【摘要】：目的： 評估MR定量磁敏感圖(quantitative susceptibility mapping, QSM)對正常人與血液透析病人腦鐵含量測量的可行性,首先利用QSM對不同年齡正常人腦鐵含量進行測量,觀察腦內(nèi)鐵含量的分布特性及其隨年齡的變化趨勢。然后,采用QSM成像技術(shù)測量血液透析病人腦內(nèi)額葉白質(zhì)及深部灰質(zhì)核團的磁敏感值并與年齡、性別均匹配的正常人所測的相應(yīng)磁敏感值進行對比分析,探討磁敏感值與神經(jīng)精神病學測試評分、流行病學及臨床血液生化指標的相關(guān)性。 資料與方法： 采用Siemens MAGNETOM Trio Tim3.0T超導(dǎo)磁共振掃描儀,首先,于2012年11月至2013年7月間從天津當?shù)鼐用袷占】涤依终Ｈ?3名,男24名,女39名,年齡20至63歲,平均年齡37±13歲。所有正常人均行常規(guī)磁共振成像(magnetic resonance imaging, MRI)和未濾波磁敏感加權(quán)成像(susceptibility weighted imaging, SWI)掃描,獲得正常顱腦SWI未濾波相位圖和幅度圖,利用SMART后處理軟件對未濾波相位圖和幅度圖進行后處理得到QSM圖,利用SPIN軟件手工繪出QSM圖中雙側(cè)額葉白質(zhì)及各灰質(zhì)核團(尾狀核、蒼白球、殼核、背側(cè)丘腦、紅核、黑質(zhì)及齒狀核)的感興趣區(qū)(region of interest, ROI),測量ROI區(qū)的磁敏感值,并與兩篇文獻中報道的分別對尸體腦組織染色及采用電耦合等離子體質(zhì)譜成像法進行元素分析所獲得的腦內(nèi)各結(jié)構(gòu)的鐵含量進行線性相關(guān)分析,觀察兩者的一致性,采用秩和檢驗比較左右兩側(cè)額葉白質(zhì)及各灰質(zhì)核團間的統(tǒng)計學差異,利用Spearman相關(guān)分析探討各ROI區(qū)的磁敏感值與年齡的相關(guān)性。然后,收集2012年11月至2013年12月在我院進行血液透析的病人53名(男31名,女22名),年齡21至75歲,平均年齡47.4±13.5歲,平均透析時間26.7個月(1至114個月),同時從天津當?shù)亟】稻用袷占?5名正常人(男18名,女27名)作為對照組,年齡25至70歲,平均年齡42.3±11.7歲。所有正常人及血液透析病人均為右利手,并采用3.0T MR掃描儀進行常規(guī)MRI與未濾波SWI掃描。利用未濾波相位圖像通過后處理獲得QSM圖,分別于QSM圖像上測量血液透析病人與正常人雙側(cè)腦內(nèi)額葉白質(zhì)與深部灰質(zhì)核團的磁敏感值,采用兩獨立樣本t檢驗比較血液透析病人與正常人之間腦內(nèi)額葉白質(zhì)與深部灰質(zhì)核團的磁敏感值、神經(jīng)精神病學測試評分的差異性。采用Spearman相關(guān)分析觀察血液透析病人腦內(nèi)額葉白質(zhì)與深部灰質(zhì)核團的磁敏感值與神經(jīng)精神病學測試評分間的相關(guān)性。采用多元逐步回歸分析法觀察血液透析病人腦內(nèi)額葉白質(zhì)與深部灰質(zhì)核團的磁敏感值與流行病學及臨床血液生化指標間的相關(guān)性。 結(jié)果： 本研究所測各ROI磁敏感值與兩篇文獻(Hallgren和Sourander及Langkammer)中報道的分別對尸檢腦組織染色及采用電耦合等離子體質(zhì)譜成像法進行元素分析所獲得的腦內(nèi)各結(jié)構(gòu)的鐵含量具有很高的正相關(guān)性(r=0.905, P=0.002; r=0.900,P=0.037): (1)正常人蒼白球的磁敏感值最大,其次為黑質(zhì),額葉白質(zhì)的磁敏感值最小(磁敏感值分別為95.019ppb、86.687ppb、-12.845ppb); (2)正常人尾狀核、黑質(zhì)、紅核及齒狀核左右兩側(cè)磁敏感值之間均存在統(tǒng)計學差異(P0.05)； (3)正常人左右兩側(cè)蒼白球的磁敏感值男女性別之間均存在統(tǒng)計學差異,左側(cè)蒼白球P值為0.024,右側(cè)蒼白球P值為0.016； (4)正常人雙側(cè)尾狀核、殼核、紅核、齒狀核的磁敏感值均與年齡具有止相關(guān)性(P0.05)；雙側(cè)尾狀核、殼核、紅核及齒狀核的平均磁敏感值亦與年齡呈正相關(guān)(P0.05)； (5)血液透析病人左右兩側(cè)尾狀核、殼核、黑質(zhì)、紅核及齒狀核的磁敏感值均高于正常人左右兩側(cè)相應(yīng)核團的磁敏感值(P均0.01)； (6)血液透析病人左右兩側(cè)尾狀核的磁敏感值與簡易精神狀態(tài)評價量表(Mini-Mental