title: Stability and trapping of magnetic resonance imaging contrast agents during high-intensity focused ultrasound ablation therapy.
abstract: OBJECTIVE
  The purpose of this study was to investigate the use of Gd-DTPA shortly before magnetic resonance guided high-intensity focused ultrasound MR-HIFU thermal ablation therapy with respect to dissociation, trapping, and long-term deposition of gadolinium (Gd) in the body.
  
  
  METHODS
  Magnetic resonance-HIFU ablation treatment was conducted in vivo on both rat muscle and subcutaneous tumor (9L glioma) using a clinical 3T MR-HIFU system equipped with a small-animal coil setup. A human equivalent dose of gadopentetate dimeglumine (Gd-DTPA) (0.6 mmol/kg of body weight) was injected via a tail vein catheter just before ablation (≤5 minutes). Potential trapping of the contrast agent in the ablated area was visualized through the acquisition of R1 maps of the target location before and after therapy. The animals were sacrificed 2 hours or 14 days after the injection (n = 4 per group, a total of 40 animals). Subsequently, the Gd content in the tissue and carcass was determined using inductively coupled plasma techniques to investigate the biodistribution.
  
  
  RESULTS
  Temporal trapping of Gd-DTPA in the coagulated tissue was observed on the R1 maps acquired within 2 hours after the ablation, an effect confirmed by the inductively coupled plasma analysis (3 times more Gd was found in the treated muscle volume than in the control muscle tissue). Two weeks after the therapy, the absolute amount of Gd present in the coagulated tissue was low compared with the amount present in the kidneys 14 days after the injection (ablated muscle, 0.009% ± 0.002% ID/g; kidney, 0.144% ± 0.165% ID/g). There was no significant increase in Gd content in the principal target organs for translocated Gdions (liver, spleen, and bone) or in the entire carcasses between the HIFU- and sham-treated animals. Finally, an in vivo relaxivity of 4.6 mmols was found in the HIFU-ablated volume, indicating intact Gd-DTPA.
  
  
  CONCLUSIONS
  Magnetic resonance-HIFU treatment does not induce the dissociation of Gd-DTPA. In small-tissue volumes, no significant effect on the long-term in vivo Gd retention was found. However, care must be taken with the use of proton resonance frequency shift-based MR thermometry for HIFU guidance in combination with Gd because the susceptibility artifact induced by Gd can severely influence treatment outcome.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Hijnen
authors.forename: Aaldert
authors.initials: A
authors.lastname: Elevelt
authors.forename: Holger
authors.initials: H
authors.lastname: Grüll
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000009:adverse effects / Q000493:pharmacokinetics*; D057086:High-Intensity Focused Ultrasound Ablation / Q000009:adverse effects / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000009:adverse effects / Q000379:methods*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D025321:Surgery, Computer-Assisted / Q000009:adverse effects / Q000379:methods*
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA