Calibration of Gamma Ray Impacts in Monolithic-Based Detectors Using Voronoi Diagrams

[EN] Molecular imaging systems, such as positron emission tomography (PET), use detectors providing energy and a 3-D interaction position of a gamma ray within a scintillation block. Monolithic crystals are becoming an alternative to crystal arrays in PET. However, calibration processes are required to correct for nonuniformities, mainly produced by the truncation of the scintillation light distribution at the edges. We propose a calibration method based on the Voronoi diagrams. We have used $50 \times 50 \times 15$ mm(3) LYSO blocks coupled to a $12\times 12$ SiPMs array. We have first studied two different interpolation algorithms: 1) weighted average method (WAM) and 2) natural neighbor (NN). We have compared them with an existing calibration based on 1-D monomials. Here, the crystal was laterally black painted and a retroreflector (RR) layer added to the entrance face. The NN exhibited the best results in terms of XY impact position, depth of Interaction, and energy, allowing us to calibrate the whole scintillation volume. Later, the NN interpolation has been tested against different crystal surface treatments, allowing always to correct edge effects. Best energy resolutions were observed when using the reflective layers (12%-14%). However, better linearity was observed with the treatments using black paint. In particular, we obtained the best overall performance when lateral black paint is combined with the RR.This work was supported in part by the European Research Council through the European Union's Horizon 2020 Research and Innovation Program under Grant 695536, and in part by the Spanish Ministerio de Economia, Industria y Competitividad under Grant TEC2016-79884-C2-1-R.Freire, M.; Gonzalez-Montoro, A.; Sánchez Martínez, F.; Benlloch Baviera, JM.; González Martínez, AJ. (2020). Calibration of Gamma Ray Impacts in Monolithic-Based Detectors Using Voronoi Diagrams. IEEE Transactions on Radiation and Plasma Medical Sciences. 4(3):350-360. https://doi.org/10.1109/TRPMS.2019.2947716S3503604

Does the ACE I/D polymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults?

We investigated the association of the angiotensin converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism, alone or in combination with the α-actinin-3 gene (ACTN3) R577X polymorphism, with jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N = 281 (214 male), mean (SD) age 21 (2) years]. We did not observe any effect of the ACE I/D polymorphism on study phenotypes. We repeated the analyses separately in men and women and the results did not materially change. Likewise, the mean estimates of the study phenotypes were similar in subjects with the genotype combinations ACE II + ID and ACTN3 XX or ACE DD and ACTN3 RR + RX. We found no association between the ACE DD and ACTN3 RR + RX genotype combination and performance (≥90th of the sex-specific percentile). In summary, though the ACE I/D polymorphism is a strong candidate to modulate some exercise-related phenotypes or athletic performance status, this polymorphism, alone or in combination with the ACTN3 R577X polymorphism, does not seem to exert a major influence in the muscle ‘explosive’ power of young healthy adults, as assessed during multi-joint exercise tests

The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes

Bioavailable testosterone linearly declines over a wide age spectrum in men and women from the Baltimore longitudinal study of aging

Background: Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation-measured bioavailable testosterone (mBT), and sex hormone-binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults. Methods: Participants included 788 White men and women aged 30-96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women. Results: mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT. Conclusion: In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated

Physical Activity Associated Proteomics of Skeletal Muscle: Being Physically Active in Daily Life May Protect Skeletal Muscle From Aging

Muscle strength declines with aging and increasing physical activity is the only intervention known to attenuate this decline. In order to adequately investigate both preventive and therapeutic interventions against sarcopenia, a better understanding of the biological changes that are induced by physical activity in skeletal muscle is required. To determine the effect of physical activity on the skeletal muscle proteome, we utilized liquid-chromatography mass spectrometry to obtain quantitative proteomics data on human skeletal muscle biopsies from 60 well-characterized healthy individuals (20–87 years) who reported heterogeneous levels of physical activity (not active, active, moderately active, and highly active). Over 4,000 proteins were quantified, and higher self-reported physical activity was associated with substantial overrepresentation of proteins associated with mitochondria, TCA cycle, structural and contractile muscle, and genome maintenance. Conversely, proteins related to the spliceosome, transcription regulation, immune function, and apoptosis, DNA damage, and senescence were underrepresented with higher self-reported activity. These differences in observed protein expression were related to different levels of physical activity in daily life and not intense competitive exercise. In most instances, differences in protein levels were directly opposite to those reported in the literature observed with aging. These data suggest that being physically active in daily life has strong and biologically detectable beneficial effects on muscle

Correlations of Calf Muscle Macrophage Content with Muscle Properties and Walking Performance in Peripheral Artery Disease

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD. Methods and Results Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients with PAD, both the absolute number and percentage of cluster of differentiation (CD) 11b+CD206+ M2‐like macrophages positively correlated to satellite cell number (r=0.461 [P=0.023] and r=0.416 [P=0.042], respectively) but not capillary density or extracellular matrix. The number of CD11b+CD206− macrophages negatively correlated to 4‐meter walk tests at normal (r=−0.447, P=0.036) and fast pace (r=−0.510, P=0.014). Extracellular matrix occupied more muscle area in PAD compared with non‐PAD (8.72±2.19% versus 5.30±1.03%, P \u3c 0.001) and positively correlated with capillary density (r=0.656, P \u3c 0.001). Conclusions Among people with PAD, higher CD206+ M2‐like macrophage abundance was associated with greater satellite cell numbers and muscle fiber size. Lower CD206− macrophage abundance was associated with better walking performance. Further study is needed to determine whether CD206+ macrophages are associated with ongoing reparative processes enabling skeletal muscle adaptation to damage with PAD. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00693940, NCT01408901, NCT0224660

Conserved and species-specific molecular denominators in mammalian skeletal muscle aging

Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species. Two downregulated pathways, the electron transport chain and oxidative phosphorylation, were common among all four species in response to aging. Quantitative PCR, biochemical analysis, mitochondrial DNA measurements, and electron microscopy revealed a conserved age-dependent decrease in mitochondrial content, and a reduction in oxidative phosphorylation complexes in monkeys and humans. Western blot analysis of key proteins in mitochondrial biogenesis discovered that (i) an imbalance toward mitochondrial fusion occurs in aged skeletal muscle and (ii) mitophagy is not overtly affected, presumably leading to the observed accumulation of abnormally large, damaged mitochondria with age. Select transcript expression analysis uncovered that the skeletal inflammatory profile differentially increases with age, but is most pronounced in humans, while increased oxidative stress (as assessed by protein carbonyl adducts and 4-hydroxynonenal) is common among all species. Expression studies also found that there is unique dysregulation of the nutrient sensing pathways among the different species with age. The identification of conserved pathways indicates common molecular mechanisms intrinsic to health and lifespan, whereas the recognition of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process

[2]共同利用研究(平成9年度)

Additional file 3: Figure S3. Correlations between minimum feret diameter of gastrocnemius fibers from PAD subjects and walking performance (n=26, approximately 1000 fibers per subject). A) type I fiber minimum feret diameter versus normal-paced 4-m walking velocity; B) type I fiber minimum feret diameter versus fastest-paced 4-m walking velocity; C) average fiber minimum feret diameter versus normal-paced 4-m walking velocity; and D) average fiber minimum feret diameter versus fastest-paced 4-m walking velocity