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MR imaging of serotonin transporter occupancy
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation using [99mTc] TRODAT-1 to assess striatal DAT availability were performed at resting state. A functional magnetic resonance imaging (fMRI) with event-related designed the IGT was conducted. 3T scanner was used. Regressors of interest included neural activity for three phases (prepare, response, and feedback) of task in each trial were modeled with the canonical hemodynamic response function. At the response phase, regressors for experimental trials were separated according to expect value (advantageous deck or disadvantageous deck). At the feedback phase, regressors were separated according to outcome (win or loss) with a parametrical modulator set by actual feedback in each trial. The neutral trials (outcome is 0), at the feedback phase, were modeled to a regressor without modulator. The region of interests (ROIs) for fMRI were left and right orbito-frontal cortex (OFC), ventral striatum (VS), medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) was. Eleven adult ADHD and eleven controls were enrolled. Spearman’s rho correlation was used to examine the relation between parametric estimate from fMRI analysis and DAT availability assess from SPECT. Result: Behavior analysis on IGT indicated that adult ADHD tend to make significant poor decision numbers of choice on bad desk − numbers of choice on good desk, average net score for adult ADHD = −19.82, controls = 6.73, Mann–Whitney U = 18, Z = 2.81, P = 0.004. DAT availability associated with BOLD response that covariated with monetary loss on medial prefrontal cortex (ø = 0.70, P = 0.016), right ventral striatum (ø = 0.72, P = 0.013), and right insula (ø = 0.66, P = 0.029) in adult ADHD. However, no similar correlation was found in controls. Discussion: The result confirmed the different role of dopaminergic tone on the rewarding system among ADHD, compared with controls. It is plausible that lower neuro-threshold accompanied with rewarding task could be exacerbated by the hypodopaminergic tone among ADHD. The hypodopaminergic tone with ADHD, together, could be associated with lack of sensitive for punishment during a risky decision. P.1.i.009 Impact of attenuation correction in hybrid PET/MR imaging of serotonin transporter occupancy L. Rischka1 ° , A. Hahn1 , G. Gryglewski1 , C. Philippe2 , L. Nics2 , M. Hartenbach2 , T. Traub-Weidinger2 , M. Mitterhauser2 , W. Wadsak2 , M. Hacker2 , S. Kasper1 , R. Lanzenberger1 1 Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria; 2 Medical University of Vienna, Department of Biomedical Imaging and Image-guided TherapyDivision of Nuclear Medicine, Vienna, Austria Objective: Hybrid PET/MR imaging systems offer novel applications for simultaneous assessment of neurotransmitter systems and brain function to acute drug challenges. However, attenuation correction (AC) suffers from the lack of correct description of bone via MRI. Since the gold standard of recording a low-dose CT is not feasible in clinical routine, we evaluated several alternative AC methods. Methods: Five healthy subjects underwent one measurement on a hybrid PET/MR scanner (Siemens mMR). [11 C]DASB was administered as bolus for the first minute plus constant infusion for 120 or 140min, respectively, with a target dose of 10MBq/kg. After 60min 7.5 mg of the selective serotonin reuptake inhibitor (SSRI) Citalopram were applied. Arterial blood samples were taken before and after drug challenge.
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Attenuation correction (AC) was performed with a low-dose CT, two MR-segmentation-based and one atlas-based AC approach for comparison. The CT was scaled bilinearly from Hounsfield units to 511keV for correct AC [1]. The MR-segmentation-based approaches are provided by the vendor. One segments fat, water and air from four different MR sequences (Dixon). The other is based on soft-tissue, bone and air segmentation computed from ultra-short echo times (UTE). The atlas-based approach uses a database with MR-CT registered pairs. The individual MR of a subject is transformed into a pseudoCT from the best fitting averaged MR-CT pairs and then scaled in the same way as the CT [2]. Time activity curves (TACs) were derived from 11 regions of interest (ROIs) covering almost the whole brain. Chosen ROIs have low and high serotonin transporter (SERT) concentration and are close or far from bone since earlier findings showed a strong bias when bone is ignored in AC [3]. The total volume of distribution (VT) was calculated from TAC points in equilibrium before and after challenge divided by the plasma activity concentration in blood at corresponding equilibrium times. For the binding potential (BPP) the non-displaceable volume of distribution of cerebellar gray matter was subtracted from VT [4]. The drug occupancy was calculated as the relative change in BPP. Finally, the differences in occupancy were calculated for all AC approaches with respect to CT. Results: For regions with higher BPP, also far from bone like Thalamus and Striatum all AC approaches worked well with drug occupancy differences of 0.1. . . 1.4% and 0.4. . . 