Imaging in Stem Cell Transplant and Cell-based Therapy

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based metalloproteins for MR imaging has its own drawbacks, especially

related to toxicity from iron accumulation [ 22 ]. There are also concerns

regarding signal nonlinearity. Dilutional signal loss following cell division

takes time to build up to detectable levels making correlation between detected

signal and viability of transplanted cells difficult. The R2 relaxivity of iron is

dependent on concentration. With very high iron accumulation T2 relaxation

plateaus and precludes accurate quantification of the signal. Following cell

death the reporter gene does not function but the iron already accumulated

iron inside the cell generates signal, similar to SPIOs. Hence in such situa-

tions the signal is neither representative nor linear of cell viability [ 23 ]

2. Optical Imaging: Optical imaging comes in two flavors, bioluminescence and
   fluorescent techniques. Bioluminescence as the name suggests is a technique
   where the source of light is within the organism. In this technique, a light source
   is incorporated in the organism using DNA encoding of the luminescent protein.
   The protein is incorporated in the stem cells, typically using a viral vector creat-
   ing a reporter gene. There are three common organisms that provide the light
   source. Firefly luciferase (d-luciferin) from north American firefly, Luciferase
   from Sea Pansy like Renilla luciferase (coelenterazine) and Bacterial Luciferase
   from bacteria like photorhabdus luminescent or vibrio fischeri. The light is pro-
   duced by the substrate independently or in conjunction with cofactors. For exam-
   ple oxidation of the substrate D-luciferin by the firefly luciferase (FLuc) enzyme

Fig. 1.2 MRI detection of ferritin-tagged graft in the infarcted mouse heart. (A1–A4) Unlabeled
wild-type C2C12 graft. (B1–B4) Transgenic C2C12 graft overexpressing ferritin. (A1, B1) Black-
blood proton-density-weighted turbo spin echo (PD TSE BB) sequence. (A2, B2) Black-blood
improved motion-sensitized-driven equilibrium (iMSDE) T2 sequence. (A3, B3) Bright-blood gra-
dient echo (GRE) T2 sequence. (A4, B4) Embryonic myosin immunostaining for graft detection.
LV left ventricle. (Courtesy, Naumova A et  al. Quantification of MRI signal of transgenic grafts
overexpressing ferritin in murine myocardial infarcts. NMR Biomed. 2012 Oct;25(10):1187–95)

1 Current Indications and Overview of Molecular Imaging Techniques...