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OtherClinical Investigations (Human)

Pseudo-reference regions for glial imaging with 11C-PBR28: investigation in two clinical cohorts

Daniel Strakis Albrecht, Marc David Normandin, Sergey Shcherbinin, Dustin W. Wooten, Adam J. Schwarz, Nicole R. Zurcher, Vanessa N. Barth, Nicolas J. Guehl, Oluwaseun Johnson-Akeju, Nazem Atassi, Mattia Veronese, Federico Turkheimer, Jacob M. Hooker and Marco Luciano Loggia
Journal of Nuclear Medicine August 2017, jnumed.116.178335; DOI: https://doi.org/10.2967/jnumed.116.178335
Daniel Strakis Albrecht
1 Massachusetts General Hospital / Harvard, United States;
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Marc David Normandin
1 Massachusetts General Hospital / Harvard, United States;
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Sergey Shcherbinin
2 Eli Lilly and Company, United States;
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Dustin W. Wooten
1 Massachusetts General Hospital / Harvard, United States;
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Adam J. Schwarz
3 Eli Lilly & Co;
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Nicole R. Zurcher
1 Massachusetts General Hospital / Harvard, United States;
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Vanessa N. Barth
2 Eli Lilly and Company, United States;
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Nicolas J. Guehl
1 Massachusetts General Hospital / Harvard, United States;
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Oluwaseun Johnson-Akeju
1 Massachusetts General Hospital / Harvard, United States;
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Nazem Atassi
1 Massachusetts General Hospital / Harvard, United States;
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Mattia Veronese
4 King's College London, United Kingdom
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Federico Turkheimer
4 King's College London, United Kingdom
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Jacob M. Hooker
1 Massachusetts General Hospital / Harvard, United States;
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Marco Luciano Loggia
1 Massachusetts General Hospital / Harvard, United States;
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Abstract

The translocator protein (TSPO) is a commonly used imaging target to investigate neuroinflammation. While TSPO imaging demonstrates great promise, its signal exhibits substantial interindividual variability, which needs to be accounted for to uncover group effects that are truly reflective of neuroimmune activation. Recent evidence suggests that relative metrics computed using pseudo-reference approaches can minimize within-group variability, and increase sensitivity to detect physiologically meaningful group differences. Here, we evaluated various ratio approaches for TSPO imaging and compared them with standard kinetic modeling techniques, analyzing two different disease cohorts. Patients with chronic low back pain (cLBP) or amyotrophic lateral sclerosis (ALS) and matching healthy controls received 11C-PBR28 PET scans. Occipital cortex, cerebellum and whole brain were first evaluated as candidate pseudo-reference regions by testing for the absence of group differences in Standardized Uptake Value (SUV) and distribution volume (VT) estimated with an arterial input function (AIF). SUV from target regions (cLBP study – thalamus; ALS study – precentral gyrus) was normalized with SUV from candidate pseudo-reference regions to obtain SUVRoccip, SUVRcereb, and SUVRWB. The sensitivity to detect group differences in target regions was compared using various SUVR approaches, as well as distribution volume ratio (DVR) estimated with (blDVR) or without AIF (refDVR), and VT. Additional voxelwise SUVR group analyses were performed. We observed no significant group differences in pseudo-reference VT or SUV, excepting whole-brain VT, which was higher in cLBP patients than controls. Target VT elevations in patients (P = 0.028 and 0.051 in cLBP and ALS, respectively) were similarly detected by SUVRoccip and SUVRWB, and by refDVR and blDVR (less reliably by SUVRcereb). In voxelwise analyses, SUVRoccip, but not SUVRcereb, identified regional group differences initially observed with SUVRWB, and in additional areas suspected to be affected in the pathology examined. All ratio metrics were highly cross-correlated, but generally were not associated with VT. While important caveats need to be considered when using relative metrics, ratio analyses appear to be similarly sensitive to detect pathology-related group differences in 11C-PBR28 signal as classic kinetic modeling techniques. Occipital cortex may be a suitable pseudo-reference region, at least for the populations evaluated, pending further validation in larger cohorts.

  • Image Processing
  • PET
  • Radioimmunoimaging
  • Astrocytes
  • Human
  • Microglia
  • Neuroimmunology
  • Neuroinflammation
  • Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Journal of Nuclear Medicine: 62 (2)
Journal of Nuclear Medicine
Vol. 62, Issue 2
February 1, 2021
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Pseudo-reference regions for glial imaging with 11C-PBR28: investigation in two clinical cohorts
Daniel Strakis Albrecht, Marc David Normandin, Sergey Shcherbinin, Dustin W. Wooten, Adam J. Schwarz, Nicole R. Zurcher, Vanessa N. Barth, Nicolas J. Guehl, Oluwaseun Johnson-Akeju, Nazem Atassi, Mattia Veronese, Federico Turkheimer, Jacob M. Hooker, Marco Luciano Loggia
Journal of Nuclear Medicine Aug 2017, jnumed.116.178335; DOI: 10.2967/jnumed.116.178335

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Pseudo-reference regions for glial imaging with 11C-PBR28: investigation in two clinical cohorts
Daniel Strakis Albrecht, Marc David Normandin, Sergey Shcherbinin, Dustin W. Wooten, Adam J. Schwarz, Nicole R. Zurcher, Vanessa N. Barth, Nicolas J. Guehl, Oluwaseun Johnson-Akeju, Nazem Atassi, Mattia Veronese, Federico Turkheimer, Jacob M. Hooker, Marco Luciano Loggia
Journal of Nuclear Medicine Aug 2017, jnumed.116.178335; DOI: 10.2967/jnumed.116.178335
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Keywords

  • Image Processing
  • PET
  • Radioimmunoimaging
  • Astrocytes
  • human
  • microglia
  • Neuroimmunology
  • Neuroinflammation
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