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Amyloid Imaging With Carbon 11–Labeled Pittsburgh Compound B for Traumatic Brain Injury
Open accessAbstract
OBJECTIVES: To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue. DESIGN, SETTING, AND PARTICIPANTS: In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for β-amyloid (Aβ) and β-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes. MAIN OUTCOMES AND MEASURES: We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aβ and β-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue. RESULTS: Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aβ and β-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels. CONCLUSIONS AND RELEVANCE: [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.
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“while the risk nearly doubled for players who had sustained one or more mTBIs within the previous 12 months [94].”
From The neuropathology of sport (2014) · cites this paper as [94]
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“Players who wore protective headgear during games were at a reduced risk (incident rate ratio 0.57; 95 % confidence interval [CI], 0.40–0.82)”
From The neuropathology of sport (2014) · cites this paper as [94]
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“In a cohort of 3,207 male nonprofessional rugby players followed for one or more seasons, the incidence of mTBI was 7.97 per 1,000 player game hours, with 313 players (9.8 %) sustaining 1 or more mTBIs during the study.”
From The neuropathology of sport (2014) · cites this paper as [94]
In the citing paper
“However, despite evidence for Ab deposition in moderate to severe TBI [94], Ab plaques have not been found in early or mild stages of CTE in young individuals [65, 66, 72, 91, 126] but occur in older subjects with CTE in association with increased age at death [128].”
From The neuropathology of sport (2014) · cites this paper as [94]
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“[11C]PiB PET was also performed for 11 healthy controls (median [range] age, 35 [24-60] years), none of whom had any symptoms, signs, or diagnoses of neurological disease or showed any abnormalities on magnetic resonance imaging (MRI) scans of the brain, and all of whom had a normal score on the Mini-Mental State Exam…”
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Metadata
- Authors
- Hong, Y. T., Veenith, T., Dewar, D., Outtrim, J. G., Mani, V., Williams, C., Pimlott, S., Hutchinson, P. J. A., Tavares, A., Canales, R., Mathis, C. A., Klunk, W. E., Aigbirhio, F. I., Coles, J. P., Baron, J.-C., Pickard, J. D., Fryer, T. D., Stewart, W., & Menon, D. K.
- Affiliations
- University of Pittsburgh (US)
- University of Glasgow and Southern General Hospital, Glasgow, Scotland
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2014-01-01
- Volume
- 71
- Issue
- 1
- Pages
- 23
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4084932
- OpenAlex
- W2166402688
- Cited by
- 158
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 13 · 2021: 13 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 23 · 2014: 15
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Apollo
- Funders
- National Institute for Health and Care Research (NF-SI-0508-10327, NF-SI-0512-10090, NIHR-RP-R3-12-013)
- Academy of Medical Sciences
- Medical Research Council (RG46503)
- NIHR Cambridge Biomedical Research Centre
- National Institute on Aging (P01AG025204, RF1AG025516, P50AG005133, AG025204, R37AG025516)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- traumatic brain injury, amyloid deposition, Pittsburgh compound B, amyloid-beta, amyloid precursor protein, immunocytochemistry, distribution volume ratio, standardized uptake value ratio, cortical gray matter, striatum, thalamus, white matter, autopsy brain tissue, neuroimaging biomarkers
- MeSH terms
- Adult, Aged, Aniline Compounds, Brain, Brain Injuries, Carbon Radioisotopes, Female, Humans, Male, Middle Aged, Thiazoles, Time Factors, Tritium, Cohort Studies, Amyloid beta-Peptides, Positron-Emission Tomography, Young Adult
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