Abstract
The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo, e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation.
Highlights
The use of ultrasound (US) in clinical practice is no longer limited to diagnostic imaging and needle guidance in tumor biopsy, thanks to the possibility of using high intensity focused ultrasound (HIFU) which opened the door for promoting US as a non-invasive therapeutic method to treat different diseases [1,2]
Mechanical effects induced by HIFU involves non-thermal tissue destruction and are associated with high intensity acoustic pulses, resulting in cavitations, micro-streaming, and radiation force leading to disruption of the vascular structure, connective tissue, and cellular damage [5, 6]
We can distinguish the presence of accumulated fragmented tumor cells, chromatin and collagen debris in mouse 1, Fig. 2(e) as well as the presence of red blood cells delineated with a blue dotted line in the zoomed image
Summary
The use of ultrasound (US) in clinical practice is no longer limited to diagnostic imaging and needle guidance in tumor biopsy, thanks to the possibility of using high intensity focused ultrasound (HIFU) which opened the door for promoting US as a non-invasive therapeutic method to treat different diseases [1,2]. The thermal effect relies on temperature increase due to the absorption of US at the focal spot. This increase can vary depending on the intensity and treatment time leading to different stages of tissue destruction ranging from reversible heat induced injury (43 to 45 °C) to coagulation necrosis when the temperature exceeds 50 °C [4]. Mechanical effects induced by HIFU involves non-thermal tissue destruction and are associated with high intensity acoustic pulses, resulting in cavitations, micro-streaming, and radiation force leading to disruption of the vascular structure, connective tissue, and cellular damage [5, 6]. One of the mechanical ablation methods that have been investigated in recent years are cavitation cloud histotripsy and boiling histotripsy [10,11,12,13]
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