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Purpose: Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [18F]PI-2620 and resting-state functional MRI (fMRI). Material and methods: Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [18F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05). Results: In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05). Conclusions: PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy. [ABSTRACT FROM AUTHOR]

Sapphirine‐bearing granulite from Usilampatti in the Madurai block of southern India preserves a variety of mineral textures and reactions that help in reconstructing a three‐stage metamorphic evolution. Corroded biotite, sillimanite and quartz inclusions within garnet represent relics from the prograde history. Peak metamorphic conditions were attained with the development of sapphirine + quartz in textural equilibrium (Stage 1). This was followed by nearly isothermal decompression, leading to the formation of sapphirine + cordierite at Stage 2. Subsequent retrograde hydration (Stage 3) is only locally evident. Using the Perple_X software and the model system NCKFMASH, the peak P‐T conditions were estimated from core compositions, and the retrograde evolution was deduced from rim or symplectite compositions of different minerals as computed by isopleths of XMg garnet, XCa garnet, XMg orthopyroxene, XMg sapphirine and XMg biotite. The P‐T conditions for Stage 1 thus obtained, and supported by thermodynamic modelling using the winTWQ programme, is approximately 9 kbar and 940°C. Stage 2 conditions were constrained as 6.7 kbar and 900°C. Dating of zircon and monazite in the sapphirine‐bearing granulite and associated gneisses by the U‐Pb method using LA‐ICP‐MS indicates metamorphic overprint of zircon (lower intercept ages of discordant data arrays) at 546 ± 8 and 547 ± 11 Ma and metamorphic growth of monazite between 542 ± 3 and 551 ± 2 Ma. Upper intercept ages for zircon point to zircon growth at approximately 2514 ± 66 Ma. Although it remains unclear whether the metamorphic age data refer to Stage 1 or Stage 2 or, most likely, a continuum between both, they clearly document a late Ediacaran age for ultra‐high temperature (UHT) metamorphism in the area, which, based on the obtained P‐T path, was most likely the result of crustal thickening followed by uplift and erosion. Thus, it is concluded that the sapphirine‐bearing granulites formed in response to Pan‐African orogeny that led to the collision of the western and eastern Madurai domains, whereas initial zircon growth probably took place during late Neoarchaean arc magmatism that formed much of the western domain. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The National archive for polar samples (NAPA) in Berlin-Spandau is a long-term storage of rock samples, which stem preferably from geoscientific projects in the Arctic and Antarctic regions. It serves for documentation, comparison and for further scientific work with these samples. Since 2007, the archive grew up to 50 collection cabinets. The hitherto stored samples stem from different areas of the Arctic (e.g. Spitsbergen, Ellesmere Island) and Antarctic regions (e.g. Victoria Land, Dronning Maud Land, Shackleton Range, Marie Byrd Land) and comprise major rock collections like those from the University of Aachen (Antarctica; Spaeth & Bauer) with c. 1300 samples, the University of Frankfurt (Antarctica; Kleinschmidt and PhD students) with more than 3000 samples and the University of Bremen (Arctic; Scheibner and students) with c. 1500 samples. All samples are listed in a database and documented in outcrop maps. Currently, a new joint database system is invented, which shall also comprise all samples of the NAPA and which shall be used for online research. Research will be possible for different features as name, location, rock type, researcher, etc. Additionally, during the next year, all samples will be documented by photos, which will be added to the database as well. Together with the polar rock collection at BGR (Hannover), which comprise all samples taken by BGR members, the NAPA offers a large pool of polar rock samples for further projects and research. The NAPA is under supervision of the working group Polar Geology at BGR in Hannover. For requests, please contact: [ABSTRACT FROM AUTHOR]

The origin and emplacement of the exotic Precambrian Pearya terrane (northern Ellesmere Island, Canada) is still a matter of debate. The boundary between Pearya and the passive margin of the Franklinian basin is assumed within the Petersen Bay Fault Zone (Piepjohn & von Gosen 2017). Within this fault zone, amphibolitic rocks of the Kulutingwak Formation crop out, for which some authors (Trettin et al. 1987; Trettin 1998; Beranek et al. 2015) assume an island-arc affinity and an age of 450 Ma has been determined (Trettin 1998). In contrast, a recent study by (Hadlari et al. 2014) suggests a pericratonic model for the Pearya terrane. During the CASE19 expedition 2017, amphibolite and metasediments of the Kulutingwak Formation were collected within the Petersen Bay Fault Zone west of Kulutingwak Fiord. Some samples were immediately analysed for preliminary data: The volcanic rocks can be classified as subalkaline andesitic basalt to andesite with tholeiitic to calc-alkaline geochemical signature and oceanic island arc affinity. The metasediments are rich in SiO2 and Fe2O3 and indicate an arc setting. Preliminary geochemical results in combination with the 450-Ma age of Trettin (1998) might be an indicator for the existence of an oceanic island arc during Ordovician times and, therefore, an open oceanic basin between Pearya and the northern margin of Laurentia. In this case, the Kulutingwak Formation rocks would represent a suture zone. However, further investigation of the whole sample set is necessary to constrain these preliminary results and to consider a new assignment of the Kulutingwak Formation. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "Physiology: Does Gut Hormone PYY [sub 3-36] Decrease Food Intake in Rodents?," by M. Tschop and colleagues, pusblished in the September 2004 issue of the periodical "Nature".

