RESUMEN
The impact of brain imaging on the assessment of tissue status is likely to increase with the advent of treatment methods for acute cerebral ischemia. Multimodal magnetic resonance imaging (MRI) demonstrates potential for selecting stroke therapy patients by identifying the presence of acute ischemia, delineating the perfusion defect, and excluding hemorrhage. Yet, the identification of tissue subject to reversible or irreversible ischemia has proven to be difficult. Here, the authors show that T1 relaxation time in the rotating frame, so-called T1rho, serves as a sensitive MRI indicator of cerebral ischemia in the rat. The T1rho prolongs within minutes after a drop in the CBF of less than 22 mL 100 g(-1) min(-1). Dependence of T1rho on spin-lock amplitude, termed as T1rho dispersion, increases by approximately 20% on middle cerebral artery (MCA) occlusion, comparable with the magnitude of diffusion reduction. The T1rho dispersion change dynamically increases to be 38% +/- 10% by the first 60 minutes of ischemia in the brain region destined to develop infarction. Following reperfusion after 45 minutes of MCA occlusion, the tissue with elevated T1rho dispersion (yet normal diffusion) develops severe histologically verified neuronal damage; thus, the former parameter unveils an irreversible condition earlier than currently available MRI methods. The T1rho dispersion as a novel MRI index of cerebral ischemia may be useful in determination of the therapeutic window for acute ischemic stroke.
Asunto(s)
Isquemia Encefálica/diagnóstico , Imagen por Resonancia Magnética/métodos , Animales , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/patología , Arteriopatías Oclusivas/fisiopatología , Temperatura Corporal , Encéfalo/fisiopatología , Isquemia Encefálica/fisiopatología , Arterias Cerebrales , Circulación Cerebrovascular , Masculino , Proteínas del Tejido Nervioso/metabolismo , Fantasmas de Imagen , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
T1 relaxation in the rotating frame (T1rho) is a sensitive magnetic resonance imaging (MRI) contrast for acute brain insults. Biophysical mechanisms affecting T1rho relaxation rate (R1rho) and R1rho dispersion (dependency of R1rho on the spin-lock field) were studied in protein solutions by varying their chemical environment and pH in native, heat-denatured, and glutaraldehyde (GA) cross-linked samples. Low pH strongly reduced R1rho in heat-denatured phantoms displaying proton resonances from a number of side-chain chemical groups in high-resolution 1H NMR spectra. At pH of 5.5, R1rho dispersion was completely absent. In contrast, in the GA-treated phantoms with very few NMR visible side chain groups, acidic pH showed virtually no effect on R1rho. The present data point to a crucial role of proton exchange on R1rho and R1rho dispersion in immobilized protein solution mimicking tissue relaxation properties.