Neuroinflammation PET Imaging: Current Opinion and Future Directions

Jain, Poorva; Chaney, Aisling M.; Carlson, Mackenzie; Jackson, Isaac M.; Rao, Anoushka; James, Michelle L.

doi:10.2967/jnumed.119.229443

Cited by 82 publications

(70 citation statements)

References 38 publications

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“…Given prior results focusing on monocytic responses in this population, future neuroimaging work should seek methods for monitoring brain macrophagic reesponses. Despite the shortcomings of TSPO radioligands, TSPO PET remains the most widely used tool for assessing neuroinflammation and there is currently no better validated inflammatory radiotracer available (for review, see ( Jain et al., 2020 )).…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging

Deri

Clouston

DeLorenzo

et al. 2021

Brain, Behavior, & Immunity - Health

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Background Neuroinflammation has long been theorized to arise from exposures to fine particulate matter and to be modulated when individuals experience chronic stress, both of which are also though to cause cognitive decline in part as a result of neuroinflammation. Objectives Hypothesizing that neuroinflammation might be linked to experiences at the World Trade Center (WTC) events, this study explored associations between glial activation and neuropsychological measures including post-traumatic stress disorder (PTSD) symptom severity and WTC exposure duration. Methods Translocator protein 18-kDa (TSPO) is overexpressed by activated glial cells, predominantly microglia and astrocytes, making TSPO distribution a putative biomarker for neuroinflammation. Twenty WTC responders completed neuropsychological assessments and in vivo PET brain scan with [ 18 F]-FEPPA. Generalized linear modeling was used to test associations between PTSD, and WTC exposure duratiioni as the predictor and both global and regional [ 18 F]-FEPPA total distribution volumes as the outcomes. Result Responders were 56.0 ± 4.7 years-old, and 75% were police officers on 9/11/2001, and all had at least a high school education. Higher PTSD symptom severity was associated with global and regional elevations in [ 18 F]-FEPPA binding predominantly in the hippocampus ( d = 0.72, P = 0.001) and frontal cortex ( d = 0.64, P = 0.004). Longer exposure duration to WTC sites was associated with higher [ 18 F]-FEPPA binding in the parietal cortex. Conclusion Findings from this study of WTC responders at midlife suggest that glial activation is associated with PTSD symptoms, and WTC exposure duration. Future investigation is needed to understand the important role of neuroinflammation in highly exposed WTC responders.

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Section: Discussionmentioning

confidence: 99%

Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging

Deri

Clouston

DeLorenzo

et al. 2021

Brain, Behavior, & Immunity - Health

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“…and relevant neuropathology. Future studies integrating emerging markers of synaptic function and neuroinflammation (e.g., PET markers of synaptic vesicle and translocator proteins 30 ), as well as neuropathological assessment are key to this goal. Studies in LGI1 antibody encephalitis patients may be particularly insightful as the LGI1 protein is most strongly expressed in the hippocampus, 31 and LGI1 antibody encephalitis preferentially affects older individuals, 1,2 who are most susceptible to AD neuropathology.…”

Section: Discussionmentioning

confidence: 99%

Flortaucipir (tau) PET in LGI1 antibody encephalitis

Day

Gordon

McCullough

et al. 2021

Ann Clin Transl Neurol

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The contributors to persistent cognitive impairment and hippocampal atrophy in leucine‐rich glioma‐inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [18F]flortaucipir PET neuroimaging associated with persistent cognitive impairment and hippocampal atrophy in four recovering LGI1 patients (3 men; median age, 67 [37–88] years). Imaging findings in cases were compared with those observed in age‐ and gender‐similar cognitively normal individuals (n = 124) and individuals with early‐symptomatic Alzheimer disease (n = 11). Elevated [18F]flortaucipir retention was observed in the two LGI1 patients with hippocampal atrophy and persistent cognitive impairment, including one with autopsy‐confirmed Alzheimer disease. Tau neuropathology may associate with cognitive complaints and hippocampal atrophy in recovering LGI1 patients.

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“…One way to identify pain generators is through the use of positron emission tomography (PET), a noninvasive imaging tool that allows spatiotemporal visualization of cellular responses to injury. PET ligands that specifically target different cell types and varying cellular activation states can be utilized to monitor disease progression or measure treatment success ( Jain et al, 2020 ). We previously used longitudinal 18 F-TSPO-PET imaging in the tibial fracture mouse model to track the activation of peripheral and central myeloid cells during the acute-to-chronic pain transition ( Cropper et al, 2019 ).…”

Section: Pre-clinical Measurements In Orthopedic Trauma: Connection Tmentioning

confidence: 99%

Modeling Complex Orthopedic Trauma in Rodents: Bone, Muscle and Nerve Injury and Healing

et al. 2021

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Orthopedic injury can occur from a variety of causes including motor vehicle collision, battlefield injuries or even falls from standing. Persistent limb pain is common after orthopedic injury or surgery and presents a unique challenge, as the initiating event may result in polytrauma to bone, muscle, and peripheral nerves. It is imperative that we understand the tissue-specific and multicellular response to this unique type of injury in order to best develop targeted treatments that improve healing and regeneration. In this Mini Review we will first discuss current rodent models of orthopedic trauma/complex orthotrauma. In the second section, we will focus on bone-specific outcomes including imaging modalities, biomechanical testing and immunostaining for markers of bone healing/turnover. In the third section, we will discuss muscle-related pathology including outcome measures of fibrosis, muscle regeneration and tensile strength measurements. In the fourth section, we will discuss nervous system-related pathology including outcome measures of pain-like responses, both reflexive and non-reflexive. In all sections we will consider parallels between preclinical outcome measures and the functional and mechanistic findings of the human condition.

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Neuroinflammation PET Imaging: Current Opinion and Future Directions

Cited by 82 publications

References 38 publications

Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging

Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging

Flortaucipir (tau) PET in LGI1 antibody encephalitis

Modeling Complex Orthopedic Trauma in Rodents: Bone, Muscle and Nerve Injury and Healing

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