It has been reported that acoustic waves are generated when a high-energy pulsed proton beam is deposited in a small volume within tissue. One possible application of proton-induced acoustics is to get real-time feedback for intra-treatment adjustments by monitoring such acoustic waves. A high spatial resolution in ultrasound imaging may reduce proton range uncertainty. Thus, it is crucial to understand the dependence of the acoustic waves on the proton beam characteristics. In this manuscript, firstly, an analytic solution for the proton-induced acoustic wave is presented to reveal the dependence of the signal on the beam parameters; then it is combined with an analytic approximation of the Bragg curve. The influence of the beam energy, pulse duration and beam diameter variation on the acoustic waveform are investigated. Further analysis is performed regarding the Fourier decomposition of the proton-acoustic signals. Our results show that the smaller spill time of the proton beam upsurges the amplitude of the acoustic wave for a constant number of protons, which is hence beneficial for dose monitoring. The increase in the energy of each individual proton in the beam leads to the spatial broadening of the Bragg curve, which also yields acoustic waves of greater amplitude. The pulse duration and the beam width of the proton beam do not affect the central frequency of the acoustic wave, but they change the amplitude of the spectral components.

Photoacoustic microscopy (PAM) is a promising imaging modality that combines optical and ultrasound imaging. It combines the advantages of high ultrasonic spatial resolution and high optical contrast. When a short laser pulse illuminates the tissue, absorbed light leads to an acoustic emission via thermoelastic expansion [1]. The laser system needs to generate short enough pulses, i.e., several nanoseconds, to create photoacoustic signals with high efficiency and emit wavelengths in the visible range to excite tissue chromophores in their absorption peaks. To increase penetration depth of imaging, it is also desirable to utilize a wavelength in the NIR range, from 600 to 1200 nm, where biological tissues are relatively transparent.Here, we developed a tunable fiber based laser system producing nanosecond pulses, covering the spectrum from 450 nm to 1100 nm, specifically for PAM and tested it for imaging with multiple photoacoustic probes inside microfluidic channels. The laser system can be examined in three subsystems; i) fiber laser ii) supercontinuum iii) harmonic generator. The supercontinuum part of the laser is all fiber-integrated; guided-beam-propagation renders it misalignment-free and mostly immune to mechanical perturbations. Total supercontinuum output power is over 1 W, and visible output power is around 270 mW at 65 kHz repetition rate corresponding to 4 μJ pulse energy. Free space harmonic generation creates higher pulse energy for a particular band, i.e. 532 nm, and also generates ultraviolet (UV) light with wavelengths of 355 and 266 nm. One of the novelties here is the improvement of wavelength tunability, output power, and pulse energy when fiber-based lasers are benchmarked. The tunability of the laser parameters allows using only one laser for many different PAM applications, and also high repetition rate enables fast scanning. The coverage of near-UV spectrum gives an opportunity to image cell nuclei. As certain morphological changes such as size and shapes irregularities in the nuclei are known indicators of various cancers[2], we believe our system may also be useful for cell nuclei studies as well. Fig. 1 a) The fiber laser system, supercontinuum and harmonic generation outputs, b) OR-PAM system based on the fiber laser system c) PAM image of Bombay Indian Ink inside microfluidic channels, excitation wavelength is 680 nm, d) Red blood cells inside microfluidic channels, excitation wavelength is 532 nmWe demonstrated the capability of the laser system in PAM by utilizing it for experiments for different probes inside home developed microfluidic channels. In Figure 1c, microfluidic chip filled with Indian Ink that is excited by the 680 nm light filtered from supercontinuum part of the laser can be seen. In Figure 1d, red blood cells that are excited by the 532 nm harmonic generation output of the same system is imaged. References[1] Xu, M., and L.V. Wang. "Photoacoustic imaging in biomedicine." Rev. Sci.

