超顺磁性氧化铁（SPIO）在MR脑灌注成像初步应用实验研究
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摘要
研究目的
1．探讨SPIO应用于MR脑灌注成像的可行性。
2．研究SPIO在MR脑灌注成像的方法学及质量控制；优化选择其应用于PWI的最适剂量。
3．与Gd-DTPA相比较，探讨SPIO在大鼠超急性脑梗塞MRPWI的应用价值。
4．探讨SPIO灌注成像联合弥散加权成像对大鼠超急性脑梗死再灌注的评价作用。
材料与方法
1．健康新西兰大白兔30只，随机法平均分为A、B、c、D、E五个小组，每小组各6只。其中A、B、C、D四个小组分别给予不同剂量的SPIO(4umolFe／kgBW，8umolFe／kgBW，16umolFe／kgBW，32umolFe／kgBW)，E组设为对照，给予0.2mmol／kgBW的Gd-DTPA。全部动物行磁共振灌注成像(MR PWI)扫描，获得相应信号强度-时间曲线图并分别计算灰质、白质的SRR_(max)和rCBV值，进一步比较其Q_(rCBV)和Q_(SRRmax)值。MR检查结束后，B、D、E三组各取1只实验兔脑切片行普鲁士蓝染色。
2．30只Wistar大鼠，随机法平均分成A_1、B_1两组，A_1组为8umolFe／kg体重SPIO MR PWI组，B_1组为0.2mmol／kg体重Gd-DTPA MR PWI组，两类不同对比剂剂量的选择是以在正常脑组织的MR PWI中获得相同的最大信号强度变化为标准。全部动物均在左侧大脑中动脉栓塞时间一小时后行MR PWI扫描。PWI原始图像重建获得病灶中心区以及脑缺血半暗带CBV、CBF、MTT参数形态图。比较两组各项参数变化并与病理检查及红四氮唑染色(TTC)对照。
3．30只Wistar大鼠，随机法平均分成A_2、B_2两组，分别于左侧大脑中动脉栓塞时间1h、5h后再灌注2h，于再灌注前后分别行PWI、DWI和常规FSE T_2WI、SE T_1WI扫描，PWI扫描时对比剂选用8umolFe／kg体重的SPIO；PWI和DWI原始图像重建获得ADC、CBV、CBF、MTT参数形态图。观察各栓塞时间点再灌注2h后各项参数变化并与病理检查及红四氮唑染色(TTC)对照。
4．对比剂：本实验所用SPIO为Resovist，由先灵公司提供。Resovist又名SHU555A(ScheringAG Berlin，Germany．国内相应产品的商品名为内二显)，是由羧基右旋糖苷(Carboxydextran)包裹的氧化铁颗粒，平均直径61.1nm，氧化铁核心颗粒直径4.2nm，浓度为0.5mmol Fe／ml。外被的羧基右旋糖苷使其具有良好的水溶性及稳定性，另外还含有40mg／ml甘露醇及2mg／ml乳酸，37℃时pH值6.5。
结果
1．SPIO能快速团注，在四个不同剂量的SPIO都能对正常兔脑灰白质有良好的分辨。各组相应参数值(Q_(rCBV)／Q_(SRRmax))分别为：1.98±0.07／1.85±0.11，2.09±0.11／1.88±0.06，2.09±0.07／2.06±0.25，1.50±0.01／1.49±0.09，2.05±0.03／1.94±0.12。A、B、C三组(4umolFe／kgB W，8umolFe／kgBW，16umolFe／kgBW)随着对比剂剂量的加大，Q_(rCBV)值和Q_(SRRmax)值未见显著性差异；而D组(32umolFe／kgBW)Q_(rCBV)值和Q_(SRRmax)值显著低于A组(P＜0.01)。
2．SPIO在四个不同剂量组均获得满意的信号强度-时间曲线图。但当剂量达到一定范围时(16umolFe／kgBW以上)，随着注射剂量的增加，灌注的信号强度-时间曲线显示信号强度恢复到稳态水平的距离加大，我们将此现象称为“信号丢失”，C组(16umolFe／kgBW)及D组(32umolFe／kgBW)分别为10％、20％。
3．静脉注射SPIO 6小时后D组(32umolFe／kgBW)实验兔脑切片Prussian blue染色显示胞浆中含有铁颗粒，而注射SPIO 1小时后B组(8umolFe／kgBW)实验兔脑切片Prussian blue染色呈阴性。
4．A_1、B_1两组大鼠在脑缺血中心区以及病灶边缘区(即影像半暗带)所获得的信号-时间曲线基本一致，分别比较各兴趣区rCBV、rMTT及TTP值，均无显著性差异。
5．A_2、B_2两组再灌注2h后ADC值轻度降低或基本不变；A_2组再灌注后2h DWI显示病灶范围稍有减小，B_2组则无明显缩小。A_2组再灌注后影像半暗带区PWI各参数指标恢复和维持正常，而B_2组的信号强度-时间曲线图有3种表现，分别为高灌注、低灌注和正常灌注。
结论
1．SPIO应用于MR脑灌注是可行的，适宜剂量范围在4～16umolFe／kgBW，推荐最适剂量为8umolFe／kgBW。
2．在急性脑梗塞的MRPWI应用中，SPlO与Gd-DTPA同样有效，且所需剂量更小，因此，SPIO在颅脑灌注具有广阔的应用前景。
3．在超急性脑梗死再灌注可限制病灶进一步扩大，保护缺血半影区。应用SPIO磁共振脑灌注成像联合MR DWI能反映急性脑缺血再灌注后脑损伤的变化，同时又能反映再灌注后脑组织血流灌注情况。
4．高剂量组SPIO(32umolFe／kgBW)铁颗粒能透过正常实验兔血脑屏障，可能与多种转运机制有关。
Objective
1. To study the feasibility of cerebral perfusion weighted imaging(PWI) using superparamagnetic iron oxide particles in normal rabbits.
2. To investigate the methodology and quality control of cerebral MR PWI using superparamagnetic iron oxide particles, and a prospective study was undertaken to determine the proper contrast agent dose of SPIO used in PWI.
3. To compare the evaluation of perfusion weighted imaging(PWI) using Gd-DTPA and the superparamagnetic iron oxide particles in the experimental model of hyperacute cerebral infarction in rats.
4. To assess the role of diffusion-perfusion MRI using SPIO in evaluating the experimental model of hyperacute cerebral infarction reperfusion in rats.
Materials and Methodes
1. All 30 rabbits were randomly divide into 5 groups(n=6 for each), group A, B, C, D were divided according to the different dose of SPIO(4, 8, 16 and 32umolFe/kgBW) and group E was operated for control study with 0.2mmol/kgBW Gd-DTPA. The dynamic MR perfusion imaging sequence was acquired in each group. The signal intensity time curves were analyzed in gray matter and white matter, the parameters (rCBV, SRR_(max), Q_(rCBV), Q_(SRRmax)) were calculated and compared in all groups and correlated with control group. The pathologic examination of Prussian blue was practised in three normal rabbits coming from group B, D and E.
2. All 30 Wistar rats were randomly divided into 2 groups(n=15 for each), group A_1, and B_1 for the different contrast agents PWI. After occluding the left middle cerebral artery with thread about 1 hour in all rats, the dynamic MR perfusion imaging sequence was acquired after intravenous bolus injections of 8umolFe/kgBW SPIO in group A_1 and 0.2mmol/kgBW Gd-DTPA in group B_1, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The perfusion parameters at the regions of interest(ROI) in the core area and the penumbra area with ischemia lesion on the perfusion image were measured and compared. The data were correlated with pathologic findings and TTC stain.
3. All 30 Wistar rats were randomly divide into 2 groups(n=15 for each), group A_2 and B_2, which were divided according to time intervals of 1 hour and 5 hours after occluding the left middle cerebral artery with thread and reflowed about 2 hours. The MR sequences included diffusion weighted imaging(DWI), perfusion weighted imaging(PWI), FSE T_2WI, SE T_1WI during their occlusion and 2 hours after reperfusion. The perfusion parameters were calculated and correlated with light, electron microscopic findings and TTC stain.
4. Contrast medium: Resovist was an alternative SPIO in our study. Resovist compromised SPIO microparticles coated with carboxydextran and an overall hydrodynamic diameter of 61.1 nm as measured with photon-correlation spectroscopy. The polycrystalline iron oxide core consisted of multiple single crystals, each 4.2nm in diameter as measured with electron microscopy. The carboxydextran coating ensured aqueous solubility of the microparticles and prevented aggregation. Resovist contained 0.5mmol/L of iron per liter, including 40mg/mL mannitol and 2mg/mL of lactatic acid, adjusted to a PH of 6.5 at 37℃.
Results
1. SPIO enabled rapid injections and a dose-dependent strong reduction in gray and white matter signal intensity in all groups. The parameters (Q_(rCBV)/Q_(SRRmax)) values were 1.98±0.07/1.85±0.11, 2.09±0.11/1.88±0.06, 2.09±0.07/2.06±0.25,1.50±0.01/1.49±0.09 and 2.05±0.03/1.94±0.12 for group A, B, C, D and E, respectively, without significant difference in group A, B and C and with significant difference between group A and D(P＜0.01).
2. The signal-time curve could be obtained satisfactorily through MR PWI in all groups. A decrease in normalized signal instensity of approximately 10% and 20% remained for the duration of the acquisitions after intravenous adminastration of 16umolFe/kgBW and 32umolFe/kgBW, which was defined as signal drop.
3. The iron particles on Prussian blue stain was found within the brain cells after intravenous administration of 32umolFe/kgBW about 6 hours, but none was found in group B(SumolFe/kgBW) at 1 hour.
4. The similar first-passage profiles were found in the core area and the penumbra area with ischemia lesions in this rat stroke model for Gd-DTPA and SPIO. The parameters (CBV, MTT, TTP) values of PWI for ischemic penumbra in group A_1 and B_1 had not statistical disparity.
5. In groups A_2 and B_2, ADC was slightly decreased or unchanged after reflow. It could be seen that the initial DWI high-intensity signal shadow disappeared slightly in group A_2 and unchanged in group B_2. Although parameters (CBV, CBF, MTT) values of PWI for ischemic penumbra in group A_2 recovered and remained normal, but in group B_2, there were 3 typical fashions of appearance after reperfusion in ischemic penumbra, which included hyperperfusion, hypoperfusion and normal perfusion respectively.
Conclusion
1. SPIO could be used in the study of MR perfusion weighted imaging in the brain. The proper contrast agent dose was 4～16umolFe/kgBW and the dose of 8umolFe/kgBW may be chosen firstly.
2. The efficacy of the SPIO used in the MR PWI was similar to Gd-DTPA for diagnosis of the perfusion reduction in the rat stroke model. The strong susceptibility effects may be achieved with small injection volumes.
3. The ischemic penumbra could be protected by recanalisation in hyperacute cerebral infarction. Combination DWI with PWI using SPIO could evaluate the extent of the ischemic lesions and detect hemodynamic changes in hyperacute cerebral infarction.
4. The iron particles of SPIO could permeate blood-brain-barrier of normal rabbits after intravenous adminastration of 32umolFe/kgBW, which may be relative with multiple transport factors.
