High pulse energy fibre laser as an excitation source for photoacoustic tomography.

A custom fibre laser designed as an excitation source for biomedical photoacoustic tomography has been developed. It is based on a custom-drawn large core diameter fibre (200 µm) that enables high pulse energies (∼10 mJ) to be achieved. The system can provide variable pulse durations (10 - 500 ns) and pulse repetition frequencies (100 Hz - 1 kHz), as well as arbitrary pulse bursts according to specific user defined sequences. The system is also compact and does not require external water cooling. This, along with the flexibility in the temporal characteristics of its output that it offers, will aid the translation of photoacoustic imaging to practical application in medicine and biology.

Ultrasound modulated imaging of luminescence generated within a scattering medium.

Ultrasound modulated optical tomography modulates scattered light within tissue by deterministically altering the optical properties of the sample with the ultrasonic pressure. This allows the light to be "tagged" and the degradation in spatial resolution associated with light scattering to be reduced. To our knowledge, this is the first demonstration of ultrasound modulated imaging of light generated within a scattering medium without an external light source. The technique has the potential to improve the spatial resolution of chemi- or bioluminescence imaging of tissue. Experimental results show that ultrasound modulated luminescence imaging can resolve two chemiluminescent objects separated by 5 mm at a 7 mm depth within a tissue phantom with a scattering coefficient of 30 cm-1. The lateral resolution is estimated to be 3 mm. Monte Carlo simulations indicate that, with the current system signal to noise ratio, it is feasible to apply the approach to bioluminescence imaging when the concentration of bacteria in the animal organ is above 3.4×105/µL.

Effect of object size and acoustic wavelength on pulsed ultrasound modulated fluorescence signals.

Detection of ultrasound (US)-modulated fluorescence in turbid media is a challenge because of the low level of fluorescent light and the weak modulation of incoherent light. A very limited number of theoretical and experimental investigations have been performed, and this is, to our knowledge, the first demonstration of pulsed US-modulated fluorescence tomography. Experimental results show that the detected signal depends on the acoustic frequency and the fluorescent target's size along the ultrasonic propagation axis. The modulation depth of the detected signal is greatest when the length of the object along the acoustic axis is an odd number of half wavelengths and is weakest when the object is an integer multiple of an acoustic wavelength. Images of a fluorescent tube embedded within a 22- by 13- by 30 mm scattering gel phantom (µ(s)∼15 cm(-1), g=0.93) with 1-, 1.5-, and 2 MHz frequency US are presented. The modulation depth of the detected signal changes by a factor of 5 depending on the relative size of the object and the frequency. The approach is also verified by some simple experiments in a nonscattering gel and using a theoretical model.

Application of a maximum likelihood algorithm to ultrasound modulated optical tomography.

In pulsed ultrasound modulated optical tomography (USMOT), an ultrasound (US) pulse performs as a scanning probe within the sample as it propagates, modulating the scattered light spatially distributed along its propagation axis. Detecting and processing the modulated signal can provide a 1-dimensional image along the US axis. A simple model is developed wherein the detected signal is modelled as a convolution of the US pulse and the properties (ultrasonic/optical) of the medium along the US axis. Based upon this model, a maximum likelihood (ML) method for image reconstruction is established. For the first time to our knowledge, the ML technique for an USMOT signal is investigated both theoretically and experimentally. The ML method inverts the data to retrieve the spatially varying properties of the sample along the US axis, and a signal proportional to the optical properties can be acquired. Simulated results show that the ML method can serve as a useful reconstruction tool for a pulsed USMOT signal even when the signal-to-noise ratio (SNR) is close to unity. Experimental data using 5 cm thick tissue phantoms (scattering coefficient µ(s) = 6.5 cm(-1), anisotropy factor g=0.93) demonstrate that the axial resolution is 160 µm and the lateral resolution is 600 µm using a 10 MHz transducer.