Recent developments and challenges in positron emission tomography imaging of gliosis in chronic neuropathic pain

Pain, Journal Year: 2024, Volume and Issue: 165(10), P. 2184 - 2199

Published: May 7, 2024

Understanding the mechanisms that underpin transition from acute to chronic pain is critical for development of more effective and targeted treatments. There growing interest in contribution glial cells this process, with cross-sectional preclinical studies demonstrating specific changes these cell types capturing timepoints phase phase. In vivo longitudinal assessment evolution experimental animals humans has presented a significant challenge. Recent technological advances clinical positron emission tomography, including radiotracers gliosis, offer great promise field. These now permit tracking over time provide ability relate pain-relevant symptomology, comorbid psychiatric conditions, treatment outcomes at both group an individual level. article, we summarize evidence gliosis overview available measure highlighting their potential, particularly when combined ex / vitro techniques, understand pathophysiology neuropathic pain. complementary investigations can be used bridge existing gap field concerning identify potential targets interventions.

Language: Английский

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Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method

Diagnostics, Journal Year: 2022, Volume and Issue: 12(5), P. 1161 - 1161

Published: May 7, 2022

There is a growing interest in using 18F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of binding can be achieved kinetic modeling analysis with an arterial input function (AIF) measured blood sampling procedures, invasiveness such procedures has been obstacle for wide application. To address these challenges, we developed image-derived (IDIF) that noninvasively estimates from images acquired quantification. Methods: The method entails three fully automatic steps extract IDIF, including segmentation voxels highest likelihood being over carotid artery, model-based matrix factorization signal, scaling optimization procedure scale extracted signal into activity concentration unit. Two cohorts human subjects were used evaluate IDIF. In first cohort five subjects, was performed, calculated IDIF validated against AIF comparison distribution volumes (VT,AIF) (VT,IDIF). second cohort, studies twenty-eight healthy controls without compare VT,IDIF VT,REF reference region-based whether it distinguish high-affinity (HAB) mixed-affinity (MAB) binders. Results: blood-sampling VT derived found accurate surrogate AIF. bias VT, −5.8 ± 7.8% when compared VT,AIF, linear mixed effect model showed high correlation between VT,AIF (p < 0.001). nonblood-sampling significance difference HAB MAB controls. standard uptake values (SUV) superior results distinguishing than VT,REF. Conclusions: A novel evaluated this study. This provides noninvasive alternative measurement quantify TSPO brain dynamic scans.

Language: Английский

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Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 3, 2022

Abstract In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic has not previously been assessed vivo humans. We used Positron Emission Tomography (PET) with radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, assess correlations between age regional brain TSPO group of healthy subjects (n = 43, 19 female, aged 23–78), focusing on hypothalamus. found robust age-correlated expression thalamus but hypothalamus combined women men. This pattern differs from what described rodents. Prominent humans, could reflect evolutionary changes size function versus hypothalamus, may be relevant appropriateness using rodents model human aging. When examining PET results men separately, we that only showed expression. suggest this novel result is understanding stark sex difference aging: undergo loss fertility—menopause—at mid-life. Our finding have implications for perhaps altering reproductive women.

Language: Английский

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Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study

American Journal of Neuroradiology, Journal Year: 2023, Volume and Issue: 44(7), P. 776 - 782

Published: June 15, 2023

The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, CP has been recognized as critical in modulating inflammation. MRI-measured enlargement reported neuroinflammatory disorders like MS well with aging and neurodegeneration. basis of unknown. On tissue studies demonstrating calcification a common pathology associated disease, we hypothesized that previously unmeasured contributes volume may be more specifically neuroinflammation.

Language: Английский

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In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease

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

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