## 4 Biological Applications
### Diagnostic Applications
#### 4.1.2 Bioimaging  
The use of nanoparticles in bioimaging applications includes imaging at the molecular level and at markedly larger scales (e.g., organs). Plasmonic nanoparticles are typically limited to molecular imaging or can act as contrast agents in bioimaging applications. Gold nanoparticles of various shapes and sizes have been reported for bioimaging applications due to their low toxicity and biocompatibility [172; 173]. Recently, [PERSON] et al. developed gold-silver alloy nanoparticles (GSAN) to improve the efficiency of an imaging probe for breast cancer [71]. In this study, the GSAN enhanced the imaging contrast for dual-energy mammography (DEM)--an X-ray-based imaging technique used to screen for breast cancer. Magnetic resonance imaging (MRI) is one of the most powerful imaging techniques in medical diagnosis. MRI measures the change in magnetization of protons under a magnetic field exposed to a radio frequency pulse [36]. The principle of the technique is based on the nuclear magnetic resonance effect where the local magnetic field produced by magnetic nanoparticles induces a change in the relaxation times of the surrounding protons. To investigate the enhancement of MRI signal, contrast agents act by accelerating the rate of relaxation of nearby water molecules, which increases the contrast between the tissue or organ of interest and the surrounding tissue [37]. Magnetic resonance (MR) contrast agents either accelerate the longitudinal relaxation (T\({}_{1}\)) of water and produce bright \"positive\" contrast images or accelerate the transverse relaxation (T\({}_{2}\)) and produce dark \"negative\" contrast images. For nanoparticle-based contrast agents, the relatively high magnetic moments of magnetic nanoparticles have been commonly used to shorten the T\({}_{2}\) of water protons in their vicinity, giving rise to an enhanced T\({}_{2}\)-weigthed MR images. The measurement and the effect of the contrast agents are typically measured as the T\({}_{2}\) relaxation time of water protons with a spin-echo pulse sequence and presented as the spin-spin relaxation rate R\({}_{2}\) where R\({}_{2}=1/\)T\({}_{2}\). The degree to which the contrast enhances the relaxation rate is denoted as the transverse relaxivity coefficient (r\({}_{2}\)), which is determined from the change of R\({}_{2}\) (spin-spin relaxation rate) as a function of the concentration of the magnetic material [37; 174]. Particles that are large and have higher saturation magnetization values have been reported to provide higher relaxivity (r\({}_{2}\)) [175]. Bimetallic nanoparticles with high magnetization, have thus attracted attention as contrast materials for MRI [39; 110; 111]. Several types of bimetallic nanoparticles such as biophosphonated-functionalized FeNi nanoparticles, dextran-coated FeCo nanoalloys, PEGylated Pt\({}_{3}\)Co nanoparticles, and CuNi have been reported as T\({}_{2}\) contrast agents [19; 40; 110; 111; 115]. [PERSON] et al. synthesized FePt nanoparticles capped with tetramethylammonium hydroxide (TMAOH) and found, by magnetic resonance relaxometry measurements, that TMAOH-capped FePt nanoparticles exhibit short T\({}_{2}\) relaxation times, which renders them attractive for use as negative contrast agents in MRI [103]. Similarly, [PERSON] et al. developed amphiphilic FePt nanoparticles capped with tetraethylene glycol and oleic acid [80]. The amphiphilic FePt nanoparticles can be efficiently endocytosed in living HeLa cells and offer good biocompatibility and high T\({}_{2}\) relaxivities at 122 mM\({}^{-1}\) s\({}^{-1}\)[105]. Dual modal imaging, using only one type of nanoparticle, can offer a more comprehensive diagnosis of cellular and in vivo imaging via CT/MRI [176]. For example, FePt nanoparticles have been conjugated with cysteamine and the antibody anti-Her2 and used as dual contrast agents for CT/MRI molecular imaging, as illustrated in Figure 11[106].