Serial MRI After Transient Focal Cerebral Ischemia in Rats

Abstract

Background and Purpose-With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats. Methods-Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days. Results-In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7). Conclusions-Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours). Key Words: blood-brain barrier Ⅲ brain edema Ⅲ cerebral ischemia, focal Ⅲ magnetic resonance imaging Ⅲ reperfusion Ⅲ rats M RI techniques, including diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), have been used increasingly in recent years to evaluate various treatment modalities in both experimental stroke models [1][2][3][4][5][6] and acute stroke patients. 7,8 In human stroke, only agents that lead to a reopening of the occluded artery (ie, to reperfusion, before ischemic tissue injury is complete) have proved to be beneficial so far. 9,10 However, even with thrombolytic treatment, which is the current treatment standard for selected patients within 3 hours of stroke onset, overall patient benefit remains less than optimal. This is in part due to an increase in the risk of symptomatic intracranial hemorrhage among patients treated with recombinant tissue plasminogen activator (rtPA). 11 However, various reperfusion-induced processes ("reperfusion injury") are believed to play an important role as well, and they have been investigated extensively in See Editorial Comment, page 1972 experimental stu...

Cerebral Blood Volume Affects Blood–Brain Barrier Integrity in an Acute Transient Stroke Model

“…31,32 Many previous studies have reported significantly decreased ADC and R 2 in cases of overt BBB disruption, suggesting that these parameters may be correlative indices for describing strokeinduced BBB damage. [13][14][15][16][17] On the contrary, in the current study, we observed similar infarct ADC and R 2 values that were independent of the WEI. The discrepancy principally results from different scales of BBB injury between studies.…”

“…According to previous study results, alterations in CBV, ADC, and R 2 were positively predictive of BBB disruption, as all of these parameters significantly decreased in ischemic stroke characterized by extravasation of contrast materials. [13][14][15][16][17] However, under such heavy ischemic stresses that lead to overt vascular disruption, changes in these MRI parameters may be derived not only from the weakened BBB itself, but also from other ischemia-affected tissue/vascular conditions including cytotoxicity, inflammation, and edema formation. 3,18,19 Therefore, overly simplified dichotomous division of stroke cases according to the presence of apparent trans-BBB leakage does not definitively identify the causative factors in the BBB disruption.…”

Temporal profile of T2-Weighted MRI Distinguishes between Pannecrosis and Selective Neuronal Death after Transient Focal Cerebral Ischemia in the Rat

“…In shorter follow-up MR time series after MCAO (7 days), incomplete recovery of T 1 and T 2 values has been observed in some studies after transient (Neumann-Haefelin et al, 2000) and even permanent (Helpern et al, 1993;Knight et al, 1991) MCAO in rats. Knight et al (1994) described a heterogeneous response of MR relaxation times to MCAO, and noted large increases in T 2 times in the dorsolateral striatum with only moderate histological damage.…”

“…'Apparent' lesion volumes as well as relaxation times decrease slightly thereafter, and stabilize or increase again slightly (when cysts are formed) over the next 2 weeks (Ishii et al, 1998;Li et al, 2000;Lin et al, 2002a, b;Neumann-Haefelin et al, 2000;Palmer et al, 2001;van Dorsten et al, 2002;Virley et al, 2000). Even though T 1 -w and T 2 -w MRI have been shown to closely reflect the extent of irreversibly damaged tissue in the past, there is evidence that this correlation will not always hold in certain brain regions and at later time points (Knight et al, 1994;Neumann-Haefelin et al, 2000). Paramagnetic properties of inflammatory cells or blood degradation products, as well as regionspecific changes in water content and breakdown of macromolecular structures with influence on relaxation times, have been discussed as possible reasons for this phenomenon (Dijkhuizen et al, 1998;Lin et al, 2002a).…”

Detection of the Ischemic Penumbra Using pH-Weighted MRI

“…The same anesthesia procedure was repeated at the 24 h follow-up MRI. T 2 -hyperintensity was used to quantify infarction, which has been shown to be a reliable approach (Neumann-Haefelin et al, 2000;Palmer et al, 2001;van Dorsten et al, 2002).…”