Effect of high intensity focused ultrasound ablation on skeletal growth in infant Sprague-Dawley rats bearing human neuroblastoma

Abstract

Objective To explore the effects of high intensity focused ultrasound (HIFU) ablation on skeletal growth in infant rats bearing human neuroblastoma.Methods A total of 135 healthy 4-week-old male Sprague-Dawley (SD) rats were divided randomly into normal control group (A),HIFU group (B) and surgery group (C) (n =45 each).Human neuroblastoma SK-N-SH cells were inoculated into renal fascia of left adrenal gland for constructing a tumor-bearing rat model in HIFU and surgery groups.The rats of HIFU group received HIFU with a power of 70-90 W at Days 7-9 post-inoculation (tumor diameter 1.0-1.5 cm).While those of normal control and surgery groups were untreated.The data of length,skeletal malformations under macroscopic observation and radiography were recorded at study entry and after 3 days,2 weeks and 4 weeks in all groups.The serum level of bone alkaline phosphatase (BALP) was measured by enzyme-linked immunosorbent assay (ELISA)and histopathological examinations of spine and ribs around HIFU radiation zone were made with hematoxylin & eosin stain.Results No obvious macroscopic and radiographic malformations were found at study entry and different stages after HIFU.The height growth at day 3 in HIFU group [(0.900 ± 0.338) cm] was significantly lower than that in control group [(1.497 ± 0.362) cm] and surgery group [(1.243 ± 0.378) cm](P＜0.05).At week 2,it was also lower in HIFU group (2.500 ± 0.445) cm than control group (3.633 ± 0.434) cm and surgery group [(3.333 ± 0.372) cm] (P＜ 0.05).However,no difference existed among HIFU group [(2.533 ± 0.543)cm],control group [(2.900 ± 0.541) cm] and surgery group [(2.633 ± 0.696) cm] at Week 4 (P＞ 0.05).The serum concentration of BALP decreased after HIFU treatment 3 days in HIFU group [(951.697 ± 251.618)pg/ml] than that in control group [(1 168.847 ± 121.638) pg/ml] and surgery group [(1 088.359 ± 176.919) pg/ml](P＜0.05).Significant statistical differences existed when HIFU group [(1 037.507 ± 297.013) pg/ml] compared with control group [(1 675.691 ± 309.506) pg/ml] and surgery group [(1 915.433 ± 212.364) pg/ml] at 2 weeks later(P＜0.05).However,no statistical difference existed in the serum concentration of BALP among HIFU group [(1 106.551 ± 235.832) pg/ml],control group [(1 219.494 ± 77.615) pg/ml] and surgery group [(1 092.835 ± 164.593) pg/ml] at Week 4(P ＞0.05).Histopathological examination showed that bone trabeculae narrowed,primary marrow cavity significantly expanded at day 3 and week 2 post-HIFU in HIUF group.At week 4,bone trabecular density was similar in three groups.Conclusions HIFU may transiently inhibit skeletal growth in infant rats bearing human neuroblastoma.Such an effect shall disappear with a peak of adolescent bone growth and development. Key words: Neuroblastoma; High intensity focused ultrasound ablation; Skeleton