This study investigated the effect of PET/CT reconstruction using TOF on assessment of patients with TKA when using the established four-point visual grading system. Although TOF reconstruction had no significant impact on the final visual grade, we found that the visual grade for all regions assessed was significantly higher in the TOF-PET/CT group than in the non-TOF-PET/CT group. An earlier study demonstrated the effect of TOF reconstruction on uptake in the normal aorta15; however, subjects with suspected large-vessel vasculitis were excluded in that study. Therefore, the present study is the first to investigate the effect of TOF reconstruction on assessment of TKA.
An earlier review showed that a visual grade of 2 was possibly indicative and that a grade of 3 was positive when assessing disease activity in large-vessel vasculitis.3 In our study, 18/150 regions were regarded as active on non-TOF-PET/CT and 24/150 were regarded as active on TOF-PET/CT when grade 2 or 3 uptake was defined as active (Table 2). Assessment of disease activity by non-TOF-PET/CT and TOF-PET/CT was inconsistent for 6 (4%) of 150 regions when grade 2 or 3 was considered as active. These regions were shown in case 4 (4 regions) and case 14 (2 regions). In these cases, TOF reconstruction had no effect on the final visual grades; in 2 of 10 cases there was a discrepancy between the final visual grade and disease activity according to the NIH criteria (cases 3 and 14). Furthermore, when we defined grade 3 uptake as active, there was inconsistency between non-TOF-PET/CT and TOF-PET/CT in 5 (3.3%) of 150 regions. These 5 inconsistencies were in cases 1 (3 regions), 2 (1 region), and 13 (1 region). In case 2, there was a difference in the final grade between non-TOF-PET/CT and TOF-PET/CT; however, the disease activity based on the visual grade assessed by TOF-PET/CT and by the NIH criteria were consistent (Table 1, Fig. 4). These findings indicate that use of different reconstruction algorithms before and after treatment may lead to incorrect evaluation of the response to therapy in patients with TKA. Therefore, we recommend use of the same reconstruction algorithm when evaluating their response to treatment.
As shown in Table 3, the visual grade increased from 0/1 to 2 in 2 cases (4 and 14) when TOF-PET/CT was used. In case 4, new-onset bruit and vascular obstruction in the right subclavian region were detected and the visual grade was elevated near the right subclavian artery (innominate and right common carotid arteries), even though the visual grade for the right subclavian artery in this case was assessed as 0 by both reconstruction algorithms. In case 14, aortic surgery was performed 37 days after PET/CT, at which time pathology specimens were obtained from the ascending aorta, left subclavian artery, and left common carotid artery. Infiltration of focal lymphocytes and neutrophils with disruption of elastic fibres and broad adventitial fibrosis were observed in the left common carotid artery, indicating coexistence of acute and chronic inflammation.16 Elevation of the visual grade may reflect mild chronic inflammation in these regions. Moreover, the visual grade was elevated from 2 to 3 on TOF-PET/CT in 4 regions (Table 3). Vascular pain was observed in 3 of these 4 regions (the right subclavian artery in case 1, left common carotid artery in case 2, and right common carotid artery in case 13). The symptomatology suggested acute inflammation in these regions, and TOF-PET/CT may reflect acute inflammation more accurately. TOF reconstruction has been reported to increase the standard uptake value for lymph node metastases,11,17 and this finding is compatible with our present results. In previous studies that used semi-quantitative analysis, there was no significant difference in FDG uptake in the normal aorta or liver between non-TOF-PET/CT and TOF-PET/CT.15,18 Furthermore, Daube-Witherspoon et al. demonstrated that TOF reconstruction improved the accuracy and precision of measurement of FDG uptake using clinical whole-body patient data with embedded artificial lesions that had known activity uptake.19 Therefore, on the basis of the above findings, elevation of the visual grade from non-TOF-PET/CT to TOF-PET/CT may reflect a more accurate assessment of FDG uptake in the arterial wall.
There was no significant difference in the effect of TOF reconstruction on visual grade between the patchy and diffuse uptake patterns. As shown in an earlier phantom study, TOF reconstruction improved the contrast of hot lesions, particularly if they were small.10 Therefore, we expected that the difference in visual grade for the patchy uptake pattern would be higher than that for the diffuse uptake pattern because the patchy uptake pattern was smaller. We speculate that the arterial wall lesions were so small that there was no significant difference between the patchy and diffuse uptake pattern.
In most cases, FDG uptake was detected at the aortic arch and innominate artery. This finding is consistent with previous studies showing that TKA involves predominantly the thoracic and cervical arteries in the Japanese population.20,21
Finally, as shown in Fig. 3, the effect of TOF reconstruction was not significantly different between the 10 vascular regions assessed. This is in contrast with an earlier study that found a difference in the gain in the signal-to-noise ratio as a result of TOF reconstruction in three body regions, i.e., the head and neck, abdomen, and lung.22 In that study, the gain in the abdominal lesions showed a clear increase as a function of body mass index (BMI) in the range of 1.1–1.8. In contrast, the gain in the head and neck lesions showed a slight increase as a function of BMI in the range of 1.1–1.4. In our study, the effect of TOF on assessment of TKA was not significantly different between the 10 vascular regions, which included the abdominal aorta and carotid arteries. This finding may reflect the relatively low mean BMI (20.1 ± 2.3) in our cohort.
This study has several limitations. First, the sample size was small, which was inevitable given the rarity of TKA. Second, patients with types of vasculitis other than TKA were included. Third, our investigation of the association between visual grade and clinical findings was inadequate because of the small sample size and our lack of ability to assess disease activity fully using the NIH criteria. A further prospective study would be required to investigate the relationship between the findings of TOF-FDG-PET/CT and the activity of TKA. Fourth, this study was performed at a single centre in a Japanese population. Therefore, studies in other populations may be needed. Fifth, we used the four-point visual grading system without semi-quantitative analysis. However, this grading system is recommended for assessment of TKA in the clinical setting.3 The present study was the first to evaluate the effect of TOF reconstruction on assessment of TKA using this system.