含铁模型建立及高铁动物体内器官铁沉积规律MRI研究
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摘要
目的：探讨能顺利完成MRI铁定量测定的含铁模型的建立方法；研究高铁动物实验模型体内器官的铁沉积分布规律。
材料与方法：
1、含铁模型的制备
单纯不同浓度含铁水模的制作：模型1,不同铁浓度多根小试管捆扎模型：1-16个50ml试管内分别从50-48.5ml依次递减O.1ml装入不等量蒸馏水,然后,从1～16管按等差递增依次注入剂量为150 mg／ml的右旋糖酐铁0-1.5ml,相邻管内铁剂量差别为O.1m1,将试管按浓度递增的顺序分4层摆放并固定；模型2,不同铁浓度多根大试管捆扎模型：1～12个300ml试管内分别从300-298.9ml依次递减O.1ml装入不等量蒸馏水。然后,从1-12管按等差递增依次注入右旋糖酐铁0-1.1ml,相邻管内铁剂量差别为0.1ml,将试管按浓度递增的顺序分3层摆放并固定；模型3,不同铁浓度单根小试管模型：1.5L塑料瓶,内装1.45L蒸馏水,每次MRI扫描后注入右旋糖酐铁1ml,共注射35ml；模型4,不同铁浓度单根大试管模型：5L塑料瓶,内装4.3L蒸馏水,每次MRI扫描后注入右旋糖酐铁10ml,共注射700ml。
不同浓度含铁模型的制作：模型5,模型3同人体捆扎模型：将模型3固定于正常人体的右季肋区；模型6,模型3同肌肉标本捆扎模型：将模型3同0.5kg猪肉标本捆绑固定；模型7,模型3与肌肉标本及纯水水袋捆扎模型：在模型3及0.5kg猪肉标本周围包裹1000ml的纯水水袋并固定；模型8,模型4同肌肉标本及纯水水袋捆扎模型：将模型4同2kg猪肉标本、3500ml纯水水袋按模型7摆放并固定；模型9,模型4同肌肉标本及动物皮层脂肪捆扎模型：将模型8的纯水水袋置换成富含脂肪的新鲜猪皮。含铁水模、肌肉标本及猪皮的摆放及固定同模型8。
2、高铁动物模型的制备
成年雄性新西兰白兔20只作为实验组。同种兔1只作为正常对照组。实验组兔按15mg／kg剂量深部肌肉注射含铁量为150mg／ml的右旋糖酐铁,每周注射一次,左右两侧后腿轮流注射,共注射15周。注射右旋糖酐铁前,对所有兔子进行MRI检查,定量分析正常兔的肝脏／肌肉信号强度比及肝脏T2值。每次注射右旋糖酐铁一周后复查MRI检查,并于第二天随机选取1或2只白兔,处死取部分肝脏、脾脏、心肌、肾脏、肠管、肺、睾丸与淋巴结进行铁沉积病理诊断,剩余肝组织烘干测LIC。正常对照组兔第一次进行MRI检查后,并取上述脏器组织进行病理检查。
3、MRI检查设备及扫描序列
含铁模型与高铁动物模型MRI检查设备及扫描序列相同。
扫描设备：3.0T PHILIPS磁共振。扫描参数：(1)信号强度比值采用GRE序列横断面扫描：TR 48ms,TE2.5ms,翻转角度60。,层厚4mm,层间距3mm,扫描层数4层。(2)T2值测量采用多回波序列横断面扫描：8回波横断位扫描：TR 2000ms,TE分别为8、16、24、32、40、48、56、64ms,层厚4mm,扫描1层,扫描时间约8分钟；4回波横断位扫描：TR2000ms,TE分别为6、12、18、24ms,层厚4mm,扫描1层,扫描时间约5～7分钟。
结果：
1、含铁模型MRI扫描表现
模型1和模型2 MRI扫描获得的图像质量欠佳,信号不均,伪影多,不能完成MRI测量；模型3与模型4 MRI扫描的图像质量好,信号均匀,未见明显伪影,只能进行T2值的测量。模型5 MPd图像信号均匀,未见明显伪影,但测得的信号强度比是含铁水模／人体肌肉信号强度比,未能完全脱离人体；模型6 MRI图像信号均匀,未见明显伪影,但是当含铁水模铁浓度升高到一定程度时MRI便停止扫描,未能成功完成MRI测量；模型8的MRI图像上,含铁水模的中央或与纯水水袋交界区产生范围很大的伪影,不能成功完成MRI扫描；模型7及模型9获得的MRI图像信号均匀,未见明显伪影,可以成功的完成信号强度比及T2值的测量。
2、高铁动物模型内脏铁沉积分布及MRI表现
肝脏及脾脏的铁沉积：正常组兔子,肝脏、脾脏病理铁染色未见铁沉积颗粒。注射1次铁剂后,仅有少量的肝窦有少许铁颗粒,LIC尚在正常值范围内,肝脏GRE图像信号未见明显减低,但肝脏／肌肉信号强度比及T2值均低于正常值范围,此时脾脏红髓已有较多的铁沉积颗粒。注射2次铁剂后,肝窦及少量肝细胞内见少量铁沉积颗粒,LIC超过正常值范围,GRE图像肝脏信号较前轻度减低,肝脏／肌肉信号强度比及T2值较前减低,此时脾脏红髓大量铁颗粒较前增多,铁沉积量变化较肝明显。此后,随注射次数的增多,出现铁沉积的肝窦及肝细胞逐渐增多,且其内的铁颗粒数目也逐渐增多,同时LIC随铁沉积颗粒的增多呈增加的趋势,肝脏／肌肉信号强度比、T2值及肝脏GRE图像信号随铁沉积颗粒的增多呈减低的趋势。注射12次铁剂以后,GRE图像肝脏信号达最低。而脾脏在第1次注射铁剂时,红髓已有较多的铁沉积颗粒,且随注射次数的增多而明显增加,当第4次注射铁剂后,虽然红髓的铁沉积颗粒随注射次数的增加仍较前增多,但增加的幅度很小。
