Focused ultrasound surgery

Focused ultrasound surgery: HIFU induced effects on the vasculature

GR ter Haar, C Jayadewa, I Rivens in collaboration with MO Leach, Y Jamin and S Robinson Cancer Research UK Clinical Magnetic Resonance Research Group
Source of funding: ICR, Cancer Research UK

The aim of this study was to characterise the effect of HIFU on the vasculature of target tissue. This was tackled by developing a wide range of novel, complementary histological techniques which were used in conjunction with radiological techniques to assess vessel changes. In addition, the effect that vasculature of varying sizes may have on HIFU lesions was investigated.

Injected histological perfusion indicator (Hoechst) showed that perfusion is inhibited inside HIFU lesions. There was also evidence for the creation of ischaemic damage when one or more vessels at a lesion site were damaged. The histological data was verified using radiological data from MRI and US.  Further analysis showed that whilst no vessels in the centre of lesion were viable, some of the vessels at the periphery survived. The smallest vessels spared at the margin were 30 μm in diameter, whilst the furthest distance from the margin in which a spared vessel was observed was 1500 μm. The size range of the vessels spared was 30-250 μm. The viability of the vessels was ascertained using picrosirius stain which enables differentiation between normal and denatured collagen. This is vital new information which could be used to avoid under treatment of tumours and hence ensure clinical efficacy. This study has been one of the first to characterise the disruption to vessels during HIFU exposures in which the different damage mechanisms have been explored using a new suite of cavitation detection techniques. 

This has been undertaken using a wide range histological techniques including some which have never before been used to look at HIFU exposures, and supporting evidence from higher resolution radiological techniques than have been used previously as been pivotal to gaining a fuller understanding of the data. The histological techniques developed during this study for characterisation of vascular damage can be applied to different experimental models and tumours to provide further understanding of the effect of different sized vessels at the treatment site.

Figure 1: Radiological data showed that HIFU lesions lack perfusion, and that ischaemic damage may result from damage to vessels at the lesion site. Perfusion staining (1) showed a lack of perfusion within lesion centres (in both lesions where boiling was detected or undetected) but some vessels >30 m at close to the lesion margin showed perfusion both at 3 hrs and 24 hrs after HIFU. Hypoxia staining (2) showed that the tissue at the perfusion margin was hypoxic. The vessels spared at the margin also showed hypoxic tissue surrounding them, indicating that the vessels were stressed or had compromised perfusion. The collagen patency stain (Picrosirius red) (3) confirmed that the vessels in the lesion centre were not viable, but that some vessels at the margin were viable. Whilst vessels were spared at the periphery, these were not completely normal as indicated by the expression of clotting factors (4), which were not expressed within the vessels in the centre of the lesions.