1．探讨SPIO应用于MR脑灌注成像的可行性。
2．研究SPIO在MR脑灌注成像的方法学及质量控制；优化选择其应用于PWI的最适剂量。
3．与Gd-DTPA相比较，探讨SPIO在大鼠超急性脑梗塞MRPWI的应用价值。
4．探讨SPIO灌注成像联合弥散加权成像对大鼠超急性脑梗死再灌注的评价作用。
材料与方法
1．健康新西兰大白兔30只，随机法平均分为A、B、c、D、E五个小组，每小组各6只。其中A、B、C、D四个小组分别给予不同剂量的SPIO(4umolFe／kgBW，8umolFe／kgBW，16umolFe／kgBW，32umolFe／kgBW)，E组设为对照，给予0.2mmol／kgBW的Gd-DTPA。全部动物行磁共振灌注成像(MR PWI)扫描，获得相应信号强度-时间曲线图并分别计算灰质、白质的SRR_(max)和rCBV值，进一步比较其Q_(rCBV)和Q_(SRRmax)值。MR检查结束后，B、D、E三组各取1只实验兔脑切片行普鲁士蓝染色。
2．30只Wistar大鼠，随机法平均分成A_1、B_1两组，A_1组为8umolFe／kg体重SPIO MR PWI组，B_1组为0.2mmol／kg体重Gd-DTPA MR PWI组，两类不同对比剂剂量的选择是以在正常脑组织的MR PWI中获得相同的最大信号强度变化为标准。全部动物均在左侧大脑中动脉栓塞时间一小时后行MR PWI扫描。PWI原始图像重建获得病灶中心区以及脑缺血半暗带CBV、CBF、MTT参数形态图。比较两组各项参数变化并与病理检查及红四氮唑染色(TTC)对照。
3．30只Wistar大鼠，随机法平均分成A_2、B_2两组，分别于左侧大脑中动脉栓塞时间1h、5h后再灌注2h，于再灌注前后分别行PWI、DWI和常规FSE T_2WI、SE T_1WI扫描，PWI扫描时对比剂选用8umolFe／kg体重的SPIO；PWI和DWI原始图像重建获得ADC、CBV、CBF、MTT参数形态图。观察各栓塞时间点再灌注2h后各项参数变化并与病理检查及红四氮唑染色(TTC)对照。
4．对比剂：本实验所用SPIO为Resovist，由先灵公司提供。Resovist又名SHU555A(ScheringAG Berlin，Germany．国内相应产品的商品名为内二显)，是由羧基右旋糖苷(Carboxydextran)包裹的氧化铁颗粒，平均直径61.1nm，氧化铁核心颗粒直径4.2nm，浓度为0.5mmol Fe／ml。外被的羧基右旋糖苷使其具有良好的水溶性及稳定性，另外还含有40mg／ml甘露醇及2mg／ml乳酸，37℃时pH值6.5。
结果
1．SPIO能快速团注，在四个不同剂量的SPIO都能对正常兔脑灰白质有良好的分辨。各组相应参数值(Q_(rCBV)／Q_(SRRmax))分别为：1.98±0.07／1.85±0.11，2.09±0.11／1.88±0.06，2.09±0.07／2.06±0.25，1.50±0.01／1.49±0.09，2.05±0.03／1.94±0.12。A、B、C三组(4umolFe／kgB W，8umolFe／kgBW，16umolFe／kgBW)随着对比剂剂量的加大，Q_(rCBV)值和Q_(SRRmax)值未见显著性差异；而D组(32umolFe／kgBW)Q_(rCBV)值和Q_(SRRmax)值显著低于A组(P＜0.01)。
2．SPIO在四个不同剂量组均获得满意的信号强度-时间曲线图。但当剂量达到一定范围时(16umolFe／kgBW以上)，随着注射剂量的增加，灌注的信号强度-时间曲线显示信号强度恢复到稳态水平的距离加大，我们将此现象称为“信号丢失”，C组(16umolFe／kgBW)及D组(32umolFe／kgBW)分别为10％、20％。
3．静脉注射SPIO 6小时后D组(32umolFe／kgBW)实验兔脑切片Prussian blue染色显示胞浆中含有铁颗粒，而注射SPIO 1小时后B组(8umolFe／kgBW)实验兔脑切片Prussian blue染色呈阴性。
4．A_1、B_1两组大鼠在脑缺血中心区以及病灶边缘区(即影像半暗带)所获得的信号-时间曲线基本一致，分别比较各兴趣区rCBV、rMTT及TTP值，均无显著性差异。
5．A_2、B_2两组再灌注2h后ADC值轻度降低或基本不变；A_2组再灌注后2h DWI显示病灶范围稍有减小，B_2组则无明显缩小。A_2组再灌注后影像半暗带区PWI各参数指标恢复和维持正常，而B_2组的信号强度-时间曲线图有3种表现，分别为高灌注、低灌注和正常灌注。
结论
1．SPIO应用于MR脑灌注是可行的，适宜剂量范围在4～16umolFe／kgBW，推荐最适剂量为8umolFe／kgBW。
2．在急性脑梗塞的MRPWI应用中，SPlO与Gd-DTPA同样有效，且所需剂量更小，因此，SPIO在颅脑灌注具有广阔的应用前景。
3．在超急性脑梗死再灌注可限制病灶进一步扩大，保护缺血半影区。应用SPIO磁共振脑灌注成像联合MR DWI能反映急性脑缺血再灌注后脑损伤的变化，同时又能反映再灌注后脑组织血流灌注情况。
4．高剂量组SPIO(32umolFe／kgBW)铁颗粒能透过正常实验兔血脑屏障，可能与多种转运机制有关。
Objective
1. To study the feasibility of cerebral perfusion weighted imaging(PWI) using superparamagnetic iron oxide particles in normal rabbits.