心肌、肾脏、肺脏、肠管、睾丸及淋巴结注射在注射第3次铁剂前均未见铁沉积颗粒,自注射第3次铁剂后,不同注射时期兔子的上述器官病理切片上间或出现少量的铁染色颗粒。但由于所用动物模型的上述器官太小,MRI显示图像欠佳,或由于MRI检查线圈对受检器官的限制,不能进行MRI研究。
结论：
1、用不同铁浓度的含铁水模、动物肌肉标本及纯水水袋(或动物皮层脂肪)制备的含铁模型,能够成功的完成含铁水模／肌肉信号强度比值及T2值的测量。
2、不同方法制备的含铁模型各有优劣,其中模型3同肌肉标本及纯水水袋捆扎模型(模型7)与模型4同肌肉标本及动物皮层脂肪捆扎模型(模型9)在MRI铁定量测定中的应用价值最高。
3、高铁动物模型肝脏铁沉积颗粒数量随注射剂量的增加呈逐渐增多的趋势,且同LIC、GRE图像信号及MRI测量值之间相关性明显,具有较强的规律性；其它铁沉积的脏器规律性不明显,且由于器官太小或检查技术的限制,MRI难于进行评价。肝脏是铁沉积定量研究的最佳器官。
Objective
To explore the establishment methods of iron modle which can complete MRI quantitative determination; To study the iron distribution in Organs of Iron overload animal.
Materials and Methods
1、Preparation of iron modle
Making of simple iron water mold of different iron concentrations:Modle 1, Different iron concentrations of small multi-tube banding model:Injecting 50～48.5 ml distilled water in Number 1～16 50ml tubes respectively, and the difference of water amount in tubes in turn decreasing 0.1ml. Then increasingly injecting 0～1.5ml iron dextran for iron 150mg/ml in turn, and the difference of water amount in adjadjacent tubes is 0.1ml, and divided into 4 layers and placed and fixed increasingly; Modle 2, Different iron concentrations of big multi-tube banding model:Injecting 300～298.9ml distilled water in Number 1～12 300ml tubes respectively, and the difference of water amount in tubes in turn decreasing 0.1ml. Then increasingly injecting 0～1.1 ml iron dextran in turn, and the difference of water amount in adjadjacent tubes is 0.1ml, and divided into 3 layers and placed and fixed increasingly; Modle 3, Different iron concentrations of single small tube model:1.5L plastic bottle containing 1.45L distilled water, injected lml of iron dextran after each MRI scan for 35 times; Modle 4, Different iron concentrations of single big tube model:5L plastic bottle containing 4.3L distilled water, injected 10ml of iron dextran after each MRI scan for 70 times.