Fiber-optic hydrophones (FOHs) are widely used to detect high-intensity focused ultrasound (HIFU) fields. The most common type consists of an uncoated single-mode fiber with a perpendicularly cleaved end face. The main disadvantage of these hydrophones is their low signal-to-noise ratio (SNR). To increase the SNR, signal averaging is performed, but the associated increased acquisition times hinder ultrasound field scans. In this study, with a view to increasing SNR while withstanding HIFU pressures, the bare FOH paradigm is extended to include a partially reflective coating on the fiber end face. Here, a numerical model based on the general transfer-matrix method was implemented. Based on the simulation results, a single-layer, 172 nm TiO2-coated FOH was fabricated. The frequency range of the hydrophone was verified from 1 to 30 MHz. The SNR of the acoustic measurement with the coated sensor was 21 dB higher than that of the uncoated one. The coated sensor successfully withstood a peak positive pressure of 35 MPa for 6000 pulses.

Photoacoustic microscopy (PAM) research, as an imaging modality, has shown promising results in imaging angiogenesis and cutaneous malignancies like melanoma, revealing systemic diseases including diabetes, hypertension, coronery artery, cardiovascular disease from their effect on the microvasculature, tracing drug efficiency and assessment of therapy, monitoring healing processes such as wound cicatrization, brain imaging and mapping, neuroscientific evaluations. Clinically, PAM can be used as a diagnostic and predictive medicine tool; even have a part in disease prevention [1].Parameters of the laser used in PAM, such as pulse duration, energy, PRF (pulse repetition frequency), and pulse-to-pulse stability affect signal amplitude and quality, data acquisition speed and obliquely the spatial resolution. Current lasers used in photoacoustic imaging are commercially available Q-switched lasers, low-power laser diodes, and very recently, fiber lasers with non-adjustable properties. In all of these systems, the key parameters cannot be adjusted independently of each other, bringing about certain systematic limitations on optimization of current microscopy systems. For example, microvasculature and cellular imaging require rather different laser properties. Thus, there is need for a laser system that offers largely independent control over the key parameters.Here, we report a unique, all-fiber-integrated, fiber laser system producing nanosecond pulses covering a wavelength range of 600 nm to 1100 nm, developed specifically as a source for photoacoustic excitation. The system comprises of an oscillator (Yb-doped NOLM laser) and amplifier, which generates and amplifies nanosecond pulses respectively, an acousto-optic modulator to control pulse repetition rate and a photonic-crystal fiber to generate supercontinuum. Complete control over the pulse train, including generation of non-uniform pulse trains, is achieved via the AOM through custom-developed field-programmable gate-array (FPGA) electronics. The system is unique in terms of offering adjustability for all the important parameters over broad ranges, namely, the pulse duration (1-3 or longer ns), pulse energy (up to 10 μJ, e.g., at 50 kHz) and repetition rate (50 kHz -3 MHz). Moreover, different photocoustic imaging probes can be excited using this single laser system thanks to its broadspectrum output (600 nm to 1300 nm) based on supercontinuum generation. The entire system is fiber-integrated, meaning that beam propagation is waveguided in fiber everywhere, making it misalignment free and largely immune to mechanical vibrations. The laser system is robust, compact, low-cost and built using only readily available standard components.(c) Fig. 1 (a) Fiber laser system generating supercontinuum spectrum and nanosecond pulses (b) spectrum graph of the photoniccrystal fiber output (c) photo taken at the output of PCF, different colours are visible due to supercontinuum in visible range. References[1] H.

Previous studies showed that it is possible make image reconstruction based on the dose dependence of the therapeutic XA (X-ray induced acoustic signal) amplitude which is then used to make dose mapping. We aimed to bring further explicit parametrization for the acoustic signal in terms of the absorption parameters, since this would mean encoding more information regarding the absorption process to XA signals. The first step is to obtain pressure waveform due to a point dose absorption by solving the thermo-acoustic equation Elfed Lewis. An optical fibre-based sensor for real-time monitoring of clinical linear accelerator radiotherapy delivery.