NMR Imaging of the Apparent Diffusion Coefficient (ADC) for the Evaluation of Metabolic Suppression and Recovery after Prolonged Cerebral Ischemia

Adult normothermic cats were submitted to 1-h complete cerebrocirculatory arrest by intrathoracic occlusion of the internal mammary, the innominate, and the subclavian arteries in combination with pharmacologically induced hypotension. After ischemia, recirculation was initiated at different blood pressure levels to manipulate the postischemia resuscitation conditions. The resulting spectrum of postischemic recovery was studied by combining nuclear magnetic resonance imaging of the apparent diffusion coefficient (ADC) with pictorial assays of brain tissue pH, ATP, glucose, and lactate. Before ischemia, the mean ADC (average of seven coronal slices of five cats) was 713 ± 40 × 10⁻⁶ mm²/s. After 10-min ischemia, ADC declined to 68% of control and after 50 min slightly further to 63% of control. During recirculation after 1-h ischemia, recovery of ADC varied depending on the initial reperfusion pressure and other systemic variables. In two animals ADC only transiently increased followed by a secondary decline below the postischemic level. In three other animals ADC returned to near control within 1 h of recirculation. The comparison of ADC changes with previously reported changes in extracellular volume revealed a close relationship, supporting the notion that ADC is a function of the intra/extracellular water compartmentation. Recovery of ADC correlated closely with tissue pH and metabolic recovery, studied 3 h after the initiation of recirculation. Animals without recovery of ADC exhibited global depletion of ATP and glucose and severe lactacidosis, whereas animals with recovery of ADC showed replenishment of ATP and glucose to near control and a substantial reversal of lactacidosis. Our data demonstrate that imaging of ADC provides reliable information about the metabolic state of the brain and can be used to monitor, with high temporal and regional resolution, the manifestation and reversal of ischemic brain injury.