Making of different concentrations of iron model:Modle 5, Modle 3-Body banding model:Banding Modle 3 with right rib area of normal human; Modle 6, Modle 3-Muscle specimens banding model:Banding Modle 3 with 0.5kg pork specimens; Modle 7, Modle 3-Pure waterm bag-Muscle specimens banding model:Iron water mold and pork specimens as Modle 6, banded with 1000ml iron water bag arround them; Modle 8, Modle 4-Pure waterm bag-Muscle specimens banding model:Banded Modle 4 with 3500ml iron water bag and 0.5kg pork specimens as Modle 7; Modle 9, Modle 4-Muscle specimens-Animal fat cortex banding model:Just changeing the pure water bags of Modle 8 as fresh pig skin, and others are the same as Modle 8.
2、iron overload animal modle
20 adult male New Zealand white rabbits as the experimental group, one same species rabbit as a normal control group. Deep intramuscular injected iron dextran for iron 150mg/ml with the dose of 15mg/kg weekly in the experimental group, alternate the injection position right to left hind leg. Injected a total of 15 weeks. Before the iron dextran injection,MRI inspection was made to all rabbits, quantitative analysis of normal rabbit liver/muscle signal intensity ratio and T2 value of the liver. Every time one week after the injection of iron dextran to review the MRI,and the next day one or two rabbits were killed randomly, and getting some tissue of liver, spleen, heart, kidney, myocardium, lung, testosterone and lymph node to pathological diagnosis, and the remaining liver tissue were dried for the measurement of LIC by atomic spectrophotometer. Rabbit of control group were killed after the first MRI examination, Excise the tissue of multi-organ for pathological examination.
3、MRI examination equipment and sequences
MRI examination equipment and sequences are the same in the tests of iron modle and iron overload animal modle。
Magnetic resonance imaging studies were performed using a 3.0 T Philips system (Achieva 3.0T X-series). Scan parameters:(1) Transverse GRE sequences for signal intensity ratio were acquired with TR of 48ms, TE of 2.5ms, flip angle of 60°, sLICe thickness of 4mm, gap of 3mm, scanning four sLICes, completed scan within one breath. (2) T2 value measurement with a multiple spin-echo (SE) pulse sequence:8-echo axial scan for mild iron deposition were acquired with TR of 2000ms, TE of 8,16,24,32,40,48,56 and 64 ms, sLICe thickness of 4mm, scanning one sLICe, take time of about 8 minutes; 4-echo axial scan for severe iron deposition in the were acquired with TR of 2000ms, TE of 6,12,18 and 24 ms, sLICe thickness of 4mm, scanning one sLICe, take time of about 5 or 7 minutes.
Results
1、MRI features of the iron model