2. To investigate the methodology and quality control of cerebral MR PWI using superparamagnetic iron oxide particles, and a prospective study was undertaken to determine the proper contrast agent dose of SPIO used in PWI.
3. To compare the evaluation of perfusion weighted imaging(PWI) using Gd-DTPA and the superparamagnetic iron oxide particles in the experimental model of hyperacute cerebral infarction in rats.
4. To assess the role of diffusion-perfusion MRI using SPIO in evaluating the experimental model of hyperacute cerebral infarction reperfusion in rats.
Materials and Methodes
1. All 30 rabbits were randomly divide into 5 groups(n=6 for each), group A, B, C, D were divided according to the different dose of SPIO(4, 8, 16 and 32umolFe/kgBW) and group E was operated for control study with 0.2mmol/kgBW Gd-DTPA. The dynamic MR perfusion imaging sequence was acquired in each group. The signal intensity time curves were analyzed in gray matter and white matter, the parameters (rCBV, SRR_(max), Q_(rCBV), Q_(SRRmax)) were calculated and compared in all groups and correlated with control group. The pathologic examination of Prussian blue was practised in three normal rabbits coming from group B, D and E.
2. All 30 Wistar rats were randomly divided into 2 groups(n=15 for each), group A_1, and B_1 for the different contrast agents PWI. After occluding the left middle cerebral artery with thread about 1 hour in all rats, the dynamic MR perfusion imaging sequence was acquired after intravenous bolus injections of 8umolFe/kgBW SPIO in group A_1 and 0.2mmol/kgBW Gd-DTPA in group B_1, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The perfusion parameters at the regions of interest(ROI) in the core area and the penumbra area with ischemia lesion on the perfusion image were measured and compared. The data were correlated with pathologic findings and TTC stain.
3. All 30 Wistar rats were randomly divide into 2 groups(n=15 for each), group A_2 and B_2, which were divided according to time intervals of 1 hour and 5 hours after occluding the left middle cerebral artery with thread and reflowed about 2 hours. The MR sequences included diffusion weighted imaging(DWI), perfusion weighted imaging(PWI), FSE T_2WI, SE T_1WI during their occlusion and 2 hours after reperfusion. The perfusion parameters were calculated and correlated with light, electron microscopic findings and TTC stain.
4. Contrast medium: Resovist was an alternative SPIO in our study. Resovist compromised SPIO microparticles coated with carboxydextran and an overall hydrodynamic diameter of 61.1 nm as measured with photon-correlation spectroscopy. The polycrystalline iron oxide core consisted of multiple single crystals, each 4.2nm in diameter as measured with electron microscopy. The carboxydextran coating ensured aqueous solubility of the microparticles and prevented aggregation. Resovist contained 0.5mmol/L of iron per liter, including 40mg/mL mannitol and 2mg/mL of lactatic acid, adjusted to a PH of 6.5 at 37℃.
Results
1. SPIO enabled rapid injections and a dose-dependent strong reduction in gray and white matter signal intensity in all groups. The parameters (Q_(rCBV)/Q_(SRRmax)) values were 1.98±0.07/1.85±0.11, 2.09±0.11/1.88±0.06, 2.09±0.07/2.06±0.25,1.50±0.01/1.49±0.09 and 2.05±0.03/1.94±0.12 for group A, B, C, D and E, respectively, without significant difference in group A, B and C and with significant difference between group A and D(P＜0.01).
2. The signal-time curve could be obtained satisfactorily through MR PWI in all groups. A decrease in normalized signal instensity of approximately 10% and 20% remained for the duration of the acquisitions after intravenous adminastration of 16umolFe/kgBW and 32umolFe/kgBW, which was defined as signal drop.
3. The iron particles on Prussian blue stain was found within the brain cells after intravenous administration of 32umolFe/kgBW about 6 hours, but none was found in group B(SumolFe/kgBW) at 1 hour.
4. The similar first-passage profiles were found in the core area and the penumbra area with ischemia lesions in this rat stroke model for Gd-DTPA and SPIO. The parameters (CBV, MTT, TTP) values of PWI for ischemic penumbra in group A_1 and B_1 had not statistical disparity.
5. In groups A_2 and B_2, ADC was slightly decreased or unchanged after reflow. It could be seen that the initial DWI high-intensity signal shadow disappeared slightly in group A_2 and unchanged in group B_2. Although parameters (CBV, CBF, MTT) values of PWI for ischemic penumbra in group A_2 recovered and remained normal, but in group B_2, there were 3 typical fashions of appearance after reperfusion in ischemic penumbra, which included hyperperfusion, hypoperfusion and normal perfusion respectively.
Conclusion
1. SPIO could be used in the study of MR perfusion weighted imaging in the brain. The proper contrast agent dose was 4～16umolFe/kgBW and the dose of 8umolFe/kgBW may be chosen firstly.
2. The efficacy of the SPIO used in the MR PWI was similar to Gd-DTPA for diagnosis of the perfusion reduction in the rat stroke model. The strong susceptibility effects may be achieved with small injection volumes.
3. The ischemic penumbra could be protected by recanalisation in hyperacute cerebral infarction. Combination DWI with PWI using SPIO could evaluate the extent of the ischemic lesions and detect hemodynamic changes in hyperacute cerebral infarction.
4. The iron particles of SPIO could permeate blood-brain-barrier of normal rabbits after intravenous adminastration of 32umolFe/kgBW, which may be relative with multiple transport factors.
