Molecular imaging of oxidative stress using an LED-based photoacoustic imaging system

Abstract

LED-based photoacoustic imaging has practical value in that it is affordable and rugged; however, this technology has largely been confined to anatomic imaging with limited applications into functional or molecular imaging. Here, we report molecular imaging reactive oxygen and nitrogen species (RONS) with a near-infrared (NIR) absorbing small molecule (CyBA) and LED-based photoacoustic imaging equipment. CyBA produces increasing photoacoustic signal in response to peroxynitrite (ONOO − ) and hydrogen peroxide (H 2 O 2 ) with photoacoustic signal increases of 3.54 and 4.23-fold at 50 µM of RONS at 700 nm, respectively. CyBA is insensitive to OCl − , ˙NO, NO 2 − , NO 3 − , tBuOOH, O 2 − , C 4 H 9 O˙, HNO, and ˙OH, but can detect ONOO − in whole blood and plasma. CyBA was then used to detect endogenous RONS in macrophage RAW 246.7 cells as well as a rodent model; these results were confirmed with fluorescence microscopy. Importantly, CyB suffers photobleaching under a Nd:YAG laser but the signal decrease is <2% with the low-power LED-based photoacoustic system and the same radiant exposure time. To the best of our knowledge, this is the first report to describe molecular imaging with an LED-based photoacoustic scanner. This study not only reveals the sensitive photoacoustic detection of RONS but also highlights the utility of LED-based photoacoustic imaging.

Photoacoustic Imaging Quantifies Drug Release from Nanocarriers via Redox Chemistry of Dye‐Labeled Cargo

“…The photoacoustic signal showed a linear increase with respect to the percentage drug released (Figure c). The increased absorbance and photoacoustic signal are attributed to the release of PTX‐LMB and its oxidation to PTX‐MB …”

Biosensors Based on Mechanical and Electrical Detection Techniques

“…In addition to imaging tissue, PA techniques can detect molecules of interest, which is exciting as it presents the opportunity for non-invasive glucose monitoring, as an example [ 56 ]. It has further been demonstrated to detect gases at concentrations of parts per trillion in air [ 57 ], as well as reactive oxygen and nitrogen species down to tens of micromolar concentrations at a depth of 1 cm using labelling molecules [ 58 ]. The drawbacks to PA imaging is the large, complex equipment and the fast photobleaching of the lasers [ 58 , 59 ].…”

“…It has further been demonstrated to detect gases at concentrations of parts per trillion in air [ 57 ], as well as reactive oxygen and nitrogen species down to tens of micromolar concentrations at a depth of 1 cm using labelling molecules [ 58 ]. The drawbacks to PA imaging is the large, complex equipment and the fast photobleaching of the lasers [ 58 , 59 ]. Some of these issues may be solved with the use of LEDs instead of lasers, and the use of new improved transducers is reducing the complexity of the equipment.…”

“…Photoacoustics is a rapidly developing field, with multiple applications, from structural flaw detection to novel micropumps [ 61 , 62 ]. One of the primary uses of PA is in biological imaging, due to its ability to provide real-time imaging of the body enabling easy identification of tumours [ 63 , 64 ], as well as probing of reactive species in order to detect inflammation [ 58 ]. The technique relies on ultrasound emission from the thermoelastic effect.…”

“…Fortunately, Hariri et al have demonstrated an alternative to lasers with LED technology instead. Due to its stable, low intensity light, photobleaching is greatly reduced, with the further advantages that the LED technology is smaller, simpler and cheaper, suggesting this will be an important area of research in the future [ 58 ].…”