Intelligent tissue mimicking ultrasonic phantom and method of preparing the same

Abstract

An intelligent tissue mimicking ultrasonic phantom, which is a temperature-sensitive polymer gel having the following acoustic properties and other physical characteristics: acoustic velocity: 1500-1550 m/s; acoustic impedance: (1.50−1.60)×10 6 Pa·s/m; density: 1.01-1.06 g/cm 3 ; and a denaturation temperature, namely, a Lower Critical Solution Temperature (LCST) or a Volume Phase Transition Temperature at which the volume of the phantom changes, adjustable by changing the ratio of raw materials, around which there is a reversible phase transformation between the opaque phase and the transparent phase. Said gel can be a polymer of isopropylacrylamide (NIPA). Said ultrasonic phantom has a transparent appearance, and an adjustable thermal denaturation temperature; the thermal denaturation region of the ultrasonic phantom is distinct and has a well-defined boundary; the material of the phantom is stable and deterioration-resistant, and can ensure the consistency of the quality; the phantom is thermal denaturable with the appearance thereof turning white, while the phantom recovers when the heat is removed, such that it can be used repeatedly.

1 . An intelligent tissue mimicking ultrasonic phantom, characterized in that said phantom is a temperature-sensitive polymer gel having the following acoustic properties and other physical characteristics:
 acoustic velocity: 1500-1550 m/s; acoustic impedance: (1.50−1.60)×10 6  Pa·s/m; density: 1.01-1.06 g/cm 3 ; and a denaturation temperature, namely, a Lower Critical Solution Temperature (LCST) or a Volume Phase Transition Temperature at which the volume of the phantom changes, adjustable by changing ratios of raw materials, around which there is a reversible phase transformation between an opaque phase and a transparent phase.   
     
     
         2 . The intelligent tissue mimicking ultrasonic phantom according to  claim 1 , characterized in that said temperature-sensitive polymer gel is a isopropylacrylamide polymer hydrogel, a poly N-vinyl caprolactam hydrogel, or a β-hydroxypropyl acrylate-N-cinnamoyloxymethacrylamide copolymer hydrogel. 
     
     
         3 . The intelligent tissue mimicking ultrasonic phantom according to  claim 2 , characterized in that said isopropylacrylamide polymer hydrogel used for the intelligent tissue mimicking ultrasonic phantom comprises isopropylacrylamide, water; an initiating reductant, a crosslinking agent, an initiating oxidant; and a denaturation temperature regulator, wherein the weight percentage of each component is: 8-15% of isopropylacrylamide monomer, 0-4% of the denaturation temperature regulator, 0.02-0.05% of the initiating reductant, 0.1-0.15% of the crosslinking agent, 0.03-0.07% of the initiating oxidant, and 91.85-80.73% of water, and the denaturation temperature is between 30° C. and 70° C. 
     
     
         4 . The intelligent tissue mimicking ultrasonic phantom according to  claim 3 , characterized in that said water is deionized and degassed water, said crosslinking agent is N,N′-methylene bisacrylamide (BIS), said initiating oxidant is ammonium persulfate (APS), and said initiating reductant is sodium metabisulfite. 
     
     
         5 . The intelligent tissue mimicking ultrasonic phantom according to  claim 3 , characterized in that said denaturation temperature regulator is acrylamide. 
     
     
         6 . The intelligent tissue mimicking ultrasonic phantom according to  claim 3 , characterized in that said isopropylacrylamide polymer hydrogel further comprises a preservative with weight percentage of 0-0.4%. 
     
     
         7 . A method of making an isopropylacrylamide polymer hydrogel for an intelligent tissue mimicking ultrasonic phantom, including steps of:
 (1) determining a formulation of a isopropylacrylamide (NIPA) polymer hydrogel, weight percentage of each component being: 8-15% of isopropylacrylamide, 0-4% of denaturation temperature (LCST) regulator, 0.02-0.05% of initiating reductant, 0.1-0.15% of crosslinking agent, 0.03-0.07% of initiating oxidant, and 91.85-80.73% of water;   (2) dissolving an isopropylacrylamide monomer in a portion of the water;   (3) adding a crosslinking agent to the solution obtained in step 2, and dissolving the same by stirring;   (4) dissolving the initiating reductant and the initiating oxidant in portions of the water, respectively;   (5) mixing aqueous solutions of the isopropylacrylamide monomer, the crosslinking agent, and the initiating reductant uniformly in a container;   (6) replacing the air at the surface of and around the container with nitrogen;   (7) adding the aqueous solution of the initiating oxidant to the container, and mixing sufficiently while replacing the air at the surface of and around the liquid with nitrogen continuously;   (8) sealing the container in a pure nitrogen environment after adding the aqueous solution of the initiating oxidant is completed, allowing the solution to react for 3 to 24 hours, the temperature being controlled at 15° C.-25° C., so as to obtain a gel product.   
     
     
         8 . The method according to  claim 7 , further comprising the following step:
 (9) washing the obtained gel product with water for a plurality of times at room temperature, wherein every washing comprises a cycle of soaking its surface with deionized and degassed water for several hours and drying for another several hours after discarding the water, the cycle is repeated for a plurality of times to remove residual monomers and initiators on the surface, so as to eliminate toxicity;   (10) after the gel is washed in step (9), adding a preservative solution prepared with distilled water to wet the surface of the gel.   
     
     
         9 . The method according to  claim 7 , characterized in that,
 in step (1), a denaturation temperature regulator is acrylamide; and in step (2), acrylamide is added to the aqueous solution of the isopropylacrylamide monomer.   
     
     
         10 . The method according to  claim 7 , characterized in that,
 when molar ratio of isopropylacrylamide to acrylamide varies between (100˜70):(0˜30), denaturation temperature can be adjusted in a range of 30° C.-70° C.   
     
     
         11 . The method according to  claim 7 , characterized in that,
 in step (2), the mixture can be properly heated to help the dissolution of the isopropylacrylamide monomer, but the temperature should not exceed 40° C., and the solution upon heating should be cooled to below 25° C. before subsequent operations.   
     
     
         12 . The method according to  claim 7 , characterized in that,
 in step (1), the water used is deionized and degassed water.   
     
     
         13 . The method according to  claim 7 , characterized in that,
 the isopropylacrylamide polymer hydrogel in step (1) further comprises a preservative at a weight percentage of 0-0.4%., in step (3), the preservative added to the solution in step (2) is also included, and the preservative is dissolved in the solution in step (2) together with the crosslinking agent by stirring.   
     
     
         14 . The method according to  claim 7 , characterized in that,
 an elasticity of the gel can be changed by adjusting the content of the crosslinking agent according to usage requirements, and N,N′-methylene bisacrylamide can be used as the crosslinking agent.   
     
     
         15 . The method according to  claim 7 , characterized in that,
 said initiating oxidant is ammonium persulfate, and said initiating reductant is sodium metabisulfite.   
     
     
         16 . The method according to  claim 7 , characterized in that,
 in step (8), the reaction in the sealed container is carried out under nitrogen atmosphere to exclude the oxygen in the air from the polymerization reaction to ensure smooth polymerization and quality of the gel.   
     
     
         17 . The method according to  claim 8 , characterized in that,
 in step (10), said preservative is Kathon, formaldehyde, or Nipagin series, and concentration of the preservative solution prepared with distilled water is: 40-100 μg/mL for a Kathon solution, 0.5-1 mg/mL for a formaldehyde solution, and 5-10 mg/mL for a Nipagin solution.