The image quality of Modle 1 and Modle 2 is poor, that having heterogeneous signals and much MRI artifacts, and MRI could not complete measure; The image quality of Modle 3 and Modle 4 is GREat, that having intensity signals and rarely MRI artifacts, but only to be measure the value of T2; The signals of Modle 5 are intensity, and having rarely MRI artifacts, but to be measure iron water mold / demic body muscle signal intensity ratio, which was not completely out of the body; The signals of Modle 6 are intensity, and having rarely MRI artifacts, but MRI stop scan as the concentration uppers to certain extent。The image of Modle 8 has much MRI artifacts in the middle of iron water mold or relating to the border area of iron water mold and pure water mold, so Modle 8 cannot complete measure; The signals of Modle 7 and Modle 9 are intensity, and having rarely MRI artifacts, and they can complete GRE scanning for iron water mold / muscle signal intensity ratio and multi-echo scanning for the T2 value of iron water mold。
2、iron distribution and MRI features of iron overload animal organs
Iron overload of liver and spleen:liver and spleen of normal rabbits had no iron deposition particle。After inject iron one time, small part sinusoids existed small number of particles, and LIC and signal of GRE image were narmal, but liver / muscle signal intensity ratio and T2 value were lower than normals, at the same time there were abundant iron particles in spleen。After inject iron twice time, sinusoids and some liver cells existed small number of particles, LIC was higher than normals, and signal of GRE image, liver / muscle signal intensity ratio and T2 value were lower than normals, there were more iron particles than it used to in spleen, and in which the quantity amount of iron particles were larger than in liver。After that, With increase injections, liver iron deposition particles gradual increased from part of sinusoids with small number of particles to all sinusoids and liver cells with abundant particles, and LIC showed an increasing trend, and signal of GRE image, liver / muscle signal intensity ratio and T2 value showed decreased trends。But, after the first injection, there were abundant iron particles in spleen, and in which the quantity amount of iron particles were GREat increased than ever, but after the fourth injection, with the increase of injections, the increase rate is diminishing。
In early Heart、kidney、lung、intestine、testis,、lymph node are without iron deposition before the thired injection, only after the thired injection of individual rabbits to see a small amount of iron particles. Because these animal model organs for use is too small, and image of MRI is not fine, or the limit of MRI coil for the examined organs, so these organs can not be examined。
Conclusion
1、The iron modle which were made up of iron water mold、animal specimens and pure water mold( or animal fat cortex)can complete quantitative determination of iron water mold / muscle signal intensity ratio and the T2 value of iron water mold。
2、The different iron models have different value, and among them, Modle 7 and Modle 9 are the best vitro models in the MRI quantitative determination。
