9ment. Various single and multimodality imaging strategies have been adopted that
form the cornerstone of translational research with bench to bedside applications in
clinical care.
Any modality that needs to be used for stem cell imaging should fulfill several
criteria. It should be capable of real rime visualization of stem cell delivery. Once
stem cells are implanted it should be able to locate them at the target site. It should
also allow quantification of viable stem cells and estimate long-term survival.
Finally the modality should be able to study stem cell biology, like interaction of
stem cells among one another and with their microenvironment. Moreover, the
modality itself should not alter the stem cells in any way. The method of stem cell
labeling employed by a particular modality must be biocompatible with minimal
toxicity when released by the stem cell. If an intermediary agent is required for this
process then that agent must not interfere with normal regulatory or differentiation
pathways of the cells. Moreover, the imaging technique must be sensitive enough to
the label such that it can still be detected, at least following initial stem cell division
and replication.
Three different strategies are used for stem cell labeling. The first involves direct
non-specific labeling of the stem cells. The second method involves an indirect,
receptor mediated specific cell labeling and the third technique employs a reporter
gene probe labeling [ 16 ]. Typically a labeling agent is introduced into the stem cells
prior to transplantation. Following transplantation of the cells non-invasive imaging
is performed. The modalities that are most useful in direct stem cell labeling include
Optical imaging, MRI, PET, SPECT and ultrasound. The appropriate labeling strat-
egy for each modality is discussed below. A summary of the various stem cell imag-
ing strategies is shown in Table 1.1.
- Magnetic Resonance Imaging (MRI): Magnetic resonance imaging is the most
extensively studied technique to directly label and image stem cells non-
invasively [ 16 ]. MR imaging can utilize both T1 and T2 properties to label stem
cells. T1 agents employ use of paramagnetic metal chelates like gadolinium to
directly label stem cells. Contrary to expectations, a T1 agent does not produce
a hyper intense signal when internalized inside the stem cell. This is due to
reduced water exchange across the cell membrane limiting the “conventional”
dipole-dipole interaction. In this situation the outer sphere magnetic susceptibil-
ity predominate resulting in a hypo-intense signal [ 17 ]. However, the pharmaco-
kinetics of the T1 W agents is not predictable. For example the de-chelated form
of gadolinium is highly toxic. On the other hand, the T2 properties of the super
paramagnetic iron oxide (SPIO) contrast agents is robust and extensively studied
in labeling of the stem cells.
(a) MRI Labeling techniques:
1 Current Indications and Overview of Molecular Imaging Techniques...