title: MRI investigation of the threshold for thermally induced blood-brain barrier disruption and brain tissue damage in the rabbit brain.
abstract: The ability of MRI-derived thermometry to predict thermally induced tissue changes in the brain was tested, and the thermal thresholds for blood-brain barrier (BBB) disruption and brain tissue damage were estimated. In addition, the ability of standard MRI to detect threshold-level effects was confirmed. These safety thresholds are being investigated to provide guidelines for clinical thermal ablation studies in the brain. MRI-monitored focused ultrasound heating was delivered to 63 locations in 26 rabbits. Tissue changes were detected in T(2)-weighted imaging and T(1)-weighted imaging (with and without contrast) and with light microscopy. The probability for tissue damage as a function of the accumulated thermal dose, the peak temperature achieved, the applied acoustic energy, and the peak acoustic power was estimated with probit regression. The discriminative abilities of these parameters were compared using the areas under the receiver operator characteristic (ROC) curves. In MRI, BBB disruption was observed in contrast-enhanced T(1)-weighted imaging shortly after the ultrasound exposures, sometimes accompanied by changes in T(2)-weighted imaging. Two days later, changes in T(2)-weighted imaging were observed, sometimes accompanied by changes in T(1)-weighted imaging. In histology, tissue damage was seen at every location where MRI changes were observed, ranging from small (diameter <1.0 mm) areas of tissue necrosis to severe vascular damage and associated hemorrhagic infarct. In one location, small (diameter: 0.8 mm) damage was not detected in MRI. The thermal dose and peak temperature thresholds were between 12.3-40.1 equivalent min at 43 degrees C and 48.0-50.8 degrees C, respectively, and values of 17.5 equivalent min at 43 degrees C and 48.4 degrees C were estimated to result in tissue damage with 50% probability. Thermal dose and peak temperature were significantly better predictors than the applied acoustic energy and peak acoustic power (P < 0.01). BBB disruption was always accompanied by tissue damage. The temperature information was better than the applied acoustic power or energy for predicting the damage than the ultrasound parameters. MRI was sensitive in detecting threshold-level damage.
authors.affiliation: Department of Radiology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. njm@bwh.harvard.edu
authors.forename: Nathan
authors.initials: N
authors.lastname: McDannold
authors.forename: Natalia
authors.initials: N
authors.lastname: Vykhodtseva
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Jolesz
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000473:pathology; D004056:Differential Threshold; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009336:Necrosis; D012372:ROC Curve; D011817:Rabbits; D013696:Temperature; D013821:Thermometers; D014465:Ultrasonics