3、With the increase of injections, Liver iron deposition in iron overload animal increased gradually, which has obvious regularity, that are related with LIC, signal of GRE image and MRI determinational value, and regularities of the other organs are not obviously。Other iron overload organs can not be examined, because these organs are too small or examine technologies are limited.liver is the best organ in MRI iron quantitative analysis。
材料与方法：
1、含铁模型的制备
单纯不同浓度含铁水模的制作：模型1,不同铁浓度多根小试管捆扎模型：1-16个50ml试管内分别从50-48.5ml依次递减O.1ml装入不等量蒸馏水,然后,从1～16管按等差递增依次注入剂量为150 mg／ml的右旋糖酐铁0-1.5ml,相邻管内铁剂量差别为O.1m1,将试管按浓度递增的顺序分4层摆放并固定；模型2,不同铁浓度多根大试管捆扎模型：1～12个300ml试管内分别从300-298.9ml依次递减O.1ml装入不等量蒸馏水。然后,从1-12管按等差递增依次注入右旋糖酐铁0-1.1ml,相邻管内铁剂量差别为0.1ml,将试管按浓度递增的顺序分3层摆放并固定；模型3,不同铁浓度单根小试管模型：1.5L塑料瓶,内装1.45L蒸馏水,每次MRI扫描后注入右旋糖酐铁1ml,共注射35ml；模型4,不同铁浓度单根大试管模型：5L塑料瓶,内装4.3L蒸馏水,每次MRI扫描后注入右旋糖酐铁10ml,共注射700ml。
不同浓度含铁模型的制作：模型5,模型3同人体捆扎模型：将模型3固定于正常人体的右季肋区；模型6,模型3同肌肉标本捆扎模型：将模型3同0.5kg猪肉标本捆绑固定；模型7,模型3与肌肉标本及纯水水袋捆扎模型：在模型3及0.5kg猪肉标本周围包裹1000ml的纯水水袋并固定；模型8,模型4同肌肉标本及纯水水袋捆扎模型：将模型4同2kg猪肉标本、3500ml纯水水袋按模型7摆放并固定；模型9,模型4同肌肉标本及动物皮层脂肪捆扎模型：将模型8的纯水水袋置换成富含脂肪的新鲜猪皮。含铁水模、肌肉标本及猪皮的摆放及固定同模型8。
2、高铁动物模型的制备
成年雄性新西兰白兔20只作为实验组。同种兔1只作为正常对照组。实验组兔按15mg／kg剂量深部肌肉注射含铁量为150mg／ml的右旋糖酐铁,每周注射一次,左右两侧后腿轮流注射,共注射15周。注射右旋糖酐铁前,对所有兔子进行MRI检查,定量分析正常兔的肝脏／肌肉信号强度比及肝脏T2值。每次注射右旋糖酐铁一周后复查MRI检查,并于第二天随机选取1或2只白兔,处死取部分肝脏、脾脏、心肌、肾脏、肠管、肺、睾丸与淋巴结进行铁沉积病理诊断,剩余肝组织烘干测LIC。正常对照组兔第一次进行MRI检查后,并取上述脏器组织进行病理检查。
3、MRI检查设备及扫描序列
含铁模型与高铁动物模型MRI检查设备及扫描序列相同。
扫描设备：3.0T PHILIPS磁共振。扫描参数：(1)信号强度比值采用GRE序列横断面扫描：TR 48ms,TE2.5ms,翻转角度60。,层厚4mm,层间距3mm,扫描层数4层。(2)T2值测量采用多回波序列横断面扫描：8回波横断位扫描：TR 2000ms,TE分别为8、16、24、32、40、48、56、64ms,层厚4mm,扫描1层,扫描时间约8分钟；4回波横断位扫描：TR2000ms,TE分别为6、12、18、24ms,层厚4mm,扫描1层,扫描时间约5～7分钟。
结果：
1、含铁模型MRI扫描表现
模型1和模型2 MRI扫描获得的图像质量欠佳,信号不均,伪影多,不能完成MRI测量；模型3与模型4 MRI扫描的图像质量好,信号均匀,未见明显伪影,只能进行T2值的测量。模型5 MPd图像信号均匀,未见明显伪影,但测得的信号强度比是含铁水模／人体肌肉信号强度比,未能完全脱离人体；模型6 MRI图像信号均匀,未见明显伪影,但是当含铁水模铁浓度升高到一定程度时MRI便停止扫描,未能成功完成MRI测量；模型8的MRI图像上,含铁水模的中央或与纯水水袋交界区产生范围很大的伪影,不能成功完成MRI扫描；模型7及模型9获得的MRI图像信号均匀,未见明显伪影,可以成功的完成信号强度比及T2值的测量。
2、高铁动物模型内脏铁沉积分布及MRI表现
肝脏及脾脏的铁沉积：正常组兔子,肝脏、脾脏病理铁染色未见铁沉积颗粒。注射1次铁剂后,仅有少量的肝窦有少许铁颗粒,LIC尚在正常值范围内,肝脏GRE图像信号未见明显减低,但肝脏／肌肉信号强度比及T2值均低于正常值范围,此时脾脏红髓已有较多的铁沉积颗粒。注射2次铁剂后,肝窦及少量肝细胞内见少量铁沉积颗粒,LIC超过正常值范围,GRE图像肝脏信号较前轻度减低,肝脏／肌肉信号强度比及T2值较前减低,此时脾脏红髓大量铁颗粒较前增多,铁沉积量变化较肝明显。此后,随注射次数的增多,出现铁沉积的肝窦及肝细胞逐渐增多,且其内的铁颗粒数目也逐渐增多,同时LIC随铁沉积颗粒的增多呈增加的趋势,肝脏／肌肉信号强度比、T2值及肝脏GRE图像信号随铁沉积颗粒的增多呈减低的趋势。注射12次铁剂以后,GRE图像肝脏信号达最低。而脾脏在第1次注射铁剂时,红髓已有较多的铁沉积颗粒,且随注射次数的增多而明显增加,当第4次注射铁剂后,虽然红髓的铁沉积颗粒随注射次数的增加仍较前增多,但增加的幅度很小。
心肌、肾脏、肺脏、肠管、睾丸及淋巴结注射在注射第3次铁剂前均未见铁沉积颗粒,自注射第3次铁剂后,不同注射时期兔子的上述器官病理切片上间或出现少量的铁染色颗粒。但由于所用动物模型的上述器官太小,MRI显示图像欠佳,或由于MRI检查线圈对受检器官的限制,不能进行MRI研究。
结论：
1、用不同铁浓度的含铁水模、动物肌肉标本及纯水水袋(或动物皮层脂肪)制备的含铁模型,能够成功的完成含铁水模／肌肉信号强度比值及T2值的测量。
2、不同方法制备的含铁模型各有优劣,其中模型3同肌肉标本及纯水水袋捆扎模型(模型7)与模型4同肌肉标本及动物皮层脂肪捆扎模型(模型9)在MRI铁定量测定中的应用价值最高。
3、高铁动物模型肝脏铁沉积颗粒数量随注射剂量的增加呈逐渐增多的趋势,且同LIC、GRE图像信号及MRI测量值之间相关性明显,具有较强的规律性；其它铁沉积的脏器规律性不明显,且由于器官太小或检查技术的限制,MRI难于进行评价。肝脏是铁沉积定量研究的最佳器官。
Objective
To explore the establishment methods of iron modle which can complete MRI quantitative determination; To study the iron distribution in Organs of Iron overload animal.
