[¹⁸F]-Sodium Fluoride PET MR–Based Localization and Quantification of Bone Turnover as a Biomarker for Facet Joint–Induced Disability

Patient Population

This prospective feasibility study recruited patients after obtaining human study institutional review board approval and complying with Health Insurance Portability and Accountability Act regulations. Patients served as internal controls with diseased and healthy subregions. Patients with a history of suspected lower lumbar facetogenic syndrome were recruited from UCSF Radiology Spine Clinic. Written informed consent was acquired before entry into the study. The study began in November 2014 and concluded in August 2015.

Inclusion and Exclusion Criteria

Inclusion criteria were as follows: 1) at least 18 years of age with the capacity for informed consent, 2) a reported history of axial nonradicular low back pain, and 3) recommended by the spine interventional radiologists. Exclusion criteria were as follows: 1) a history of fracture or tumor of the spine, including osteoblastic metastases, 2) women who were pregnant or breastfeeding, 3) contraindications to MR imaging or administration of tracer or contrast, and 4) prior lumbar surgery or instrumentation.

Immediately before PET/MR imaging, subjects completed questionnaires measuring pain (numeric rating scale, from 0 to 10 with 0 equal to no pain and 10, the most severe intensity of pain), quality of life (Oswestry Disability Index Low Back Pain Disability Questionnaire [ODI]), and activity (International Physical Activity Questionnaire [IPAQ]).^7,8

PET/MR Protocol and Image Review

A 3T Signa PET/MR imaging scanner (GE Healthcare, Milwaukee, Wisconsin) was used for a simultaneous PET and MR image acquisition. Dynamic PET was initiated as 0.08 mCi/Kg of [¹⁸F]-NaF (mean dose, 4.6 ± 0.8 mCi) injected intravenously.

Acquisition Parameters

Clinical MR imaging sequences included the following: sagittal T1 (TR/TE = 510/8.6 ms), sagittal T2 fat-saturated (TR/TE = 4208/86.2 ms), axial T2 fast recovery fast spin-echo with and without fat saturation (TR/TE = 750/9.2 ms), axial T1 fast spin-echo (TR/TE = 575/8.9 ms), and axial T1 fast spin-echo postgadolinium (TR/TE = 562/8.6 ms) imaging. The MR imaging attenuation correction for the lumbar spine region was calculated with the accepted standard 2-point Dixon method.⁹ Sixty minutes of dynamic PET data were acquired across 3 temporal phases (phase 1 = 12 frames of 10 seconds each, phase 2 = 4 frames of 30 seconds each, phase 3 = 14 frames of 4 minutes each). PET reconstruction included postprocessing to correct for decay, attenuation, scatter, and dead time.

MR Imaging Facet Joint Grading

Two board-certified neuroradiologists with 3 (J.F.T.) and >30 (W.P.D.) years' postfellowship experience were blinded to the clinical data and interpreted clinical MR imaging sequences on a reprocessing workstation. Facet synovitis was graded as previously described by Czervionke and Fenton (On-line Fig 1).¹⁰

Data Analysis

Quantitative and semiquantitative PET analysis included all facet joints from the L1–L2 to L5–S1 levels. Volumes of interest were selected using anatomic T2 MR images. A spheric VOI (7.5-mm diameter) was constructed around the center of each facet joint. A 5-mm-diameter VOI was placed in the right iliac crest in the central marrow cavity as a reference region. All PET analysis was performed with PMOD licensed software (PMOD Technologies, Zurich, Switzerland). This software facilitates model-based analysis of dynamic PET data. PMOD allows only validated kinetic models that have been extensively studied, and the output of the results is highly reproducible.

Standard Uptake Value Calculations and Kinetic Data

Placement of facet joint (FJ) VOIs is shown in On-line Fig 2A. A cylindric VOI covering 2 axial sections was placed on the abdominal aorta, and the partial volume correction coefficient was calculated. Maximum standard uptake value (SUV_max) and SUV_mean values (Equation 1) for each subsite were calculated using the 60-minute time point.

The 3-compartment model used for kinetic modeling is shown in On-line Fig 2B. In Equation 2, C_i represents the bone tissue activity concentration and is the sum of C_e (extravascular compartment) and C_t (target tissue bound compartment); C_p is the concentration of tracer in the blood; V is the effective distribution volume of the tracer.¹¹ A 3-compartment irreversible linear model was used for the Patlak linear model.¹¹ The 2-tissue irreversible compartment model was used to calculate the region-specific influx rate constants (in minute⁻¹) for [¹⁸F]-NaF.¹² Uptake was normalized by using the iliac crest as the reference region. The tracer influx rate from the blood pool to the bone matrix was calculated with Equation 2 for K_{i_Patlak}. K_{i_Patlak} represents the rate at which [¹⁸F]-NaF leaves the arterial blood pool and irreversibly binds to a subsite bone matrix. The kinetic analysis was performed by using PMOD. For each subject, FJs with maximum uptake were identified, henceforth referred to as FJ_max.

Equation 2 is the Patlak graphical kinetic model:

Statistical Analyses

The statistical significance of the correlations between PET/MR imaging and clinical disability metrics was tested with the Pearson correlation. A 2-samples t test was used (P < .05) to assess the significance of differences in the K_{i_Patlak} influx rate between the mean FJ_max and mean FJ_{minimum (min)} K_{i_Patlak} and among FJ MR imaging grades.