Brain Research 885 2000 208–219 www.elsevier.com locate bres
Research report
Diffusion- and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under
conditions of mild hypothermia
a,b,d , a,d
c,d c,d ,1
Midori A. Yenari , David Onley
, Maj Hedehus , Alexander deCrespigny
,
a,d c,d
a,d
Guo Hua Sun , Michael E. Moseley
, Gary K. Steinberg
a
Department of Neurosurgery , Stanford University Medical Center, 120 Welch Road, HSLS Bldg. P304, Stanford, CA 94305-5487, USA
b
Department of Neurology , Stanford University Medical Center, Stanford, CA, USA
c
Department of Radiology , Stanford University Medical Center, Stanford, CA, USA
d
Stanford Stroke Center , Stanford University Medical Center, Stanford, CA, USA
Accepted 29 August 2000
Abstract
In a model of experimental stroke, we characterize the effects of mild hypothermia, an effective neuroprotectant, on fluid shifts, cerebral perfusion and spreading depression SD using diffusion- DWI and perfusion-weighted MRI PWI. Twenty-two rats
underwent 2 h of middle cerebral artery MCA occlusion and were either kept normothermic or rendered mildly hypothermic shortly after MCA occlusion for 2 h. DWI images were obtained 0.5, 2 and 24 h after MCA occlusion, and maps of the apparent diffusion
coefficient ADC were generated. SD-like transient ADC decreases were also detected using DWI in animals subjected to topical KCl application n
54 and ischemia n56. Mild hypothermia significantly inhibited DWI lesion growth early after the onset of ischemia as well as 24 h later, and improved recovery of striatal ADC by 24 h. Mild hypothermia prolonged SD-like ADC transients and further
decreased the ADC following KCl application and immediately after MCA occlusion. Cerebral perfusion, however, was not affected by temperature changes. We conclude that mild hypothermia is neuroprotective and suppresses infarct growth early after the onset of
ischemia, with better ADC recovery. The ADC decrease during SD was greater during mild hypothermia, and suggests that the source of the ADC is more complex than previously believed.
2000 Elsevier Science B.V. All rights reserved.
Theme : Disorders of the nervous system
Topic : Ischemia
Keywords : Mild hypothermia; Rat; Magnetic resonance imaging; Stroke; Spreading depression
1. Introduction the extent of protection seen with only modest reductions
in brain temperature [14]. Diffusion-weighted magnetic While mild hypothermia has been shown to be neuro-
resonance imaging DWI is capable of non-invasively protective against cerebral ischemia, the precise mecha-
detecting fluids shifts following experimental stroke with nisms are not well known. Alterations in cerebral metabo-
quantitative estimates determined by computing the appar- lism and blood flow are known to play some role in this
ent diffusion coefficient ADC [38,40]. ADC abnor- protective effect [33,39], although this cannot fully explain
malities detected by DWI have been correlated with ATP
1 1
depletion, tissue acidosis, decreases in Na ,K -ATPase
1
activity and K concentration [2,38]. These metabolic
Corresponding author. Tel.: 11-650-723-4448; fax: 11-650-723-
disturbances occur when the ADC decreases 35–50 of
4451.
normal or more. If mild hypothermia’s protective effects
E-mail address : yenaristanford.edu M.A. Yenari.
1
are, in part, due to preservation of ion gradients, DWI
Present address: NMR Center, Massachusetts General Hospital, Boston, MA, USA.
should be capable of detecting this. Perfusion-weighted
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 4 2 - 5
M .A. Yenari et al. Brain Research 885 2000 208 –219
209
MRI PWI can be used to evaluate cerebral perfusion. within cerebral cortex and striata. Brain temperature was
Although PWI does not precisely reflect regional cerebral reduced to 35
8C, 338C, 308C and 288C by placing the blood flow rCBF, it is a non-invasive technique which
animal on a cooling blanket and spraying ethanol onto the can provide information regarding microvascular patency
body, then applying cool air from a hair dryer hose. [41,62]. As these techniques [3,58,60] and hypothermic
Temperature was maintained for 15–20 min prior to therapies [35,51] are beginning to gain interest at the
cooling to the next level. To determine the effects of clinical level, we utilize DWI and PWI to study the
temperature changes during ischemia, temperature probes temporal and regional evolution of mild hypothermia in an
were stereotaxically placed into each striata and a third experimental model of transient focal cerebral ischemia.
probe was placed in the rectum. Temperatures were DWI can also be used to detect transient declines in
monitored during conditions of ischemic normothermia ADC which correspond electrophysiologically with the
n 51 and mild hypothermia n51 as described sub-
transient depolarizations or spreading depressions SD sequently.
observed following ischemia [5,6,17,20,31,48–50,54]. SDs which occur during cerebral ischemia are thought to
2.2. Effects of temperature on ADC contribute to infarct growth by altering ion gradients or
increasing extracellular glutamate [20]. The extent and As micromolecular diffusion is altered with temperature
distribution of SDs also appear to be correlated with changes, the relationship between brain ADC and tempera-
expression of various genes, such as immediate early genes ture was established in our model. Using the correlation
[19], cyclooxygenase [37] and protein kinase C PKC data from the above experiment, we monitored rectal
[29]. While the SDs may result in worsening of ischemic temperature during scanning in this experiment and all
injury, pre-insult induction of SDs by KCl application may subsequent experiments. Three anesthetized non-ischemic
actually protect the brain from subsequent ischemic events animals underwent DWI imaging with brain temperatures
ischemic tolerance [26,27,36]. An earlier report showed varied from 30
8C to 408C. Rectal temperatures were varied that mild hypothermia slows the propagation of the SDs
as described above and DWI images were performed at within cortex, as detected by DC potential measurements
each temperature. Trace DWI images were generated as [59]. We now show complementary results using DWI,
described subsequently in the MRI protocol section. Re- which has the advantage of being non-invasive and offers
gions of interest ROIs were identified within regions of anatomical resolution. To our knowledge, this is the first
cortex, striatum and thalamus, and ADCs from fitted maps report characterizing the temperature dependence of SD-
were measured within these ROIs. Correction curves were like ADC changes in ischemia and KCl models using
determined for each of the structures as a function of DWI.
temperature. 2.3. Ischemia model
2. Materials and methods