Materials and Methods
1、Preparation of iron modle
Making of simple iron water mold of different iron concentrations:Modle 1, Different iron concentrations of small multi-tube banding model:Injecting 50～48.5 ml distilled water in Number 1～16 50ml tubes respectively, and the difference of water amount in tubes in turn decreasing 0.1ml. Then increasingly injecting 0～1.5ml iron dextran for iron 150mg/ml in turn, and the difference of water amount in adjadjacent tubes is 0.1ml, and divided into 4 layers and placed and fixed increasingly; Modle 2, Different iron concentrations of big multi-tube banding model:Injecting 300～298.9ml distilled water in Number 1～12 300ml tubes respectively, and the difference of water amount in tubes in turn decreasing 0.1ml. Then increasingly injecting 0～1.1 ml iron dextran in turn, and the difference of water amount in adjadjacent tubes is 0.1ml, and divided into 3 layers and placed and fixed increasingly; Modle 3, Different iron concentrations of single small tube model:1.5L plastic bottle containing 1.45L distilled water, injected lml of iron dextran after each MRI scan for 35 times; Modle 4, Different iron concentrations of single big tube model:5L plastic bottle containing 4.3L distilled water, injected 10ml of iron dextran after each MRI scan for 70 times.
Making of different concentrations of iron model:Modle 5, Modle 3-Body banding model:Banding Modle 3 with right rib area of normal human; Modle 6, Modle 3-Muscle specimens banding model:Banding Modle 3 with 0.5kg pork specimens; Modle 7, Modle 3-Pure waterm bag-Muscle specimens banding model:Iron water mold and pork specimens as Modle 6, banded with 1000ml iron water bag arround them; Modle 8, Modle 4-Pure waterm bag-Muscle specimens banding model:Banded Modle 4 with 3500ml iron water bag and 0.5kg pork specimens as Modle 7; Modle 9, Modle 4-Muscle specimens-Animal fat cortex banding model:Just changeing the pure water bags of Modle 8 as fresh pig skin, and others are the same as Modle 8.
2、iron overload animal modle
20 adult male New Zealand white rabbits as the experimental group, one same species rabbit as a normal control group. Deep intramuscular injected iron dextran for iron 150mg/ml with the dose of 15mg/kg weekly in the experimental group, alternate the injection position right to left hind leg. Injected a total of 15 weeks. Before the iron dextran injection,MRI inspection was made to all rabbits, quantitative analysis of normal rabbit liver/muscle signal intensity ratio and T2 value of the liver. Every time one week after the injection of iron dextran to review the MRI,and the next day one or two rabbits were killed randomly, and getting some tissue of liver, spleen, heart, kidney, myocardium, lung, testosterone and lymph node to pathological diagnosis, and the remaining liver tissue were dried for the measurement of LIC by atomic spectrophotometer. Rabbit of control group were killed after the first MRI examination, Excise the tissue of multi-organ for pathological examination.
3、MRI examination equipment and sequences
MRI examination equipment and sequences are the same in the tests of iron modle and iron overload animal modle。
Magnetic resonance imaging studies were performed using a 3.0 T Philips system (Achieva 3.0T X-series). Scan parameters:(1) Transverse GRE sequences for signal intensity ratio were acquired with TR of 48ms, TE of 2.5ms, flip angle of 60°, sLICe thickness of 4mm, gap of 3mm, scanning four sLICes, completed scan within one breath. (2) T2 value measurement with a multiple spin-echo (SE) pulse sequence:8-echo axial scan for mild iron deposition were acquired with TR of 2000ms, TE of 8,16,24,32,40,48,56 and 64 ms, sLICe thickness of 4mm, scanning one sLICe, take time of about 8 minutes; 4-echo axial scan for severe iron deposition in the were acquired with TR of 2000ms, TE of 6,12,18 and 24 ms, sLICe thickness of 4mm, scanning one sLICe, take time of about 5 or 7 minutes.
