Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator?

Abstract

Background and Purpose-In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined. Methods-An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm 2 ) was applied through a piece of temporal bone (TUS group; nϭ9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; nϭ12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure. Results-The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (Pϭ0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6Ϯ13.9%) was significantly greater than that of the tPA group (9.9Ϯ6.8%) at 60 minutes (Pϭ0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis. Conclusions-Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.

Sonolysis in prevention of brain infarction during cardiac surgery (Sonorescue): a randomized, controlled trial

“…9,17,18 The mechanisms responsible for a reduced prevalence and volume of lesions after sonolysis in the present study could include acceleration of enzymatic fibrinolysis by the direct activation of a fibrinolytic system and increased transport of fibrinolytic agents (eg, plasmin) into the thrombus by mechanical disruption of thrombus structure, destruction of gaseous bubbles, and transient peripheral vasodilatation. [9][10][11][12][13][14][15][16][17][18][19][20] DW-MRI is sufficiently sensitive for detection of small ischemic lesions in the brain after CABG or valve surgery. [24][25][26] Conversely, relatively few TIAs or strokes are expected after these types of cardiac surgery (%3%) [1][2][3] , similar to the levels seen in patients undergoing carotid endarterectomy or stenting.…”

“…9 Animal studies (in vitro and in vivo) undertaken as early as the 1970s reported that ultrasound intensity of 0.2ï-ï2.0ïW/cm 2 at 20 kHz to 2 MHz can accelerate thrombus dissolution. [10][11][12][13][14] More recently, several randomized control trials and case-control studies have demonstrated improved clinical outcome using a diagnostic 2-MHz frequency and maximal diagnostic intensity (%1.2 W/ cm 2 ) in patients with ischemic stroke owing to middle cerebral artery (MCA) occlusion. [15][16][17][18] Underlying mechanisms for thrombus dissolution are incompletely understood, but they may include acceleration of enzymatic fibrinolysis 19 and mechanical effects such as acoustic radiation force and acoustic cavitation.…”

Safety and efficacy of sonothrombolysis using bilateral TCD monitoring by diagnostic 2 MHz probes - a pilot study

“…1,2,4,6,14,[20][21][22][23] ), the effect of TCD monitoring in acute IS patients was reported for the first time in 2000 (ref. 24 ) and the results of the first randomized study, testing the effect of sonothrombolysis showed the safety and efficacy of sonothrombolysis using the diagnostic 2-MHz TCD probe 7 .…”

“…[1][2][3][4][5][6] ). In the last ten years, several studies have found this effect also in patients with ischemic stroke (IS) and middle cerebral artery (MCA) occlusion [7][8][9][10][11][12] .…”

Temperature estimation of focused ultrasound exposures for stroke treatment

“…If this temperature elevation can not be controlled will cause unwanted tissue damage during sonication [25]. There are also cases when either low intensities or low frequencies are applied and temperature elevation drops below the 3˚C [23,26]. We have shown that temperature elevation can be controlled and kept within the safe region by adjusting various parameters such as the duty factor, the operating frequency, and the acoustic power.…”