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Imaging
interestingly, increased enhancement was seen at the rim of the are well established for the assessment of disease activity during the
transplant, yet no reason for this was given in the study. clinical work-up of patients with RA in the hands.
22,23
Due to the direct
visualisation of increased blood supply to the tissue during disease
Diseases leading to disturbance of microcirculation can be diagnosed activity, both methods are, in principle, superior to other clinical and
with fluorescence-based optical imaging, e.g. for patients with imaging tests, which do not show this early pathophysiological
tumours of the eye. Schaller et al.
14
studied 13 patients with choroidal process of inflammation.
24
In a review of the evaluation of treatment
melanomas before and for one year after brachytherapy using ICG- response to modern treatment, Brown
6
has clearly stated the need for
based fluorescence imaging. Microcirculation of the tumours was imaging on the basis of early pathophysiological processes for RA. On
this basis it is clear that an appropriate imaging test is superior to
currently established clinical procedures.
Overall, ICG-based fluorescence optical
Experimental Evidence
As outlined above, optical imaging with a fluorophor such as ICG is
imaging is well suited to delineating
capable of delineating microvascular changes in humans, and
changes of the microcirculation
microvascular alterations are an integral part of active inflammatory
processes, e.g. in RA. Hansch et al.
25
used Cy5.5 as a fluorophor in an
throughout a variety of clinical entities.
experimental study with mice suffering from arthritis. In joints with acute
arthritis, a significant increase of the fluorescence signal was noted
compared with the contralateral, healthy joints. The authors believe that
the enhancement was caused by the increased and alterated perfusion
visualised. In 10 of the 13 patients the microvascular effects of of the inflamed tissue. This process was further enhanced by the protein
brachytherapy were seen, causing a reduction of visible binding of Cy5.5 with its unspecific targeting. They concluded that
microvascular vessels. The authors concluded that this information fluorescence imaging in the NIR spectral range, using Cy5.5 as a
was helpful for clinical assessment of the therapy. fluorophor, is suited for delineation of arthritic joints in vivo.
In two further studies of the same group, the diagnostic potential of In a slightly different experimental set-up, Wall et al.
26
were able to
ICG-based microcirculation imaging was further substantiated. In one prove that tumoral 1,1’-bis-(4-sulfobutyl)indotricarbocyanine-5,5’-
study,
15
50 non-treated choroidal melanomas were imaged with dicarboxylic (SIDAG) enhancement, a fluorophor chemically related to
fluorescein- and ICG-based angiography. Fluorescein angiography was ICG, closely correlates to the tumour’s angiogenic activity, supporting
capable of showing microvessels in 12 patients (24%). Using ICG-based the evidence mentioned above that perfusion-type cyanine dyes can
optical imaging, microvessels in 47 of the 50 tumours (94%) were indeed delineate tissue angiogenesis non-invasively.
identified in vivo. ICG is thus better suited for imaging of microvessels
and is able to show microcirculation in vivo, which otherwise only Fischer et al.
27
were able to demonstrate the potential of direct
histology can. The authors concluded that these findings open up the fluorescence optical imaging of inflamed joints. In a study with induced
possibility of assessing the potential biological course of individual Lyme arthritis in mice (n=20) and 20 healthy control animals, ICG and
tumours to a treatment without invasive histology. an ICG-like contrast agent (SIDAG) were used. Optical imaging was
In a prospective study, Mueller et al.
16
studied the potential of ICG-
based imaging of the microcirculation in the eye. Overall, 98 patients
with small choroidal melanomas were classified using a variety of
Besides the clinical possibilities of
different parameters. Microcirculation parameters, collected with
fluorescence optical imaging, a variety
ICG-based optical imaging, had the strongest association with the
time of prospective defined tumour growth. Thus, depiction of
of further clinical diagnostic applications
clinically relevant changes in microcirculation patterns gives
for imaging of rheumatoid arthritis can
relevant clinical information.
be envisaged.
Overall, ICG-based fluorescence optical imaging is well suited to
delineate changes of the microcirculation throughout a variety of
clinical entities. performed with an excitation wavelength of 740nm. Fluorescence
signals were detected above 800nm. Both tested fluorescence dyes
Fluorescence Imaging of Rheumatoid Arthritis were able to differentiate affected from non-affected joints. The
Pathophysiology authors stated that fluorescence optical imaging of hand and foot
The true cause of RA remains unclear, despite intensive research. joints with ICG is a clinically applicable method.
Varieties of immune cells are activated during active disease and
secrete proinflammatory cytokines, interleukins and other factors. Berger et al.
28
designed a device for clinical use with a scanning laser.
These mediators promote inflammation and result in destruction of Applicability was shown with phantom experiments. The ability to
the adjacent synovial structures. In addition, neoangiogenesis is differentiate healthy from affected joints with this device was shown in
triggered in the region of the synovial membrane.
17–20
However, this two Lewis rats. The signal distribution in these animals matched signal
leads to synovial contrast enhancement in contrast-enhanced distribution in contrast-enhanced MRI, as well as inflammatory activity
ultrasound, as well as in contrast-enhanced MRI.
21
Both techniques in histology.
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