Multispectral photoacoustic imaging of tumours in mice injected with an enzyme-activatable photoacoustic probe

Abstract

Photoacoustic (PA) imaging offers depth-resolved images of optical absorbers with the spatial resolution of ultrasound imaging. To enhance tumour contrast, tumour-specific probes are used as contrast agents. We synthesised a colourless PA probe that is activated in the presence of γ-glutamyltranspeptidase, a cancer-associated enzyme, to show its original colour and fluorescence. We have acquired high specificity fluorescence images of small tumours, using a fluorescent probe based on similar enzymatic reactions. Here, we developed a PA imaging technique to detect the PA probe. In PA imaging, depending on the concentration and excitation wavelength of the probe, the intensities of the probe signals may be lower than those of the background signals produced by intrinsic optical absorbers such as haemoglobin. For probe imaging in the presence of strong background signals, multispectral photoacoustic (MS-PA) imaging was evaluated. In MS-PA imaging, the spectral fitting method, which distinguishes the probe signals from background signals using reference spectra, has been widely used. To compensate for the decrease of fluence due to optical attenuation in biological tissue, we used a simplified compensation method that calculates fluence inside biological tissues by the Monte-Carlo model using published data on optical properties of biological tissues. The validity of the method was confirmed using tissue-mimicking phantoms. Finally, MS-PA imaging of a mouse subcutaneous tumour injected with the activatable probe was demonstrated. In conclusion, our MS-PA imaging technique afforded successful detection of the activated probe in the tumour, and time-increase of PA signals were successfully observed.

Spectroscopic photoacoustic microscopic imaging during single spatial scan using broadband excitation light pulses with wavelength-dependent time delay

“…The motorized stage, digital oscilloscope, light source, and analog counter were synchronized with a LabVIEW program. The PA signals were enveloped using the Hilbert transform to calculate the intensities [39] . Image distortion because of fluctuation in the stage translation speed was compensated using a linear gauge.…”

Recent progress in photoacoustic molecular imaging

“…, light illumination) [36, 74] or internally ( e.g. , chemical cleavage) [75, 76, 83]. For example, several groups (including the authors’) have explored the reversible photoswitching capability of several fluorescent (Dronpa, rsTagRFP) and non-fluorescent (BphP1, AGP1) proteins [36, 74, 84].…”

Photoacoustic imaging for monitoring of stroke diseases: A review

“…The tumor is a type of disease in the vascular system that can also lead to stroke. Many studies on PAI for tumor imaging have shown good performance [ [99] , [100] , [101] , [102] , [103] ]. Furthermore, a peripheral vascular system disease can influence the cerebrovascular system and lead to the occurrence of stroke [ 104 ].…”