Patients
This single-center prospective study was conducted on 23 patients with axial or mixed SpA who were between the ages of 18 and 45 when the diagnosis was made, according to the ASAS or modified New York criteria. These patients were recruited at our institute between January 2013 and October 2014.
The inclusion criteria were the following: active SpA (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and/or in NSAID treatment failure) and with inflammation in the spine (at least three inflammatory vertebral corners) and/or the SIJ (inflammatory sacroiliitis according to ASAS criteria). After providing information, the patients were included and provided informed consent (IDRCB: 2012-A00568-35; ClinicalTrials.gov: NCT 02869100). 18F-NaF PET/CT, CT scans, and MRI were performed within a month. In order not to interfere with the results of 18F-NaF PET, the treatment could not be changed until it was complete.
The exclusion criteria as related to the realization of PET/CT were the following: a confirmed or suspected ongoing pregnancy or breastfeeding, kidney failure with creatinine clearance under 60 mL/min, previous or current chronic alcoholism or drug addiction, psychiatric disease, severe comorbidities, and a legal protection measure.
The following data were recorded: age, tobacco use, familial history, disease duration, extra-articular involvement, treatment, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Disease Activity Score (ASDAS), and biologic parameters (HLA-B27, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatinine, and creatinine clearance).
All patients underwent a conventional pelvic radiograph, MRI, and CT scan dedicated to the SIJ along with a18F-NaF PET/CT within a month.
This study was approved by the French ethic committee (“comité de protection des personnes”: CPP number 12.06.03).
Imaging and scoring
Conventional radiography
Anteroposterior radiography of the pelvis was completed and analyzed according to the New York modified criteria by one rheumatologist who defined the presence or absence of sacroiliitis.
MRI
The MRI centered on the SIJ was completed on a 3T MRI machine (SignaHDxT MR 750 W, GE Healthcare) with a matrix of 416 × 320. The images were reconstructed in the semicoronal plane parallel to the superior border of the sacrum with T1-weighted (TR 400 to 600 ms; TE < 20 ms, ETL 3) and T2-weighted sequences with fat suppression (TR 3000 ms, TE > 65 ms, ETL 28). The slice thickness was 3.5 mm with a gap of 0.5 mm. The SIJ exam was performed on approximately 20 slices for a complete exploration of the SIJ.
CT scans
Dedicated SIJ CT scans were conducted the same day on a TOSHIBA Aquillion One imager. The acquisition parameters were as follows: field of view, 12 cm; acquisition matrix size, 512 × 512 pixels; tube voltage 120–130 kV; tube current, 200 mA; rotation time, 0.75 s; axial slice thickness, 0.5 mm; and interslice gap, 0.25 mm. Morphological assessment of the SIJ was performed on 30 semi-coronal reconstructions without gap with a slice thickness of 1.5 mm and a bone filter.
18F-NaF PET/CT
The examination was started 60 min after direct intravenous injection of 4 MBq/kg of 18F-NaF using a hybrid imaging PET/CT Biograph 6 (SIEMENS, Knoxville, TN). First, a scan was performed using a true whole body field of view without contrast agent (intensity 130 kV for 80 mAs, 0.6 s of tube rotation time, cuts of 3 mm, and pitch of 1.5). Second, the PET acquisition was also performed with a true whole body field of view with 9–12 bed positions for a complete examination duration of 20 to 30 min. The image reconstruction was done using an iterative method (3 iterations, 8 subsets, 168 × 168 matrix with zoom 1, Gaussian filter, and 5.0 mm FWHM) before being displayed on a Leonardo® workstation (SIEMENS, Knoxville, TN). PET analysis of the SIJ was done using a slice thickness of 5 mm.
Scoring method
Conventional radiographies were analyzed according to the modified New York criteria to define structural sacroiliitis (at least bilateral grade 2 or unilateral grade 3).
CT scans
First, diagnosis of structural sacroiliits was performed based on the presence of erosion (interruption of the sacral or iliac cortical bone present on at least two consecutive slices) and/or ankylosis (partial or complete bone bridge present on at least two consecutive slices) on the cartilaginous part of the SIJ.
