In vitro and in vivo evaluations of increased effective beam width for heat deposition using a split focus high intensity ultrasound (HIFU) transducer

Figures & data

Figure 1. Water coupled system. (a) Cylindrical phantoms (5) were held in a tank of degassed water at the focal distance of the single focus transducer (4). Temperature of degassed water was monitored (1) and held constant. Temperature elevations were monitored by thermal couples in controls (no exposure) (2) and HIFU exposed phantoms (3). (b) Mice were anesthetized and held in the tank in the same manner as phantoms. Similarly, temperature elevations by thermal couples were monitored in controls (no exposure) (2) and HIFU exposed tumors (3).

Figure 2. Membrane coupled system. Both single and split focus transducers were housed in a sealed chamber of degassed water. Planar phantoms (3) were placed on the membrane (2) and held at the focal distance of both transducers (1).

Table I.  Experimental exposures.

		Exposed object	Transducer	Power (W)	Duty cycle (%)	n
I	1	Cylindrical phantom	Single focus	20	10	3
	2	Cylindrical phantom	Single focus	80	10	5
	3	Cylindrical phantom	Single focus	80	20	5
	4	Cylindrical phantom	Single focus	80	30	5
	5	Cylindrical phantom	Single focus	80	40	5
	6	Mouse tumor	Single focus	20	10	5
II	7	Planar phantom	Single focus	20	50	7
	8	Planar phantom	Split focus	30	50	7
	9	Planar phantom	Split focus	40	50	7
	10	Planar phantom	Split focus	50	50	7
	11	Planar phantom	Split focus	80	50	7
III	12	Mouse muscle^a	Single focus	20	10	5
	13	Mouse muscle^a	Split focus	80	10	5
	14	Mouse muscle^a	n/a	n/a	n/a	5
	15	Mouse muscle^b	n/a	n/a	n/a	5

All exposures were given at 1 MHz, pulse repetition frequency of 1 Hz, and 120 pulses per exposure. ^aLow temperature sensitive liposomes; ^bfree doxorubicin.

Figure 3. (a) Temperature elevation in cylindrical phantoms at 80W compared to tumor tissue at 20W. A significant difference was not found between the two. At 20W, temperature elevations in the phantoms were not sufficiently high to be determined accurately. Columns, mean (n = 5); bars, standard deviation. (b) Linear relationship between duty cycle (%) and peak temperature elevation in cylindrical phantoms (80W). Points, mean (n = 5); bars, standard deviation.

Figure 4. Spatial temperature elevation greater than 3°C and 5°C during HIFU exposure with single focus and split focus transducers. Points, mean (n = 7); bars, standard deviation.

Table II.  Single to split focus comparisons.

	X-intercept	Slope	R^2	AUC*	Fold increase
3°C increase
Single focus	2.34	5.47	0.9941	37891	1.0
Split focus	4.97	18.44	0.9957	121979	3.2 (P < 0.001)
5°C increase
Single focus	3.89	3.09	0.9935	20814	1.0
Split focus	14.69	10.62	0.9804	58880	2.8 (P < 0.002)

*AUC, area under the curve as determined by integrating the equation describing the linear relationship between area increase and time.

Figure 5. Area under the curve for spatial temperature elevation greater than 3°C and 5°C during HIFU exposure with single focus and split focus transducers. Columns, mean (n = 7); bars, standard deviation.

Figure 6. Representative IR heating images for treatment of planar phantoms with single focus and split focus transducers, for a 120s exposure with each device. Images at early time points for the split focus device allow individual foci to be observed, which eventually meld together into a single larger focal spot (compared to the single focus device) by the end of the exposure. (Scale bar = 1 cm).

Figure 7. (a) Total doxorubicin extracted from muscle in HIFU exposed extremity and control (unexposed) extremity for single focus and split focus transducers. (b) Concentration of doxorubicin found in muscle following treatment with free doxorubicin and LTSL-doxorubicin. No HIFU exposure. Columns, mean (n = 5); bars, standard deviation.

Table

	Liver	Phantom
Density (kg m^−3)	1065	1044
Speed of sound (m s^−1)	1549	1544
Attenuation (Np cm^−1 MHz^−1)	0.049	0.009 – 0.021**
Specific heat (J kg^−1 K^−1)	3600	4270*

*Lafon et al. [24] more recently found this value of specific heat [39] to be more accurate than 5100, as originally presented. **The attenuation slope for the phantom is given as 0.009 to 0.021 Np cm⁻¹ MHz⁻¹ for a range of BSA concentrations from 3 to 9%. Assuming a linear relationship exists between both factors, the following equation can be used for determining the attenuation at a set BSA concentration:

Lafon C, Zderic V, Noble ML, Yuen JC, Kaczkowski PJ, Sapozhnikov OA, Chavrier F, Crum LA, Vaezy S. Gel phantom for use in high-intensity focused ultrasound dosimetry. Ultrasound Med Biol 2005; 31: 1383–1389

 PubMed Web of Science ®Google Scholar

Divkovic GW, Liebler M, Braun K, Dreyer T, Huber PE, Jenne JW. Thermal properties and changes of acoustic parameters in an egg white phantom during heating and coagulation by high intensity focused ultrasound. Ultrasound Med Biol 2007; 33: 981–986

 PubMed Web of Science ®Google Scholar