引文
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[6] Kopp AF, Laniado M, Dammann F, et al. MR imaging of the liver with Resovist: Safty, efficacy, and pharmacodynamic properties. Radiology, 1997; 204:749
[7] Forsting M, Reith W, Dorfler A, et al. MRI in acute cerebral ischaemia: perfusion imaging with superparamagnetic iron oxide in a rat model. Neuroradiology, 1994; 36:23-26
[8] Reith W, Forsting M, Vogler H, et al. Early MR detection of experimentally induced cerebral ischemia using magnetic susceptibility contrast agents: comprarison between gadopentetate dimeglumine and iron oxide particles. AJNR, 1995; 16:53-60
[9] Olav Haraldseth MD, Richard A, Tomm B, et al. Comprarison of dysprosium DTPA-BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischaemia in the rat. JMRI, 1996; 6:714-717
[10] Peter R, Gerhard S, Thomas B, et al.Application of superparamagnetic iron oxide (Resovist) for MR imaging of human cerebral blood volume.MRM,1995;34: 694-697
[11] Petre J, Provenzale JM. MR perfusion imaging of the brain: techniques and applications. AJR, 2000; 175:207
[12] Runge VM, Kirsch JE, Wells JW, et al. Assessment of cerebral perfusion by fiest-pass, dynamic, contrast-enhanced, steady-state free-precession MR imaging: an animal study. AJR, 1993; 160:593
[13] 殷信道，冯晓源，符荣，等．超急性脑梗死及再灌注功能磁共振成像的实验模型制作．中国医学计算机成像杂志，2001；7：367
[14] Sugahara T, Korogi Y, Kochi M, et al. Perfusion-sensitive MR imaging of gliomas: Comparison between gradient-echo and spin-echo echo-planar imaging techniques. AJNR, 2001; 22:1306-1315
[15] Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast enhanced T2~*-weighted MR imaging. Radiology, 1999; 211:791-798
[16] Shin JH, Lee HK, Kwun BD,et al. Using relative cerebral blood flow and volume to evaluate the histopathologic grade of cerebral gliomas: Preliminary results. AJR, 2002; 179:783-789
[17]Essig M, Wenz F, Scholdei R, et al. Dynamic susceptibility contrast enhanced echo-planar imaging of cerebral gliomas. Acta Radiol, 2002; 43: 354-359
[18]Cha S,Knopp EA,Johnson G,et al.Intracranial mass lesion: Dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology, 2002;223: 11-29
[1] Hamberg LM, McFarlance R, Tasdemiroglu E, et al. Measurement of cerebrovascular changes in cats after transient ischemia using dynamia magnetic resonance imaging. Stroke, 1993; 24:444-451
[2] Kucharczyk J, Vexler ZS, Roberts TP, et al. Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia. Radiology, 1993; 188:711-717
[3] Sorensen AG, Buonanno FS, Schwamm L, et al. Diffusion and perfusion weighted MR imaging in the clinical diagnosis of acute stroke(abstract). In: Book of abstracts: Society of Magnetic Resonance 1995. Nice: Society of Magnetic Resonance, 1995
[4] Reimer P, Schuierer G, Bralzer T, et al. Application of a superparamagnetic iron oxide (Resovist) for MR imaging of human cerebral blood volume. Magn Reson Med, 1995; 34:694-697
[5] Wendland MF, White DL, Aicher KP, et al. Detection with echo-planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia. J Magn Reson Imaging, 1991; 1:185-292
[6] Petrella JR, Provenzale JM. MR perfusion imaging of the brain: techniques and applications[J]. AJR, 2000; 175:207-219
[7] Wong JC, Provnzale JM, Petrella JR. Perfusion MR imaging of the brain neoplasms[J]. A JR, 2000; 174:1147-1157
[8] Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast enhanced T2~*-weighted MR imaging[J]. Radiology, 1999; 211: 791-798
[9] De Ryck M, Verhoye M, Van der Linden AM. Diffusion-weighted MRI of infarct growth in a rat photochemical stroke model: effect of lubeluzole. Neuropharmacology. 2000; 39:691-670
[10] Takamatsu H, Tsukad H, Kakiuchi T, et al. Changes in local cerebral blood flow in photo chemically induced thrombotic occlusion model in rats. Eur J Pharmacol. 2000; 398: 375-379
[11] ZeaLonga E, Weinstein PR, Carison S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20: 84-91
[12]Villringer A, Rosen BR, Belliveau JW, et al. Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects[J]. Magn Reson Med, 1998; 6: 164-174
[13] Smith AM, Grandin CB, Duprez T, et al. Whole brain quantitative CBF, CBV and MTT measurement using MRI bolus tracking; Implementation and application to data acquire from hyperacute stroke patients. JMRI, 2000; 12: 400
[14]Ueda T, Yuh WT, Maley JE, et al. Outcome of acute ischemia lesion evaluated by diffusion and perfusion MR imaging. AJNR, 1999; 20: 893
[15]Thijs VN, Adami A, Neumann-Haefelin T, et al. Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology, 2001; 57: 1205
[16] Stark D, Weissleder R, Elizondo G, et al. Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver. Radiology, 1988; 168: 297-301
[17]Duda S, Laniado M, Kopp A, et al. Superparamagnetic iron oxide: detection of focal liver lesions at high-field-strength MR imaging. JMRI, 1994; 4: 309-314
[18]Reimer P, Rummeny E, Daldrup H, et al. Clinical results with Resovist: a phase 2 clinical trial. Radiology, 1995; 195: 489-496
[1] Smith AM, Grandin CB, Duprez T, et al. Whole brain quantitative CBF, CBV and MTT measurement using MRI bolus tracking; Implementation and application to data acquire from hyperacute stroke patients. JMRI, 2000; 12:400
[2] Ueda T, Yuh WT, Maley JE, et al. Outcome of acute ischemia lesion evaluated by diffusion and perfusion MR imaging. AJNR, 1999; 20:893
[3] Yhijs VN, Adami A, Neumann-Haefelin T, et al. Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology, 2001; 57:1205
[4] Sakoh M, Rohl L, Gyldensted C, et al. Cerebral blood flou and blood volume measured by magnetic resonance imaging bolus tracking after acute stroke in pigs: comparison with [~(15)O]H_2O positron emission tomography. Stroke, 2000; 31: 1958-1964
[5] Koenig M, Kraus M, Theek C, et al. Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT. Stroke, 2001; 32:431
[6] Li F, Silva MD, Sotak CH, et al. Temporal evolution of ischemic injury evaluated with diffusion-, perfusion-, and T_2-weighted MRI. Neurology, 2000; 54:689-696
[7] Piepadi C, Alger JR, Righini A, et al. High temporal resolution diffusion MRI of globe cerebral ischemia and reperfusion. J Cereb Blood Flow Metab, 1996; 16: 892-905
[8] Li F, Liu KF, Silva MD, et al. Transient and permanent resolution of ischemic lesion on diffusion-weighted imaging after brief periods of focal ischemia in rats. Stroke, 2000; 31:964-954
[9] Karonen JO, Liu Y, Vanninen RL, et al. Combined perfusion and diffusion weighted MR. Radiology, 2000; 217:886-894
[10] Tong DC, Albers GW. Diffusion and perfusion magnetic resonance imaging for the evaluation of acute stroke: potential use in guiding thrombolytic therapy. Curr Opin Neurol, 2003; 13:45-50
[11] Moonis M, Fisher M. Imaging of acute stroke. Cerebrovasc Dis, 2001; 11: 143-150
[12] Flacke SM, Urbach H, Keller E, et al. Middle cerebral artery(MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT. Radiology, 2003; 215:476-482
[13] Tong DC, Adami A, Moseley ME, et al. Prediction of hemorrhagic transformation following acute stroke: role of diffusion and perfusion weighted magnetic resonance imaging. Arch Neurol, 2001; 58:587-593
[14] Sunshine JE, Bambakidis N, Tarr RW, et al. Benefits of perfusion MR imaging relative to diffusion MR imaging in the diagnosis and treatment of hyperacute stroke. AJNR, 2004; 22:915-921
[15] 焦力群，凌锋，卢洁，等．利用灌注MRI技术评价颈内动脉狭窄或闭塞的血流动力学状态．临床放射学杂志，2004；23：835-838
[16] Meng X, Fisher M, Shen Q, et al. Characterizing the diffusion/perfusion mis match in experimental focal cerebral ischemia. Ann Neurol, 2004; 55:207-212
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[1] 张成英，菌华，田鹤村，等．大鼠椎-基底动脉的解剖学观察及其在脑缺血模型中的应用．中国临床解剖学杂志，1995；13(1)：53-55
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[1] Villringer A, Rosen BR, Belliveau JW, et al. Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects. Magn Reson Med, 1998; 6(2): 164-174
[2] Jezzard P. Advances in perfusion MR imaging. Radiology, 1998; 208(1): 296-299
[3] Petrella JR, Provenzale JM. MR perfusion imaging of the brain: techniques and applications. AJR, 2000; 175:207-219
[4] Wong JC, Provnzale JM, Petrella JR. Perfusion MR imaging of the brain neoplasms. AJR, 2000; 174:1147-1157
[5] Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast enhanced T2~*-weighted MR imaging. Radiology, 1999; 211 : 791-798
[6] Simonsen CZ, Ostergaard L, Vestergaard-Pousen P, et al. CBF and CBV measuremengs by USPIO bolus tracking: reproducibility and comparison with Gd-based values. J Magn Reson Imaging, 1999; 9:342-347
[7] Sugahara T, Korogi Y, Kochi M, et al. Perfusion-sensitive MR imaging of gliomas: Comparison between gradient-echo and spin-echo echo-planar imaging techniques. AJNR, 2001; 22(8): 1306-1315
[8] Shin JH, Lee HK, Kwun BD,et al. Using relative cerebral blood flow and volume to evaluate the histopathologic grade of cerebral gliomas: Preliminary results. AJR, 2002; 179(9): 783-789
[9] Essig M, Wenz F, Scholdei R, et al. Dynamic susceptibility contrast enhanced echo-planar imaging of cerebral gliomas[J]. Acta Radiol, 2002; 43(4): 354-359
[10]Cha S, Knopp EA, Johnson G, et al. Intracranial mass lesion: Dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology, 2002; 223(1): 11-29
[11] Griffiths PD, Wilkinson ID, Wels T, et al. Brain MR perfusion imaging in humans: Advantages of high-molarity gadolinium chelates[J]. Acta Radiol, 2001; 42(6): 555-559
[12]Kirchin MA, Pirovano GP, Spinazzi A. Gadobenate dimeglumine ( Gd-BOPTA). An overview. Invest Radiol, 1998; 33: 798
[13]Runge VM. A review of contrast media research in 1999-2000. Investigative Radiology, 2001; 36: 123
[14]Oudkerk M, Van den Heuvel AG, Wielopolski PA, et al. Hepatic lesions :Detection with Ferumoxide-enhanced Tl-weighted MR imaging. Radiology; 1997,203:449
[15]Kopp AF, Laniado M, Dammann F, et al. MR imaging of the liver with Resovist: Safty, efficacy, and pharmacodynamic properties. Radiology, 1997; 204: 749
[16]Forsting M, Reith W, Dorfler A, et al.MRI in acute cerebral ischaemia: perfusion imaging with superparamagnetic iron oxide in a rat model. Neuroradiology, 1994; 36: 23-26
[17] Reith W, Forsting M, Vogler H, et al. Early MR detection of experimentally induced cerebral ischemia using magnetic susceptibility contrast agents: comprarison between gadopentetate dimeglumine and iron oxide particles. AJNR, 1995; 16:53-60
