Nienke D. Sijtsema1,2, Steven F. Petit1, Dirk H.J. Poot2, Gerda M. Verduijn1, Esther A.H. Warnert2, Mischa S. Hoogeman1,3, and Juan A. Hernandez-Tamames2
1Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 2Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands, 3Department of Medical Physics and Informatics, HollandPTC, Delft, Netherlands
Synopsis
Arterial spin labeling (ASL) has potential
for response prediction of tumor and healthy tissue in the head and
neck region after radiotherapy. Since little is known about blood flow (BF)
values in this region, we measured BF and the repeatability of BF in several
tissues simultaneously using multi-delay pseudo-continuous ASL. This enables
investigation of the correlation between perfusion and severity of radiotherapy
side-effects in a future study. Of the tissues we assessed, we found the
parotids have the highest and the tonsils have the lowest perfusion.
Introduction
Recently, the potential value of measuring
perfusion with arterial spin labeling (ASL) in the head and neck (H&N) region
has been demonstrated for detection, characterization, and early treatment
response assessment after
(chemo-)radiotherapy of head and neck tumors1-7. Additionally, blood flow (BF) obtained from ASL could be a potential imaging biomarker for predicting radiotherapy
side-effects. However, little is known about BF values in the
organs at risks involved in these side effects. Therefore, the aim of this
study is to measure the values and repeatability of BF with ASL in several
healthy tissues in the H&N region. Methods
Nine healthy subjects were scanned on a 3T
MR750 Discovery with a 12 channel H&N coil (GE Healthcare, Waukesha, WI). The scan protocol consisted of 3D MAGiC8 (0.5x0.5x2
mm3 voxels, scan time 4 min 4 s) and four repeats of three-delay
pseudo-continuous ASL (pCASL) (Post-labeling delay (PLD): 1000, 1634, 2483 ms,
Labeling Duration (LD): 3000 ms, 2x2x4 mm3 voxels, 26 slices, scan
time 5-7 min). For the ASL acquisition, the most caudal slice of the
acquisition was placed on the chin to ensure the labeling plane, which is
automatically placed 2 cm below the most caudal slice, was situated in the neck area (Figure 1). The ASL acquisition yielded a perfusion weighted (control-labeled)
image for each PLD and a saturation recovery image. The 3D MAGiC acquisition yielded synthetic T1-weighted (T1w), T2-weighted (T2w) and
proton density weighted (PDw) images, and a T1 map. The synthetic T1w and T2w images were
used to manually delineate the tissues of interest: the parotid and
submandibular glands, and the tonsils. For reference purposes, a region of
interest (ROI) was also placed in the cerebellum. For each of the ASL
acquisitions, the saturation recovery image was rigidly registered to the synthetic PDw
image and the ROIs were propagated to the ASL image.
To minimize the contribution of any
delineation or registration uncertainty all ROIs were eroded by 2 mm in 3D.
ASL
BF was quantified voxel-wise for each tissue ROI by fitting the following
equation:
$$BF=\frac{6000\lambda e^{\delta/T1_a}}{2\varepsilon T1_t(e^{-\frac{max(PLD-\delta,0)}{T1_t}}-e^{-\frac{max(LD+PLD-\delta
,0)}{T1_t}})}\frac{SI_{PW}}{\frac{SI_{SR}}{S_c}}$$
Where SIPW is the signal intensity
of the perfusion weighted image and SISR is the signal intensity in
the 2 second saturation recovery image, which is scaled by a factor $$$S_c=1-e^{-\frac{2}{T1_t}}$$$ to correct for partial signal recovery. δ is the arterial transit time that is estimated by
the signal weighted delay method9. λ is the blood-tissue partition coefficient, which
is set to 1 g/ml10. ε is a correction factor to account for labeling
efficiency and background suppression and is set to 0.6 conform manufacturer
guidelines. T1a is the T1 of arterial blood and is set to 1664 ms11,12. T1t
is the T1 of tissue and was taken voxel-wise from the T1 map obtained from
MAGiC. Next, the mean BF was determined in each ROI of each repeated
acquisition, unless the ROI contained >20% negative voxels, in which case it
was deemed corrupted and not taken into account in further analyses. Subsequently, the
overall mean over the repeats was determined per volunteer and the within
subject coefficient of variation (wCV) was determined for each ROI. Additionally,
the T1 values of the tissues are reported.
Results
Figure 2 shows an example of a synthetic T2w image, T1 map, and
BF map overlayed on a synthetic T2w image with the ROIs indicated. As shown in Figure 3,
mean BF over the parotid glands ranged from 51 to 100 ml/100 g/min, mean BF of
the submandibular glands was slightly lower at 31 to 77 ml/100 g/min, and the
mean BF in tonsils ranged from 21 to 48 ml/100 g/min. The wCV was 16% for both
parotid glands, 19% for both submandibular glands, and 18% and 22% for the
right and left tonsil respectively. The cerebellum (control) had a BF range from
37 to 74 ml/100 g/min and a wCV of 9%. Figure 4 shows the mean T1 per tissue of
interest, which ranged from 916 to 1521 ms for the parotid glands, from 1075 to
1755 ms for the submandibular glands, from 1902 to 2551 ms for the tonsils, and
from 1282 to 1678 ms for the cerebellum.Discussion
For BF and T1, boxplots show similar values for both parotid glands, both submandibular glands and both tonsils, as expected. Additionally, the BF and T1 we measured in the
cerebellum is in the same range as reported in literature for grey matter13,14. The
wCV in all tissues in the H&N is notably larger than in the cerebellum.
This might be caused by motion that is affecting this region, especially the tonsils and submandibular glands. Motion correction for ASL
would be an interesting topic for further research. Nevertheless, we can
distinguish differences in perfusion according to tissue. Conclusion
Using multi-delay pCASL it is possible to
assess BF in several tissues in the H&N simultaneously. This enables
investigation of the correlation between perfusion and severity of radiotherapy
side-effects in a future study. Of the tissues we assessed, we found the
parotids to have the highest perfusion (range 51-100 ml/100 g/min), followed by
the submandibular glands (range 31-77 ml/100 g/min), while the tonsils (range
21-48 ml/100 g/min) showed the lowest perfusion.Acknowledgements
No acknowledgement found.References
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