164 IEEE TRANSACTION ON RADIATION AND PLASMA MEDICAL SCIENCES, VOL. 1, NO. 2, MARCH 2017 Hyperpolarized 13 C-MRSI and PET (hyperPET) in an Osteomyelitis Pig Model: A Pilot Study Soﬁe Rahbek, Henrik Gutte, Helle H. Johannesen, Janne Koch, Louise K. Jensen, Kristine Dich-Jorgensen, Henrik E. Jensen, Adam E. Hansen, and Andreas Kjaer Abstract—AIM: Hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) is a real-time metabolic imaging technique, which can be combined with positron emission tomography (PET). In this pilot study, we explore the potential of combined hyperpolarized 13C-MRSI and FDG-PET for imaging of infection. METHODS: Three pigs were inoculated with S. aureusbacteria in the right tibia and saline in the left tibial bone. FDG-PET, 1H-MRI and 13C-MRSI was performed using a clinical whole-body PET/MR system (Siemens Biograph mMR, Erlangen, Germany). Hyperpolarized13C-pyruvate was prepared using a SpinLab System (GE Healthcare, Pittsburgh, PA, USA). 13C-lactate to 13C-pyruvate ratio and FDG SUV was reported in anatomical regions of interest covering bone and regions of inﬂammation and abscess deﬁned on 1H-MRI. Histopathological examination was performed of both legs. RESULTS: An abscess was observed outside the right (infected bone) on 1H-MRI and conﬁrmed by histopathology. In the abscess the 13C-lactate to 13C-pyruvate ratio was increased as compared to the inﬂammatory region of the control leg. 18F-FDG uptake showed no clear trend when comparing abscess versus inﬂammation, but showed an increase considering the infected bone versus the control. In the abscess, the FDG-PET signal distribution had highest intensity in the abscess membrane, whereas the maximum of the13C lactate ratio appears in the abscess cavity. DISCUSSION: The apparent different spatial enhancement pattern of FDG uptake and 13C lactate ratio in abscess suggests that they are independent biomarkers and that hyperpolarized 13C-MRSI is a method with potential for clinical imaging of infection and treatment response. Index Terms— 13 C-Pyruvate, 18 F-FDG-PET, hyperpolarized, infection, molecular imaging, MRSI, osteomyelitis, PET/MR. Manuscript received July 15, 2016; revised October 15, 2016 and November 24, 2016; accepted December 8, 2016. Date of publication December 20, 2016; date of current version March 24, 2017. S. Rahbek, H. H. Johannesen, and A. E. Hansen are with the Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Denmark (e-mail: soﬁe89falko@gmail.com; helle.hjorth.johannesen.01@regionh.dk; adam.espe.hansen@regionh.dk). H. Gutte and A. Kjaer are with the Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Denmark, and also with the Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Denmark (e-mail: henrikgb@gmail.com; akjaer@sund.ku.dk). J. Koch and K. Dich-Jorgensen are with the Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark (e-mail: jako@sund.ku.dk; kristinedich@sund.ku.dk). L. K. Jensen and H. E. Jensen are with the Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (e-mail: louise-k@sund.ku.dk); elvang@sund.ku.dk. Color versions of one or more of the ﬁgures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identiﬁer 10.1109/TNS.2016.2642478 I. AIM T HE COMBINATION of hyperpolarized 13 C-pyruvate magnetic resonance spectroscopic imaging (MRSI) with positron emission tomography (PET) (hyperPET), feasible with a clinical PET/MRI scanner, is a new tool for dual- modality functional imaging and has shown promising results for investigation of cancer [1,2]. Hyperpolarized 13 C-MRSI is a technique that non-invasively reveals real-time cellular metabolism by following e.g. the conversion of 13 C-pyruvate to 13 C-lactate, 13 C-alanine, and 13 C-bicarbonate [3]. In this pilot study, we explore the potential of hyperPET for imaging of infection in an osteomyelitis pig model [4]. PET using 18 F-ﬂuorodeoxyglucose ( 18 F-FDG) is an often used modality for detection of infected foci [5]. The use of hyper- polarized 13 C-MRSI in this context is novel, however, lactate levels are known to be increased e.g. in bacterial abscess. Here we show the ﬁrst, preliminary results. II. METHODS Data was collected from three healthy pigs (female Yorkshire-Landrace). Holes were drilled in the tibial meta- physis and inoculated with S. aureus bacteria in the right tibia and with saline in the left “sham” tibial bone. The imaging was performed 4-6 days after innoculation. A 3 Tesla PET/MR system (Siemens Biograph mMR, Erlangen, Germany) was used. A single-bed PET was performed 60-110 min post injection of 6 MBq/Kg 18 F-FDG and reconstructed with 3 iter- ations, 21 subsets, matrix 344, 4 mm post Gaussian, and vendor supplied attenuation correction based on segmentation of water and fat derived from Dixon MRI sequence. MRSI utilized a dual tuned ﬂex coil (RAPID Biomedical, Rimpar, Germany). 13 C-MRSI was performed 40 s post injec- tion of 0.68 mL/kg hyperpolarized 13 C-pyruvate (250 mM), prepared using a SpinLab System (GE Healthcare, Pittsburgh, PA, USA). Acquisition parameters included: repetition time 80 ms, ﬂip angle 10 ◦ , bandwidth 10,000 Hz, FOV 200 x 120 mm, 1 slice of thickness 13 mm, matrix 16x16 (circular truncation), and total imaging time 11 s. 13 C ﬂip angle calibra- tion was carried out as described in [6]. A previous dynamic 13 C-MRS acquisition was used to verify the 40 s delay for the 13 C-lactate signal peak. 13 C-MRSI was planned to capture both sites of inoculation. Subsequent, a MRSI-aligned T2-tse MRI and axial T1-tse with fat saturation following gadolin- ium (Gd) injection (0.2 mL/kg Dotarem) was performed. 2469-7311 c  2016 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.