Background: Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4-repeat (4R) tauopathies and its role in accelerating disease progression., Objective: We tested whether microglial activation (1) progresses in similar spatial patterns as the primary pathology tau spreads across interconnected brain regions, and (2) whether the degree of microglial activation parallels tau pathology spreading., Methods: We examined in vivo associations between tau aggregation and microglial activation in 31 patients with clinically diagnosed 4R tauopathies, using 18F-PI-2620 PET and 18F-GE180 (translocator protein [TSPO]) PET. We determined tau epicenters, defined as subcortical brain regions with highest tau PET signal, and assessed the connectivity of tau epicenters to cortical regions of interest using a 3-T resting-state functional magnetic resonance imaging template derived from age-matched healthy elderly controls., Results: In 4R tauopathy patients, we found that higher regional tau PET covaries with elevated TSPO-PET across brain regions that are functionally connected to each other (β = 0.414, P < 0.001). Microglial activation follows similar distribution patterns as tau and distributes primarily across brain regions strongly connected to patient-specific tau epicenters (β = -0.594, P < 0.001). In these regions, microglial activation spatially parallels tau distribution detectable with 18F-PI-2620 PET., Conclusions: Our findings indicate that the spatial expansion of microglial activation parallels tau distribution across brain regions that are functionally connected to each other, suggesting that tau and inflammation are closely interrelated in patients with 4R tauopathies. The combination of in vivo tau and inflammatory biomarkers could therefore support the development of immunomodulatory strategies for disease-modifying treatments in these conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Aim: To investigate the relationship between off-target binding of the amyloid tracer [ 18 F]florbetaben (FBB) in the skull and skull density., Methods: Forty-three consecutive patients were included retrospectively (age 70.2±7.5y, 42% females, 65% amyloid-positive). For each patient, CT skull density (in Hounsfield units) and (late) FBB uptake in the skull were obtained using an individual skull mask generated by warping the skull tissue probability map provided by the statistical parametric mapping software package (version SPM12) to the native patient space. Skull FBB uptake (mean of the 10% hottest voxels) was scaled to the individual median FBB uptake in the pons. The association between skull FBB uptake and skull density was tested by correlation analyses. Univariate analysis of variance (ANOVA) of skull FBB uptake with dichotomized skull density (low: ≤ median, high), sex (female, male) and amyloid-status (positive, negative) as between-subjects factors was used to assess the impact of sex and amyloid status., Results: There was a significant inverse correlation between skull FBB uptake and skull density (Pearson correlation coefficient -0.518, p < 0.001; Spearman rho -0.321, p = 0.036). The ANOVA confirmed the bone density effect on the FBB uptake in the skull (p = 0.019). In addition, sex (p = 0.012) and density*sex interaction (p = 0.016) had a significant impact. Skull FBB uptake was significantly higher in females with low skull density than for all other combinations of sex and skull density. Amyloid status did not reach statistical significance (p = 0.092)., Conclusion: Off-target binding of FBB in the skull is inversely associated with skull density. The relationship is mainly driven by females. Amyloid status does not have a major impact on skull FBB binding., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: (4 S )-4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) positron emission tomography/computed tomography (PET/CT) provides a readout of system x c - transport activity and has been used for cancer detection in clinical studies of different cancer types. As system x c - provides the rate-limiting precursor for glutathione biosynthesis, an abundant antioxidant, [ 18 F]FSPG imaging may additionally provide important prognostic information. Here, we performed an analysis of [ 18 F]FSPG radiotracer distribution between primary tumors, metastases, and normal organs from cancer patients. We further assessed the heterogeneity of [ 18 F]FSPG retention between cancer types, and between and within individuals., Methods: This retrospective analysis of prospectively collected data compared [ 18 F]FSPG PET/CT in subjects with head and neck squamous cell cancer (HNSCC, n = 5) and non-small-cell lung cancer (NSCLC, n = 10), scanned at different institutions. Using semi-automated regions of interest drawn around tumors and metastases, the maximum standardized uptake value (SUV max ), SUV mean , SUV standard deviation and SUV peak were measured. [ 18 F]FSPG time-activity curves (TACs) for normal organs, primary tumors and metastases were subsequently compared to 18 F-2-fluoro-2-deoxy-D-glucose ([ 18 F]FDG) PET/CT at 60 min post injection (p.i.)