Second, a score for structural lesions (as defined above) was established using a methodology similar to that described in the SpA Research Consortium of Canada (SPARCC) MRI SIJ inflammation score on the cartilaginous part of the SIJ [20] (Fig. 1). The most anterior slice was defined as a visible joint ≥ 1 cm in vertical height. When the vertical height was less than 3 cm, the SIJ was defined as having only 2 quadrants (upper iliac and upper sacrum), whereas a visible joint ≥ 3 cm in vertical height was defined as having 4 quadrants (upper iliac, lower iliac, upper sacrum, and lower sacrum). At the posterior aspect of the SIJ, each quadrant was assessed individually until < 1 cm of vertical height was visible when it was no longer scored. Each SIJ was divided into these four quadrants for erosions or into two halves for ankylosis (upper and lower). The readers scored the lesions on all of the quadrants for each slice on a dichotomous basis (present/absent) with the slice scores for erosion and ankylosis varying from 0 to 8 and 0 to 4, respectively. The final score was the sum of the scores for all of the slices, with a maximum of 20 slices (the final score for erosions and ankylosis ranged from 0 to 160 and from 0 to 80, respectively).
MRI
First, the presence of inflammation was assessed on a binary approach according to ASAS criteria by defining active sacroiliitis as subchondral or periarticular bone marrow edema, present on more than one lesion, even if in a single section, or present on at least two sections if there was only one lesion.
Second, inflammation was scored according to the SPARCC MRI SIJ inflammation score [20] in consecutive slices on a dichotomous basis (present/absent) on the entire cartilaginous part of the SIJ, using the same methodology of 2 or 4 quadrants depending on the size of the joint (Fig. 1). The final score for inflammation was the sum of the scores for all of the slices, with a maximum of 8 slices, and ranged from 0 to 64.
For both CT scans and MRI, the presence of structural lesions and inflammation was retained if it was scored by at least two readers, and the mean score among the three readers was calculated. Both the MRI and CT scans were scored independently by two rheumatologists and one radiologist blindly on a website (carearthritis.com) after anonymization and randomization.
Before starting the lectures, the three readers completed a calibration exercise on a population of 46 SpA patients with paired MRI and CT exams using the same methodology. The results of this calibration showed good concordance for global diagnosis of structural sacroiliitis on CT scan (ICC[IC95] = 0.65–0.74[0.37; 1]) and for the presence of erosions (ICC[IC95] = 0.65–0.82[0.34; 1]) and ankyloses (ICC[IC95] = 0.55–0.88[0.16; 1]). On MRI, a calibration exercise obtained good concordance (ICC[IC95] = 0.62–0.72[0.29; 1]) for the diagnosis of inflammatory sacroiliitis.
18F-NaF PET/CT
The analysis was blinded from clinical data, MRI, and CT scans. The SIJ assessment was made by three readers. The signal was considered abnormal if it was higher than the signal in the center of the sacrum (S2).
First, a qualitative assessment was conducted on the articular part of the SIJ based on an adaptation from the ASAS criteria for MRI. The exam was considered positive if there was unilateral uptake on two consecutives slices or bilateral uptake on one slice.
Second, a quantitative assessment was conducted using two methods:
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1)
The PET activity score was calculated based on the SPARCC MRI SIJ inflammation score method: cartilaginous part of the SIJ was divided into the same 2 or 4 quadrants depending on the size of the joint, and the abnormal uptake was scored in each quadrant for each slice on a dichotomous basis (present/absent) (Fig. 1). The final score was the sum of the scores for all slices, with a maximum 6 slices, and ranged from 0 to 48.
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2)
The maximum standardized uptake value (SUVmax) was measured slice-by-slice for each SIJ on a predefined circular region of interest, and the highest SUVmax value was considered for each SIJ. The ratio between the SUVmax for each SIJ and the SUVmax in the center of the sacrum (S2) was calculated (SUVmax SIJ/sacrum).
As for CT scans and MRIs, the presence of increased uptake was retained if it was scored by at least two readers, and the mean score among the three readers was calculated for the quantitative assessments.
Statistical analysis
The intensity or quality of the agreement between the inflammatory sites in MRI and 18F-NaF PET uptake was done by Kappa concordance coefficients. To compare qualitative variables, Fisher’s test was carried out, and for quantitative variables, Student’s t test was used, as the data were normally distributed. Statistical analysis was performed using SAS 9.3 software.
The same statistical analysis was performed between the CT scans and PET data.