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Coppery titi monkeys ( Plecturocebus cupreus ) are socially monogamous monkeys that display strong pair bonds similar to human romantic attachments, preceded by infant attachment to their fathers. To understand how father-daughter bonds impact adult relationship dynamics, we established a novel method for quantifying expression of bond-related behaviors. We assessed behavioral and neural correlates of preference, stress buffering, and separation distress to identify how females’ current and former attachment figures impact female attachment. Whereas all females ( n  = 9) shifted to preferring their partner over father six-months post-pairing, females that exhibited higher expression of juvenile parent preference maintained a relationship with their father six-months post-pairing, as evidenced by higher-than-expected father proximity. Higher expression of juvenile measures of proximity following a brief separation predicted slightly increased partner proximity in adulthood. Neural activity patterns in brain regions assessed pre- and post-pairing showed high similarity in glucose metabolism, despite overall activity being lower post-pairing. While there was some inconsistency in results, higher expression of juvenile proximity following a separation was associated with enhanced reduction in activity within social bonding brain regions (social salience network, periaqueductal gray, cerebellum), suggesting a potential stress buffering benefit via reduced threat-related brain activation, like that seen in high-quality human relationships. These findings advance current knowledge of how early relationships may shape adult bond-related behavior and neural activity.

Carpal instability is defined as a condition where wrist motion and/or loading creates mechanical dysfunction, resulting in weakness, pain and decreased function. When conventional methods do not identify the instability patterns, yet clinical signs of instability exist, the diagnosis of dynamic instability is often suggested to describe carpal derangement manifested only during the wrist's active motion or stress. We addressed the question: can advanced MRI techniques provide quantitative means to evaluate dynamic carpal instability and supplement standard static MRI acquisition? Our objectives were to (i) develop a real-time, three-dimensional MRI method to image the carpal joints during their active, uninterrupted motion; and (ii) demonstrate feasibility of the method for assessing metrics relevant to dynamic carpal instability, thus overcoming limitations of standard MRI. Twenty wrists (bilateral wrists of ten healthy participants) were scanned during radial-ulnar deviation and clenched-fist maneuvers. Images resulting from two real-time MRI pulse sequences, four sparse data-acquisition schemes, and three constrained image reconstruction techniques were compared. Image quality was assessed via blinded scoring by three radiologists and quantitative imaging metrics. Real-time MRI data-acquisition employing sparse radial sampling with a gradient-recalled-echo acquisition and constrained iterative reconstruction appeared to provide a practical tradeoff between imaging speed (temporal resolution up to 135 ms per slice) and image quality. The method effectively reduced streaking artifacts arising from data undersampling and enabled the derivation of quantitative measures pertinent to evaluating dynamic carpal instability. This study demonstrates that real-time, three-dimensional MRI of the moving wrist is feasible and may be useful for the evaluation of dynamic carpal instability.

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS + proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1 + microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3 + pro-inflammatory and S100A10 + anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

Purpose The kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, with growing evidence linking it to stress induced by social isolation and separation. Despite this, tools for studying KOR in clinically relevant social contexts remain limited. The socially monogamous coppery titi monkey offers a translational model for investigating pair bonding. This study evaluated the feasibility of [11C]GR103545 PET imaging to characterize KOR activity in vivo, and its pharmacological blockade for the first time in titi monkeys. Methods Adult titi monkeys (N = 6) underwent [11C]GR103545 PET brain scans at baseline and following administration of the KOR antagonist CERC-501. Non-displaceable binding potential (BPND) was calculated across 14 brain volumes of interest (VOIs) implicated in social bonding, using Simplified and Logan reference tissue models (SRTM and LRTM), with the cerebellum as the reference region. Results Baseline [11C]GR103545 uptake patterns across VOIs were consistent with reports in humans, other primates and published autoradiography data. CERC-501 pretreatment significantly reduced BPND (SRTM: 55.99%, LRTM: 59.68%) across several, but not all brain VOIs. Conclusions This study establishes [11C]GR103545 PET as a viable tool for assessing KOR binding dynamics in titi monkeys, providing new opportunities to explore KOR modulation in social bonding and separation.

