Biomedical Engineering Reference
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phenomenon was demonstrated using NSC labelled with a gadolium-dextran T2
agent (Modo et al.
2002
). When transplanted to the ipsilateral side of the stroke,
ferumoxide-labelled NSC were reported to migrate along the infarct periphery
(Guzman et al.
2007
). In a Huntington's disease model where lesions were induced
by quinolinic acid, ferumoxide-labelled MSC showed a distinct migration route
toward the lesions (Sadan et al.
2008
).
6.2
Clinical Studies of Cellular MRI
Although there have only been four completed clinical trials of MRI cellular tracking
to date, another four active studies are ongoing or recruiting, according to the NIH
database
clinicaltrial.gov
. In one of the completed studies, autologous dendritic
cells (DC) were labelled with ferumoxide or
111
In-oxine prior to injection into the
lymph nodes of 11 stage-III melanoma patients (de Vries et al.
2005
). Post-injection
verification by MRI was found to be superior to ultrasound-guided injection.
In three out of eight patients, MRI showed unsuccessful intranodal delivery, an
observation corresponding to the lack of DC migration to the draining lymph nodes.
Verified by histology of resected nodes, the detection of migrated DC to draining
lymph nodes was more reliable by MRI than scintigraphy. An inherent advantage
of MRI is the anatomical localisation of DC at injection sites or after migration.
Scintigraphy is a superior quantification modality and
111
In-oxine labelling may
remain a useful co-label with MRI contrast agents until MRI quantification matures.
The other clinical trial involved patients with traumatic, open head injuries where
loose neural tissue is cultured in a media known to proliferate NSC (Zhu et al.
2006
). Following labelling with ferumoxide, the NSC were injected intra-cerebrally
at four sites around the lesion. Weekly MRI assessments subsequently showed that
the lesion periphery began to darken progressively while hypo-intensity at the
injection site faded from 1 to 3 weeks post-transplantation. This was not observed
in the control patient that received unlabelled NSC. As the patients survived the
trauma and transplantation, histology has not been possible. The third completed
study stands out with the use of nonclinical 4.5 mm particles (Callera and de Melo
2007
). Human CD34+ cells with surface-bound particles were tracked over time to
the traumatic brain injury in ten patients, an observation absent in the six control
patients who were given only particles without cells. Although no adverse effect
was observed over 35 days post-transplantation, the attachment of cell graft with
particles of comparable sizes, in particular nonbiodegradable, nonclinical particles,
raises concern about the long term safety in patients. In the most recently completed
study, four diabetic patients were given ferucarbotran-labelled islet cells intraportally
(Toso et al.
2008
). Labelled islet cells were functionally competent as observed by
the insulin independence of all four patients. However, fewer hypointense spots were
observed compared to the number of islet cells injected, prompting the postulation
that the labelling efficiency was sufficient only for the MR-visibility of islet cell
clusters, but not individual cells.
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