The Influence of Blood Supply on High Intensity Focused Ultrasound

Rationale and Objectives

The aim of this study was to explore the effects of blood supply on high-intensity focused ultrasound (HIFU) applied to rabbit hepatic VX2 tumors of different ages.

Materials and Methods

Eighteen rabbits with VX2 hepatic tumors were randomly divided into three groups according to the time of sacrifice after tumor implantation: 10, 15, or 20 days. Contrast-enhanced ultrasound was performed immediately before HIFU ablation. The same settings for HIFU dose parameters were used to ablate the central tumor area in each group, and the real-time temperature of the targeted site of the tumor was measured. After HIFU, the coagulation necrosis volumes of tumor tissue and the microvascular density of residual tumor tissue were determined.

Results

Histopathologic analysis showed that the extent of a tumor’s blood supply followed the order 10-day group > 15-day group > 20-day group ( P < .01). Contrast-enhanced ultrasound showed the same results. There was no statistically significant difference among the three groups in terms of temperature-increase parameters during HIFU treatment ( P > .05). However, there were statistically significant differences between the groups in terms of temperature-decrease parameters during HIFU treatment and in terms of necrosis volumes after HIFU treatment ( P < .05). Necrosis volume was inversely related to absolute enhanced intensity ( r = −0.823, P < .001).

Conclusions

The extent of a tumor’s blood supply had a significant effect on the temperature-decrease phase but not on the temperature-increase phase during HIFU treatment. The longer the temperature-decrease phase, the more slowly heat dissipated after HIFU, resulting in larger coagulation necrosis volumes.

High-intensity focused ultrasound (HIFU) is a rapidly developing noninvasive technology for thermal treatment. HIFU ablation of tumors is based on the absorption of ultrasound energy in a focal zone located at a distance from the therapeutic ultrasound transducer. In recent years, the technique has been used clinically to treat a variety of solid tumors, with promising prospects . Nevertheless, many studies of HIFU ablation have shown that tissue heating and lesion coagulation are affected by many factors, such as overlying ribs, abdominal gas, and the extent of blood perfusion within tumors . Tumor blood supply has been identified as one of the most important predictive factors. Early studies reported that HIFU ablation was less effective in the presence of abundant tumor blood perfusion, which was able to carry part of the focused ultrasound energy away. This was especially true in malignant tumors with high neovascularity and vascular invasion . Thus, the extent of blood perfusion within the focused region can limit ablation size and alter ablation shape by lowering the maximal temperature induced with HIFU .

The splanchnic circulation in rabbits is similar to that in humans . Rabbit hepatic VX2 tumors are highly vascularized by the hepatic artery because of the induction of neovascularity in the host animals, thereby resembling human hepatic carcinoma . This tumor model has thus been widely used for research on interventional therapy and imaging evaluation. Lorelius and Stridbeck found age-related changes in VX2 tumor vascularity of the rabbit hind leg. We propose that rabbit hepatic VX2 tumors of different ages may also possess age-related changes in blood supply.

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Materials and methods

Experimental Setup and Animal Handling

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CEUS Examinations

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HIFU Treatments

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Histology

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Statistical Analysis

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Results

CEUS Evaluation of Blood Supply to VX2 Liver Tumors

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Table 1

Comparison of AEI in VX2 Rabbit Tumor Tissues

Group_n_ AEI (Level) 10 day 6 30.04 ± 11.11 15 day 6 0.60 ± 20.38 ∗ 20 day 6 −32.36 ± 8.88 ∗ †

AEI, absolute enhanced intensity.

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Temperature Changes in Tumors Targeted Site During HIFU Treatment

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Table 2

TTC Parameters at Different Times During VX2 Rabbit Tumors Undergoing HIFU Irradiation

Group_n__T_ max (°C)t 1 (s)t 2 (s)k 1 (°C/s)k 2 (°C/s) 10 day 6 79.7 ± 2.60 4.3 ± 0.69 12.5 ± 0.47 9.7 ± 2.10 4.9 ± 0.36 15 day 6 79.8 ± 3.92 4.3 ± 0.50 14.1 ± 0.66 ∗ 9.5 ± 1.12 4.2 ± 0.70 ∗ 20 day 6 83.2 ± 5.58 4.5 ± 0.55 17.5 ± 1.21 ∗ † 9.9 ± 1.75 3.4 ± 0.36 ∗ †

HIFU, high-intensity focused ultrasound; TTC, time-temperature curve.

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Pathologic Analysis of Rabbit Hepatic VX2 Tumors after HIFU Treatment

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Table 3

Comparison of Volume of Coagulation Necrosis in VX2 Rabbit Tumor Tissues

Group_n_ Volume of Coagulation Necrosis (mm 3 ) 10 day 6 31.33 ± 6.28 15 day 6 45.00 ± 4.39 ∗ 20 day 6 57.00 ± 2.55 ∗ †

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Table 4

Comparison of MVD in Rabbit Hepatic VX2 Tumors and Normal Tissues

MVD 10-Day Group

( n = 6) 15-Day Group

( n = 6) 20-Day Group

( n = 6) Tumor 37.71 ± 6.13 ∗ 25.63 ± 4.33 † 15.31 ± 3.17 Normal liver tissue 18.55 ± 3.33 19.63 ± 2.62 18.21 ± 2.07

MVD, microvessel density.

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Discussion

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Conclusions

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References

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The Influence of Blood Supply on High Intensity Focused Ultrasound

Rationale and Objectives

Materials and Methods

Results

Conclusions

Materials and methods

Experimental Setup and Animal Handling

CEUS Examinations

HIFU Treatments

Histology

Statistical Analysis

Results

CEUS Evaluation of Blood Supply to VX2 Liver Tumors

Temperature Changes in Tumors Targeted Site During HIFU Treatment

Pathologic Analysis of Rabbit Hepatic VX2 Tumors after HIFU Treatment

Discussion

Conclusions

References

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