Non-invasive imaging techniques such as magnetic resonance imaging (MRI) provide the ability to evaluate the complex anatomy of bone and soft tissues of the wrist without the use of ionizing radiation. Dynamic instability of wrist--occurring during joint motion--is a complex condition that has assumed increased importance in musculoskeletal medicine. The objective of this study was to develop an MRI protocol for evaluating the wrist during continuous active motion, to show that dynamic imaging of the wrist is realizable, and to demonstrate that the resulting anatomical images enable the measurement of metrics commonly evaluated for dynamic wrist instability. A 3-Tesla \"active-MRI\" protocol was developed using a bSSFP sequence with 475 ms temporal resolution for continuous imaging of the moving wrist. Fifteen wrists of 10 asymptomatic volunteers were scanned during active supination/pronation, radial/ulnar deviation, \"clenched-fist\", and volarflexion/dorsiflexion maneuvers. Two physicians evaluated distal radioulnar joint (DRUJ) congruity, extensor carpi ulnaris (ECU) tendon translation, the scapholunate (SL) interval, and the SL, radiolunate (RL) and capitolunate (CL) angles from the resulting images. The mean DRUJ subluxation ratio was 0.04 in supination, 0.10 in neutral, and 0.14 in pronation. The ECU tendon was subluxated or translated out of its groove in 3 wrists in pronation, 9 wrists in neutral, and 11 wrists in supination. The mean SL interval was 1.43 mm for neutral, ulnar deviation, radial deviation positions, and increased to 1.64 mm during the clenched-fist maneuver. Measurement of SL, RL and CL angles in neutral and dorsiflexion was also accomplished. This study demonstrates the initial performance of active-MRI, which may be useful in the investigation of dynamic wrist instability in vivo.

Objective18F-FDG PET is widely used to accurately stage numerous types of cancers. Although 18F-FDG PET/CT features of tumors aid in predicting patient prognosis, there is increasing interest in mining additional quantitative body composition data that could improve the prognostic power of 18F-FDG PET/CT, without additional examination costs or radiation exposure. The aim of this study was to determine the association between overall survival and body composition metrics derived from routine clinical 18F-FDG PET/CT examinations.MethodsPatients who received baseline 18F-FDG PET/CT imaging during workup for newly diagnosed esophageal adenocarcinoma (EAC) were included. From these studies, psoas cross-sectional area (CSA), muscle attenuation (MA), SUVmean, and SUVmax were obtained. Correlation with overall survival was assessed using a Cox Proportional Hazards model, controlling for age, body mass index, 18F-FDG dose, glucose level, diabetes status, in-hospital status, and tumor stage.ResultsAmong the 59 patients studied, psoas MA and SUVmax were found to be significant predictors of survival (HR 0.94, 95% CI 0.88–0.99, p = 0.04, and HR 0.37, 95% CI 0.14–0.97, p = 0.04, respectively) and remained independent predictors. Psoas CSA and SUVmean did not significantly influence survival outcomes.ConclusionsCharacterization of psoas muscles as a surrogate marker for sarcopenia on baseline 18F-FDG PET/CT imaging is relatively easily obtained and may offer additional prognostic value in patients with EAC.

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.

We present a large whole-body and total-body curated dataset of dual-modality 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) studies, consisting of 1,683 PET/CT images and the corresponding CT-derived segmentations of 130 target regions. This multi-center dataset includes images from individuals without overt disease and patients with a range of malignant and inflammatory pathologies, including arthritis, lymphoma, and melanoma, as well as cancers of the lung, head-neck, and genito-urinary tract. Target regions were first automatically segmented from CT images using an in-house software and subsequently verified and corrected by physicians-in-training. In total, the segmented regions encompass 130 volumes, including abdominal organs, muscles, bones, cardiac subregions, vessels, adipose tissue, and skeletal muscle around the third lumbar vertebra. PET/CT images and corresponding CT-derived segmentations are provided in anonymized NIfTI format. The dataset can be used for deep learning training, validation, or multi-modality image analysis and thus fills an important gap in available resources to advance the use of PET/CT data in clinical management.

We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. The system consisted of a lutetium oxyorthosilicate-based dual-planar head PET camera (crystal size, 3 x 3 x 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with (18)F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

BACKGROUNDTraffic-related air pollution (TRAP) is a risk factor for Alzheimer disease (AD), where unresolved brain inflammation has been linked to deficits in the levels of free lipid mediators that enable the resolution of inflammation. It is unknown whether these deficits are due to reductions in esterified lipid pools, the main source of free bioactive proresolving lipids in the brain, and whether they are related AD pathophysiology.METHODSThis unknown was tested by measuring brain esterified lipid mediators and pathogenic markers of AD in TgF344-AD and WT male and female rats exposed to filtered air or TRAP for 14 months; it was also tested in human postmortem prefrontal cortex of individuals with or without AD.RESULTSSignificant reductions in proresolving lipid mediators esterified to neutral lipids and/or phospholipids were seen in AD and TRAP-exposed female rats, where levels were associated with inflammation, synaptic loss, and impaired glucose metabolism. Lower esterified proresolving lipid mediator concentrations were associated with older age in prefrontal cortex of humans with AD compared with controls.CONCLUSIONImpaired resolution in AD is due to depletion of esterified proresolving lipid pools that supply the brain with free bioactive mediators involved in inflammation resolution. TRAP exposure alters the same esterified resolution pathways, reflecting convergent mechanisms underlying AD.