title: Localised drug release using MRI-controlled focused ultrasound hyperthermia.
abstract: OBJECTIVE
  Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo.
  
  
  METHODS
  Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue.
  
  
  RESULTS
  Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test).
  
  
  CONCLUSIONS
  The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.
authors.affiliation: Centre for Research in Image-Guided Therapeutics, Sunnybrook Health Sciences Centre, Toronto, Canada. staruchr@sri.utoronto.ca
authors.forename: Robert
authors.initials: R
authors.lastname: Staruch
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chopra
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004317:Doxorubicin / Q000008:administration & dosage*; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006979:Hyperthermia, Induced / Q000379:methods*; D008081:Liposomes; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D011817:Rabbits; D013696:Temperature
chemical_list: D008081:Liposomes; D004317:Doxorubicin