[18]Olav Haraldseth MD, Richard A, Tomm B, et al. Comprarison of dysprosium DTPA-BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischaemia in the rat. JMRI, 1996; 6(5): 714-717
[19] Peter R, Gerhard S, Thomas B, et al. Application of superparamagnetic iron oxide(Resovist) for MR imaging of human cerebral blood volume. MRM, 1995; 34: 694-697
[20]Kazuhiro S, Hiroaki S, Taizo O, et al. Perfusion study hypervascular hepatocellular carcinoma with SPIO. Magnetic Resonance in Medical Sciences, 2005; 4(4): 151-158
[21] Smith AM, Grandin CB, Duprez T, et al. Whole brain quantitative CBF, CBV and MTT measurement using MRI bolus tracking; Implementation and application to data acquire from hyperacute stroke patients. JMRI, 2000; 12: 400
[22]Ueda T, Yuh WT, Maley JE, et al. Outcome of acute ischemia lesion evaluated by diffusion and perfusion MR imaging. AJNR, 1999; 20: 893
[23]Thijs VN, Adami A, Neumann-Haefelin T, et al. Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology, 2001; 57: 1205
[24]Karonen JO, Liu Y, Vanninen RL, et al. Combined perfusion and diffusion weighted MR. Radiology, 2000; 217: 886-894
[25]Tong DC, Albers GW. Diffusion and perfusion magnetic resonance imaging for the evaluation of acute stroke: potential use in guiding thrombolytic therapy. Curr OpinNeurol, 2003; 13: 45-50
[26]Moonis M, Fisher M. Imaging of acute stroke. Cerebrovasc Dis, 2001; 11: 143-150
[27]Flacke SM, Urbach H, Keller E, et al. Middle cerebral artery(MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT. Radiology, 2003; 215: 476-482
[28]Tong DC, Adami A, Moseley ME, et al. Prediction of hemorrhagic transformation following acute stroke: role of diffusion and perfusion weighted magnetic resonance imaging. Arch Neurol, 2001; 58: 587-593
[29] Sunshine JE, Bambakidis N, Tarr RW, et al. Benefits of perfusion MR imaging relative to diffusion MR imaging in the diagnosis and treatment of hyperacute stroke. AJNR, 2004; 22: 915-921
[30]Sugahara T, Korogi Y, Tomiguchi S, et al. Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast enhancing tissue. AJNR, 2000; 21: 901-909
[31]Cha S, Knopp EA, Johnson G, et al. Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin. AJNR, 2003; 21: 881-890
[2] Jezzard P. Advances in perfusion MR imaging. Radiology, 1998; 208:296-299
[3] Oudkerk M, Van den Heuvel AG, Wielopolski PA, et al. Hepatic lesions: Detection with Ferumoxide-enhanced T1-weighted MR imaging. Radiology, 1997; 203:449
[4] Matsuo M, Kanematsu M, Itoh K, et al. Detection of malignant hepatic tumors: comparison of gadolinium and ferumoxide-enhanced MR imaging. AJR Am J Roentgenol. 2001; 177:637-643
[5] Kazuhiro S, Hiroaki S, Taizo O, et al. Perfusion study hypervascular hepatocellular carcinoma with SPIO. Magnetic Resonance in Medical Sciences, 2005; 4:151-158
[6] Kopp AF, Laniado M, Dammann F, et al. MR imaging of the liver with Resovist: Safty, efficacy, and pharmacodynamic properties. Radiology, 1997; 204:749
[7] Forsting M, Reith W, Dorfler A, et al. MRI in acute cerebral ischaemia: perfusion imaging with superparamagnetic iron oxide in a rat model. Neuroradiology, 1994; 36:23-26
[8] Reith W, Forsting M, Vogler H, et al. Early MR detection of experimentally induced cerebral ischemia using magnetic susceptibility contrast agents: comprarison between gadopentetate dimeglumine and iron oxide particles. AJNR, 1995; 16:53-60
[9] Olav Haraldseth MD, Richard A, Tomm B, et al. Comprarison of dysprosium DTPA-BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischaemia in the rat. JMRI, 1996; 6:714-717
[10] Peter R, Gerhard S, Thomas B, et al.Application of superparamagnetic iron oxide (Resovist) for MR imaging of human cerebral blood volume.MRM,1995;34: 694-697
[11] Petre J, Provenzale JM. MR perfusion imaging of the brain: techniques and applications. AJR, 2000; 175:207
[12] Runge VM, Kirsch JE, Wells JW, et al. Assessment of cerebral perfusion by fiest-pass, dynamic, contrast-enhanced, steady-state free-precession MR imaging: an animal study. AJR, 1993; 160:593
[13] 殷信道，冯晓源，符荣，等．超急性脑梗死及再灌注功能磁共振成像的实验模型制作．中国医学计算机成像杂志，2001；7：367
[14] Sugahara T, Korogi Y, Kochi M, et al. Perfusion-sensitive MR imaging of gliomas: Comparison between gradient-echo and spin-echo echo-planar imaging techniques. AJNR, 2001; 22:1306-1315
[15] Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast enhanced T2~*-weighted MR imaging. Radiology, 1999; 211:791-798
[16] Shin JH, Lee HK, Kwun BD,et al. Using relative cerebral blood flow and volume to evaluate the histopathologic grade of cerebral gliomas: Preliminary results. AJR, 2002; 179:783-789
[17]Essig M, Wenz F, Scholdei R, et al. Dynamic susceptibility contrast enhanced echo-planar imaging of cerebral gliomas. Acta Radiol, 2002; 43: 354-359
[18]Cha S,Knopp EA,Johnson G,et al.Intracranial mass lesion: Dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology, 2002;223: 11-29
[1] Hamberg LM, McFarlance R, Tasdemiroglu E, et al. Measurement of cerebrovascular changes in cats after transient ischemia using dynamia magnetic resonance imaging. Stroke, 1993; 24:444-451
