Tracer Distribution Research Articles

Submesoscale Vertical Heat Transport at the Kuroshio Extension: Characteristics and Mechanisms

AbstractSubmesoscale processes significantly influence the air‐sea interaction, heat budget and the distribution of physical and biogeochemical tracers in the upper‐ocean. We study the spatiotemporal characteristics and generation mechanisms of submesoscale vertical heat transport (SVHT) at the Kuroshio Extension using a submesoscale‐permitting simulation. Compared with the commonly used Boxcar and Hanning filters, the clean‐cut feature of the Butterworth filter in the wavenumber domain makes it a proper filter to diagnose SVHT. SVHT is systematically upward, peaking in winter. Through causality analysis, we find that, among the basic factors (mixed layer depth, strain rate, surface wind stress, and horizontal buoyancy gradient) from the conventional submesoscale generation mechanism scalings, mixed layer depth plays the leading role in modulating the intraseasonal variation of SVHT. Using the budget of submesoscale temperature variance and causality analysis, we find that advection also plays an important role in regulating SVHT. This work suggests that the choice of appropriate spatial filter is important for SVHT diagnosis and including advection may help improve submesoscale parameterization schemes.

PET Imaging of Neurofibromatosis Type 1 with a Fluorine-18 Labeled Tryptophan Radiotracer.

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [1⁸F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.

Anesthesia Blunts Carbon Dioxide Effects on Glymphatic Cerebrospinal Fluid Dynamics in Mechanically Ventilated Rats.

Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain edema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial cerebrospinal fluid (CSF)-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, this study examined the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences: vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane. End-tidal carbon dioxide (ETco2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (Etco2, 80 mmHg) or hyperventilation (Etco2, 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 min in (1) normoventilated (Etco2, 40 mmHg) K/DEX; (2) normoventilated isoflurane; (3) hypercapnic K/DEX; and (4) hyperventilated isoflurane groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging. Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries, and intracranial CSF volume were higher under K/DEX compared with isoflurane (cortical maximum percentage of injected dose ratio, 2.33 [95% CI, 1.35 to 4.04]; perivascular size ratio 2.20 [95% CI, 1.09 to 4.45]; and intracranial CSF volume ratio, 1.90 [95% CI, 1.33 to 2.71]). Under isoflurane, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under isoflurane despite a 28% increase in CSF volume around middle cerebral arteries. K/DEX and isoflurane overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia, whereas hyperventilation was insufficient to increase cerebral CSF perfusion under isoflurane.

ETFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors.

Integrating radioactive and optical imaging techniques can facilitate the prognosis and surgical guidance for cancer patients. Using a single dual-labeled tracer ensures consistency in both imaging modalities. However, developing such molecule is challenging due to the need to preserve the biochemical properties of the tracer while introducing bulky labeling moieties. In our study, we designed a trifunctional chelate that facilitates the coupling of the targeting vector and fluorescent dye at opposite sites to avoid undesired steric hindrance effects. The synthesis of the trifunctional chelate N3-Py-DOTAGA-(tBu)3 (7) involved a five-step synthetic route, followed by conjugation to the linear peptidyl-resin 8 through solid-phase synthesis. After deprotection and cyclization, the near-infrared fluorescent dye sulfo-Cy.5 was introduced using copper free click chemistry, resulting in eTFC-01. Subsequently, eTFC-01 was labeled with [111In]InCl3. In vitro assessments of eTFC-01 binding, uptake, and internalization were conducted in SSTR2-transfected U2OS cells. Ex-vivo biodistribution and fluorescence imaging were performed in H69-tumor bearing mice. eTFC-01 demonstrated a two-fold higher IC50 value for SSTR2 compared to the gold standard DOTA-TATE. Labeling of eTFC-01 with [111In]InCl3 gave a high radiochemical yield and purity. The uptake of [111In]In-eTFC-01 in U2OS.SSTR2 cells was two-fold lower than the uptake of [111In]In-DOTA-TATE, consistent with the binding affinity. Tumor uptake in H69-xenografted mice was lower for [111In]In-eTFC-01 at all-time points compared to [111In]In-DOTA-TATE. Prolonged blood circulation led to increased accumulation of [111In]In-eTFC-01 in highly vascularized tissues, such as lungs, skin, and heart. Fluorescence measurements in different organs correlated with the radioactive signal distribution. The successful synthesis and coupling of the trifunctional chelate to the peptide and fluorescent dye support the potential of this synthetic approach to generate dual labeled tracers. While promising in vitro, the in vivo results obtained with [111In]In-eTFC-01 suggest the need for adjustments to enhance tracer distribution.

Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics

Background and objectiveTreatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET.Methods23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map.ResultsInconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach.ConclusionOur results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map.

TAI-GAN: A Temporally and Anatomically Informed Generative Adversarial Network for early-to-late frame conversion in dynamic cardiac PET inter-frame motion correction

Inter-frame motion in dynamic cardiac positron emission tomography (PET) using rubidium-82 (82Rb) myocardial perfusion imaging impacts myocardial blood flow (MBF) quantification and the diagnosis accuracy of coronary artery diseases. However, the high cross-frame distribution variation due to rapid tracer kinetics poses a considerable challenge for inter-frame motion correction, especially for early frames where intensity-based image registration techniques often fail. To address this issue, we propose a novel method called Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) that utilizes an all-to-one mapping to convert early frames into those with tracer distribution similar to the last reference frame. The TAI-GAN consists of a feature-wise linear modulation layer that encodes channel-wise parameters generated from temporal information and rough cardiac segmentation masks with local shifts that serve as anatomical information. Our proposed method was evaluated on a clinical 82Rb PET dataset, and the results show that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, the motion estimation accuracy and subsequent myocardial blood flow (MBF) quantification with both conventional and deep learning-based motion correction methods were improved compared to using the original frames. The code is available at https://github.com/gxq1998/TAI-GAN.

How heating tracers drive self-lofting long-lived stratospheric anticyclones: simple dynamical models

Abstract. Long-lived “bubbles” of wildfire smoke or volcanic aerosol have recently been observed in the stratosphere, co-located with ozone, carbon monoxide, and water vapour anomalies. These bubbles often survive for several weeks, during which time they ascend through vertical distances of 15 km or more. Meteorological analysis data suggest that this aerosol is contained within strong, persistent anticyclonic vortices. Absorption of solar radiation by the aerosol is hypothesised to drive the ascent of the bubbles, but the dynamics of how this heating gives rise to a single-sign anticyclonic vorticity anomaly have thus far been unclear. We present a description of heating-driven stratospheric vortices, based on an axisymmetric balanced model. The simplest version of this model includes a specified localised heating moving upwards at fixed velocity and produces a steadily translating solution with a single-signed anticyclonic vortex co-located with the heating, with corresponding temperature anomalies forming a vertical dipole, matching observations. A more complex version includes the two-way interaction between a heating tracer, representing the aerosol, and the dynamics. An evolving tracer provides heating which drives a secondary circulation, and this in turn transports the tracer. Through this two-way interaction an initial distribution of tracer drives a circulation and forms a self-lofting tracer-filled anticyclonic vortex. Scaling arguments show that upward velocity is proportional to heating magnitude, but the magnitude of peak quasigeostrophic vorticity is O(f) (f is the Coriolis parameter) and independent of the heating magnitude. Estimates of vorticity from observations match our theoretical predictions. We discuss 3-D effects such as vortex stripping and dispersion of tracer outside the vortex by the large-scale flow, which cannot be captured explicitly by the axisymmetric model and are likely to be important in the real atmosphere. The large O(f) vorticity of the fully developed anticyclones explains their observed persistence and their effective confinement of tracers. To further investigate the early stages of formation of tracer-filled vortices, we consider an idealised configuration of a homogeneous tracer layer. A linearised calculation reveals that the upper part of the layer is destabilised due to the decrease in tracer concentrations with height there, which sets up a self-reinforcing effect where upward lofting of tracer results in stronger heating and hence stronger lofting. Small amplitude disturbances form isolated tracer plumes that ascend out of the initial layer, indicative of a self-organisation of the flow. The relevance of these idealised models to formation and persistence of tracer-filled vortices in the real atmosphere is discussed, and it is suggested that a key factor in their formation is the time taken to reach the fully developed stage, which is shorter for strong heating rates.

