Mohammad Mehdi Khalighi1, Mathias Engström2, Mark Lubberink3, and Greg Zaharchuk4
1Applied Science Lab, GE Healthcare, Menlo Park, CA, United States, 2Applied Science Lab, GE Healthcare, Uppsala, Sweden, 3Nuclear Medicine & PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden, 4Radiology Department, Stanford University, Palo Alto, CA, United States
Synopsis
Accurate measurement of the arterial input function (AIF) is essential in
quantitative analysis of cerebral blood flow (CBF) using 15O-water
PET imaging. The time-of-flight enabled SIGNA PET/MR scanner (GE Healthcare,
Waukesha, WI, USA) provides high quality PET images, which can be used for non-invasive
Image Derived Input Function (IDIF) estimation. AIF was measured using a
proposed IDIF method on 4 patients and the results were compared with the gold
standard, arterial blood sampling. The comparison shows excellent correspondence
between IDIF and blood sampling, thus validating the IDIF method.
Purpose
Quantification of cerebral blood
flow (CBF) is important in the assessment of brain disorders such as stroke or
Alzheimer’s disease1. 15O-water PET imaging is an
accurate method to measure CBF but it requires the measurement of an arterial
input function (AIF), which is usually acquired using invasive arterial blood
sampling. A non-invasive Image Derived Input Function (IDIF) method was recently
introduced for AIF measurement on a PET/MR scanner2, which estimated
spill-over and spill-in artifacts using a PET angiogram (PETA) along with an MR
angiogram. Here we have compared the AIF estimation using the proposed IDIF
method to the gold standard, arterial blood sampling.
Theory
The ToF SIGNA PET/MR scanner (GE Healthcare, Waukesha, WI) has
enough sensitivity to provide quality PET images over a few seconds of 15O-water PET imaging. Using an appropriate time window during the 15O
arrival, the cervical arteries can be identified and segmented (PETA)2.
These PETA images were used to estimate the spill-over and spill-in artifacts2.
An MR phase contrast series was used to image the vessels in the cervical
region. These images were used to segment the corresponding cervical arteries
in PETA images and the precise volume of those arteries was measured. The total
counts from the cervical arteries, after taking the spill-over and spill-in into
the account, were divided by the true volume of those arteries (measured from
the MR images) to estimate the AIF. Methods
The
study was performed in compliance with regulations of the local IRB in Uppsala and
all subjects were consented prior to the study. Four subjects (31-50 years old) were injected with 408±62 MBq of 15O-water simultaneously
with the start of a 10 min PET scan on the SIGNA PET-MR. During PET scanning, a
sagittal vascular (inhance 3D velocity) MR series was used with the following
parameters: TR=8.7 ms, TE=4.1 ms, FOV=24×21.6 cm, slice thickness=3 mm, 32 slices,
velocity encoding=40, phase acceleration=2.0, and scan time=1:21 min. The PET
list file was unlisted for every second and total true and
scatter coincident events were plotted to identify tracer arrival into the
brain arteries2. Then, a
short time frame over the arrival of the tracer to the cervical region was
reconstructed to obtain a PET angiogram. The cervical arteries were then
segmented using the MR vascular images and PETA images. Spill-over and spill-in
artifacts were estimated using PETA images and the actual arterial volume was
measured from the MR vascular images. The PET list file was unlisted and images were reconstructed for
every 1 s (using a 3 s sliding window) for the first minute, every 5 s for the
2nd minute, every 10 s for the 3rd and 4th
minute and every 30 s for 5th to 10th minutes. The AIF
was estimated by dividing total counts from the cervical arteries of each frame
by the MR-based arterial volume. For each patient, blood samples were continuously
drawn from the radial artery at the wrist using a peristaltic pump, and the
tracer concentration in the arterial blood was measured using a Twilite two
detector (Swisstrace) to estimate the AIF. In order to calculate the AIF at the
brain arteries from these blood samples, the delay and dispersion of the
arterial input function was corrected using standard PET-based methods3.Results
Figure 1 shows the PETA and MR vascular images for
one of the patients. The PETA images clearly show the arteries and the extent
of the spill-over. Figure 2 shows the cervical arteries mask from PETA and MR
images used to estimate spill-over and spill-in artifacts. These masks were
used to measure the AIF from the dynamic PET images. Figure 3 compares the AIF
curve estimated by the proposed IDIF method2 and the AIF curve
measured by the blood samples3. The comparison shows excellent
correspondence between the IDIF method and the gold standard blood sampling
method with 9% and 11% difference for the 1st pass and the entire
AIF, respectively. The IDIF
captures the AIF peak correctly and has increased signal-to-noise ratio
compared to the blood sampling method. The delay and the dispersion of the AIF
curve is nearly identical between the two methods.
Discussion
As the
results show, the proposed method is capable of determining a high-fidelity
IDIF from simultaneous PET/MRI data. Having
a “blood-free” method that obviates the need for direct arterial sampling is of
benefit to both investigators and subjects, because of the high costs,
inconvenience, and potential risks associated with arterial cannulation. It has
applications beyond 15O-water PET, enabling pharmacokinetic modeling
to be performed that is required for quantitative PET tracer studies.
Acknowledgements
GE
Healthcare, Stanford University Lucas Center, Uppsala
University.References
[1]
Alsop
DC, Detre JB. Perfusion magnetic resonance imaging with continuous arterial
spin labeling: methods and clinical applications in the central nervous system.
Eur J. of Radiology 1999; 30:115-124.
[2] Khalighi MM, Fan A, Delso G, Gulaka P, Shen B, Hoehne A, Singh P, Park JH, Holley D, Chin F, Zaharchuk G. Non-Invasive Estimation of Arterial Input Function for Imaging of Cerebral Blood Flow on a PET/MR Scanner, ISMRM 2016, p4321.
[3] Meyer E. Simultaneous correction for tracer arrival delay and dispersion in CBF
measurements by the H2 15O autoradiographic method and dynamic PET. J Nucl
Med. 1989; 30:1069-1078.