Diagnostic accuracy of [18F]PSMA-1007 PET/CT in biochemical recurrence of prostate cancer.

AIM Despite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [18F]PSMA-1007 remains only partially investigated. The aim of this study was to determine the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for PC-local recurrence and metastases on a per region basis. MATERIALS AND METHODS One hundred seventy-seven consecutive patients undergoing [18F]PSMA-1007 PET/CT for rPC were retrospectively analysed. Six body regions were defined: prostate fossa, pelvic lymph nodes (LN), retroperitoneal LN, supradiaphragmatic LN, bones, and soft tissue. A region was counted positive if at least one PSMA-positive lesion suspicious for PC was observed. Confirmation of a true-positive PSMA-avid lesion was defined as positive by histopathology, fall in serum prostate-specific antigen (PSA) (> 50%) after targeted therapy or confirmatory further CT, MRI, PET/CT, or bone scan imaging. Regions where additional imaging was able to confirm the absence of suspicious PC lesions or regions outside exclusively targeted RT with serum PSA decline (> 50%) were counted as true-negative regions. SE, SP, PPV, and NPV were calculated for all six regions. RESULTS The overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90-0.98), 89% (CI: 0.83-0.93), 86% (0.80-0.90), and 96% (CI: 0.92-0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83-0.99) for local recurrence, 93% (CI: 0.78-0.98) for pelvic LN, 87% (CI: 0.62-0.96) for retroperitoneal LN, 82% (CI: 0.52-0.95) for supradiaphragmatic LN, and 79% (0.65-0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis. CONCLUSION The known high PET-positivity rate of [18F]PSMA-1007 PET/CT in rPC was confirmed, with corresponding high (> 90%) sensitivity and NPV on a per region basis. However, overall PPV was limited (86%), particularly for bone lesions (79%), which are a potential diagnostic weaknesses when using this tracer

A cross-scanner and cross-tracer deep learning method for the recovery of standard-dose imaging quality from low-dose PET

PURPOSE: A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers. METHODS: Brain [(18)F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [(18)F]FDG PET images of 45 patients scanned with three different scanners, [(18)F]FET PET images of 18 patients scanned with two different scanners, as well as [(18)F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting. RESULTS: The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = −0.71, p < 0.05) and normalized dose acquisition (r = −0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05). CONCLUSION: The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05644-1

Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

PURPOSE The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET. MATERIALS AND METHODS A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aβ42 ( 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses. RESULTS Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis. CONCLUSION Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group

Emergence of fractal geometries in the evolution of a metabolic enzyme

Fractals are patterns that are self-similar across multiple length-scales. Macroscopic fractals are common in nature; however, so far, molecular assembly into fractals is restricted to synthetic systems. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution

H. N. Werkman

A piece commissioned for COLDFRONT – Singular Vispo :: First Encounters. Artists were asked to talk about their introduction to Visual Poetry and the piece of work that changed the way they saw language

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

The design, construction, and commissioning of the KATRIN experiment

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [1] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [2]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts