SPIO Label Macrophages Of Experimental Autoimmune Encephalomyelitis Model In Vivo And Study Of Multiple Sclerosis By ESWAN

PART ONE VALUE OF SUPERPARAMAGNETIC IRON OXIDE IN THE EXPERIMENTAL AUTOIMMNUNE ENCEPHALOMYELITIS MODELObjective:To compare the differences of T₂-weighted imaging(T₂W I ), gadolinium-diethvlenetriamine pentaacetic acid( Gd-D TPA) and superparamagnetic iron oxide( SPIO) in experimental autoimmune encephalomyelitis( EAE) model, and to explore the cytology marker of the active inflammation lesions by macrophages in multiple sclerosis ( MS ). Methods:In the subclinical phase, initial phase and peak-time phase of the clinical symptom in EAE model, 13 rats with EAE and 13 control rats were performed with T₂-weighted imaging(T₂WI) before the tail intravenous injection contrast agents, respectively. Then, all the rats were performed with T₁- weighted imaging (T₁ WI ) after 5 minutes by injection of Gd-DTPA and underwent with T₂*WI after 24 hours by injection of SPIO. The brains were removed instantly after the second magnetic resonance imaging ( MRI ). The pathology examinations included ED1 immunohistochemistry staining and Prussian blue staining.Results:Clinical symptoms of the rats in EAE model were present at the 11th day(D11), and reached peak-time phase at D14. MRI findings: SPIO images showed more hypointense lesions in EAE model, compared with the conventional T₂WI and Gd-DTPA enhancing images. Pathology examinations: ED1 immunohistochemistry staining revealed the infiltration of the inflammatory cells(mainly macrophages) at the site where the hypointense areas were seen on SPIO enhancing images. Prussian blue staining displayed the presence of blue particles within the cytoplasm of macrophages in the lesions. All the control rats were negative. Conclusion:SPIO is superior to Gd-DTPA to display the activity of macrophages in the EAE model, and it confirms the infiltration of perivascular inflammatory cells(mainly macrophages).PART TWO STUDY OF PATIENTS WITH MULTIPLE SCLEROSIS BY 3-D ENHANCED T₂-STAR ANGIOGRAPHYCHAPTER ONE ANALYSIS OF IRON DEPOSITION IN THE BRAIN LESIONS OF PATIENTS WITH MULTIPLE SCLEROSIS BY 3-D ENHANCED T₂-STAR ANGIOGRAPHYObjective:To explore the values of 3-D enhanced T₂-star angiography (ESWAN) in detecting the iron deposition of the brain in patients with MS. Methods:1) Conventional MRI and 3-D ESWAN were performed in the 22 patients with releaseing-r emitting MS (RR- MS )and in the 22 age- and gender-matched normal control group.2) Both the magnitude images and the phase images were available after original ESWAN data post processing. The manifests of MS lesions were evaluated on conventional MRI and ESWAN by two experienced radiologists with blind methods. Fllow up the phase changes of the lesions in 10 patients with MS after half a year.3) The phase values were measured for MS lesions between the semioval center and periventricular white matter and corresponding to the regions in the normal control group.4) The Wilcoxon rank test was used to compare the differences of the phase values between the lesions in the MS patients and the corresponding to the regions in the normal control group, and to compare the phase differences of the lesions between the basin time and follow-up. Spearman rank correlation analysis were used to analyze the correlations among the phase values of MS lesions, expanded disability status scale( EDSS) scores and disease duration of MS patients.Results:1) MS lesions were observed in the magnitude images and the phase images, respectively and together. 