The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, 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 first in vivo demonstration 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.
An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution ؍ 234 ؋ 468 m 2 ) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average ؎ SD) was 5.5 ؎ 0.7 ml g -1 min -1 . In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 ؎ 1.9 ml g -1 min -1 . The proposed method is particularly useful for the study of small rodents at high fields.Magn Reson Med 51:62-67, 2004.
Traditional setups for in situ MR investigation of skeletal muscle function in animals use invasive systems for muscle stimulation and force measurement. These systems require surgical preparation and therefore exclude repetitive investigations on the same animal. This article describes a new experimental setup allowing strictly noninvasive MR investigations of muscle function in contracting rat gastrocnemius muscle using MR has proven its ability to investigate skeletal muscle function in situ. 31 P-Magnetic resonance spectroscopy ( 31 P-MRS) has been widely used to characterize muscle energy metabolism. It can measure intracellular pH and the concentration of the major phosphorylated compounds in contracting muscle with a time resolution of less than a second (1,2). These measurements may be used to quantify energy production of the different metabolic pathways, i.e., phosphocreatine (PCr) degradation, anaerobic glycolysis, and mitochondrial phosphorylation (3), as long as force output is recorded simultaneously with 31 P-MRS acquisition.
We tested whether the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle was related to fatigue level. Muscles (n= 44) were electrically stimulated to perform 6 min repeated isometric contractions at different frequencies; one non‐fatiguing protocol (stimulation at 0.8 Hz) and five fatiguing protocols (2, 3.2, 4, 5.2 and 7.6 Hz) were used. Anaerobic and oxidative ATP turnover rates were measured non‐invasively using 31P‐magnetic resonance spectroscopy. At the onset of the stimulation period, no signs of fatigue were measured in the six protocols and ATP cost of contraction did not differ significantly (P= 0.45) among protocols (mean value of 1.76 ± 0.11 mm (N s)−1). For the six protocols, ATP cost of contraction was significantly reduced (P < 0.05) at the end of the stimulation period when compared with the initial value. This reduction did not differ significantly (P= 0.61) among the five fatiguing protocols (averaging 35 ± 3 % of initial value), whereas isometric force decreased significantly as stimulation frequency increased. No significant correlation (P= 0.87, r2= 0.01) was observed between isometric force and ATP cost of contraction at the end of the stimulation period. In addition, this reduction was significantly lower (P < 0.05) for the non‐fatiguing protocol (67 ± 9 % of initial value) when compared with the fatiguing protocols. These results demonstrate that (i) the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle is not related to the fatigue level; (ii) surprisingly, this reduction was significantly larger during the fatiguing protocols compared with the non‐fatiguing protocol.
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