This retrospective exploratory proof of concept study used LVV disease severity as a clinical reference to assess the utility of integrated PET/MR in patients with LVV. The examined clinical subgroups of LVV in this study were associated with statistically different findings on PET/MR; however, inflammatory markers and quantitative PET measurements showed no statistically significant difference between patient subgroups. The findings of our study broadly agree with the findings in other studies, yet direct comparisons are complicated by varied LVV classification approaches.

In this study, qualitative evaluation of positive findings with either PET or MR when read in conjunction on the fused PET/MR was able to distinguish severe from non-severe LVV, while a combined consideration of positive PET and MR findings was unable to distinguish these groups. Using a distinct LVV classification method, Laurent et al. used a review of simultaneous PET and MR positivity to define an inflammatory pattern (Laurent et al. 2019), and found that an inflammatory pattern was associated with active disease in both GCA (as defined by the presence of clinical signs and increased CRP level (> 10 mg/L)) and TA (as defined by a National Institute of Health stroke score > 2). Although an “inflammatory pattern” was identically characterized in our study [PET positive and MR positive], we did not find a statistically significant difference in our clinically defined groups. In our study, the added consideration of isolated PET positive findings was able to identify a statistically different distinction between severe and non-severe LVV. LVV clinical status has been shown to correlate with PET (p < 0.01) and not magnetic resonance (p = 0.70) in a previous study by Quinn et al., which further supports the added benefit of PET imaging in LVV patients (Quinn et al. 2018). In cases where the spatial resolution of MR is too low, PET activity may be able to provide a new basis on which to identify inflammatory changes, yet this application may be inappropriate for the examination of smaller vessels. There are certain physical limitations to PET imaging which create a fundamental limit for improvements in spatial resolution. PET spatial resolution is largely restricted by the size of the detector element, positron range, acollinearity, decoding, penetration, and sampling error. Given these barriers, practical PET cameras can only be made with up to 2.36 mm full width at half-maximum spatial resolution (Moses 2011). Attempting to detect radiotracer uptake in target volumes of a few cubic millimeters has been suggested as a flawed application of PET imaging (Alavi et al. 2017). Using high-frequency ultrasound, Svensson et al. determined that the intima media thickness of the common femoral and subclavian arteries was 0.49 ± 0.11 and 0.53 ± 0.13 mm, respectively (Svensson et al. 2022), which reinforces our inability to localize PET uptake in many of these vessels. With PET, vasculitis-associated large-vessel inflammation detection may be most appropriately used to detect thickened vessels or inflamed aortic foci. Future work should compare PET and MR findings under various MR field strengths and with improved PET resolution to see if there is a higher association between the two, on a vessel-by-vessel basis.

In our study, the trends and values of biomarkers did not show statistically significant differences between severe and non-severe LVV subgroups. Biomarkers have previously been studied with reference to vasculitis disease activity (Kerr et al. 1994; Tso et al. 2002; Rodriguez-Pla et al. 2020) and in with reference to PET imaging findings (Walter et al. 2005). Tissue inhibitor of metalloproteinase-1 (TIMP-1), ESR, and B cell-attracting chemokine 1 (BCA)-1/CXC motif ligand 13 (CXCL 13) were shown to be higher in active GCA than GCA in remission when disease activity was assessed by physician’s global assessment of disease activity (0–10 scale) (Rodriguez-Pla et al. 2020). In contrast, Kerr et al. and Tso et al. found poor correlations between inflammatory markers and disease activity in LVV (Kerr et al. 1994; Tso et al. 2002). In a study by Walter et al., patients’ grades of LVV uptake (grades I-III) were positively correlated with ESR (p = 0.007) and CRP (p = 0.002) (Walter et al. 2005). Our preliminary findings suggest that biomarkers may not be able to distinguish clinical LVV subtypes, but future studies with larger cohorts are warranted.

For each scan’s maximum blood- and liver-normalized SUVmean value, no statistically significant difference was found between severe and non-severe LVV. In a study by Laurent et al., it was shown that the median (of all observed vessels) SUVmax value was higher in LVV patients with PET positive and MR positive scans (i.e., an inflammatory pattern) compared to isolated MR positive scans (i.e., fibrous pattern) or normal scans (Laurent et al. 2019). In contrast to the study by Laurent et al., our study tested quantitative measurements when qualitative measurements did not necessarily indicate higher metabolic activity. We used quantitative PET SUVmax to assess the maximum uptake to test the hypothesis that severe LVV patients show higher metabolic activity in the most metabolically active vessels compared to non-severe LVV patients. To our knowledge, prior studies have not compared quantitative metabolic activity measurements in patient groups that may not have necessarily had higher amounts of qualitatively-assessed metabolic activity. In our study, because the qualitative PET findings were also not significantly different between clinical subgroups, we have confidence that our PET assessment techniques were valid. Though we did not find significant quantitative differences between our patient subgroups, we believe that more studies of this kind are warranted for research purposes.

PET/MR alternatives

Alternative imaging techniques may still be appropriate means to evaluate LVV. It appears that the benefit of combined modality PET/MR stems from its ability to allow multi-modality comparison. Several false-positive pitfalls emerge when a single modality is used to evaluate LVV, such as an atheromatous plaque leading to PET uptake (Rudd et al. 2002). Vascular inflammation is best supported by the presence of several imaging findings, and this multimodality corroboration of LVV disease status can be obtained with an isolated modality, such as PET or MR, or a combined modality, such as PET/CT] (Lee et al. 2016). Although simultaneous PET/MR acquisitions facilitate the co-localization of vasculitis-associated lesions, [combined modality PET/CT] and [isolated PET and isolated MR] offer this same benefit though with slightly more radiation exposure and patient inconvenience.

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