^1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable forthrombolytic therapy

BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy (1H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN: Randomly controlled animal study. SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES: ① Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS: Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P < 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P < 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P < 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P < 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA > 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum. CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.

1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable for thrombolytic therapy

BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 'H-magnetic resonance spectroscopy ('H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke.OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 'H-MRS technology and investigate its adaptability. DESIGN: Randomly controlled animal study. SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260 - 300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 1H/kg urokinase was dissolved in 2 Ml saline and the operation lasted for 5 minutes. ②1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 'H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope.MAIN OUTCOME MEASURES: ①Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ②T2W image at 24 hours after the thrombolysis; ③pathological observation of brain tissue.RESULTS: Eleven rats were all involved in the final analysis. ①Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P ＜ 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P ＜ 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P ＜ 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P ＜ 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ②T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA ＞ 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pylcnosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum.CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination.②1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.