title: Helium gas microbubbles. Experimental study on a new ultrasound contrast material.
abstract: OBJECTIVE
  To evaluate histological changes and duration of enhancement after the intra-arterial injection of helium gas microbubbles in comparison with conventionally used carbon dioxide (CO2) microbubbles at US.
  
  
  METHODS
  Four different doses of helium gas microbubbles (0, 0.1, 0.2 and 0.5 ml/kg) mixed with normal saline and own blood were injected into the celiac artery of 8 rabbits. After one week, autopsies were performed on all animals and histological changes in the liver, stomach and spleen were studied on hematoxylin-eosin stains. In addition, VX-2 tumor strains were transplanted into the femoral muscle in 5 other rabbits. Four weeks after transplantation, we catheterized the femoral artery and either CO2 or helium gas microbubbles were injected under US observation. We evaluated the duration of enhancement in the tumors with the two types of microbubbles.
  
  
  RESULTS
  On histological evaluation, damage in hepatic cells as well as multiple areas of gastritis in the stomach were seen when a dose of 0.5 ml/kg of helium gas was used. Damage in the liver and stomach was slight at a dose of 0.2 ml/kg. The spleen was not damaged at doses of under 0.5 ml/kg. In the evaluation of tumor enhancement, the duration of enhancement with helium gas microbubbles ranged from 28 to 45 min (average 36 min) while that with CO2 ranged from 4 to 12 min (average 9 min) (p<0.01 at paired t-test).
  
  
  CONCLUSIONS
  Intra-arterial injection of helium gas should not exceed 0.2 ml/kg: a dose of 0.5 ml/kg may cause damage to the liver and stomach. The duration of enhancement with helium gas microbubbles is significantly longer than that with CO2 microbubbles.
authors.affiliation: Department of Radiology, Kumamoto University Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishiharu
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: A
authors.initials: A
authors.lastname: Arakawa
authors.forename: K
authors.initials: K
authors.lastname: Mitsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Matsukawa
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage; D002277:Carcinoma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D002445:Celiac Artery; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D006371:Helium / Q000008:administration & dosage; D007089:Image Enhancement / Q000379:methods; D007269:Injections, Intra-Arterial; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D011817:Rabbits; D013154:Spleen / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D013270:Stomach / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D002245:Carbon Dioxide; D006371:Helium