[2] Kucharczyk J, Vexler ZS, Roberts TP, et al. Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia. Radiology, 1993; 188:711-717
[3] Sorensen AG, Buonanno FS, Schwamm L, et al. Diffusion and perfusion weighted MR imaging in the clinical diagnosis of acute stroke(abstract). In: Book of abstracts: Society of Magnetic Resonance 1995. Nice: Society of Magnetic Resonance, 1995
[4] Reimer P, Schuierer G, Bralzer T, et al. Application of a superparamagnetic iron oxide (Resovist) for MR imaging of human cerebral blood volume. Magn Reson Med, 1995; 34:694-697
[5] Wendland MF, White DL, Aicher KP, et al. Detection with echo-planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia. J Magn Reson Imaging, 1991; 1:185-292
[6] Petrella JR, Provenzale JM. MR perfusion imaging of the brain: techniques and applications[J]. AJR, 2000; 175:207-219
[7] Wong JC, Provnzale JM, Petrella JR. Perfusion MR imaging of the brain neoplasms[J]. A JR, 2000; 174:1147-1157
[8] Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrast enhanced T2~*-weighted MR imaging[J]. Radiology, 1999; 211: 791-798
[9] De Ryck M, Verhoye M, Van der Linden AM. Diffusion-weighted MRI of infarct growth in a rat photochemical stroke model: effect of lubeluzole. Neuropharmacology. 2000; 39:691-670
[10] Takamatsu H, Tsukad H, Kakiuchi T, et al. Changes in local cerebral blood flow in photo chemically induced thrombotic occlusion model in rats. Eur J Pharmacol. 2000; 398: 375-379
[11] ZeaLonga E, Weinstein PR, Carison S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20: 84-91
[12]Villringer A, Rosen BR, Belliveau JW, et al. Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects[J]. Magn Reson Med, 1998; 6: 164-174
[13] Smith AM, Grandin CB, Duprez T, et al. Whole brain quantitative CBF, CBV and MTT measurement using MRI bolus tracking; Implementation and application to data acquire from hyperacute stroke patients. JMRI, 2000; 12: 400
[14]Ueda T, Yuh WT, Maley JE, et al. Outcome of acute ischemia lesion evaluated by diffusion and perfusion MR imaging. AJNR, 1999; 20: 893
[15]Thijs VN, Adami A, Neumann-Haefelin T, et al. Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology, 2001; 57: 1205
[16] Stark D, Weissleder R, Elizondo G, et al. Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver. Radiology, 1988; 168: 297-301
[17]Duda S, Laniado M, Kopp A, et al. Superparamagnetic iron oxide: detection of focal liver lesions at high-field-strength MR imaging. JMRI, 1994; 4: 309-314
[18]Reimer P, Rummeny E, Daldrup H, et al. Clinical results with Resovist: a phase 2 clinical trial. Radiology, 1995; 195: 489-496
[1] Smith AM, Grandin CB, Duprez T, et al. Whole brain quantitative CBF, CBV and MTT measurement using MRI bolus tracking; Implementation and application to data acquire from hyperacute stroke patients. JMRI, 2000; 12:400
[2] Ueda T, Yuh WT, Maley JE, et al. Outcome of acute ischemia lesion evaluated by diffusion and perfusion MR imaging. AJNR, 1999; 20:893
[3] Yhijs VN, Adami A, Neumann-Haefelin T, et al. Relationship between severity of MR perfusion deficit and DWI lesion evolution. Neurology, 2001; 57:1205
[4] Sakoh M, Rohl L, Gyldensted C, et al. Cerebral blood flou and blood volume measured by magnetic resonance imaging bolus tracking after acute stroke in pigs: comparison with [~(15)O]H_2O positron emission tomography. Stroke, 2000; 31: 1958-1964
[5] Koenig M, Kraus M, Theek C, et al. Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT. Stroke, 2001; 32:431
[6] Li F, Silva MD, Sotak CH, et al. Temporal evolution of ischemic injury evaluated with diffusion-, perfusion-, and T_2-weighted MRI. Neurology, 2000; 54:689-696
[7] Piepadi C, Alger JR, Righini A, et al. High temporal resolution diffusion MRI of globe cerebral ischemia and reperfusion. J Cereb Blood Flow Metab, 1996; 16: 892-905
[8] Li F, Liu KF, Silva MD, et al. Transient and permanent resolution of ischemic lesion on diffusion-weighted imaging after brief periods of focal ischemia in rats. Stroke, 2000; 31:964-954
[9] Karonen JO, Liu Y, Vanninen RL, et al. Combined perfusion and diffusion weighted MR. Radiology, 2000; 217:886-894
[10] Tong DC, Albers GW. Diffusion and perfusion magnetic resonance imaging for the evaluation of acute stroke: potential use in guiding thrombolytic therapy. Curr Opin Neurol, 2003; 13:45-50
[11] Moonis M, Fisher M. Imaging of acute stroke. Cerebrovasc Dis, 2001; 11: 143-150
[12] Flacke SM, Urbach H, Keller E, et al. Middle cerebral artery(MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT. Radiology, 2003; 215:476-482
[13] Tong DC, Adami A, Moseley ME, et al. Prediction of hemorrhagic transformation following acute stroke: role of diffusion and perfusion weighted magnetic resonance imaging. Arch Neurol, 2001; 58:587-593
[14] Sunshine JE, Bambakidis N, Tarr RW, et al. Benefits of perfusion MR imaging relative to diffusion MR imaging in the diagnosis and treatment of hyperacute stroke. AJNR, 2004; 22:915-921
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