Results
1、MRI features of the iron model
The image quality of Modle 1 and Modle 2 is poor, that having heterogeneous signals and much MRI artifacts, and MRI could not complete measure; The image quality of Modle 3 and Modle 4 is GREat, that having intensity signals and rarely MRI artifacts, but only to be measure the value of T2; The signals of Modle 5 are intensity, and having rarely MRI artifacts, but to be measure iron water mold / demic body muscle signal intensity ratio, which was not completely out of the body; The signals of Modle 6 are intensity, and having rarely MRI artifacts, but MRI stop scan as the concentration uppers to certain extent。The image of Modle 8 has much MRI artifacts in the middle of iron water mold or relating to the border area of iron water mold and pure water mold, so Modle 8 cannot complete measure; The signals of Modle 7 and Modle 9 are intensity, and having rarely MRI artifacts, and they can complete GRE scanning for iron water mold / muscle signal intensity ratio and multi-echo scanning for the T2 value of iron water mold。
2、iron distribution and MRI features of iron overload animal organs
Iron overload of liver and spleen:liver and spleen of normal rabbits had no iron deposition particle。After inject iron one time, small part sinusoids existed small number of particles, and LIC and signal of GRE image were narmal, but liver / muscle signal intensity ratio and T2 value were lower than normals, at the same time there were abundant iron particles in spleen。After inject iron twice time, sinusoids and some liver cells existed small number of particles, LIC was higher than normals, and signal of GRE image, liver / muscle signal intensity ratio and T2 value were lower than normals, there were more iron particles than it used to in spleen, and in which the quantity amount of iron particles were larger than in liver。After that, With increase injections, liver iron deposition particles gradual increased from part of sinusoids with small number of particles to all sinusoids and liver cells with abundant particles, and LIC showed an increasing trend, and signal of GRE image, liver / muscle signal intensity ratio and T2 value showed decreased trends。But, after the first injection, there were abundant iron particles in spleen, and in which the quantity amount of iron particles were GREat increased than ever, but after the fourth injection, with the increase of injections, the increase rate is diminishing。
In early Heart、kidney、lung、intestine、testis,、lymph node are without iron deposition before the thired injection, only after the thired injection of individual rabbits to see a small amount of iron particles. Because these animal model organs for use is too small, and image of MRI is not fine, or the limit of MRI coil for the examined organs, so these organs can not be examined。
Conclusion
1、The iron modle which were made up of iron water mold、animal specimens and pure water mold( or animal fat cortex)can complete quantitative determination of iron water mold / muscle signal intensity ratio and the T2 value of iron water mold。
2、The different iron models have different value, and among them, Modle 7 and Modle 9 are the best vitro models in the MRI quantitative determination。
3、With the increase of injections, Liver iron deposition in iron overload animal increased gradually, which has obvious regularity, that are related with LIC, signal of GRE image and MRI determinational value, and regularities of the other organs are not obviously。Other iron overload organs can not be examined, because these organs are too small or examine technologies are limited.liver is the best organ in MRI iron quantitative analysis。
引文
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[31]St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance[J]. Blood,2005,105(2):855-861.
[32]路建平,林肇辉.大鼠铁过剩及铁缺乏对脾脏ED1、ED2表达的调控[J].中华病理学杂志.1995,24(1)：21-24.
[33]路建平,林肇辉,胡锡琪,等.铁过剩时铁在肝小叶内区域性沉积的机理[J].中华病理学杂志,1995,24(2)：75-77.
[34]朱航,张守华,雷蕾等.不同剂量铁对小鼠肝脏损伤作用的实验研究[J].热带医学杂志,2007,7(2)：129-132.
[2]Bonkovsky HL. Iron and liver[J]. The American Journal of the Medical Sciences,1991,301(15):32-43.
[3]Andrews, NC. Disorders of iron metabolism. N Engl J Med,1999,341(26): 1986-1995.
[4]Kaltwasser JP, Gottschalk R, Schalk KP, et al. Noninvasive quantitation of liver iron-overload by magnetic resonance imaging[J]. Br J Haematol,1990, 74(3):360-363.
[5]Chezmar JL, Nelson RC, Malko JA, et al. Hepatic iron overload:diagnosis and quantification by noninvasive imaging[J]. Gastrointest Radiol,1990,15(1): 27-31.