., Results: The mean administered activity of [ 18 F]FSPG was 309.3 ± 9.1 MBq in subjects with NSCLC and 285.1 ± 11.3 MBq in those with HNSCC. The biodistribution of [ 18 F]FSPG in both cohorts showed similar TACs in healthy organs from cancer patients. There was no statistically significant overall difference in the average SUV max of tumor lesions at 60 min p.i. for NSCLC (8.1 ± 7.1) compared to HNSCC (6.0 ± 4.1; p = 0.29) for [ 18 F]FSPG. However, there was heterogeneous retention between and within cancer types; the SUV max at 60 min p.i. ranged from 1.4 to 23.7 in NSCLC and 3.1-12.1 in HNSCC., Conclusion: [ 18 F]FSPG PET/CT imaging from both NSCLC and HNSCC cohorts showed the same normal-tissue biodistribution, but marked tumor heterogeneity across subjects and between lesions. Despite rapid elimination through the urinary tract and low normal-background tissue retention, the diagnostic potential of [ 18 F]FSPG was limited by variability in tumor retention. As [ 18 F]FSPG retention is mediated by the tumor's antioxidant capacity and response to oxidative stress, this heterogeneity may provide important insights into an individual tumor's response or resistance to therapy.

The marine habitat beneath Antarctica's ice shelves spans ∼1.6 million km 2 , and life in this vast and extreme environment is among Earth's least accessible, least disturbed and least known, yet likely to be impacted by climate-forced warming and environmental change. Although competition among biota is a fundamental structuring force of ecological communities, hence ecosystem functions and services, nothing was known of competition for resources under ice shelves, until this study. Boreholes drilled through a ∼ 200 m thick ice shelf enabled collections of novel sub-ice-shelf seabed sediment which contained fragments of biogenic substrata rich in encrusting (lithophilic) macrobenthos, principally bryozoans - a globally-ubiquitous phylum sensitive to environmental change. Analysis of sub-glacial biogenic substrata, by stereo microscopy, provided first evidence of spatial contest competition, enabling generation of a new range of competition measures for the sub-ice-shelf benthic space. Measures were compared with those of global open-water datasets traversing polar, temperate and tropical latitudes (and encompassing both hemispheres). Spatial competition in sub-ice-shelf samples was found to be higher in intensity and severity than all other global means. The likelihood of sub-ice-shelf competition being intraspecific was three times lower than for open-sea polar continental shelf areas, and competition complexity, in terms of the number of different types of competitor pairings, was two-fold higher. As posited for an enduring disturbance minimum, a specific bryozoan clade was especially competitively dominant in sub-ice-shelf samples compared with both contemporary and fossil assemblage records. Overall, spatial competition under an Antarctic ice shelf, as characterised by bryozoan interactions, was strikingly different from that of open-sea polar continental shelf sites, and more closely resembled tropical and temperate latitudes. This study represents the first analysis of sub-ice-shelf macrobenthic spatial competition and provides a new ecological baseline for exploring, monitoring and comparing ecosystem response to environmental change in a warming world., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: 18 F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke., Methods: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18 F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset. 18 F-GP1 uptake (maximum target-to-background ratio) was assessed in the carotid arteries and brain., Results: 18 F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only, and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 participants had >50% stenosis and 3 had nonstenotic disease. One case had bilateral stenotic disease (>70%), but only the culprit carotid artery demonstrated 18 F-GP1 uptake. The average uptake was higher in the culprit (median maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18 F-GP1 uptake (maximum target-to-background ratio, 6.45 [4.89-7.65]), areas of acute infarction on computed tomography correlated with brain 18 F-GP1 uptake in 6 cases. Ex vivo autoradiography of postmortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage., Conclusions: 18 F-GP1 positron emission tomography and computed tomography angiography is a novel noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03943966., Competing Interests: Disclosures N. Koglin and A.W. Stephens are employees of Life Molecular Imaging, who provided reagents for 18F-GP1 production. The other authors report no conflicts.

