Dynamic PET with 11C- and 18F- tracers for measuring cerebrospinal fluid alterations in multiple sclerosis
ECTRIMS Online Library. Schubert J. 09/13/19; 278496; P1294
Julia Johanna Schubert
Julia Johanna Schubert
Contributions
Abstract

Abstract: P1294

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

J.J. Schubert1, M. Veronese1, B. Bodini2, M. Tonietto2, B. Stankoff2, A. Martin-Bastida3, M. Politis1, P. Piccini3, F.E. Turkheimer1

1Neuroimaging, King's College London, IoPPN, London, United Kingdom, 2Sorbonne Université, ICM, Hôpital de la Pitié Salpêtrière, Paris, France, 3Centre for Neuroinflammation and Neurodegeneration, Imperial College London, London, United Kingdom

Introduction: Positron emission tomography (PET) has been used to quantify myelin in multiple sclerosis (MS) and to measure cerebrospinal fluid (CSF)-mediated brain clearance in neurological disease. CSF plays an important role in the brain's clearance pathways and lower lateral ventricle PET signal could indicate reduced CSF-mediated brain clearance. Fluorinated PET tracers have longer half-lives than 11C-labeled tracers previously used for assessing CSF dynamics in neurological disease. Use of fluorinated tracers could allow for measuring CSF-mediated clearance in a clinical setting.
Objectives: To investigate and compare the PET signal in the lateral ventricles of MS patients and healthy controls (HC) using 11C-PiB and 18F-flutemetatmol PET tracers.
Methods: Analysis was performed on two datasets: one containing 5 patients with relapsing-remitting MS and 4 HC that underwent 18F-flutemetamol PET and another containing 20 relapsing-remitting MS patients and 8 HC that underwent 11C-PiB PET. All subjects also had structural MRI scans. Preprocessing of the MRI and PET data and extraction of time activity curves were performed using a MIAKATTM pipeline. A manual region of interest (ROI) was generated for the lateral ventricles of each subject. A cerebellar cortex reference region was used to calculate standard uptake value ratios (SUVRs) for the lateral ventricle ROI. These methods have previously been validated by Schubert et al. (2019). Statistical analyses were performed in SPSS.
Results: The average lateral ventricle 11C-PiB SUVR was significantly lower in MS (mean=0.77 ± 0.19) than HC (mean=1.01 ± 0.21) (t(26)=2.87, P=0.008). The average lateral ventricle 18F-flutemetamol SUVR was lower in MS (mean=0.60 ± 0.05) than HC (mean=0.69 ± 0.10), although not statistically significant (t(7)=1.72, P=0.13).
Conclusions: The observation of a lower lateral ventricle PET signal in MS compared to HC supports previous suggestions of CSF-mediated brain clearance reductions in MS. Although the 18F-flutemetamol results did not reach significance, there was a trend towards reduced 18F-flutemetamol signal in the lateral ventricles in MS. The current sample of 18F-flutemetamol PET data may lack statistical power to measure a significant group difference. These results show promise for the use of fluorinated tracers for assessing CSF-mediated brain clearance and additional investigations with larger sample sizes are required.
Disclosure: Julia J. Schubert: nothing to disclose.
Mattia Veronese: nothing to disclose.
Benedetta Bodini: nothing to disclose.
Matteo Tonietto: nothing to disclose.
Bruno Stankoff has received fees for advisory boards and lectures from Genzyme, Merck-Serono, Novartis, Teva and Biogen, and research support from Roche, Genzyme and Merck-Serono.
Antonio Martin-Bastida: nothing to disclose.
Marios Politis: nothing to disclose.
Paola Piccini: nothing to disclose.
Federico E. Turkheimer: nothing to disclose.
This abstract represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The 11C-PiB data presented here was originally collected for a study funded by specific grants from ELA (European Leukodystrophy Association; grant no.: 2007-0481) and INSERM-DHOS (grant no.: 2008-recherche Clinique et translationnelle).

Abstract: P1294

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

J.J. Schubert1, M. Veronese1, B. Bodini2, M. Tonietto2, B. Stankoff2, A. Martin-Bastida3, M. Politis1, P. Piccini3, F.E. Turkheimer1

1Neuroimaging, King's College London, IoPPN, London, United Kingdom, 2Sorbonne Université, ICM, Hôpital de la Pitié Salpêtrière, Paris, France, 3Centre for Neuroinflammation and Neurodegeneration, Imperial College London, London, United Kingdom

Introduction: Positron emission tomography (PET) has been used to quantify myelin in multiple sclerosis (MS) and to measure cerebrospinal fluid (CSF)-mediated brain clearance in neurological disease. CSF plays an important role in the brain's clearance pathways and lower lateral ventricle PET signal could indicate reduced CSF-mediated brain clearance. Fluorinated PET tracers have longer half-lives than 11C-labeled tracers previously used for assessing CSF dynamics in neurological disease. Use of fluorinated tracers could allow for measuring CSF-mediated clearance in a clinical setting.
Objectives: To investigate and compare the PET signal in the lateral ventricles of MS patients and healthy controls (HC) using 11C-PiB and 18F-flutemetatmol PET tracers.
Methods: Analysis was performed on two datasets: one containing 5 patients with relapsing-remitting MS and 4 HC that underwent 18F-flutemetamol PET and another containing 20 relapsing-remitting MS patients and 8 HC that underwent 11C-PiB PET. All subjects also had structural MRI scans. Preprocessing of the MRI and PET data and extraction of time activity curves were performed using a MIAKATTM pipeline. A manual region of interest (ROI) was generated for the lateral ventricles of each subject. A cerebellar cortex reference region was used to calculate standard uptake value ratios (SUVRs) for the lateral ventricle ROI. These methods have previously been validated by Schubert et al. (2019). Statistical analyses were performed in SPSS.
Results: The average lateral ventricle 11C-PiB SUVR was significantly lower in MS (mean=0.77 ± 0.19) than HC (mean=1.01 ± 0.21) (t(26)=2.87, P=0.008). The average lateral ventricle 18F-flutemetamol SUVR was lower in MS (mean=0.60 ± 0.05) than HC (mean=0.69 ± 0.10), although not statistically significant (t(7)=1.72, P=0.13).
Conclusions: The observation of a lower lateral ventricle PET signal in MS compared to HC supports previous suggestions of CSF-mediated brain clearance reductions in MS. Although the 18F-flutemetamol results did not reach significance, there was a trend towards reduced 18F-flutemetamol signal in the lateral ventricles in MS. The current sample of 18F-flutemetamol PET data may lack statistical power to measure a significant group difference. These results show promise for the use of fluorinated tracers for assessing CSF-mediated brain clearance and additional investigations with larger sample sizes are required.
Disclosure: Julia J. Schubert: nothing to disclose.
Mattia Veronese: nothing to disclose.
Benedetta Bodini: nothing to disclose.
Matteo Tonietto: nothing to disclose.
Bruno Stankoff has received fees for advisory boards and lectures from Genzyme, Merck-Serono, Novartis, Teva and Biogen, and research support from Roche, Genzyme and Merck-Serono.
Antonio Martin-Bastida: nothing to disclose.
Marios Politis: nothing to disclose.
Paola Piccini: nothing to disclose.
Federico E. Turkheimer: nothing to disclose.
This abstract represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The 11C-PiB data presented here was originally collected for a study funded by specific grants from ELA (European Leukodystrophy Association; grant no.: 2007-0481) and INSERM-DHOS (grant no.: 2008-recherche Clinique et translationnelle).

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