The firstin vivomagnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected withPlasmodium bergheiANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the firstin vivodemonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

Genetically modified mouse models of many human diseases reflecting cardiovascular alterations are currently available. To date, little information on absolute myocardial perfusion in mice is found in the literature. High‐resolution quantitative myocardial blood flow maps (in‐plane resolution 156 × 312 μm², slice thickness 1.5 mm) have been obtained noninvasively within 25 min at 4.7 T in 30 freely breathing C57/Bl6J mice using electrocardiogram‐ and respiration‐gated spin labeling magnetic resonance imaging (MRI). Regional myocardial blood flow measurements were carried out, and the effects of isoflurane at two different concentrations and ketamine/xylazine anesthesia were assessed. The mean blood flow value in the left ventricular myocardium was 6.0 ± 1.9 mL g⁻¹ min⁻¹ under ketamine/xylazine and 6.9 ± 1.7 mL g⁻¹ min⁻¹ (group average ± SD) under isoflurane (1.25%). Under the influence of higher isoflurane concentration (2.00%), myocardial blood flow increased dramatically to 16.9 ± 1.8 mL g⁻¹min⁻¹ with no significant change in heart rate. This work illustrates the feasibility of noninvasive quantitative myocardial perfusion mapping in mice using MRI. The study of the influence of anesthesia shows that myocardial blood flow is highly sensitive to isoflurane concentration. The method employed offers a noninvasive approach to longitudinal studies of murine models of cardiac disease. Magn Reson Med 53:601–606, 2005.