Voxel-wise body composition analysis using image registration of a three-slice CT imaging protocol: methodology and proof-of-concept studies.

BACKGROUND: Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data. METHODS: The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies. RESULTS: Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information. CONCLUSION: The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors.

Spatial mapping of tumor heterogeneity in whole-body PET-CT: a feasibility study.

BACKGROUND: Tumor heterogeneity is recognized as a predictor of treatment response and patient outcome. Quantification of tumor heterogeneity across all scales may therefore provide critical insight that ultimately improves cancer management. METHODS: An image registration-based framework for the study of tumor heterogeneity in whole-body images was evaluated on a dataset of 490 FDG-PET-CT images of lung cancer, lymphoma, and melanoma patients. Voxel-, lesion- and subject-level features were extracted from the subjects' segmented lesion masks and mapped to female and male template spaces for voxel-wise analysis. Resulting lesion feature maps of the three subsets of cancer patients were studied visually and quantitatively. Lesion volumes and lesion distances in subject spaces were compared with resulting properties in template space. The strength of the association between subject and template space for these properties was evaluated with Pearson's correlation coefficient. RESULTS: Spatial heterogeneity in terms of lesion frequency distribution in the body, metabolic activity, and lesion volume was seen between the three subsets of cancer patients. Lesion feature maps showed anatomical locations with low versus high mean feature value among lesions sampled in space and also highlighted sites with high variation between lesions in each cancer subset. Spatial properties of the lesion masks in subject space correlated strongly with the same properties measured in template space (lesion volume, R = 0.986, p < 0.001; total metabolic volume, R = 0.988, p < 0.001; maximum within-patient lesion distance, R = 0.997, p < 0.001). Lesion volume and total metabolic volume increased on average from subject to template space (lesion volume, 3.1 ± 52 ml; total metabolic volume, 53.9 ± 229 ml). Pair-wise lesion distance decreased on average by 0.1 ± 1.6 cm and maximum within-patient lesion distance increased on average by 0.5 ± 2.1 cm from subject to template space. CONCLUSIONS: Spatial tumor heterogeneity between subsets of interest in cancer cohorts can successfully be explored in whole-body PET-CT images within the proposed framework. Whole-body studies are, however, especially prone to suffer from regional variation in lesion frequency, and thus statistical power, due to the non-uniform distribution of lesions across a large field of view.

Cascading effects of earthworm invasion increase graminoid density and rodent grazing intensities.

Human-mediated dispersal of non-native earthworms can cause substantial changes to the functioning and composition of ecosystems previously earthworm-free. Some of these earthworm species have the potential to "geoengineer" soils and increase plant nitrogen (N) uptake. Yet the possible consequences of increased plant N concentrations on rodent grazing remains poorly understood. In this study, we present findings from a common garden experiment with two tundra communities, meadow (forb dominated) and heath (shrub dominated), half of them subjected to 4 years of earthworm presence (Lumbricus spp. and Aporrectodea spp.). Within four summers, our earthworm treatment changed plant community composition by increasing graminoid density by, on average, 94% in the heath vegetation and by 49% in the meadow. Rodent winter grazing was more intense on plants growing in soils with earthworms, an effect that coincided with higher N concentrations in plants, indicating a higher palatability. Even though earthworms reduced soil moisture, plant community productivity, as indicated by vegetation greenness (normalized difference vegetation index), was not negatively impacted. We conclude that earthworm-induced changes in plant composition and trophic interactions may fundamentally alter the functioning of tundra ecosystems.

Neurological function before and after an in-hospital cardiac arrest - a nationwide registry-based cohort study.