0.9% compared to CT-based AC, respectively (table). Differently, the disparities in the amygdala are 17.2%, with pseudoCT, 167.8% for Dixon and 26.1% for UTE. In comparison, the frontal superior medial gyrus, a low binding region close to bone, showed a small bias for pseudoCT of 0.9%, while UTE and Dixon gave a bias of 8.5% and 9.2%, respectively. Conclusion: The results indicate different performances of the presented AC approaches, depending on the location of the ROI in the brain. The closer a ROI is to the bone, the more important are the correct attenuation coefficients. However, we could show that no additional CT scan is necessary for robust occupancy calculation in regions with high SERT binding that are close to the center of the brain, such as the striatum, thalamus and midbrain. References [1] Carney, J.P.J., Townsend, D.W., Rappoport, V., Bendriem, B., 2006. Method for transforming CT images for attenuation correction in PET/ CT imaging. Med. Phys. 33, 976–983. [2] Burgos, N., Cardoso, M.J., Thielemans, K., Modat, M., Pedemonte, S., Dickson, J., Barnes, A., Ahmed, R., Mahoney, C.J., Schott, J.M., Duncan, J.S., Atkinson, D., Arridge, S.R., Hutton, B.F., Ourselin, S., 2014. Attenuation correction synthesis for hybrid PET-MR scanners: Application to brain studies. IEEE Trans Med Imaging 33(12), 2332−41. [3] Andersen, F.L., Ladefoged, C.N., Beyer, T., Keller, S.H., Hansen, A.E., Højgaard, L., Kjær, A., Law, I., Holm, S., 2014. Combined PET/ MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone. Neuroimage 84, 206–216. [4] Innis, R.B., Cunningham, V.J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R.N., Holden, J., Houle, S., Huang, S.C., Ichise, M., Iida, H., Ito, H., Kimura, Y., Koeppe, R.A., Knudsen, G.M., Knuuti, J., Lammertsma, A.A., Laruelle, M., Logan, J., Maguire, R.P., Mintun, M.A., Morris, E.D., Parsey, R., Price, J.C., Slifstein, M., Sossi, V., Suhara, T., Votaw, J.R., Wong, D.F., Carson, R.E., 2007. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27, 1533–1539.
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Attenuation correction (AC) was performed with a low-dose CT, two MR-segmentation-based and one atlas-based AC approach for comparison. The CT was scaled bilinearly from Hounsfield units to 511keV for correct AC [1]. The MR-segmentation-based approaches are provided by the vendor. One segments fat, water and air from four different MR sequences (Dixon). The other is based on soft-tissue, bone and air segmentation computed from ultra-short echo times (UTE). The atlas-based approach uses a database with MR-CT registered pairs. The individual MR of a subject is transformed into a pseudoCT from the best fitting averaged MR-CT pairs and then scaled in the same way as the CT [2]. Time activity curves (TACs) were derived from 11 regions of interest (ROIs) covering almost the whole brain. Chosen ROIs have low and high serotonin transporter (SERT) concentration and are close or far from bone since earlier findings showed a strong bias when bone is ignored in AC [3]. The total volume of distribution (VT) was calculated from TAC points in equilibrium before and after challenge divided by the plasma activity concentration in blood at corresponding equilibrium times. For the binding potential (BPP) the non-displaceable volume of distribution of cerebellar gray matter was subtracted from VT [4]. The drug occupancy was calculated as the relative change in BPP. Finally, the differences in occupancy were calculated for all AC approaches with respect to CT. Results: For regions with higher BPP, also far from bone like Thalamus and Striatum all AC approaches worked well with drug occupancy differences of 0.1. . . 1.4% and 0.4. . . 0.9% compared to CT-based AC, respectively (table). Differently, the disparities in the amygdala are 17.2%, with pseudoCT, 167.8% for Dixon and 26.1% for UTE. In comparison, the frontal superior medial gyrus, a low binding region close to bone, showed a small bias for pseudoCT of 0.9%, while UTE and Dixon gave a bias of 8.5% and 9.2%, respectively. Conclusion: The results indicate different performances of the presented AC approaches, depending on the location of the ROI in the brain. The closer a ROI is to the bone, the more important are the correct attenuation coefficients. However, we could show that no additional CT scan is necessary for robust occupancy calculation in regions with high SERT binding that are close to the center of the brain, such as the striatum, thalamus and midbrain. References [1] Carney, J.P.J., Townsend, D.W., Rappoport, V., Bendriem, B., 2006. Method for transforming CT images for attenuation correction in PET/ CT imaging. Med. Phys. 33, 976–983. [2] Burgos, N., Cardoso, M.J., Thielemans, K., Modat, M., Pedemonte, S., Dickson, J., Barnes, A., Ahmed, R., Mahoney, C.J., Schott, J.M., Duncan, J.S., Atkinson, D., Arridge, S.R., Hutton, B.F., Ourselin, S., 2014. Attenuation correction synthesis for hybrid PET-MR scanners: Application to brain studies. IEEE Trans Med Imaging 33(12), 2332−41. [3] Andersen, F.L., Ladefoged, C.N., Beyer, T., Keller, S.H., Hansen, A.E., Højgaard, L., Kjær, A., Law, I., Holm, S., 2014. Combined PET/ MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone. Neuroimage 84, 206–216. [4] Innis, R.B., Cunningham, V.J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R.N., Holden, J., Houle, S., Huang, S.C., Ichise, M., Iida, H., Ito, H., Kimura, Y., Koeppe, R.A., Knudsen, G.M., Knuuti, J., Lammertsma, A.A., Laruelle, M., Logan, J., Maguire, R.P., Mintun, M.A., Morris, E.D., Parsey, R., Price, J.C., Slifstein, M., Sossi, V., Suhara, T., Votaw, J.R., Wong, D.F., Carson, R.E., 2007. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27, 1533–1539.