A Pilot Study Of Cerebral Perfusion Imaging Using Superparamagnetic Iron Oxide Particles On MR In Experimental Models

Objective1. 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 Methodes1. 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 A₁, and B₁ 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 A₁ and 0.2mmol/kgBW Gd-DTPA in group B₁, 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 A₂ and B₂, 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 T₂WI, SE T₁WI 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℃.Results1. 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 A₁ and B₁ had not statistical disparity.5. In groups A₂ and B₂, ADC was slightly decreased or unchanged after reflow. It could be seen that the initial DWI high-intensity signal shadow disappeared slightly in group A₂ and unchanged in group B₂. Although parameters (CBV, CBF, MTT) values of PWI for ischemic penumbra in group A₂ recovered and remained normal, but in group B₂, there were 3 typical fashions of appearance after reperfusion in ischemic penumbra, which included hyperperfusion, hypoperfusion and normal perfusion respectively.Conclusion1. 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.