Purpose: Amyloid positron emission tomography (PET) with [ 18 F]florbetaben (FBB) is an established tool for detecting Aβ deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification., Methods: This is a retrospective analysis of FBB PET images from 589 subjects. PET scans were quantified with 15 analytical methods using nine software packages (MIMneuro, Hermes BRASS, Neurocloud, Neurology Toolkit, statistical parametric mapping (SPM8), PMOD Neuro, CapAIBL, non-negative matrix factorization (NMF), Amyloid IQ ) that used several metrics to estimate Aβ load (SUVR, centiloid, amyloid load, and amyloid index). Six analytical methods reported centiloid (MIMneuro, standard centiloid, Neurology Toolkit, SPM8 (PET only), CapAIBL, NMF). All results were quality controlled., Results: The mean sensitivity, specificity, and accuracy were 96.1 ± 1.6%, 96.9 ± 1.0%, and 96.4 ± 1.1%, respectively, for all quantitative methods tested when compared to histopathology, where available. The mean percentage of agreement between binary quantitative assessment across all 15 methods and visual majority assessment was 92.4 ± 1.5%. Assessments of reliability, correlation analyses, and comparisons across software packages showed excellent performance and consistent results between analytical methods., Conclusion: This study demonstrated that quantitative methods using both CE marked software and other widely available processing tools provided comparable results to visual assessments of FBB PET scans. Software quantification methods, such as centiloid analysis, can complement visual assessment of FBB PET images and could be used in the future for identification of early amyloid deposition, monitoring disease progression and treatment effectiveness., (© 2023. The Author(s).)

Background: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction., Objectives: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18 F-GP1., Methods: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18 F-GP1 PET/CT angiography. Coronary artery 18 F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios., Results: 18 F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18 F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18 F-GP1 uptake. Extracoronary cardiac 18 F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus., Conclusions: Coronary 18 F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18 F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966)., Competing Interests: Funding Support and Author Disclosures The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. This work was supported by several grant funding organizations. Drs Tzolos (FS/CRTF/20/24086), Williams (FS/ICRF/20/26002, FS/11/014, and CH/09/002), Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek is supported by the Scottish Imaging Network: A Platform of Scientific Excellence. Dr Mills is supported by the British Heart Foundation through the award of Personal Chair and a Programme Grant (CH/F/21/90010 and RG/20/10/34966). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). Dr Slomka and FusionQuant analysis tools are supported by National Heart, Lung, and Blood Institute grant 5R01HL135557. Dr Dey and Autoplaque analysis tools are supported by National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. Drs Koglin and Stephens are employees of Life Molecular Imaging, which provided reagents for radiotracer production. Dr Williams is a member of the Speakers Bureau for Canon Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions., Methods: A cross-sectional cohort of 24 transgenic (PS2APP) and 25 wild-type mice (age range: 4.3-21.0 months) underwent 60 min dynamic [ 18 F]fluorodeprenyl-D2 ([ 18 F]F-DED), static 18 kDa translocator protein (TSPO, [ 18 F]GE-180) and β-amyloid ([ 18 F]florbetaben) PET imaging. Quantification was performed via image derived input function (IDIF, cardiac input), simplified non-invasive reference tissue modelling (SRTM2, DVR) and late-phase standardized uptake value ratios (SUVr). Immunohistochemical (IHC) analyses of glial fibrillary acidic protein (GFAP) and MAO-B were performed to validate PET imaging by gold standard assessments. Patients belonging to the Alzheimer's disease continuum (AD, n = 2), Parkinson's disease (PD, n = 2), multiple system atrophy (MSA, n = 2), autoimmune encephalitis (n = 1), oligodendroglioma (n = 1) and one healthy control underwent 60 min dynamic [ 18 F]F-DED PET and the data were analyzed using equivalent quantification strategies., Results: We selected the cerebellum as a pseudo-reference region based on the immunohistochemical comparison of age-matched PS2APP and WT mice. Subsequent PET imaging revealed that PS2APP mice