BACKGROUND: According to the Utstein Registry Template for in-hospital cardiac arrest (IHCA), a good neurological outcome is defined as either Cerebral Performance Category (CPC) 1-2 at discharge from hospital or unchanged CPC compared to baseline. However, the latter alternative has rarely been described in IHCA. This study aimed to examine CPC at admission to hospital, the occurrence of post-arrest neurological deterioration, and the factors associated with such deterioration. METHODS: We studied adult IHCA survivors registered in the Swedish Registry of Cardiopulmonary Resuscitation between 2007 and 2022. The CPC was assessed based on information from admission and discharge from hospital. The data were analyzed using descriptive statistics and significance tests. RESULTS: One in ten IHCA had a CPC score >1 at admission to hospital. Out of 7,677 IHCA who survived until hospital discharge and had full CPC data, 6,774 (88%) had preserved CPC, 150 (2%) had improved CPC, and 753 (10%) had deteriorated CPC. Among the factors significantly associated with deteriorated neurological function are IHCA in a general ward or intensive care unit, non-shockable rhythm, no ECG surveillance, and a higher proportion of intra-arrest and post-resuscitation treatments (all p-values < 0,05). CONCLUSION: Most patients had preserved neurological function compared to admission. Factors associated with deteriorated neurological function are mainly concordant with established risk factors for adverse outcomes and are primarily intra-arrest and post-resuscitation, making deterioration hard to predict. Further, every tenth survivor was admitted with CPC more than 1, stressing the use of unchanged CPC as an outcome in IHCA.

Improved automated tumor segmentation in whole-body 3D scans using multi-directional 2D projection-based priors.

Early cancer detection, guided by whole-body imaging, is important for the overall survival and well-being of the patients. While various computer-assisted systems have been developed to expedite and enhance cancer diagnostics and longitudinal monitoring, the detection and segmentation of tumors, especially from whole-body scans, remain challenging. To address this, we propose a novel end-to-end automated framework that first generates a tumor probability distribution map (TPDM), incorporating prior information about the tumor characteristics (e.g. size, shape, location). Subsequently, the TPDM is integrated with a state-of-the-art 3D segmentation network along with the original PET/CT or PET/MR images. This aims to produce more meaningful tumor segmentation masks compared to using the baseline 3D segmentation network alone. The proposed method was evaluated on three independent cohorts (autoPET, CAR-T, cHL) of images containing different cancer forms, obtained with different imaging modalities, and acquisition parameters and lesions annotated by different experts. The evaluation demonstrated the superiority of our proposed method over the baseline model by significant margins in terms of Dice coefficient, and lesion-wise sensitivity and precision. Many of the extremely small tumor lesions (i.e. the most difficult to segment) were missed by the baseline model but detected by the proposed model without additional false positives, resulting in clinically more relevant assessments. On average, an improvement of 0.0251 (autoPET), 0.144 (CAR-T), and 0.0528 (cHL) in overall Dice was observed. In conclusion, the proposed TPDM-based approach can be integrated with any state-of-the-art 3D UNET with potentially more accurate and robust segmentation results.

Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis.

BACKGROUND: Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin. OBJECTIVE: To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment. METHODS: Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO2), and photoplethysmographic digital pulse wave analysis variables were recorded before and at 1, 5, 20, and 60 min after drug administration. Vasopressor use, uterine tonus, total bleeding, and need for additional uterotonics were also assessed. Repeated measurement ANOVA was used for statistical analyses. RESULTS: The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO2, or subjective cardiac symptoms. Uterine tonus, need for additional uterotonics, or total bleeding did not differ significantly between the groups. CONCLUSION: Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Is frailty associated with long-term survival, neurological function and patient-reported outcomes after in-hospital cardiac arrest? - A Swedish cohort study.

BACKGROUND: Frailty is associated with poor 30-days survival after in-hospital cardiac arrests (IHCA). The aim was to assess how pre-arrest frailty was associated with long-term survival, neurological function and patient-reported outcomes in elderly survivors after IHCA. METHODS: Patients aged ≥ 65 years with IHCA at Karolinska University Hospital between 2013-2021 were studied. Frailty was assessed by the Clinical Frailty Scale (CFS) based on clinical records and categorised into non-frail (1-4) or frail (5-7). Survival was assessed in days. Neurological function was assessed by the Cerebral Performance Category scale (CPC). A telephone interview was performed six months post-IHCA and included the questionnaires EuroQoL-5 Dimensions-5 Levels and Hospital Anxiety and Depression Scale. RESULTS: Totally, 232 (28%) out of 817 eligible patients survived to 30-days. Out of 232, 65 (28%) were frail. Long-term survival was better for non-frail than frail patients (6 months (92% versus 75%, p-value < 0.01), 3 years (74% vs 22%, p-value < 0.01)). The vast majority of both non-frail and frail patients had unchanged CPC from admittance to discharge from hospital (87% and 85%, respectively, p-value 0.52). The 121 non-frail patients reported better health compared to 27 frail patients (EQ-VAS median 70 versus 50 points, p-value < 0.01) and less symptoms of depression than frail (16% and 52%, respectively, p-value < 0.01). CONCLUSION: Frail patients suffering IHCA survived with the same neurological function they had at admittance. Although one in five frail patients survived to three years, frailty was associated with a marked decrease in long-term survival as well as increased symptoms of depression and poorer general health.

An image registration method for voxel-wise analysis of whole-body oncological PET-CT.

Whole-body positron emission tomography-computed tomography (PET-CT) imaging in oncology provides comprehensive information of each patient's disease status. However, image interpretation of volumetric data is a complex and time-consuming task. In this work, an image registration method targeted towards computer-aided voxel-wise analysis of whole-body PET-CT data was developed. The method used both CT images and tissue segmentation masks in parallel to spatially align images step-by-step. To evaluate its performance, a set of baseline PET-CT images of 131 classical Hodgkin lymphoma (cHL) patients and longitudinal image series of 135 head and neck cancer (HNC) patients were registered between and within subjects according to the proposed method. Results showed that major organs and anatomical structures generally were registered correctly. Whole-body inverse consistency vector and intensity magnitude errors were on average less than 5 mm and 45 Hounsfield units respectively in both registration tasks. Image registration was feasible in time and the nearly automatic pipeline enabled efficient image processing. Metabolic tumor volumes of the cHL patients and registration-derived therapy-related tissue volume change of the HNC patients mapped to template spaces confirmed proof-of-concept. In conclusion, the method established a robust point-correspondence and enabled quantitative visualization of group-wise image features on voxel level.

Non-native species change the tune of tundra soils: Novel access to soundscapes of the Arctic earthworm invasion.

Over the last decade, an increasing number of studies have used soundscapes to address diverse ecological questions. Sound represents one of the few sources of information capable of providing in situ insights into processes occurring within opaque soil matrices. To date, the use of soundscapes for soil macrofauna monitoring has been experimentally tested only in controlled laboratory environments. Here we assess the validity of laboratory predictions and explore the use of soil soundscape proxies for monitoring soil macrofauna (i.e., earthworm) activities in an outdoor context. In a common garden experiment in northern Sweden, we constructed outdoor mesocosm plots (N = 36) containing two different Arctic vegetation types (meadow and heath) and introduced earthworms to half of these plots. Earthworms substantially altered the ambient soil soundscape under both vegetation types, as measured by both traditional soundscape indices and frequency band power levels, although their acoustic impacts were expressed differently in heath versus meadow soils. While these findings support the as-of-yet untapped promise of using belowground soundscape analyses to monitor soil ecosystem health, direct acoustic emissions from earthworm activities appear to be an unlikely proxy for tracking worm activities at daily timescales. Instead, earthworms indirectly altered the soil soundscape by 're-engineering' the soil matrix: an effect that was dependent on vegetation type. Our findings suggest that long-term (i.e., seasonal) earthworm activities in natural soil settings can likely be monitored indirectly via their impacts on soundscape measures and acoustic indices. Analyzing soil soundscapes may enable larger-scale monitoring of high-latitude soils and is directly applicable to the specific case of earthworm invasions within Arctic soils, which has recently been identified as a potential threat to the resilience of high-latitude ecosystems. Soil soundscapes could also offer a novel means to monitor soils and soil-plant-faunal interactions in situ across diverse pedogenic, agronomic, and ecological systems.

Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy.

Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological response during the menstrual cycle and in pregnancy remains elusive. By surface proteome and transcriptome analysis as well as using humanized mice, we identify a differentiation pathway of uNK cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39. uNK cell differentiation occurred continuously in response to the endometrial regeneration and was driven by interleukin-15. Differentiated uNK cells displayed reduced proliferative capacity and immunomodulatory function including enhanced angiogenic capacity. By studying human uterus transplantation and monozygotic twins, we found that the uNK cell niche could be replenished from circulation and that it was under genetic control. Together, our study uncovers a continuous differentiation pathway of human NK cells in the uterus that is coupled to profound functional changes in response to local tissue regeneration and pregnancy.

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption.

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson's disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.