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

SUMMARY: Our aim was to prospectively evaluate the relationship between low back pain–related disability and quantitative measures from [F]-sodium fluoride ([F]-NaF) MR imaging. Six patients with facetogenic low back pain underwent dynamic [F]-NaF PET/MR imaging. PET metrics were correlated with clinical measures and MR imaging grading of lumbar facet arthropathy. A significant positive correlation was observed between maximum facet joint uptake rate and clinical disability (P .05). These data suggest that dynamic [F]-NaF PET may serve as a useful biomarker for facetogenic disability. ABBREVIATIONS: FJ facet joint; IPAQ International Physical Activity Questionnaire; max maximum; min minimum; mL/ccm/min milliliters/cubic centimeter/minute; ODI Oswestry Disability Index; SUV standard uptake value Clinical assessment for facetogenic low back pain is often hampered by overlapping and nonspecific symptoms and physical examination findings. Conventional imaging techniques limited to evaluation of structural changes in the spine may identify morphologic abnormalities in asymptomatic spinal structures that are indistinguishable from degenerative structural alterations that produce severe pain and disability. Objective and quantitative biomarkers that are more specific for active generators of low back pain would greatly aid in the effective, targeted treatment of patients with low back pain. [18F]-sodium fluoride ([F]-NaF) is a positron-emission tomography radiotracer, which is chemically absorbed into hydroxyapatite in the bone matrix by osteoblasts and can noninvasively detect osteoblastic activity. [F]-NaF has been increasingly used for evaluating bone diseases, particularly for identification of bone metastases and primary tumors. The utility of [F]-NaF PET for evaluating degenerative disease of the lumbar spine remains largely unexplored. The goal of this prospective pilot study was to examine the potential correlation between facetogenic low back pain measures of disability with quantitative and semiquantitative [F]-NaF PET/MR imaging measures of bone turnover and structural MR imaging changes in lumbar facet joints. MATERIALS AND METHODS 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), Received April 20, 2017; accepted after revision June 6. From the Department of Radiology and Biomedical Imaging (N.W.J., J.F.T., V.S., P.P., Y.S., W.P.D., S.M.), University of California, San Francisco, San Francisco, California; and Department of Radiology and Biomedical Imaging (J.F.T.), Zuckerberg San Francisco General Hospital, San Francisco, California. Research support was provided by National Institutes of Health P50AR060752 and GE Healthcare. Please address correspondence to Jason F. Talbott, MD, Department of Radiology and Biomedical Imaging, Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Room 1X57C, San Francisco, CA 94110; e-mail: [email protected] Indicates open access to non-subscribers at www.ajnr.org Indicates article with supplemental on-line photos. http://dx.doi.org/10.3174/ajnr.A5348 AJNR Am J Neuroradiol ●:● ● 2017 www.ajnr.org 1 Published August 31, 2017 as 10.3174/ajnr.A5348 Copyright 2017 by American Society of Neuroradiology. quality of life (Oswestry Disability Index Low Back Pain Disability Questionnaire [ODI]), and activity (International Physical Activity Questionnaire [IPAQ]). 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 [F]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. 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). 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 (SUVmax) and SUVmean 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, Ci represents the bone tissue activity concentration and is the sum of Ce (extravascular compartment) and Ct (target tissue bound compartment); Cp is the concentration of tracer in the blood; V is the effective distribution volume of the tracer. A 3-compartment irreversible linear model was used for the Patlak linear model. The 2-tissue irreversible compartment model was used to calculate the regionspecific influx rate constants (in minute ) for [F]-NaF. 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 Ki_Patlak. Ki_Patlak represents the rate at which [F]-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 FJmax. 1) SUV Radioactivity Concentration kBq