VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.

The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease.

Low-cost three-dimensional imaging system combining fluorescence and ultrasound.

In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continuous-wave transillumination fluorescence tomography with 3D ultrasound (US) imaging. We validated the system with two phantoms, one containing fluorescent inclusions (Cy5.5) at different depths, and another varying-thickness semicylindrical phantom. Using raster scanning, the combined fluorescence/US system was used to collect the boundary fluorescent emission in the X-Y plane, as well as recovered the 3D surface and position of the inclusions from US signals. US images were segmented to provide soft priors for the fluorescence image reconstruction. Phantom results demonstrated that with priors derived from the US images, the fluorescent reconstruction quality was significantly improved. As further evaluation, we show pilot in vivo results using an Apo-E mouse to assess the feasibility and performance of this system in animal studies. Limitations and potential to be used in artherosclerosis studies are then discussed.

1/f noise in diffuse optical imaging and wavelet-based response estimation.

In diffuse optical imaging (DOI) data analysis, the functional response is contaminated with physiological noise as in functional magnetic resonance imaging (fMRI). In this work we extend a previously proposed method for fMRI to estimate the parameters of a linear model of DOI time series. The regression is performed in the wavelet domain to infer drift coefficients at different scales and to estimate the strength of the hemodynamic response function (HRF). This multiresolution approach benefits from the whitening property of the discrete wavelet transform (DWT), which approximately decorrelates long-memory noise processes. We also show that a more accurate estimation is obtained by removing some regressors correlating with the protocol. Moreover, we observe that this improvement is related to a quantitative measure of 1/f noise. The performances of the method are first evaluated against a standard spline-cosine drift approach with simulated HRF and real background physiology. Lastly, the technique is applied to experimental event-related data acquired by near-infrared spectroscopy (NIRS).