[6]Ernst O, Sergent G, Bonvarlet P, et al. Hepatic iron overload:diagnosis and quantification with MR imaging[J].AJR Am J Roentgenol,1997,168(5): 1205-1208.
[7]Gandon Y, Guyader D, Heautot JF, et al. Hemochromatosis:Diagnosis and Quantification of Liver Iron with Gradient-Echo MR Imaging[J]. Radiology, 1994,193(2):533-538.
[8]Rose C, Vandevenne P, Bourgeois E, et al. Liver iron content assessment by routine and simple magnetic resonance imaging procedure in highly transfused patients[J]. Eur J Haematol,2006,77(2):145-149.
[9]Alustizan JM, Artetxe J, Castiella A. MR Quantification of Hepatic Iron Concentration[J]. Radiology,2004,230(2):479-484.
[10]Bonkovsky HL, Rubin RB, Cable EE, et al.Hepatic Iron Concentration: Noninvasive Estimation by Means of MR Imaging Techniques [J]. Radiology, 1999,212(1):227-234.
[11]Alexopoulou E, Stripeli F, Baras P, et al. R2 relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients[J]. J Magn Reson Imaging,2006,23(2):163-170.
[12]St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance[J]. Blood,2005,105(2):855-861.
[13]Tanner MA, Galanello R, Dessi C, et al. A Randomized, Placebo-Controlled, Double-Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance[J]. Circulation,2007,115(14):1876-1884.
[14]Papakonstantinou OG, Maris TG, Kostaridou V, et al. Assessment of liver iron overload by T2-quantitative magnetic resonance imaging:correlation of T2-QMRI measurements with serum ferritin concentration and histologic grading of siderosis[J]. Magn Reson Imaging,1995,13(7):967-977.
[15]Porter JB, Davis BA. Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia[J]. Best Pract Res Clin Haematol, 2002,15(2):329-368.
[16]Gandon Y, Olivie D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI[J]. Lancet,2004,363(9406):357-362.
[17]St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance[J]. Blood,2005,105(2):855-861.
[18]Gomori JM, Grossman RI, Drott HR. MR relaxation times and iron content of thalassemic spleens:an in-vitro study[J]. Am J Radiol,1988,150(3):567-569.
[19]Gandon Y, Guyader D, Heautot JF, et al. Hemochromatosis:Diagnosis and Quantification of Liver Iron with Gradient-Echo MR Imaging[J]. Radiology, 1994,193(2):533-538.
[20]Siegelman ES. Quantification with MR Imaging[J]. Radiology,1991; 179(2):361-366
[21]Ernst O, Sergent G, Bonvarlet P, et al. Hepatic iron overload:diagnosis and quantification with MR imaging[J]. AJR Am J Roentgenol,1997,168(5): 1205-1208.
[22]Voskaridou E, Douskou M, Terpos E, et al. Deferiprone as an oral iron chelator in sickle cell disease[J]. Ann Hematol,2005,84(7):434-440.
[23]Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload[J]. Lab Invest 1993,69(20):217-222.
[24]Zhiyue J. Wang, PhD, Lurong Lian.1/T2 and Magnetic Susceptibility Measurements in a Gerbil Cardiac Iron Overload Model [J]. Radiology 2005, 234(8):749-755.
[25]John C. Wood. MD, PhD.Maya Otto-Duessel, MS. Michelle Aguilar, BS. Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy[J]. Circulation.2005,112(14):535-543.
[26]王以薇.高铁对大鼠主要脏器病理损伤动物模型的建立[J].白求恩医科大学学报,1997；23(5)494-498.
[27]路建平,林肇辉.大鼠铁过剩及铁缺乏对脾脏ED1、ED2表达的调控.中华病理学杂志[J].1995,24(1)：21-24.
[28]路建平,林肇辉,胡锡琪,等.铁过剩时铁在肝小叶内区域性沉积的机理.中华病理学杂志[J],1995,24(2)：75-77.
[29]朱航,张守华,雷蕾等.不同剂量铁对小鼠肝脏损伤作用的实验研究.热带医学杂志[J],2007,7(2)：129-132.
[30]Wood JC, Otto-Duessel M, Aguilar M, et al. Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy[J]. Circulation,2005,112(4):535-543.
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