164 ( 25.2%) lesions were detected in the magnitude images, 27 3 ( 42.0% ) lesions were detected on the phase images, and 213 ( 32.8% ) detected on the two images together. A total of 650 lesions were observed in the ESWAN. ESWAN images can detect more 42 lesions comparing to the conventional MRI scans. Among 486 ( 273+213 ) lesions observed in the phase images, 31.5% lesions were homogeneous hypointensity, 6.9% lesions were ring hypointensity, and 36.4% lesions were inhomogeneous hypointensity.2) Fllow-up the changes of the lesions in 10 MS patients. The same number of the lesions were seen on conventional MRI. However, 172 lesions were seen on the phase images, more 30 lesions were seen comparing with the basin time.3) "Penetrating veins" presented in 65.2% periventricular lesions. The "penetrating veins" were dilated and prolonged in 30.5% acute lesions, thin and short in 32.9% chronic lesions. However, the "penetrating veins" of 1.8% chronic lesions in 5 stable MS patients showed expanded and prolonged slightly.4) The average phase value of the lesions (- 0.05±0.08) in the patients with RR-MS was significantly lower than that of the corresponding regions( 0.06±0.05) in the normal control group( Z=22.30, P< 0.01 ). The phase values of the lesions were( - 0.06±0.05) and (- 0.13±0.13 )for the basin time and flow-up, respectively, there were sign ificant differences( Z =22.30 ,P< 0.01 ).5) The phase values of the MS lesions were significantly correlated to the higher EDSS and the longer disease duration of the patients with RR- MS, respectively (r_s=-0.98, P<0.01; r_s=0.99, P <0.01 ).Conclusions:ESWAN can be helpful in evaluating abnormal iron deposition in MS lesions, providing the important values for the pathogenesis and pathological study for MS patients.CHAPTER TWO STUDY OF BRAIN DEEP VEINS IN PATIENTS WITH MULTIPLE SCLEROSIS WITH 3-D ENHANCED T₂-STAR WEIGHTED ANGIOGRAPHY BY 3.0 TObjective:To explore the values of ESWAN in the changes of the cerebral internal veins and their tributaries and especially the deep medullary veins in the patients with MS. Methods:1) Conventional MRI and ESWAN were performed in 53 MS patients and 53 age- and gender-matched normal control group. MS involved the bains of 43 patints and spinal cords of 10 patients, respectively. In the 43 patients whose brains were involved by MS, the disease durations ware less than 0.5 year in 5 MS patients, between 0.5 year and 2 years in 17 MS patients, more than 2 years in 21 MS patients. In the 10 patients whose spinal cords were involved by MS, the disease durations were more than 2 years.2) ESWAN venograms were obtained by performing minimum intensity projection(MinIP) technique. The changes of the cerebral internal veins and their main tributaries and the deep medullary veins in the MS patients were evaluated by two experienced radiologists with double blind methods, comparing with the normal control group.3) Kruskal Wallis analysis and Wilcoxon rank test were used for statistics.Results:1) In the 43 patients whose brains were involved by MS, the mean scores of the cerebral internal veins and their main tributaries were(1.96±0.71) for 23 active MS patients, (1.25±0.44) for 20 chronic MS patients, and ( 3.00±0.00 ) for the normal control group, respectively, there were significant differences among them (H= 67.65, P<0.01). The mean scores of the cerebral internal veins and their main tributaries in the active and chronic MS patients were lower than that of the normal control group, respectively (1.96±0.71 vs. 3.00±0.00, Z =-6.67, P<0.01; 1.25±0.44 vs. 3.00±0.00, Z=-7.76, P<0.01). The mean score of the cerebral internal veins and their main tributaries in the active MS patients was higher than that of the chronic MS patients(Z=-3 .35 ,P<0.01).2) In the 43 patients whose brains were involved by MS, the deep medullary veins diminished and shortened in 38 MS patients whose disease duration were more than 0.5 year, while increased and prolonged in 5 MS patients whose disease duration were less than 0.5 year.3) The "penetrating veins" showed dilated and prolonged in 35 periventricular enhanced lesions in the 23 active MS patients, thin and short in 80 periventricular non-enhanced lesions in the 20 chronic MS patients, However, expanded and prolonged slightly in 6 periventricular non-enhanced lesions in 3 chronic MS patients.4) In the 10 MS patients whose spinal cords were involved by MS, the deep medullary veins also diminished and shortened.Conclusions:ESWAN can detect the changes of the cerebral internal veins and their tributaries, especially the deep medullary veins in different stage of MS patients, provide important values for the pathogenesis and pathological study for MS patients.