Advances in optical imaging for pharmacological studies

Abstract

Imaging approaches are an essential tool for following up over time representative parameters of in vivo models, providing useful information in pharmacological studies. Main advantages of optical imaging approaches compared to other imaging methods are their safety, straight-forward use and cost-effectiveness. A main drawback, however, is having to deal with the presence of high scattering and high absorption in living tissues. Depending on how these issues are addressed, three different modalities can be differentiated: planar imaging (including fluorescence and bioluminescence in vivo imaging), optical tomography, and optoacoustic approaches. In this review we describe the latest advances in optical in vivo imaging with pharmacological applications, with special focus on the development of new optical imaging probes in order to overcome the strong absorption introduced by different tissue components, especially hemoglobin, and the development of multimodal imaging systems in order to overcome the resolution limitations imposed by scattering.

Keywords: bioluminescence; data processing; fluorescence molecular tomography; hybrid systems; multispectral imaging; multispectral optoacoustic tomography; optoacoustics; planar fluorescence imaging.

FIGURE 1

In vivo monitoring of therapeutic effect of drug treatment in Alzheimer’s disease. Application of CRANAD-3 for monitoring therapeutic effects of drug treatments. (A) In vivo imaging of APP/PS1 mice with CRANAD-3 before and after treatment with the BACE-1 inhibitor LY2811376. (B) Quantitative analysis of the imaging in A (n = 4). (C) Representative images of 4-month-old APP/PS1 mice after 6 months of treatment with CRANAD-17. (Left) Age-matched WT mouse. (Center) Control APP/PS1 mouse. (Right) CRANAD-17—treated APP/PS1 mouse. Note that the NIRF signal from the CRANAD-17—treated APP/PS1 mouse (Right) is lower than the signal from the non-treated control APP/PS1 mouse (Center). (D) Quantitative analysis of the imaging in C (n = 5). (E) ELISA analysis of total Aβ40 from brain extracts. (F) Analysis of plaque counting. (G) Representative histological staining with thioflavin S. (Left) CRANAD-17—treated mouse. (Right) Control. *P < 0.05, **P < 0.01, ***P < 0.005. From Zhang et al. (2015b).

FIGURE 2

Pharmacokinetic in vivo imaging using MSOT. (A) Time series of images visualizing the biodistribution of IRdye800 in green on logarithmic scale overlaid on the vasculature. Both channels are the result of spectral unmixing. (B) Cryoslice image after approximately 15 min with overlaid fluorescence as a verification of the MSOT results. (C) A comparison of fluorescence distribution in the kidneys of mice sacrificed after approximately 2 min 30 s after injection and 15 min after injection. Note the changes in distribution similar to the time series shown in (A). (D) Temporal evolution of signal (each normalized to their smoothed maxima) in the regions of interest highlighted in the rightmost image, orange showing a region in the renal cortex that displays early and steep signal pickup and black indicating a region in the renal pelvis where probe accumulation is delayed and has a smoother profile. Time points of the images in (A) are marked using vertical lines. From Taruttis et al. (2012).