State Examination, MMSE)測試評分均呈負相關(guān)(左側(cè)r=-0.415；右側(cè)r=-0.311,P均0.05)； (7)在血液透析病人中,腦內(nèi)一些結(jié)構(gòu)的磁敏感值與流行病學及臨床血液生化指標間存在相關(guān)性。透析時間的長短與左右兩側(cè)殼核及右側(cè)背側(cè)丘腦的磁敏感值均呈正相關(guān)；膽固醇含量與左側(cè)尾狀核的磁敏感值呈正相關(guān)；未飽和鐵結(jié)合力與左側(cè)蒼白球的磁敏感值呈正相關(guān)；透析后收縮壓與右側(cè)蒼白球的磁敏感值呈正相關(guān)；β2微球蛋白與左側(cè)背側(cè)丘腦的磁敏感值呈正相關(guān)；血紅蛋白與右側(cè)齒狀核的磁敏感值呈正相關(guān)；C反應(yīng)蛋白與右側(cè)額葉白質(zhì)的磁敏感值呈正相關(guān)；透析后脈壓與右側(cè)黑質(zhì)的磁敏感值呈負相關(guān)(P0.05)； (8)血液透析病人雙側(cè)額葉白質(zhì)及腦內(nèi)深部灰質(zhì)核團的磁敏感值與血清鐵蛋白含量均無相關(guān)性(P0.05)； 結(jié)論： 利用SWI未濾波相位圖與幅度圖后處理獲得的QSM圖能清晰顯示腦內(nèi)富含鐵質(zhì)的結(jié)構(gòu),如灰質(zhì)核團,表現(xiàn)為高信號；QSM圖能較準確評估腦內(nèi)各結(jié)構(gòu)的鐵含量,與對尸檢腦組織染色獲得的各結(jié)構(gòu)鐵濃度結(jié)果一致；雙側(cè)尾狀核、殼核、紅核、齒狀核的鐵含量均隨年齡的增長具有增加的趨勢。 血液透析病人腦內(nèi)一些灰質(zhì)核團(雙側(cè)尾狀核、殼核、黑質(zhì)、紅核及齒狀核)的鐵沉積較正常人相應(yīng)灰質(zhì)核團增多,并且一些核團的鐵沉積與透析時間的長短呈正相關(guān),即隨透析時間的延長而增加。尾狀核內(nèi)磁敏感值的升高可以反映神經(jīng)認知功能的損害,尤其是執(zhí)行功能的損害。磁敏感值可以作為一種反映腦內(nèi)鐵含量變化的臨床指標。
[Abstract]:Objective:
To evaluate the feasibility of quantitative susceptibility mapping (QSM) in measuring brain iron content in normal subjects and hemodialysis patients, the distribution characteristics of brain iron content and its changing trend with age were observed by using QSM. The magnetic susceptibility values of frontal white matter and deep gray matter nuclei in hemodialysis patients were compared with those of normal subjects matched with age and sex. The correlation between magnetic susceptibility values and neuropsychiatric test scores, epidemiology and clinical blood biochemical indexes were discussed.
