M Kessler1,2, M Mamach3,4,5, R Beutelmann6, M Lukacevic3, S Eilert3, P Bascuñana3, A Fasel7, F M Bengel3, J P Bankstahl3, T L Ross3, G M Klump4,6, G Berding3,4. 1. Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Kessler.Mariella@mh-hannover.de. 2. Cluster of Excellence Hearing4all, Hannover Medical School and University of Oldenburg, Hannover, Germany. Kessler.Mariella@mh-hannover.de. 3. Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. 4. Cluster of Excellence Hearing4all, Hannover Medical School and University of Oldenburg, Hannover, Germany. 5. Department of Medical Physics and Radiation Protection, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. 6. Division of Animal Physiology and Behaviour, Department for Neuroscience, School of Medicine and Health Sciences, University of Oldenburg, Carl von Ossietzky Str. 9-11, 26129, Oldenburg, Germany. 7. ABX Advanced Biochemical Compounds GmbH, Heinrich-Glaeser-Strasse 10-14, 01454, Radeberg, Germany.
Abstract
PURPOSE: Plastic changes in the central auditory system involving the GABAergic system accompany age-related hearing loss. Such processes can be investigated with positron emission tomography (PET) imaging using [18F]flumazenil ([18F]FMZ). Here, [18F]FMZ PET-based modeling approaches allow a simple and reliable quantification of GABAA receptor binding capacity revealing regional differences and age-related changes. PROCEDURES: Sixty-minute list-mode PET acquisitions were performed in 9 young (range 5-6 months) and 11 old (range 39-42 months) gerbils, starting simultaneously with the injection of [18F]FMZ via femoral vein. Non-displaceable binding potentials (BPnd) with pons as reference region were calculated for auditory cortex (AC), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SC), and cerebellum (CB) using (i) a two-tissue compartment model (2TCM), (ii) the Logan plot with image-derived blood-input (Logan (BI)), (iii) a simplified reference tissue model (SRTM), and (iv) the Logan reference model (Logan (RT)). Statistical parametric mapping analysis (SPM) comparing young and old gerbils was performed using 3D parametric images for BPnd based on SRTM. Results were verified with in vitro autoradiography from five additional young gerbils. Model assessment included the Akaike information criterion (AIC). Hearing was evaluated using auditory brainstem responses. RESULTS: BPnd differed significantly between models (p < 0.0005), showing the smallest mean difference between 2TCM as reference and SRTM as simplified procedure. SRTM revealed the lowest AIC values. Both volume of distribution (r2 = 0.8793, p = 0.018) and BPnd (r2 = 0.8216, p = 0.034) correlated with in vitro autoradiography data. A significant age-related decrease of receptor binding was observed in auditory (AC, IC, MGB) and other brain regions (SC and CB) (p < 0.0001, unpaired t test) being confirmed by SPM using pons as reference (p < 0.0001, uncorrected). CONCLUSION: Imaging of GABAA receptor binding capacity in gerbils using [18F]FMZ PET revealed SRTM as a simple and robust quantification method of GABAA receptors. Comparison of BPnd in young and old gerbils demonstrated an age-related decrease of GABAA receptor binding.
PURPOSE: Plastic changes in the central auditory system involving the GABAergic system accompany age-related hearing loss. Such processes can be investigated with positron emission tomography (PET) imaging using [18F]flumazenil ([18F]FMZ). Here, [18F]FMZ PET-based modeling approaches allow a simple and reliable quantification of GABAA receptor binding capacity revealing regional differences and age-related changes. PROCEDURES: Sixty-minute list-mode PET acquisitions were performed in 9 young (range 5-6 months) and 11 old (range 39-42 months) gerbils, starting simultaneously with the injection of [18F]FMZ via femoral vein. Non-displaceable binding potentials (BPnd) with pons as reference region were calculated for auditory cortex (AC), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SC), and cerebellum (CB) using (i) a two-tissue compartment model (2TCM), (ii) the Logan plot with image-derived blood-input (Logan (BI)), (iii) a simplified reference tissue model (SRTM), and (iv) the Logan reference model (Logan (RT)). Statistical parametric mapping analysis (SPM) comparing young and old gerbils was performed using 3D parametric images for BPnd based on SRTM. Results were verified with in vitro autoradiography from five additional young gerbils. Model assessment included the Akaike information criterion (AIC). Hearing was evaluated using auditory brainstem responses. RESULTS: BPnd differed significantly between models (p < 0.0005), showing the smallest mean difference between 2TCM as reference and SRTM as simplified procedure. SRTM revealed the lowest AIC values. Both volume of distribution (r2 = 0.8793, p = 0.018) and BPnd (r2 = 0.8216, p = 0.034) correlated with in vitro autoradiography data. A significant age-related decrease of receptor binding was observed in auditory (AC, IC, MGB) and other brain regions (SC and CB) (p < 0.0001, unpaired t test) being confirmed by SPM using pons as reference (p < 0.0001, uncorrected). CONCLUSION: Imaging of GABAA receptor binding capacity in gerbils using [18F]FMZ PET revealed SRTM as a simple and robust quantification method of GABAA receptors. Comparison of BPnd in young and old gerbils demonstrated an age-related decrease of GABAA receptor binding.
Authors: E A Barnard; P Skolnick; R W Olsen; H Mohler; W Sieghart; G Biggio; C Braestrup; A N Bateson; S Z Langer Journal: Pharmacol Rev Date: 1998-06 Impact factor: 25.468
Authors: Isabelle Miederer; Sibylle I Ziegler; Christoph Liedtke; Mary E Spilker; Matthias Miederer; Till Sprenger; Klaus J Wagner; Alexander Drzezga; Henning Boecker Journal: Eur J Nucl Med Mol Imaging Date: 2008-11-29 Impact factor: 9.236
Authors: V W Pike; C Halldin; C Crouzel; L Barré; D J Nutt; S Osman; F Shah; D R Turton; S L Waters Journal: Nucl Med Biol Date: 1993-05 Impact factor: 2.408
Authors: M Kessler; M Mamach; R Beutelmann; J P Bankstahl; F M Bengel; G M Klump; Georg Berding Journal: Brain Struct Funct Date: 2018-09-10 Impact factor: 3.270