Validation of new image-derived arterial input functions at the aorta using 18 F-fluoride positron emission tomography Tanuj Puri a , Glen M. Blake b , Musib Siddique b , Michelle L. Frost b , Gary J.R. Cook c , Paul K. Marsden d , Ignac Fogelman b and Kathleen M. Curran a Objectives (i) To validate two new image-based methods for finding the plasma arterial input function (AIF) and evaluate the performance of these and two similar techniques against arterial sampling. (ii) To evaluate the performance of all four image-derived AIF (IDAIF) methods against arterial sampling for measuring the 18 F plasma clearance (K i ) to the lumbar spine. Methods Eight healthy postmenopausal women had a 18 F-fluoride positron emission tomography scan of the lumbar spine. Venous blood samples were used to estimate the IDAIFs from: (i) a fixed population-based partial volume correction (PVC) factor method, (ii) a variable PVC factor method, (iii) the Chen method, and (iv) the Cook–Lodge method. Continuous arterial sampling and the respective K i values were used as the gold standard against which the performance of the IDAIF methods was compared. Results The IDAIFs were compared with direct arterial sampling in terms of the area under the curve values. The percentage root mean square error in area under the curves compared with arterial sampling were: (i) fixed PVC: 12.7%, (ii) variable PVC: 12.0%, (iii) Chen: 39.0%, and (iv) Cook–Lodge: 17.3%. There were small but significant differences in the K i values found by all four methods compared with arterial sampling. Bland–Altman plots of K i values showed the best agreement for the variable and fixed PVC methods with a standard deviation of 0.0026 and 0.0030 ml/min/ml, respectively. Conclusion The differences in the K i values obtained at the lumbar spine using direct arterial sampling and any of the IDAIF methods at the aorta were clinically nonsignificant. The variable PVC and fixed PVC methods performed better than the Cook–Lodge and Chen methods. Nucl Med Commun 32:486–495  c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Nuclear Medicine Communications 2011, 32:486–495 Keywords: aorta, bone turnover, 18 F-fluoride positron emission tomography, image-derived arterial input function, osteoporosis a School of Medicine and Medical Sciences, University College Dublin, Ireland, b King’s College London, Osteoporosis Unit, Guy’s Hospital, c Department of Nuclear Medicine, Royal Marsden Hospital, Sutton, Surrey, and d King’s College London, PET Imaging Centre, St Thomas’ Hospital, UK Correspondence to Tanuj Puri, MSc, A222, Department of Diagnostic Imaging, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland Tel: + 353 1 716 6521; fax: + 353 1 716 6547; e-mail: tanuj.puri@ucd.ie Received 5 January 2011 Revised 28 January 2011 Accepted 29 January 2011 Introduction The assessment of skeletal metabolism is important in the investigation of the pathophysiology and treatment of metabolic bone diseases such as osteoporosis [1]. Although bone biopsy is considered the gold standard for quantifying regional bone turnover, it is limited to a single site at the iliac crest, and is an invasive, complex, and costly technique to perform [2]. In contrast, the measurement of biochemical markers of bone turnover in serum and urine is simple, cheap, and noninvasive, but only provides information on global bone turnover [3–5]. The functional imaging technique of dynamic 18 F- fluoride positron emission tomography ( 18 F-PET) [6–15] has the advantage of quantifying regional bone metabo- lism at specific sites of clinical importance such as the lumbar spine and hips, and has been validated by comparison with bone biopsy [16,17]. The quantitative analysis of skeletal metabolism using 18 F- PET is usually performed using the three-compartment model described by Hawkins et al. [15] (Fig. 1). A 60 min dynamic scan is acquired and the bone time activity curve (TAC) is analysed with the arterial input function (AIF) to derive the plasma clearance to the bone mineral compartment (K i : units ml/min/ml), which is dependent on bone blood flow and osteoblastic activity [18]. To obtain reliable results, the analysis of 18 F-PET data requires accurate knowledge of the AIF. This can be obtained in several different ways; for example, (i) using continuous arterial sampling using an online blood monitor, (ii) arterial blood samples obtained at discrete time points postinjection, (iii) using a population-based AIF, or (iv) an image-derived arterial input function (IDAIF) obtained by placing a region of interest (ROI) over an artery and calibrating the resulting curves against venous blood samples obtained during the later phases (30–60 min) of the dynamic scan when venous and arterial 18 F – ion concentrations become equal [7]. The derivation of the AIF using imaging methods is complicated by the partial volume effect, which is a consequence of the finite spatial resolution of the PET scanner. This results in underestimation of the activity in Original article 0143-3636  c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MNM.0b013e3283452918 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.