Small-Animal Imaging

The common use of fluorescence in small-animal imaging makes time-resolution almost mandatory. As for the other DOT applications, time-resolved small-animal imaging is performed by modulation techniques and by TCSPC. TCSPC has the benefit that it is able to resolve complex decay functions. The principle of a typical time-resolved instrument [174] is shown in Fig. 5.57. 

The animal (a mouse or a rat) is placed on a platform mounted on a translation stage. The temperature of the platform is stabilised. This is important because small animals are very susceptible to cooling, especially when they are anaesthetised. 

Typical fluorescence decay curves obtained by this instrament are shown in Fig. 5.58. The fluorescence comes from small inclusions of Cy5.5 in an intralipid solution of Pa = 0.006 mm and Ps = 1.0 mm  

A change in depth clearly changes the shape of the fluorescence signal, while a change in concentration changes only the intensity. For known scattering and absorption coefficients in the tissue the fluorescence lifetime and the depth of a fluorescent inclusion can be determined. 

Fluorescence is obtained not only from the CY5.5 but also from endogenous fluorophores, especially from food in the digestive track. The fluorescence decay is different for the endogenous and exogenous fluorophores. This makes it possible to assign the structures in the CW image to the used fluorescent markers and to track lifetime changes induced by variations in the local environment. 

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Hao L, Zhang H, Tang Z et al (2008) Micro-computed tomography for small animal imaging technological details. Prog Nat Sci 18(5) 513-521... 

Cell and Small Animal Imaging with Surface-Enhanced Raman Spectroscopic (SERS) and Other Nanoparticle Tags... 

Iwata K, MacDonald L R, Hwang A B, et al. (2002). CT-SPECT for small animal imaging with A-SPECT. J. Nucl. Med. 43(suppl.) 10P-Abst. No. 35. 

Lewis J S, Achilefu S, Garbow J R, et al. (2002). Small animal imaging Current technology and perspectives for oncological imaging. Eur. J. Cancer. 38 2173-2188. 

Certainly in human patients the condition of a well-localised inclusion in a homogeneous, nonfluorescent bulk medium is not fulfilled. The condition is better, yet not perfectly, met in small animals where the tissue depth does not exceed a few millimeters. The contribution of the bulk medium and its inhomogeneity is correspondingly smaller. Therefore DOT fluorescence is currently used mainly for small-animal imaging (see section below). 

Ma, R., et al. Multispectral optoacoustic tomography (MSOT) scanner for whole-body small animal imaging. Optics Express 17(24), 21414-21426 (2009)... 

For small-animal imaging studies, Zhang gia/. were the first to inject UCNPs subcutaneously into rats for... 

To be able to perform the same types of studies that are currently performed on humans (average adult weight of 70 kg), small animal imaging devices must have a spatial resolution scaled appropriately to the object of interest. Typical human clinical scanners have a spatial resolution of 5-10 mm. Because the typical human chest has a diameter of 30-50 cm, spatial resolution in the mouse, with a chest diameter of 2-3 cm, must improve by a factor of at least 10, that is < 1 mm. Spatial resolution demands of this sort have required new and improved technologies of both detector and overall camera design. 

Jaszczak RJ, Li J, Wang H, Zalutsky R, Coleman RE. Pinhole collimation for ultra-high-resolution, small field-of-view SPECT. Phys Med Biol 1994 39 425-437. Erlandsson K, Ivanovic M, Strand SE, Sjogren K, Weher DA. High resolution pinhole SPECT for small animal imaging. J Nucl Med 1993 34 9P. 

Kastis GA, Fruenhd LR, Wilson DW, Peterson TE, Barber HB, Barrett HH. Compact CT/SPECT small animal-imaging system. Trans Nucl Sci 2004 51 63-67. 

Del Guerra A, Damiani C, Di Domenico G, Motta A, Giganti M, Marchesini R, PiffaneUi A, Sabba N, Sartori L, Zavattini E. An integrated PET-SPECT small animal imager preliminary results. IEEE Trans Nucl Sci 2000 47 1537 1540. 

Micro-CT is becoming a very important tool for small animal imaging including imaging of mice. Different techniques have been proposed to image small... 

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