Materials and methods:
Siemens MAGNETOM Trio Tim 3.0T superconducting magnetic resonance scanner was used. Firstly, 63 healthy right-handed normal persons, 24 males and 39 females, aged 20 to 63 years, with an average age of 37 13, were collected from Tianjin residents between November 2012 and July 2013. All normal subjects underwent conventional magnetic resonance imaging (MRI) and unfiltered MRI. The unfiltered phase and amplitude maps of normal brain SWI were obtained by susceptibility weighted imaging (SWI). The unfiltered phase and amplitude maps were processed by SMART post-processing software to obtain QSM maps. The bilateral frontal white matter and gray matter nuclei (caudate nucleus, pale) in QSM maps were manually drawn by SPIN software. The region of interest (ROI) of the sphere, putamen, dorsal thalamus, red nucleus, substantia nigra and dentate nucleus was measured. The magnetic susceptibility values of the ROI were linearly correlated with the iron contents of the brain structures obtained by elemental analysis using electro-coupled plasma mass spectrometry (ECP-MS) and staining of cadaveric brain tissues, respectively, as reported in the two literatures. Then, 53 patients (31 males and 22 females) undergoing hemodialysis in our hospital from November 2012 to December 2013 were collected. Mean dialysis time was 26.7 months (1 to 114 months). Forty-five normal subjects (18 males and 27 females) aged 25 to 70 years old, with an average age of 42.3 to 11.7 years, were collected from Tianjin local healthy residents as control group. All normal subjects and hemodialysis patients were right-handed and entered with a 3.0 T MR scanner. Routine MRI and unfiltered SWI scans were performed. QSM images were obtained from unfiltered phase images. Magnetic susceptibility values of bilateral frontal white matter and deep gray matter nuclei were measured on QSM images of hemodialysis patients and normal subjects respectively. Two independent t-test samples were used to compare frontal white matter and deep gray matter between hemodialysis patients and normal subjects. Spearman correlation analysis was used to observe the correlation between magnetic susceptibility of white matter of frontal lobe and deep gray matter nucleus of hemodialysis patients and neuropsychiatric test scores. Multivariate stepwise regression analysis was used to observe the frontal lobe of hemodialysis patients. The correlation between magnetic susceptibility of white matter and deep gray nuclei and epidemiological and clinical blood biochemical indices.
Result:
The ROI magnetic susceptibility values measured in this study were positively correlated with the iron content of the brain structures obtained from autopsy brain tissue staining and elemental analysis using electro-coupled plasma mass spectrometry (r = 0.905, P = 0.002; r = 0.900, P = 0.037), respectively.
(1) The magnetic susceptibility of globus pallidus in normal subjects was the highest, followed by substantia nigra, and the magnetic susceptibility of frontal white matter was the smallest (magnetic susceptibility values were 95.019 ppb, 86.687 ppb, - 12.845 ppb, respectively).
(2) There were significant differences in magnetic sensitivity between the caudate nucleus, substantia nigra, red nucleus and dentate nucleus (P 0.05).
(3) There were significant differences in magnetic sensitivity between male and female on both sides of globus pallidus in normal subjects. The P value of left globus pallidus was 0.024, and that of right globus pallidus was 0.016.
(4) The magnetic susceptibility values of bilateral caudate nucleus, putamen nucleus, red nucleus and dentate nucleus in normal subjects were all correlated with age (P 0.05), and the mean magnetic susceptibility values of bilateral caudate nucleus, putamen nucleus, red nucleus and dentate nucleus were positively correlated with age (P 0.05).
(5) The magnetic susceptibility values of caudate nucleus, putamen nucleus, substantia nigra, red nucleus and dentate nucleus on both sides of hemodialysis patients were higher than those of normal people (P 0.01).
(6) There was a negative correlation between the magnetic sensitivity of the caudate nucleus on both sides of hemodialysis patients and the Mini-Mental State Examination (MMSE) score (r =-0.415 on the left side, R =-0.311 on the right side, P 0.05).
(7) In hemodialysis patients, the magnetic susceptibility values of some brain structures were correlated with the epidemiological and clinical blood biochemical parameters. The duration of dialysis was positively correlated with the magnetic susceptibility values of both left and right putamen and right dorsal thalamus, and the content of cholesterol was positively correlated with the magnetic susceptibility values of left caudate nucleus. Force was positively correlated with the magnetic susceptibility of the left globus pallidus; systolic blood pressure was positively correlated with the magnetic susceptibility of the right globus pallidus after dialysis; beta 2 microglobulin was positively correlated with the magnetic susceptibility of the left dorsal thalamus; hemoglobin was positively correlated with the magnetic susceptibility of the right dentate nucleus; and C-reactive protein was positively correlated with the magnetic susceptibility of the right frontal There was a negative correlation between the pulse pressure after dialysis and the susceptibility value of the right substantia nigra (P0.05).
(8) The magnetic susceptibility values of bilateral frontal white matter and deep gray matter nuclei in hemodialysis patients were not correlated with serum ferritin content (P 0.05).
Conclusion:
QSM maps obtained by SWI unfiltered phase mapping and amplitude mapping can clearly show the iron-rich structures in the brain, such as gray matter nuclei, showing high signal; QSM maps can accurately assess the iron content of brain structures, consistent with the results obtained by autopsy brain tissue staining; bilateral caudate nucleus, putamen nucleus, red nucleus, tooth. The iron content of the nucleus increased with age.
The iron deposition in some gray matter nuclei (bilateral caudate nucleus, putamen nucleus, substantia nigra, red nucleus and dentate nucleus) in hemodialysis patients was higher than that in normal subjects, and the iron deposition in some nuclei was positively correlated with the duration of dialysis, that is, increased with the prolongation of dialysis time. Magnetic susceptibility can be used as a clinical index to reflect the changes of iron content in the brain.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R445.2

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