MRI Outperforms [18F]AV-1451 PET as a Longitudinal Biomarker in Progressive Supranuclear Palsy

Jennifer Lynn Whitwell, Nirubol Tosakulwong, Christopher Schwarz, Hugo Botha, Matthew L. Senjem, Anthony J. Spychalla, J. Eric Ahlskog, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack, Val Lowe, Keith Anthony Josephs

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Elevated uptake of the [18F]AV-1451 tau-PET ligand has been observed cross-sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [18F]AV-1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy. Methods: Sixteen subjects with PSP underwent 2 serial [18F]AV-1451 tau-PET scans and 3-Tesla MRI over 12 months and were age- and sex-matched to 39 healthy controls with longitudinal [18F]AV-1451 PET. Median [18F]AV-1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo-controlled treatment trials were calculated. Results: Rate of midbrain atrophy was significantly increased in PSP compared with controls. [18F]AV-1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [18F]AV-1451 measures. Smallest sample-size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [18F]AV-1451 measures. Conclusions: [18F]AV-1451 tau-PET measures increase over time in subjects with PSP, but longitudinal [18F]AV-1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials.

Original languageEnglish (US)
JournalMovement Disorders
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Progressive Supranuclear Palsy
Mesencephalon
Biomarkers
Atrophy
Sample Size
Ligands
Cerebellar Nuclei
Globus Pallidus
Positron-Emission Tomography
Cerebellum
Placebos
Clinical Trials

Keywords

  • positron emission tomography
  • rates
  • Richardson's syndrome
  • serial
  • tau

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

@article{1fe9032450d544b0a8f50a8d446abcce,
title = "MRI Outperforms [18F]AV-1451 PET as a Longitudinal Biomarker in Progressive Supranuclear Palsy",
abstract = "Background: Elevated uptake of the [18F]AV-1451 tau-PET ligand has been observed cross-sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [18F]AV-1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy. Methods: Sixteen subjects with PSP underwent 2 serial [18F]AV-1451 tau-PET scans and 3-Tesla MRI over 12 months and were age- and sex-matched to 39 healthy controls with longitudinal [18F]AV-1451 PET. Median [18F]AV-1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo-controlled treatment trials were calculated. Results: Rate of midbrain atrophy was significantly increased in PSP compared with controls. [18F]AV-1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [18F]AV-1451 measures. Smallest sample-size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [18F]AV-1451 measures. Conclusions: [18F]AV-1451 tau-PET measures increase over time in subjects with PSP, but longitudinal [18F]AV-1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials.",
keywords = "positron emission tomography, rates, Richardson's syndrome, serial, tau",
author = "Whitwell, {Jennifer Lynn} and Nirubol Tosakulwong and Christopher Schwarz and Hugo Botha and Senjem, {Matthew L.} and Spychalla, {Anthony J.} and Ahlskog, {J. Eric} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Val Lowe and Josephs, {Keith Anthony}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/mds.27546",
language = "English (US)",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - MRI Outperforms [18F]AV-1451 PET as a Longitudinal Biomarker in Progressive Supranuclear Palsy

AU - Whitwell, Jennifer Lynn

AU - Tosakulwong, Nirubol

AU - Schwarz, Christopher

AU - Botha, Hugo

AU - Senjem, Matthew L.

AU - Spychalla, Anthony J.

AU - Ahlskog, J. Eric

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Lowe, Val

AU - Josephs, Keith Anthony

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Elevated uptake of the [18F]AV-1451 tau-PET ligand has been observed cross-sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [18F]AV-1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy. Methods: Sixteen subjects with PSP underwent 2 serial [18F]AV-1451 tau-PET scans and 3-Tesla MRI over 12 months and were age- and sex-matched to 39 healthy controls with longitudinal [18F]AV-1451 PET. Median [18F]AV-1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo-controlled treatment trials were calculated. Results: Rate of midbrain atrophy was significantly increased in PSP compared with controls. [18F]AV-1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [18F]AV-1451 measures. Smallest sample-size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [18F]AV-1451 measures. Conclusions: [18F]AV-1451 tau-PET measures increase over time in subjects with PSP, but longitudinal [18F]AV-1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials.

AB - Background: Elevated uptake of the [18F]AV-1451 tau-PET ligand has been observed cross-sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [18F]AV-1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy. Methods: Sixteen subjects with PSP underwent 2 serial [18F]AV-1451 tau-PET scans and 3-Tesla MRI over 12 months and were age- and sex-matched to 39 healthy controls with longitudinal [18F]AV-1451 PET. Median [18F]AV-1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo-controlled treatment trials were calculated. Results: Rate of midbrain atrophy was significantly increased in PSP compared with controls. [18F]AV-1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [18F]AV-1451 measures. Smallest sample-size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [18F]AV-1451 measures. Conclusions: [18F]AV-1451 tau-PET measures increase over time in subjects with PSP, but longitudinal [18F]AV-1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials.

KW - positron emission tomography

KW - rates

KW - Richardson's syndrome

KW - serial

KW - tau

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