Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines

Abstract

OverviewThere is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and give rise to good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ~20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1000). Unlike conventional chromophores, nanonaps exhibited non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution with 0.5 cm depth, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole body imaging.

Deep tissue photoacoustic computed tomography with a fast and compact laser system

“…In addition, singlewavelength-based functional and molecular imaging approaches have shown promise for various applications. For instance, for functional imaging, the blood flow can be quantified based on thermal tagging of red blood cells [49], the intestinal motility can be imaged with contrast agents [50], and the blood oxygenation can be obtained through the saturation-based PA imaging [51]. For molecular imaging, magnetomotive PA [4] and photo-switchable contrast-enhanced PA [52] allow accurate separation of contrast signals with minimum interference from background.…”

Low-power noncontact photoacoustic microscope for bioimaging applications

“…High-resolution deep tissue imaging is possible using acoustic resolution PA imaging. [46][47][48][49] PA imaging has been used to image anatomical, 50 functional, 46 molecular, 46 flow dynamic, 47 and metabolic contrasts in vivo. 47 Microscopy applications can use either acoustic resolution PAM (AR-PAM) or optical resolution PAM (OR-PAM), or a combination of both, depending on the application and imaging target.…”

Delay-multiply-and-sum-based synthetic aperture focusing in photoacoustic microscopy

“…9 Extrinsic contrast agents (e.g., metallic, carbonic, and organic nanostructures) have been widely investigated for contrastenhanced PAI. [10][11][12][13][14][15][16][17][18] As one of the PAI modes, scanning-based PA microscopy (PAM) has been significantly investigated and used in biological studies. With a single laser shot, one-dimensional (1-D) PA images (referred to as A-lines) can be acquired by measuring the times of arrivals of PA signals.…”