Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [18F]SynVesT-1 PET in Parkinson’s Disease

Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and qua...

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Published inMolecular imaging Vol. 2023; p. 1855985
Main Authors Smart, Kelly, Uribe, Carme, Desmond, Kimberly L., Martin, Sarah L., Vasdev, Neil, Strafella, Antonio P.
Format Journal Article
LanguageEnglish
Published England Hindawi 2023
Sage Publications Ltd
SAGE Publishing
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Abstract Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (BPND) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k2′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (ps>0.47). Each fitting method produced BPND estimates in close agreement with those derived from the 1TCM (subject R2s>0.98, bias<10%), with no difference in bias between the control and PD groups. With SRTM2, BPND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias<6%). While these are preliminary results from a small sample of patients with PD (n=5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
AbstractList Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential ( B P ND ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k 2 ′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ( p s > 0.47 ). Each fitting method produced B P ND estimates in close agreement with those derived from the 1TCM (subject R 2 s > 0.98 , bias < 10 % ), with no difference in bias between the control and PD groups. With SRTM2, B P ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans ( bias < 6 % ). While these are preliminary results from a small sample of patients with PD ( n = 5 ), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Synaptic density in the central nervous system can be measured in vivo using PET with [ 18 F]SynVesT-1. While [ 18 F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson's disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [ 18 F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [ 18 F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (BP ND ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k 2 ′ fixed to either a sample average value (0.037 min −1 ) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ( ps > 0.47). Each fitting method produced BP ND estimates in close agreement with those derived from the 1TCM (subject R 2 s > 0.98, bias < 10%), with no difference in bias between the control and PD groups. With SRTM2, BP ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias < 6%). While these are preliminary results from a small sample of patients with PD ( n = 5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [ 18 F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (BPND) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k2′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (ps>0.47). Each fitting method produced BPND estimates in close agreement with those derived from the 1TCM (subject R2s>0.98, bias<10%), with no difference in bias between the control and PD groups. With SRTM2, BPND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias<6%). While these are preliminary results from a small sample of patients with PD (n=5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential ( B P ND ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k 2 ′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ( p s > 0.47 ). Each fitting method produced B P ND estimates in close agreement with those derived from the 1TCM (subject R 2 s > 0.98 , bias < 10 % ), with no difference in bias between the control and PD groups. With SRTM2, B P ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans ( bias < 6 % ). While these are preliminary results from a small sample of patients with PD ( n = 5 ), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Synaptic density in the central nervous system can be measured in vivo using PET with [ 18 F]SynVesT-1. While [ 18 F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [ 18 F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [ 18 F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential ([Formula: see text]) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with [Formula: see text] fixed to either a sample average value (0.037 min -1 ) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ([Formula: see text]). Each fitting method produced [Formula: see text] estimates in close agreement with those derived from the 1TCM (subject [Formula: see text], [Formula: see text]), with no difference in bias between the control and PD groups. With SRTM2, [Formula: see text] estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans ([Formula: see text]). While these are preliminary results from a small sample of patients with PD ([Formula: see text]), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [ 18 F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Synaptic density in the central nervous system can be measured using PET with [ F]SynVesT-1. While [ F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson's disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [ F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [ F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (BP ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with ' fixed to either a sample average value (0.037 min ) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ( > 0.47). Each fitting method produced BP estimates in close agreement with those derived from the 1TCM (subject s > 0.98, bias < 10%), with no difference in bias between the control and PD groups. With SRTM2, BP estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias < 6%). While these are preliminary results from a small sample of patients with PD ( = 5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [ F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Author Vasdev, Neil
Desmond, Kimberly L.
Strafella, Antonio P.
Smart, Kelly
Uribe, Carme
Martin, Sarah L.
AuthorAffiliation 4 Edmond J. Safra Parkinson Disease Program, Neurology Division, Toronto Western Hospital & Krembil Brain Institute, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8
1 Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada M5T 1R8
2 Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada M5T 1R8
3 Unitat de Psicologia Medica, Departament de Medicina, Institute of Neuroscience, Universitat de Barcelona, Barcelona, Spain
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Copyright © 2023 Kelly Smart et al.
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Snippet Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful...
Synaptic density in the central nervous system can be measured in vivo using PET with [ 18 F]SynVesT-1. While [ 18 F]SynVesT-1 has been proven to be a powerful...
Synaptic density in the central nervous system can be measured using PET with [ F]SynVesT-1. While [ F]SynVesT-1 has been proven to be a powerful...
Synaptic density in the central nervous system can be measured in vivo using PET with [ 18 F]SynVesT-1. While [ 18 F]SynVesT-1 has been proven to be a powerful...
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SubjectTerms Bias
Blood
Central Nervous System
Density
Efflux
Estimates
Evaluation
Fluorine isotopes
Graphical methods
Humans
Medical imaging
Movement disorders
Neurodegenerative diseases
Parkinson Disease - diagnostic imaging
Parkinson's disease
Pharmaceuticals
Positron emission
Positron emission tomography
Radioactive tracers
Radiochemistry
Radioisotopes
Radionuclide Imaging
Sampling
Scanning
Synaptic density
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Title Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [18F]SynVesT-1 PET in Parkinson’s Disease
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