A Pilot Study Of Normal Rabbit's Cerebral Perfusion Using Polyaspartic Acid Surface Modified Ultrasmall Superparamagnetic Iron Oxide Particles On MR.

Background:MR examination is one of the most important methods for the nervous system. With the development of the MRI scanning equipment and scanning technology, magnetic resonance imaging has developed from the simply two-dimensional imaging to the functional imaging, which provides the possibility of the early diagnosis of some disease and the research of the function about some part of the brain. The perfusion weighted imaging is one kind of the functional imaging, which has more than twenty years history. It plays an important role in diagnosis and differential diagnosis of vascular disease and brain tumor. There are two kinds of cerebral perfusion weighted imaging, one is arterial spin labeling, another is first-pass contrast agent imaging, and the latter one is more common perfusion weighted imaging methods. The first-pass contrast agent imaging's premise is that the contrast agents must be confined to intravascular and not be dispersed extracellular. At present, the exogenous tracer for cerebral perfusion is Gd-DTP A, which is the extracellular paramagnetic contrast agents. It can pass through the blood-vessel freely and nonspecific distributes in the interstitial gap or extracellular gap,so it has a short half-life inside the blood vessel which cause a short cerebral perfusion. The short scan time window limits spatial resolution and larger space coverage. Furthermore, chelating agent gadolinium has toxicity side effects for the renal and somewhat allergic reaction, so its clinical application is limited. In addition to paramagnetic contrast agents, super paramagnetic contrast agents SPIO and USPIO has been applied to clinic currently,both of them are meshy endodermis system contrast agents. The half-life of their intravascular are extended because of different modifications and improved structure. The half-life of them about 3 to 24 hours. They extend the scanning time window and more suitable for magnetic resonance angiograms imaging and perfusion weighted imaging. Super paramagnetic contrast agents has large susceptibility and small used dosage. Its coating materials are biodegradable materials.The core of the crystal Fe3O4 and Fe2O3 final metabolize into the pool of the hemoglobin. From above we can know that the super paramagnetic contrast agents almost has no side effects.Although super paramagnetic contrast agents have more advantages than gadolinium chelating agent, its expensive cost is more than the MR examination itself and can't be accepted by most patients therefore its usage is limited in domestic. We can't ignore the advantage of super paramagnetic contrast agents, so how to develop a kind of paramagnetic contrast agents which can both exert the advantage of it and its price can be accepted by majority patients became a keen research. Our research group associated with Jilin university chemical institute developed a new kind of USPIO which surface was modified by the PASP.We test and verify the stability of the colloid and the feasible of its usage for cerebral perfusion by using different doses in normal rabbit MR cerebral perfusion weighted imaging and comparing with Gd-DTPA.Objective:To explore the colloid stability of PASP surface modified USPIO and feasibility used in normal rabbit MR cerebral perfusion and appropriate dosage.Materials and methods:The contrast agents of the experimental group is different dose of PASP surface modified USPIO, and the contrast agents of the contrast group is Gd-DTPA provide by the bayer company of German,its dosage is 0.2mmol/kg. Imaging scanned by Signa CV/type i 1.5-t superconducting magnetic resonance scanner and knee coil produced by GE company. It takes ADW4.4 workstations for image analysis and data post-processing. Thirty New Zealand rabbit were randomly divided into Group Al, A2, A3, A4 and Group C. Animals in group A1-4 were intravenously injected (i.v.) 5μmol/kg, 10μmol/kg,20μmol/kg and 40μmol/kg PASP-USPIO while animals in group C was injected (i.v.) 0.2 mmol/kg Gd-DTPA, serving as control group. Each group was treated with T2* GE-EPI-sequenced PWI to obtain signal intensity-time curve which was used to calculate the rCBV and SRRmax or QrCBv and QsRRmax values. All the measurement data were analyzed with SPSS17.0 software. Intra-group comparison was administrated with paired t-test while inter-group comparison was administrated with single factor AN OVA analysis.Result:The different dose of PASP-USPIO group got more satisfied function diagram and signal intensity-time curve. The intra-group rCBV value and SRRmax value of cerebral gray matter and white matter were significantly different while the inter-group QrcBv and QsRRmax values were significantly different. ANOVA analysis indicated that the QrcBv and QSRRmax values in Group 4 were significantly different from other groups while there was no significant difference between Group Al, A2, A3 and Group C.Conclusion:PASP surface modified USPIO has good colloid stability just as Gd-DTPA. The intra-group rCBV value and SRRmax value of cerebral gray matter and white matter were significantly different, thus its can be used at the normal rabbit MR cerebral perfusion and can reflect the capillaries density of both gray and white matter of the brain and brain hemodynamic changes. Comparing with Gd-DTPA,the dose of PASP surface modified USPIO at 5μmol/kg,10μmol/kg,20μmol/kg can be used to normal rabbit MR cerebral perfusion and the dose of 10μmol/kg is more appropriate doses. This experiment is only a initial trial and it still needs the further study about toxicology and pharmacokinetic etc.