Ra Knight

Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats.

Background and Purpose This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods. Methods Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory. Results Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the “apparent” diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions. Conclusions The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage.

HISTOPATHOLOGICAL CORRELATIONS OF NUCLEAR-MAGNETIC-RESONANCE IMAGING PARAMETERS IN EXPERIMENTAL CEREBRAL-ISCHEMIA

Changes in the nuclear magnetic resonance (NMR) parameters of spin-lattice relaxation (T1), spin-spin relaxation (T2), proton density (rho), and water diffusion (DNMR) were measured over time together with the histopathological status in three regions of rat brain cortex after permanent middle cerebral artery occlusion (MCA-O). Histological response ranged from severe irreversible damage (necrosis and cavitation) to relatively mild and apparently reversible damage. DNMR was the only NMR parameter which demonstrated a statistically significant change in all three regions of brain studied. Additionally, rho was significantly increased only in the region of brain studied which eventually progressed to necrosis and cavitation. Finally, data are presented which indicate that changes in T2, DNMR, and rho can occur independently of one another.

Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion

The regional distribution and temporal evolution of the diffusion coefficient (Dw) of water in rat brain was measured during and after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h of middle cerebral artery occlusion, induced by intracarotid insertion of a filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance imaging were performed before, and at various time points after MCA occlusion, ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles of Dw differ between the severely and the least damaged regions of tissue. In the core of the lesion, where the tissue evolved to necrosis, Dw declined significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained depressed until 24 h after withdrawal of the suture. However, no statistically significant decline in Dw was found in the perifocal regions containing morphologically intact cells. Perfusion MRI qualitatively exhibited a hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively. A significant (r > or = 0.71, P < 0.01) correlation was found between delta Dw (the difference in Dw between the ipsilateral ischemic and homologous contralateral control regions) obtained immediately before withdrawal of the suture (2 h of ischemia) and at specific early time points after withdrawal of the suture, and the degree of ischemic cell damage. No significant (P > 0.01) correlation was detected at an early time points of ischemia or at other time points after withdrawal of the suture.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats.

We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.

Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats.

We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham-operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham-operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death.

Reduction of hyperthermic ischemic acidosis by a conditioning event in cats.

We investigated the effects of multiple episodes of cerebral ischemia on intracellular brain pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Four cats were subjected to two 16-minute episodes of complete global cerebral ischemia 6 hours apart; the second episode occurred under hyperthermic conditions (mean +/- SD body temperature 40.8 +/- 0.4 degrees C). Intracellular pH in these four cats was compared with that in nine cats subjected to a single 16-minute episode of complete global cerebral ischemia under hyperthermic conditions (mean +/- SD body temperature 40.6 +/- 0.2 degrees C). Intracellular pH during hyperthermic recirculation was significantly (p less than 0.03) greater in cats subjected to a previous ischemic event than that in cats subjected to only a single hyperthermic ischemic event. We speculate that the induction of heat shock proteins by an initial ischemic event may protect brain tissue from further ischemic insult.

Changes in the Biophysical Environment of Water Following Focal Brain Ischemia in the Rat

The biophysical environment of water in living systems is of great interest to the study of cell function. Magnetic resonance imaging (MRI) offers the ability non–invasively to assess specific parameters which are sensitive to changes in the biophysical environment of water in tissue. The degree by which water is “influenced” by cellular constituents is defined as that level of influence which is sufficient to result in a measurable difference in MRI parameters. The MRI parameters of interest include the measurement of 1H spin–spin (T2) and spin–lattice (T1) relaxation times, water density (p), the apparent diffusion coefficient of water (ADCW), and exchange rates (Kw) between “bound” and “bulk” water.

Relative assessment of brain iron levels using MRI at 3 tesla

High field MR (magnetic resonance) images can be made sensitive to the relative concentration of tissue iron through the use ofT*2-weighted contrast. This has enabled tissue iron levels to be assessed noninvasively by quantification of transverse relaxation rates. High field MRI may provide a new method to investigate neurological diseases which result in alteration of brain iron levels in specific areas of the human brain. Parkinsons disease (PD) results in an increase in iron concentration within the lateral region of the substantia nigra (SN), and provides one potential application of this methodology. Preliminary results of our findings are that there is a significant difference in SN iron levels in PD patients compared with age-matched controls, assessed by quantification of the reversible line-broadening component of transverse relaxation rate,R′2.