PhotoAcoustic-Guided High-Intensity Ultrasound using time-reversal of photoacoustic waves – PAG-HIFU

In the field of biomedical ultrasound, conventional ultrasound imaging or ultrasound therapy techniques assume the investigated tissue to be homogeneous in terms of speed of sound in order to focus ultrasound. Such an assumption may be inadequate for some locations in the body. For instance, one of the most promising application in the fast emerging field of ultrasonic therapy is the possibility to non invasively treat brain tumours with high intensity focused ultrasound (HIFU). But focusing ultrasound into the brain requires focusing through the skull bone, which is a strongly aberrating medium with acoustic properties very different from those of soft tissue, and which exact shape and thickness are a priori unknown. Time-reversal of acoustic waves provides a way to automatically focus ultrasound in highly complex media, based on the recording and re-emission of the ultrasound waves generated by a localized ultrasound source. The different types of time-reversal experiments that have been performed so far, in several fields such as ocean acoustics, biomedical acoustics, seismology, have relied on the existence of some localized mechanical contrast or some exogenous active ultrasound source (explosive load in ocean acoustics, earthquakes in seismology, cavitating bubbles in tissue). In this project, we propose to use a new kind of source to perform time-reversal experiments: as opposed to all previous types of sources that have been used, we propose to use a photoacoustic source, which ultrasonic emission is related to the optical properties (absorption) of the source. The photoacoustic effect consists in the emission of sound by an illuminated optically absorbing region. Physically, photoacoustic waves are pressure waves generated by the thermoelastic expansion following the absorption of a light pulse. For optical wavelengths included in the so-called therapeutic window (700 nm to 900 nm), the absorption of light in biological tissue is relatively low (absorption length of the order of several centimetres), and multiply scattered photons can travel as deep as a few centimetres in tissue. Photoacoustic waves can therefore be generated deep in tissue, and have in particular been used so far as a way to perform passive acoustic imaging. In this proposal, we want to develop a prototype designed to perform photoacoustic-guided high-intensity focused ultrasound (PAG-HIFU) towards localized optical absorbers in biological tissue, based on the time-reversal of the photoacoustic waves emitted by the absorbers. Our final objective is to create PAG-HIFU lesions in vitro in biological tissue and in vivo in small animals (rats or mice). Towards this goal, we will : 1) develop a method to selectively detect the photoacoustic waves generated by targeted optical absorbers in biological tissue, in order to time-reverse only the desired photoacoustic waves. 2) design optical contrast agents that can be excited selectively and act as photoacoustic sources, based on absorbing quantum dots 3) design a 2D ultrasound array able both to detect photoacoustic signals and to emit high-intensity ultrasound. 4) generate high-intensity focused ultrasound based on time-reversed photoacoustic waves. 5) study and quantify the parameters which determine the feasibility of the technique in tissue. 6) test and validate the whole system in vitro on biological tissue and in vivo on small animal models (rats). The potential of time-reversal of photoacoustic waves to perform HIFU is twofold, as can be illustrated for instance in the case of tumor therapy: first, assuming the absorption of a tumor to be different from that of healthy tissue (either from natural blood contrast due to hyper-vascularization, or caused by exogenous optical contrast agent), the technique makes it possible to focus selectively on the tumour, while automatically compensating for possible aberration. This would not only benefit to brain tumours by correcting the aberrations induced by the skull bone but also to moving organs such as the liver as time-reversal performed in real time would always focus on the photoacoustic source. Second, the technique would more generally benefit to all HIFU treatments by focusing selectively on tumours that are known to have different optical properties from healthy tissues even though they have similar acoustic properties. The photoacoustic effect can therefore be used not only as a way to create a source for time-reversal, but to reveal the presence of an object (the tumor) which may have been invisible to ultrasound probing by purely ultrasonic methods based on mechanical contrast (conventional ultrasound imaging or elastography).