showed elevated hippocampal and thalamic [ 18 F]F-DED DVR when compared to age-matched WT mice at 5 months (thalamus: + 4.3%; p = 0.048), 13 months (hippocampus: + 7.6%, p = 0.022) and 19 months (hippocampus: + 12.3%, p < 0.0001; thalamus: + 15.2%, p < 0.0001). Specific [ 18 F]F-DED DVR increases of PS2APP mice occurred earlier when compared to signal alterations in TSPO and β-amyloid PET and [ 18 F]F-DED DVR correlated with quantitative immunohistochemistry (hippocampus: R = 0.720, p < 0.001; thalamus: R = 0.727, p = 0.002). Preliminary experience in patients showed [ 18 F]F-DED V T and SUVr patterns, matching the expected topology of reactive astrogliosis in neurodegenerative (MSA) and neuroinflammatory conditions, whereas the patient with oligodendroglioma and the healthy control indicated [ 18 F]F-DED binding following the known physiological MAO-B expression in brain., Conclusions: [ 18 F]F-DED PET imaging is a promising approach to assess reactive astrogliosis in AD mouse models and patients with neurological diseases., (© 2023. The Author(s).)

Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder that can be imaged by the 18 F-labeled tau PET tracer 2-(2-([ 18 F]fluoro)pyridin-4-yl)-9 H -pyrrolo[2,3- b :4,5- c ']dipyridine ( 18 F-PI-2620). The in vivo diagnosis is currently established on clinical grounds and supported by midbrain atrophy estimation in structural MRI. Here, we investigate whether 18 F-PI-2620 tau PET has the potential to improve the imaging diagnosis of PSP. Methods: In this multicenter observational study, dynamic (0-60 min after injection) 18 F-PI-2620 PET and structural MRI data for 36 patients with PSP, 22 with PSP-Richardson syndrome, and 14 with a clinical phenotype other than Richardson syndrome (i.e., variant PSP) were analyzed along with data for 10 age-matched healthy controls (HCs). The PET data underwent kinetic modeling, which resulted in distribution volume ratio (DVR) images. These and the MR images were visually assessed by 3 masked experts for typical PSP signs. Furthermore, established midbrain atrophy parameters were measured in structural MR images, and regional DVRs were measured in typical tau-in-PSP target regions in the PET data. Results: Visual assessments discriminated PSP patients and HCs with an accuracy of 63% for MRI and 80% for the combination of MRI and 18 F-PI-2620 PET. As compared with patients of the PSP-Richardson syndrome subgroup, those of the variant PSP subgroup profited more in terms of sensitivity from the addition of the visual 18 F-PI-2620 PET to the visual MRI information (35% vs. 22%). In quantitative image evaluation, midbrain-to-pons area ratio and globus pallidus DVRs discriminated best between the PSP patients and HCs, with sensitivities and specificities of 83% and 90%, respectively, for MRI and 94% and 100%, respectively, for the combination of MRI and 18 F-PI-2620 PET. The gain of sensitivity by adding 18 F-PI-2620 PET to MRI data was more marked in clinically less affected patients than in more affected patients (37% vs. 19% for visual, and 16% vs. 12% for quantitative image evaluation). Conclusion: These results provide evidence for an improved imaging-based PSP diagnosis by adding 18 F-PI-2620 tau PET to structural MRI. This approach seems to be particularly promising at earlier disease stages and could be of value both for improving early clinical PSP diagnosis and for enriching PSP cohorts for trials of disease-modifying drugs., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

We aimed to explore whether the imaging of antiporter system x C - of immune cells with (4 S )-4-(3- 18 F-fluoropropyl)-l-glutamate ( 18 F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18 F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system x C - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18 F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18 F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18 F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18 F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68 + xCT + and CD3 + xCT + cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68 + xCT + cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system x C - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18 F-FSPG PET imaging of system x C - activity may noninvasively assess the IBD activity., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The ability of 18 F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer's disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using 18 F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition., Methods: Subjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive 18 F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline 18 F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests. A 1-year follow-up 18 F-PI-2620 PET scans and cognitive assessments were done in 15 subjects., Results: Percentage of visually tau-positive scans increased with amyloid-beta deposition measured in 18 F-florbetaben Centiloids (CL) (7.7% (<36 CL), 80% (>83 CL)). 