Ultrasound mediation of bioluminescence generated inside optically scattering media

Ahmad, Junaid (2019) Ultrasound mediation of bioluminescence generated inside optically scattering media. PhD thesis, University of Nottingham.

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Abstract

Bioluminescence imaging is a commonly used non-invasive technique in biology to access the pathological information in small animals. However, due to strong light scattering properties of biological tissue, it suffers a loss of spatial resolution and significant optical signal attenuation. Therefore, obtaining accurate information about physiology is challenging. This research proposes a hybrid imaging system that couples bioluminescence imaging with ultrasound (US) to offer a significant improvement in spatial resolution and quantitative accuracy of the imaging. This improvement is achieved using focused ultrasound that modulates the bioluminescence at US frequency (3.5 MHz) inside an optically scattering medium to produce an US switchable light ‘beacon’ that overcomes the influence of light scattering.

In the beginning, this manuscript highlights the construction and model of the optical detection system that is capable of sensing incoherent optical signals. For the initial testing, incoherent light from an LED source was modulated (without US) at 1 MHz under different illumination scenarios (i.e. non-scattering and scattering) to mimic the low light levels that are obtained in conventional bioluminescence tomography. The detection system was characterised to gauge its ability of extracting the weak modulated light (AC signal, at the above-mentioned 1 MHz frequency) out of the unmodulated light (DC signal). The experiments showed our system to detect the modulated light signal with an acceptable signal to noise ratio ~15 dB. Secondly, 1 MHz ultrasound was incorporated to modulate the light inside a tissue-mimicking phantom illuminated by an LED light source to evaluate the potential of the system for real-world in vivo bioluminescence experiments. However, it was observed that with a phantom having optical properties similar as a small nude mouse and achieving a surface radiance of ~2.4 × 10^12 photons/s/cm^2/sr the system is unable to measure any AC modulation. Unlike an incoherent LED source, luminescence involves a chemical reaction. Moreover, bioluminescence is a concentration of living organisms, therefore it is necessary to test the system performance using luminescent reporters.

Lastly, the LED was replaced by a millimetre-sized light source made from a plastic tube filled with a chemiluminescent solution to mimic a bioluminescent source and investigate the effects of acoustic waves on the light emission. It was observed that, in addition to AC modulation, ultrasound also increases the DC intensity of the reporters. This is shown to be due to a temperature rise caused by the continuous insonification that was minimised to be within acceptable mammalian tissue safety thresholds by adjusting the duty cycle of the ultrasound. Line scans of both bio-and chemiluminescent objects embedded within a scattering medium were obtained using ultrasound modulated (AC) and ultrasound enhanced (DC) signals. Lateral resolution is improved by a factor of 12 and 7 respectively, as compared to conventional CCD imaging. Two chemiluminescent sources separated by ~10 mm at ~20 mm deep inside a 50 mm thick chicken breast have been successfully resolved with an average signal to noise ratio of approximately 8-10 dB.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Morgan, Stephen P.
Jayet, Baptiste
Keywords: Acousto-optics; Bioluminescence; Imaging through turbid media; Ultrasound; Imaging systems; Detection; Multiple scattering.
Subjects: R Medicine > RC Internal medicine
Faculties/Schools: UK Campuses > Faculty of Engineering
Item ID: 56100
Depositing User: Ahmad, Junaid
Date Deposited: 18 Jul 2019 04:40
Last Modified: 07 May 2020 12:02
URI: http://eprints.nottingham.ac.uk/id/eprint/56100

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