steps (45 mm total displacement) and 31 rotational steps (360
total rotation). The
XF photons of all three elements were detected with a single CdTe detector, and the
success of the measurements exemplifies that no additional hardware is required for
multitracer imaging.
To compare the molecular sensitivity of XFCT contrast agents and radionuclides,
the following approximation is made. For AuNPs (50 kDa), 1 μg/ml is equivalent to
a molar sensitivity of 20 pM, similar to PET and better than SPECT. We note that
PET imaging probes have lower molecular weight than AuNPs, so mass sensitivity
of PET and XFCT is not similar. The comparison of different signal carriers, such as
nanoparticles and radiolabeled molecules, requires the consideration of distinct
characteristics. The ability of signal carriers to accumulate in pathological tissues
or target regions influences the molecular sensitivity as well as the efficiency of
clearance from the background environment. An accurate comparison of sensitivity
needs to account for the pharmacokinetics of the agents which needs to be compared
for each specific application. For receptor imaging, for example, the number of
available receptors might limit the amount of contrast agent, and large re-excitable
nanoparticles might provide more signal per receptor than single-decay PET or
SPECT probes [49].
To compare XFCT imaging with traditional X-ray transmission imaging, the
following calculations are presented. Based on the gold bulk attenuation coefficient
of 27.5 cm
2 /g at 30 keV, the X-ray attenuation coefficient for a 10 μg/ml gold
nanoparticle aqueous solution is 0.2272 cm
2 /g, which is only 0.12% higher than the
coefficient of water. For XFCT imaging instead, the intensity of the X-ray fluorescence photons in the emission spectrum is at least 10% greater than the intensity of
the water background. Theoretically, this allows for two orders of magnitude higher
sensitivity with XFCT compared to transmission X-ray-based imaging. It enables
in vivo visualization of probes that cannot be imaged by any other means, such as
metallodrugs as well as trace minerals.
As energy resolving detectors are also under investigation for CT imaging,
preclinical and clinical spectral CT systems were established for research purposes
in recent years. As the detection event rate in CT is approximately three orders of
magnitude higher in transmission CT compared to XFCT, only detectors with rough
energy resolution (with up to six energy bins) could be developed so far. Rough
estimations predict that the molecular sensitivity of XFCT is improved by an order of
magnitude compared to state-of-the-art transmission spectral CT.
7 Imaging Modes
Until now, the majority of proof of principle XFCT measurements were performed
with pencil-beam excitation and uncollimated X-ray detectors. While this combination is the most intuitive form of image acquisition for XF imaging, other acquisition
modes were suggested and realized. The selection of the best acquisition mode for an
application is a delicate exercise due to the many parameters involved in XFCT
X-Ray Excited Fluorescent Materials for Medical Application
137
total rotation). The
XF photons of all three elements were detected with a single CdTe detector, and the
success of the measurements exemplifies that no additional hardware is required for
multitracer imaging.
To compare the molecular sensitivity of XFCT contrast agents and radionuclides,
the following approximation is made. For AuNPs (50 kDa), 1 μg/ml is equivalent to
a molar sensitivity of 20 pM, similar to PET and better than SPECT. We note that
PET imaging probes have lower molecular weight than AuNPs, so mass sensitivity
of PET and XFCT is not similar. The comparison of different signal carriers, such as
nanoparticles and radiolabeled molecules, requires the consideration of distinct
characteristics. The ability of signal carriers to accumulate in pathological tissues
or target regions influences the molecular sensitivity as well as the efficiency of
clearance from the background environment. An accurate comparison of sensitivity
needs to account for the pharmacokinetics of the agents which needs to be compared
for each specific application. For receptor imaging, for example, the number of
available receptors might limit the amount of contrast agent, and large re-excitable
nanoparticles might provide more signal per receptor than single-decay PET or
SPECT probes [49].
To compare XFCT imaging with traditional X-ray transmission imaging, the
following calculations are presented. Based on the gold bulk attenuation coefficient
of 27.5 cm
2 /g at 30 keV, the X-ray attenuation coefficient for a 10 μg/ml gold
nanoparticle aqueous solution is 0.2272 cm
2 /g, which is only 0.12% higher than the
coefficient of water. For XFCT imaging instead, the intensity of the X-ray fluorescence photons in the emission spectrum is at least 10% greater than the intensity of
the water background. Theoretically, this allows for two orders of magnitude higher
sensitivity with XFCT compared to transmission X-ray-based imaging. It enables
in vivo visualization of probes that cannot be imaged by any other means, such as
metallodrugs as well as trace minerals.
As energy resolving detectors are also under investigation for CT imaging,
preclinical and clinical spectral CT systems were established for research purposes
in recent years. As the detection event rate in CT is approximately three orders of
magnitude higher in transmission CT compared to XFCT, only detectors with rough
energy resolution (with up to six energy bins) could be developed so far. Rough
estimations predict that the molecular sensitivity of XFCT is improved by an order of
magnitude compared to state-of-the-art transmission spectral CT.
7 Imaging Modes
Until now, the majority of proof of principle XFCT measurements were performed
with pencil-beam excitation and uncollimated X-ray detectors. While this combination is the most intuitive form of image acquisition for XF imaging, other acquisition
modes were suggested and realized. The selection of the best acquisition mode for an
application is a delicate exercise due to the many parameters involved in XFCT
X-Ray Excited Fluorescent Materials for Medical Application
137