± 12% of the ipsilateral cortex in treated and 49 ± 9% in untreated animals (p < 0.(1). These observations support the hypothesis that peri-infarct depolarizations accelerate cerebral infarct growth.

The quantitative NMR parameters T1, T2, rho, and apparent diffusion coefficient (ADC) were determined during the 7 h after middle cerebral artery occlusion in rats. In the normal caudate-putamen (CP), 869 +/- 145 ms and 72 +/- 2 ms for T1 and for T2, respectively, were found; the corresponding values for cortex were 928 +/- 117 ms and 73 +/- 2 ms. The ADC showed significant dependence on gradient direction: diffusion along x resulted in 534 +/- 53 microns 2/s (CP) and 554 +/- 62 microns 2/s (cortex), and along y in 697 +/- 58 microns 2/s (CP) and 675 +/- 53 microns 2/s (cortex). In the ischemic territory, a continuous increase over time of both relaxation times was observed in the CP, leading to an increase of 29 +/- 20% (T1) and 51 +/- 41% (T2) above control level. ADC dropped to 63 +/- 15% of control in the CP and to 74 +/- 4% of control in the temporal cortex. No significant change was noted in proton density during the observation period. Strongest ADC reduction was in the center of the ischemic territory (< or = 60% of control) surrounded by a region of lesser reduction (< or = 80% of control). During the early part of the study, the area of reduced ADC was larger than that of elevated relaxation times. Toward the end of the experiment, the area of increased relaxation times approached that of decreased ADC at < or = 80% of control. Good agreement of histological presentation of infarct with the total area of decreased ADC (< or = 80%) was demonstrated.

The potential of quantitative parameter images of the relaxation times T1 and T2, the proton density rho and the apparent diffusion coefficient (ADC) to characterize three different experimental rat brain tumors (F98 glioma, RN6 Schwannoma, and E376 neuroblastoma) was studied. All parameter values, as determined in histologically confirmed regions of interest (ROI), were higher in edema than in tumor, which in turn were elevated with respect to normal brain. ROI values of ADC and T2 delivered statistically significant (P < 0.01) differentiation between tumor and edema. Multidimensional parameter combinations improved differentiation between different tissues. However, the three tumor types could not be differentiated. All parameter maps allowed the identification of the whole tumor-edema area. On T2 images, edema could be identified best, whereas the tumor itself was hardly visualized. In many cases, tumor presentation using T1 maps corresponded best with histology, nevertheless suffering from a poor tumor-edema differentiation.

Temporary focal ischaemia was induced in wild‐type C57Black/6 mice by thread occlusion of the middle cerebral artery (MCA). Recirculation was started after 60 min and maintained for 24 h, after which the mouse brain was frozen in situ. Development of the cerebral infarct was monitored by diffusion‐, perfusion‐ and T2‐weighted magnetic resonance imaging (MRI) during ischaemia, during the early reperfusion period of 90 min, and at 24 h after reperfusion. Ischaemia caused a marked reduction of the perfusion signal intensity and of the apparent diffusion coefficient (ADC) of tissue water in the ipsilateral MCA territory. In sham‐operated control animals ADC remained unchanged. Hemispheric lesion volume after 1 h MCA occlusion was 53 ± 6% (n = 6), as defined by an ADC decrease of more than 20%. Recirculation reduced hemispheric lesion volume to only 27 ± 13%, while there was a trend towards secondary lesion growth at 24 h. Post‐ischaemic recovery of perfusion was slow, heterogeneous and incomplete. A region‐of‐interest analysis showed only partial and transient recovery of the ADC, particularly in the dorsolateral cortex and lateral caudate putamen, which may be explained by inadequate reperfusion in these regions. Detailed MRI studies of cerebral ischaemia and reperfusion may now also be performed in the transgenic mice. Copyright © 1999 John Wiley & Sons, Ltd.

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