Preparation Of Thermo-sensitive Microgel Based MRI Contrast Agents

Temperature is an important indicator of metabolism,providing reliable reference for the diagnosis of certain diseases.Magnetic resonance imaging thermometry can simultaneously provide noninvasive anatomical information and temperature information for the target area.However,its application is limited due to low sensitivity and long scanning time.Microgel contrast agent based MRI thermometry could achieve temperature accuracy of 0.15? using fast scanning sequence.However the in vivo application of microgel contrast agent based MRI thermometry was severely limited due to the significant decrease in thermos-sensitivity of microgels in physiological saline solution.Therefore,it is necessary to find a new thermo-sensitive material which can efficiently work in physiological condition.Hydroxypropyl cellulose is a class of polysaccharide derivatives approved by the FDA,which has been widely used in medicine,cosmetics and other fields.It has good thermo-sensitivity in high ion solutions due to its unique polyhydroxy functional groups.In this study,the thermo-sensitive hydroxypropyl cellulose microgel contrast agent was prepared by grafting Gd-DOTA into the hydroxypropyl cellulose microgels.Its structural characteristics and the size response to temperature in physiological saline solutions were explored in order to develop microgel contrast agents working in complex physiological environment.Hydroxypropyl cellulose microgel contrast agent was prepared by conjugating chelating agent DOTA to oxidized dextran,producing microgels through reaction of dextran with hydroxypropyl cellulose by Michael addition and subsequently insertion of Gd into DOTA.In physiological saline solution,the size of microgel showed sharply 30%decrease in the temperature range of 35-39 ?,which can not be achieved using previous studied PNIPAM microgel congtrast agent.The lower critical solution temperature of microgel contrast agent is close to the physiological temperature.(37 ?),showing that hydroxypropyl cellulose microgel contrast agent with have potential for in vivo studies.In summary,thermo-sensitive hydroxypropyl cellulose microgel contrast agent is a new type of contrast agent efficiently working in physiological environment.