Although the diagnostic criteria for PJI are being improved and new tests are being evaluated, there is still no examination that perfectly meets the needs of the clinic. In addition, PET/CT is a visual inspection that can locate the lesion and delineate the extent, and its application in PJI has not received much attention16,17. In this study, we evaluated a new radionuclide, [68Ga]GaDOTAFAPI04, which has not been studied in the field of PJI, and its diagnostic efficacy in PJI was evaluated based on two criteria: SUVmax and uptake pattern. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SUVmax were 67.86%, 100%, 84.85% and 88.37%, respectively. Additionally, through the analysis of the images, we developed a new diagnostic standard based on the uptake pattern, and the sensitivity, specificity and accuracy were 100%, 92.86% and 95.35%, respectively. In the end, the method of radiomics was applied, and we found that radiomics could be used to diagnose PJI and had certain significance in ambiguous cases.
In this study, SUVmax was initially used for diagnosis. Although its diagnostic efficiency was acceptable, many other reasons could cause noninfection elevated uptake. In view of these deficiencies, the uptake patterns of [68Ga]GaDOTAFAPI04 were investigated. In reviewing all images, we found that the uptake pattern of loosening cases was linear, light or moderate intensity when the lesion was located between the bone and the acetabular cup or the femoral stem (IIa, IIb), and the pattern of infection tended to be diffuse and high intensity (IIIa, IIIb). In addition, for lesions located in the articular cavity, the uptake was moderate or no uptake in wear cases (Ib), while in infected cases, high uptake was seen on both sides of the femoral stem neck (IIIc).
To our delight, not only is the diagnostic criterion more accurate, but it also led us to several other findings. First, the different performance characteristics between Ia and Ib. Although they all had obvious wear, the life of the prosthesis of Ia was significantly longer than that of Ib, and most loose prostheses also had an Ib appearance. Based on this, we hypothesize that Ib is associated with poor prosthesis placement or inadequate soft tissue management and may indicate loosening of the prosthesis. Therefore, [68Ga]GaDOTAFAPI04 PET/CT has the potential to assess the status of the joint after arthroplasty and to detect joint problems in a timely manner. Second, the different loosening mechanisms, IIb and IIc (both can also occur at the same time), can be interpreted as proximal loosening and distal loosening. In fact, these two different manifestations of loosening have been mentioned in previous literature7; however, there is no literature discussing these two situations. We consider that proximal loosening is caused by poor bone ingrowth or cement debris in the body of the stem, while distal loosening is caused by the increase in local stress on the distal end caused by the sinking of the femoral stem. Although the above mechanisms need to be further studied, [68Ga]GaDOTAFAPI04 PET/CT could show both loosening conditions. Whether this imaging will play a suggestive role in prosthesis design, surgical technology or biomechanical will be a very interesting research direction. Finally, the types of infection were subdivided into four parts: acetabular infection, femoral infection, cavity infection and soft tissue infection. This fine classification can play a more precise and personalized role in clinical treatment, such as 1.5-stage revision or partial two-stage revision18,19.
Although the above results show that [68Ga]GaDOTAFAPI04 has bright prospects for application in PJI, there was a question puzzling at the beginning of this study: what is the basis for the specificity of [68Ga]GaDOTAFAPI04 in PJI? Fibroblasts are abundant in the human body and participate in various inflammatory, infectious and immune responses. FAP is secreted mainly by activated fibroblasts. When cells and tissues are under pressure, FAP is expressed, but not when the internal environment is stable. An important finding is that a large number of membranous structures were generated between the interface of bone and prosthesis in loosening and infection cases. The former is a fibrous membrane caused by loosening20, and the latter is a biofilm. Biofilm is an extracellular matrix produced by bacteria attached to the surface of the prosthesis, which also contains proteins that promote the expression of FAP21. FAP can also degrade and remodel the extracellular matrix through endopeptidase activity and promote the formation of microvessels and complexes with other proteins to transmit intercellular signals. Although both films have FAP expression, the biofilm is a disease with a higher degree of inflammation than the fibrous membrane caused by loosening. This is similar to the relationship between osteoarthritis and rheumatoid arthritis22,23.
Given that different cases have different metabolic patterns, in this study, the method of radiomics was preliminarily used to cluster the features of these cases. In the cluster analysis of clinical cases, the features of the PJI cohort were significantly different from those of the aseptic cohort, and this method could also play a certain auxiliary role in the diagnosis of ambiguous cases. In addition, we found that some PJIs can be successfully cured after one-stage revision, and some cases still cannot be well controlled after multiple debridements and antibiotic-loaded cement spacers. Whether the prognosis of patients can be predicted by radiomics will also be a very interesting research direction.
This study has the following limitations: (1) there is no comparison between [68Ga]GaDOTAFAPI04 PET/CT and other imaging examinations, and the so-called advantage is only at the theoretical level; (2) since not all patients had pathology and synovial fluid analysis, there was no comparison between these tests and [68Ga]GaDOTAFAPI04 PET/CT; (3) the total number of cases is small, and the number of cases subdivided into each subtype is small, so it is impossible to conduct consistency analysis on the diagnosis of each subtype; in addition, the small number of cases also has an impact on the accuracy of diagnosis and the reliability of radiomics. A more standardized prospective study is needed to verify the diagnostic efficacy of [68Ga]GaDOTAFAPI04 PET/CT.