This is the first description of applying the AMA method to the abdominal aorta. This method has excellent levels of agreement and is substantially quicker than previously described conventional PET quantification methods. Moreover, it performs much better when incorporating modifications that account for the spill-over of 18F-sodium fluoride uptake from the adjacent vertebrae and the variable aortic radius of the aneurysm. This quick and highly repeatable technique will improve the practical application and analysis of 18F-sodium fluoride PET-CT assessments of abdominal aortic aneurysms.
Analysing the entire abdominal aorta as a single region would potentially dilute and obscure differences between aneurysmal and non-aneurysmal regions. We therefore divided the aorta into three anatomically defined regions that are easily identifiable on a CT angiogram and can be easily replicated. We also used the thoracic aorta as a non-aneurysmal control segment of aorta. We appreciate that thoracic aortic disease may have a different pathophysiology to abdominal aortic aneurysm disease, and there may be differences in microcalcification activity and radiotracer uptake. However, since the study question here was the method of PET quantification, we feel that using the thoracic aorta as a control is a valid reference comparison.
We have sought to address the problem of signal spillage from the physiological uptake of 18F-sodium fluoride within vertebrae. Previous methods involved manually excluding obvious areas of activity spill-over from the vertebrae, and we applied this method when calculating the TBR values. Akerele et al have previously described other methods to correct for this problem including iterative reconstructions which incorporate a specific background correction that adjusts for this source of error. This is labour-intensive and currently there are no software packages to implement this technique. The PET activity spill-over takes place over a range of continuous values and its complete exclusion is not technically feasible. Our thresholding technique corrects for the abnormally high signal, but higher overall values of AMAmean can still occur due to activity spill-over below the region’s set threshold. Despite this, we feel that this remains one of the more effective methods available to correct for the spill-over effect from intense vertebral 18F-sodium fluoride uptake because of its rapidity and simplicity as well as the improvement in comparative values with TBRmean.
The obtained AMAmean value is dependent on a calculation involving the region’s cumulative SUV, region volume, region threshold and background SUVs. Disparities between different image analysts could potentially have an impact on the measured uptake values. However, the intra-observer and inter-observer repeatabilities were found to be very good if not excellent, especially after application of techniques to make the assessments more robust. Scan-rescan reproducibility has not been assessed within this method; however, it has already been shown to be very good in the thoracic aorta.
Forsythe et al used the “most diseased segment” TBRmax approach to measure 18F-sodium fluoride uptake in abdominal aortic aneurysms. These values demonstrated higher signal for aneurysmal segments compared to non-aneurysmal segments. This is a well-established approach that has previously been used to quantify 18F-fluorodeoxyglucose uptake in aortic and carotid atheroma and 18F-sodium fluoride uptake in the aortic valve.[16–18] The AMAmean method described here is similar to the TBRmean value: it calculates the average activity across a region of interest but it does not aim to replicate the “most diseased segment” approach which is dependent on a single voxel value across a region of interest. This explains the lower values in the aneurysmal segments in the present study. AMAmax would be more similar to this method, however it compares less well to the TBRmax across the region. The “most diseased segment” method is valuable when investigating conditions where regions of intense activity are more important than mean global activity. For example, this has been used as a measure of atherosclerotic disease activity and the risk of plaque rupture in coronary artery disease.[11, 19] It is unknown whether aneurysm rupture or expansion are dependent on the most intensely active degenerative region in the aneurysm (which would correspond to the “most diseased segment”) or whether these events may be better reflected through a global average measure of the burden of vascular degeneration within the whole vessel (AMAmean).
It is important to highlight some limitations to our study. Whilst we have introduced enhancements in our technique to deal with the spill-over effect from physiological vertebral uptake, this remains a source of error and it is unclear whether our method adequately corrects for this. Since it is not possible with the current technology to have zero signal spillage with this radiotracer, calculating a true mean error is challenging. Some more sophisticated spill-over correction methods could be performed in the future, but they may require availability of dynamic imaging. Our study population consisted of patients with abdominal aortic aneurysms and we have not assessed our technique in a truly healthy population or other diseased states. We have sought to quantify 18F-sodium fluoride uptake in abdominal aortic aneurysms. This radiotracer has not been validated for clinical use and future studies are needed to determine if this AMA method can serve as a biomarker for aortic disease.