Relative 11C-PiB delivery as a proxy of relative CBF: Quantitative evaluation using single-session 15o-water and 11C-PiB PET

Yin J. Chen, Bedda L. Rosario, Wenzhu Bi Mowrey, Charles M. Laymon, Xueling Lu, Oscar L. Lopez, William E. Klunk, Brian J. Lopresti, Chester A. Mathis, Julie C. Price

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The primary goal of this study was to assess the suitability of <sup>11</sup>CPittsburgh compound B (<sup>11</sup>C-PiB) blood.brain barrier delivery (K<inf>1</inf>) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of <sup>11</sup>C-PiB retention (amyloid-b load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, 15O-water PET, and <sup>11</sup>C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time.activity curves. Multiple analysis approaches provided regional 15O-water and <sup>11</sup>C-PiB measures of delivery and <sup>11</sup>C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial-and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., 15O-water K1 and <sup>11</sup>C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and <sup>11</sup>C-PiB SRTM2-R1) and between delivery measures and <sup>11</sup>C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (r.0.2.0.5) between 15O-water K1 and <sup>11</sup>C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K<inf>1-Water</inf> and <sup>11</sup>C-PiB SRTM2-R<inf>1</inf> (ρ.0.5.0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between <sup>11</sup>C-PiB retention and relative <sup>11</sup>C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: <sup>11</sup>C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional <sup>11</sup>C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-b load and relative CBF) through dynamic <sup>11</sup>C-PiB imaging.

Original languageEnglish (US)
Pages (from-to)1199-1205
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number8
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

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Cerebrovascular Circulation
Proxy
Water
Amyloid
Cerebellum
Social Adjustment
Brain
Cerebrospinal Fluid
Alzheimer Disease

Keywords

  • Alzheimer's disease
  • Amyloid
  • Blood flow
  • Kinetic modeling
  • PiB PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Relative 11C-PiB delivery as a proxy of relative CBF : Quantitative evaluation using single-session 15o-water and 11C-PiB PET. / Chen, Yin J.; Rosario, Bedda L.; Mowrey, Wenzhu Bi; Laymon, Charles M.; Lu, Xueling; Lopez, Oscar L.; Klunk, William E.; Lopresti, Brian J.; Mathis, Chester A.; Price, Julie C.

In: Journal of Nuclear Medicine, Vol. 56, No. 8, 01.08.2015, p. 1199-1205.

Research output: Contribution to journalArticle

Chen, YJ, Rosario, BL, Mowrey, WB, Laymon, CM, Lu, X, Lopez, OL, Klunk, WE, Lopresti, BJ, Mathis, CA & Price, JC 2015, 'Relative 11C-PiB delivery as a proxy of relative CBF: Quantitative evaluation using single-session 15o-water and 11C-PiB PET', Journal of Nuclear Medicine, vol. 56, no. 8, pp. 1199-1205. https://doi.org/10.2967/jnumed.114.152405
Chen, Yin J. ; Rosario, Bedda L. ; Mowrey, Wenzhu Bi ; Laymon, Charles M. ; Lu, Xueling ; Lopez, Oscar L. ; Klunk, William E. ; Lopresti, Brian J. ; Mathis, Chester A. ; Price, Julie C. / Relative 11C-PiB delivery as a proxy of relative CBF : Quantitative evaluation using single-session 15o-water and 11C-PiB PET. In: Journal of Nuclear Medicine. 2015 ; Vol. 56, No. 8. pp. 1199-1205.
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title = "Relative 11C-PiB delivery as a proxy of relative CBF: Quantitative evaluation using single-session 15o-water and 11C-PiB PET",
abstract = "The primary goal of this study was to assess the suitability of 11CPittsburgh compound B (11C-PiB) blood.brain barrier delivery (K1) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of 11C-PiB retention (amyloid-b load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, 15O-water PET, and 11C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time.activity curves. Multiple analysis approaches provided regional 15O-water and 11C-PiB measures of delivery and 11C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial-and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., 15O-water K1 and 11C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and 11C-PiB SRTM2-R1) and between delivery measures and 11C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (r.0.2.0.5) between 15O-water K1 and 11C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K1-Water and 11C-PiB SRTM2-R1 (ρ.0.5.0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between 11C-PiB retention and relative 11C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: 11C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional 11C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-b load and relative CBF) through dynamic 11C-PiB imaging.",
keywords = "Alzheimer's disease, Amyloid, Blood flow, Kinetic modeling, PiB PET",
author = "Chen, {Yin J.} and Rosario, {Bedda L.} and Mowrey, {Wenzhu Bi} and Laymon, {Charles M.} and Xueling Lu and Lopez, {Oscar L.} and Klunk, {William E.} and Lopresti, {Brian J.} and Mathis, {Chester A.} and Price, {Julie C.}",
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TY - JOUR

T1 - Relative 11C-PiB delivery as a proxy of relative CBF

T2 - Quantitative evaluation using single-session 15o-water and 11C-PiB PET

AU - Chen, Yin J.

AU - Rosario, Bedda L.

AU - Mowrey, Wenzhu Bi

AU - Laymon, Charles M.

AU - Lu, Xueling

AU - Lopez, Oscar L.

AU - Klunk, William E.

AU - Lopresti, Brian J.

AU - Mathis, Chester A.

AU - Price, Julie C.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - The primary goal of this study was to assess the suitability of 11CPittsburgh compound B (11C-PiB) blood.brain barrier delivery (K1) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of 11C-PiB retention (amyloid-b load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, 15O-water PET, and 11C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time.activity curves. Multiple analysis approaches provided regional 15O-water and 11C-PiB measures of delivery and 11C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial-and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., 15O-water K1 and 11C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and 11C-PiB SRTM2-R1) and between delivery measures and 11C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (r.0.2.0.5) between 15O-water K1 and 11C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K1-Water and 11C-PiB SRTM2-R1 (ρ.0.5.0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between 11C-PiB retention and relative 11C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: 11C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional 11C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-b load and relative CBF) through dynamic 11C-PiB imaging.

AB - The primary goal of this study was to assess the suitability of 11CPittsburgh compound B (11C-PiB) blood.brain barrier delivery (K1) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of 11C-PiB retention (amyloid-b load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods: Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, 15O-water PET, and 11C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time.activity curves. Multiple analysis approaches provided regional 15O-water and 11C-PiB measures of delivery and 11C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial-and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., 15O-water K1 and 11C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and 11C-PiB SRTM2-R1) and between delivery measures and 11C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results: Primary analysis showed positive correlations (r.0.2.0.5) between 15O-water K1 and 11C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K1-Water and 11C-PiB SRTM2-R1 (ρ.0.5.0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between 11C-PiB retention and relative 11C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion: 11C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional 11C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-b load and relative CBF) through dynamic 11C-PiB imaging.

KW - Alzheimer's disease

KW - Amyloid

KW - Blood flow

KW - Kinetic modeling

KW - PiB PET

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