18 F-PI-2620 standardized uptake value ratio (SUVR) was correlated with increased 18 F-florbetaben CL in several regions of interest. Elevated 18 F-PI-2620 SUVR (fusiform gyrus) was associated to high CSF p-tau and t-tau (p=0.0006 and p=0.01, respectively). Low hippocampal volume was associated with increased tau load at baseline (p=0.006 (mesial temporal); p=0.01 (fusiform gyrus)). Significant increases in tau SUVR were observed after 12 months, particularly in the mesial temporal cortex, fusiform gyrus, and inferior temporal cortex (p=0.04, p=0.047, p=0.02, respectively). However, no statistically significant increase in amyloid-beta load was measured over the observation time. The MMSE (Recall score), ADAS-Cog14 (Word recognition score), and CBB (One-card learning score) showed the strongest association with tau deposition at baseline., Conclusions: The findings support the hypothesis that 18 F-PI-2620 PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD with significant correlations with hippocampal volume, CSF biomarkers, and amyloid-beta load. Furthermore, quantifiable increases in 18 F-PI-2620 SUVR over a 12-month period in regions with early tau deposition are consistent with the hypothesis that cortical tau is associated with cognitive impairment. This study supports the utility of 18 F-PI-2620 PET to assess tau deposits in an early AD population. Quantifiable tau load and its corresponding increase in early AD cases could be a relevant target engagement marker in clinical trials of anti-amyloid and anti-tau agents., Trial Registration: Data used in this manuscript belong to a tau PET imaging sub-study of the elenbecestat MissionAD Phase 3 program registered in ClinicalTrials.gov ( NCT02956486 ;  NCT03036280 )., (© 2022. The Author(s).)

Background: Bioprosthetic valve thrombosis may have implications for valve function and durability., Objectives: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves., Methods: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT., Results: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake., Conclusions: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875)., Competing Interests: Funding Support and Author Disclosures This work was funded by the British Heart Foundation, London, United Kingdom (RG/16/10/32375 and PG/19/40/34422). The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland (NRS) through National Health Service Lothian Health Board. This work and Drs Bing, Tzolos, Williams, Dweck, and Newby are supported by the British Heart Foundation (PG/19/40/34422, FS/ICRF/20/26002, FS/CRTF/20/24086, FS/14/78/31020, CH/09/002, RG/16/10/32375, RE/18/5/34216, FS/SCRF/21/32010). Dr van Beek is supported by the Scottish Imaging Network. Dr Sellers is supported by fellowships from the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. Drs Koglin and Stephens are employees of Life Molecular Imaging GmbH, who provided reagents for radiotracer production. Dr Leipsic is supported by a Canadian Research Chair in Advanced CardioPulmonary Imaging and the Jon DeHaan Award for Innovation in Cardiology; is a consultant for Edward Lifesciences; and provides computed tomography core laboratory services to Edwards Lifesciences, Medtronic, Neovasc, Aegis, and Tendyne, for which no direct compensation is received. Dr Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background The PET tracer (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) targets the system x C - cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18 F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors ( n = 17) or brain metastases ( n = 9) were enrolled in this prospective, single-center study (ClinicalTrials.gov identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18 F-FSPG PET/CT scan and a static whole-body (WB) 18 F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18 F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18 F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18 F-FDG PET was performed, 18 F-FSPG permitted visualization of non- 18 F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant K i and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18 F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group ( P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18 F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.