In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease DOI Creative Commons
Romain Schollhammer,

Sébastien Lepreux,

Nicole Barthe

et al.

EJNMMI Research, Journal Year: 2021, Volume and Issue: 11(1)

Published: May 5, 2021

Abstract Background Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation help select patients who would benefit from appropriate therapeutic interventions. This study sought assess usefulness 18 kDa translocator protein (TSPO) tracers [ 11 C]-PBR28 and F]-PBR06 for imaging inflammatory in vitro vivo. Immunohistochemistry macrophage infiltration well autoradiography with were performed on eight paraffin-embedded, formalin-fixed atherosclerosis prospectively collected after carotid endarterectomy affected by stroke. Six different patients, one whom was also included study, underwent PET imaging. Two stenosis associated stroke imaged PET/CT, four other (three large vessel vasculitis bilateral but without stroke) C]-PBR28. Results All sections showed specific binding F]-PBR06, which co-localized immunohistochemistry markers inflammation. However, vivo TSPO either negative all participants. Conclusion Despite good uptake surgical samples vitro, are not viable clinical tools disease. Trial registration : NCT02513589, registered 31 July 2015 NCT00547976, 23 October 2007. https://clinicaltrials.gov .

Language: Английский

Imaging chronic active lesions in multiple sclerosis: a consensus statement DOI Creative Commons
Francesca Bagnato, Pascal Sati, Christopher C. Hemond

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(9), P. 2913 - 2933

Published: Jan. 16, 2024

Abstract Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery innovative MRI PET-derived biomarkers has made it possible to detect CAL, some extent quantify them, brain persons with sclerosis, vivo. Paramagnetic rim on susceptibility-sensitive sequences, MRI-defined slowly expanding T1-weighted T2-weighted scans, 18-kDa translocator protein-positive PET promising candidate CAL. While partially overlapping, these do not equivalent sensitivity specificity histopathological Standardization use available imaging measures CAL identification, quantification monitoring is lacking. To fast-forward clinical translation North American Imaging Multiple Sclerosis Cooperative developed a consensus statement, which provides guidance radiological definition measurement The proposed manuscript presents this summarizes multistep process leading it, identifies remaining major gaps knowledge.

Language: Английский

Citations

54
TSPO PET brain inflammation imaging: A transdiagnostic systematic review and meta-analysis of 156 case-control studies DOI Creative Commons
Livia De Picker, Manuel Morrens, Igor Branchi

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 113, P. 415 - 431

Published: Aug. 3, 2023

The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity TSPO to identify brain processes appears vary greatly across disorders, disease stages, applied quantification methods. To advance potential biomarker evaluate inflammation anti-inflammatory therapies, better understanding its applicability disorders needed. We conducted transdiagnostic systematic review meta-analysis all vivo human case-control studies CNS. Specifically, we investigated direction, strength, heterogeneity associated with signal pre-specified regions, explored demographic methodological sources heterogeneity.We searched English peer-reviewed articles that differences. extracted details, outcomes, technical variables procedure. A random-effects was estimate standardized mean differences (SMD) lobar/whole-brain cortical grey matter (cGM), thalamus, cortico-limbic circuitry between different illness categories. Heterogeneity evaluated I2 statistic using subgroup meta-regression analyses radioligand generation, method, age, sex, publication year. Significance set at False Discovery Rate (FDR)-corrected P < 0.05.156 individual were included review, incorporating data 2381 healthy controls 2626 patients. 139 documented meta-analysable grouped into 11 Across categories, observed significantly higher cases compared cGM (n = 121 studies, SMD 0.358, PFDR 0.001, 68%), significant difference categories (P 0.004). increases only Alzheimer's (SMD 0.693, 64%) other neurodegenerative 0.929, 73%). Cortico-limbic 97 0.541, 67%) most prominent disease, mild cognitive impairment, mood multiple sclerosis. Thalamic involvement 79 0.393, 71%) sclerosis, chronic pain functional (all 0.05). Main outcomes systemic immunological viral infections, substance use schizophrenia traumatic injury not significant. identified between-study variance including strong effect method (explaining 25% variance; VT-based 0.000 versus reference tissue-based 0.630; F 20.49, df 1;103, 0.001), patient age (9% variance), generation (5% variance).This study first overarching findings humans several regions. robust specific types which widespread or focal depending on category. also found large horizontal (positive) shift estimates studies. Our results can support future optimize experimental design power calculations, by taking account type disorder, region-of-interest, radioligand, method.

Language: Английский

Citations

27
Imaging transcriptomics: Convergent cellular, transcriptomic, and molecular neuroimaging signatures in the healthy adult human brain DOI Creative Commons
Daniel Martins, Alessio Giacomel, Steven Williams

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 37(13), P. 110173 - 110173

Published: Dec. 1, 2021

The integration of transcriptomic and neuroimaging data, "imaging transcriptomics," has recently emerged to generate hypotheses about potential biological pathways underlying regional variability in features. However, the validity this approach is yet be examined depth. Here, we sought bridge gap by performing decoding distribution well-known molecular markers spanning different elements biology healthy human brain. Imaging transcriptomics identifies cell that are consistent with known a wide range markers. extent which it can capture patterns gene expression align well neuroinflammatory axis, at least controls without proinflammatory challenge, inconclusive. might constitute an interesting improve our understanding phenotypes.

Language: Английский

Citations

54
Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update DOI
Dominique Gouilly,

Laure Saint‐Aubert,

Maria-João Ribeiro

et al.

European Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 55(5), P. 1322 - 1343

Published: Jan. 27, 2022

Neuroinflammation is a significant contributor to Alzheimer's disease (AD). Until now, PET imaging of the translocator protein (TSPO) has been widely used depict neuroimmune endophenotype AD. The aim this review was provide an update results from 2018 and advance characterization biological basis TSPO in AD by re-examining function expression methodological aspects interest. Although signal obviously related microglia astrocytes AD, observed process remains uncertain might not be directly neuroinflammation. Further studies are required re-examine cellular significance underlying variation

Language: Английский

Citations

37
Microglia measured by TSPO PET are associated with Alzheimer's disease pathology and mediate key steps in a disease progression model DOI Creative Commons
Samantha Rossano, Aubrey S. Johnson, Anna Smith

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2397 - 2407

Published: Feb. 1, 2024

Abstract INTRODUCTION Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aβ) local neurodegeneration, resulting cognitive impairment. METHODS Florbetaben, PBR28, MK‐6240 PET, T1 magnetic resonance imaging, measures were performed 19 cognitively unimpaired older adults 22 patients mild impairment or to examine associations among activation, Aβ, tau, cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of along model. RESULTS Higher PBR28 uptake was associated higher lower MMSE score, independent mediated between early middle Braak stages, cognition. DISCUSSION Microglia are pathology cognition may mediate relationships subsequent steps progression.

Language: Английский

Citations

8
Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease DOI Creative Commons
Xiaoqi Ma,

Dan Xin,

Ruining She

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 17, 2023

Ischemic stroke, a primary cause of disability and the second leading mortality, has emerged as an urgent public health issue. Growing evidence suggests that Cyclic GMP-AMP synthase (cGAS)- Stimulator interferon genes (STING) pathway, component innate immunity, is closely associated with microglia activation, neuroinflammation, regulated cell death in ischemic stroke. However, mechanisms underlying this pathway remain inadequately understood. This article comprehensively reviews existing literature on cGAS-STING its multifaceted relationship Initially, it examines how various risk factors pre-disease such metabolic dysfunction senescence (e.g., hypertension, hyperglycemia, hyperlipidemia) affect relation to Subsequently, we explore depth potential pathophysiological between oxidative stress, endoplasmic reticulum neuroinflammation well including ferroptosis PANoptosis following cerebral ischemia injury. Finally, intervention targeting may serve promising therapeutic strategies for addressing Taken together, review concludes shed light exploration new against

Language: Английский

Citations

16
Technical opportunities and challenges in developing total-body PET scanners for mice and rats DOI Creative Commons
Junwei Du, Terry Jones

EJNMMI Physics, Journal Year: 2023, Volume and Issue: 10(1)

Published: Jan. 2, 2023

Abstract Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used studying pharmaceutical biodistribution and disease progression over time by a wide range of biological processes. However, it remains true that almost all small studies using mouse or rat as preclinical models are either limited spatial resolution sensitivity (especially for dynamic studies), both, reducing quantitative accuracy precision results. Total-body scanners, which have axial lengths longer than nose-to-anus length mouse/rat can provide high across entire body mouse/rat, realize new opportunities PET. This article aims to discuss technical challenges developing total-body scanners mice rats.

Language: Английский

Citations

15
Influences on PET Quantification and Interpretation DOI Creative Commons
Julian M.M. Rogasch, Frank Hofheinz,

Lutz van Heek

et al.

Diagnostics, Journal Year: 2022, Volume and Issue: 12(2), P. 451 - 451

Published: Feb. 10, 2022

Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology-both imaging hardware reconstruction software-into clinical care, we now find ourselves a transition period which traditional technologies coexist. The effects on value its routine practice require careful reevaluation. In this review, provide comprehensive summary important influencing quantification with focus recent developments technology. Finally, discuss relationship between subjective interpretation.

Language: Английский

Citations

21
TSPO Radioligands for Neuroinflammation: An Overview DOI Creative Commons
Silvia Salerno, Monica Viviano, Emma Baglini

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(17), P. 4212 - 4212

Published: Sept. 5, 2024

The translocator protein (TSPO) is predominately localized on the outer mitochondrial membrane in steroidogenic cells. In brain, TSPO expression, low under normal conditions, results upregulated response to glial cell activation, that occurs neuroinflammation. As a consequence, has been extensively studied as biomarker of such conditions by means TSPO-targeted radiotracers. Although [11C]-PK11195, prototypical radioligand, still widely used for vivo studies, it endowed with severe limitations, mainly sensitivity and poor amenability quantification. Consequently, several efforts have focused design new radiotracers imaging TSPO. present review will provide an outlook latest advances radioligands neuroinflammation imaging. final goal pave way (radio)chemists future development novel effective sensitive radiopharmaceuticals targeting

Language: Английский

Citations

4
Implications and pathophysiology of neuroinflammation in pediatric patients with traumatic brain injury: an updated review DOI Creative Commons
Shalin Shah, Arya Shetty, David T. Johnston

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 15, 2025

Traumatic Brain Injury (TBI) in children is a profound public health issue with the potential to disrupt cognitive, behavioral, and psychosocial development significantly. This review provides an updated examination of role neuroinflammation pediatric TBI, emphasizing its dual impact on injury progression recovery. Highlighted complex interplay primary secondary mechanisms, including critical contributions neuroinflammatory responses mediated by central peripheral immune cells. Advances biomarker identification imaging techniques are discussed, showcasing how tools like diffusion tensor (DTI) positron emission tomography (PET) enhance our understanding processes. The also explores current therapeutic strategies targeting neuroinflammation, underscoring emerging treatments such as pharmacologic agents that modulate novel therapies stem cell interventions. comprehensive seeks deepen neuroinflammation’s pathophysiological roles TBI propose directions for future clinical research efforts.

Language: Английский

Citations

0