Population-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification

The high noise level of dynamic Positron Emission Tomography (PET) images degrades the quality of parametric images. In this study, we aim to improve the quality and quantitative accuracy of Ki images by utilizing deep learning techniques to reduce the noise in dynamic PET images. We propose a novel denoising technique, Population-based Deep Image Prior (PDIP), which integrates population-based prior information into the optimization process of Deep Image Prior (DIP). Specifically, the population-based prior image is generated from a supervised denoising model that is trained on a prompts-matched static PET dataset comprising 100 clinical studies. The 3D U-Net architecture is employed for both the supervised model and the following DIP optimization process. We evaluated the efficacy of PDIP for noise reduction in 25%-count and 100%-count dynamic PET images from 23 patients by comparing with two other baseline techniques: the Prompts-matched Supervised model (PS) and a conditional DIP (CDIP) model that employs the mean static PET image as the prior. Both the PS and CDIP models show effective noise reduction but result in smoothing and removal of small lesions. In addition, the utilization of a single static image as the prior in the CDIP model also introduces a similar tracer distribution to the denoised dynamic frames, leading to lower Ki in general as well as incorrect Ki in the descending aorta. By contrast, as the proposed PDIP model utilizes intrinsic image features from the dynamic dataset and a large clinical static dataset, it not only achieves comparable noise reduction as the supervised and CDIP models but also improves lesion Ki predictions.

Image analysis technique for quantifying fluorescein concentration profiles in clays

The image analysis technique approach links the dye concentration and color intensity, enabling quantification of spatial and temporal dye dynamics in clay media. In this study, batch adsorption tests and two-dimensional diffusion experiments with three types of clays (kaolinite, montmorillonite, and bentonite) were conducted for quantifying the vertical distribution of fluorescein dye tracer to evaluate the feasibility of the image analysis technique. In clay domains, color intensities were measured using images obtained during diffusion experiments, and these intensities were converted to aqueous fluorescein concentrations. Concentration profiles simulated from a one-dimensional analytical solution agreed well with those measured by the LRV technique with a single-channel application for kaolinite (blue channel, EB = 0.94 and 0.96) and montmorillonite (green channel, EG = 0.99 and 0.91) in the early (31.1, 54.6 PVs) and later (75.7, 93.9 PVs) diffusion times, respectively. The single-channel application for the bentonite was appropriate for concentration ranges of 0 − 400 mg/L for the blue channel and 400 − 1800 mg/L for the green channel. For quantifying the bentonite concentration profile with a wide range of dye concentrations (0 − 1800 mg/L), multi-channel application (blue + green channels) was required. Measured LRV concentration profiles with the multi-channel application showed better agreement (EB+G = 0.94) with simulated concentration profiles from the analytical solution than those with the single-channel application (EB = 0.56). The results of this study offer guidance on the application of the LRV approach as a non-destructive optical dye measurement method to diffusion problems between high and low permeability zones.

Evaluating the biodistribution for [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET/CT with an inter- and intrapatient based analysis

BackgroundLiver uptake in [68Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [177Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [68Ga]Ga-PSMA-11 was replaced by [18F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007.MethodsFifty patients who underwent PET examinations in two centers with both [18F]F-PSMA-1007 and [68Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUVmean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison.ResultsLiver SUVmean was significantly higher with [18F]F-PSMA-1007 (11.7 ± 3.9) compared to [68Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUVmean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUVmean on [18F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUVmean [68Ga]Ga-PSMA-11 = 0.33 x SUVmean [18F]F-PSMA-1007 + 1.52 (r = .78, p < .001).ConclusionComparing biodistribution of [68Ga]Ga and [18F]F tracers, liver uptake on [68Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [18F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [18F]F-PSMA-1007 as a basis for RLT selection.

PET and SPECT imaging as a solid guide to detect and discriminate atypical phenotypes of neurodegenerative disorders

Introduction and aim. Atypical or mixed presentations of neurodegenerative disorders may postpone or confound the final diagnosis. Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radioligands provide target-specific information and may anticipate the diagnosis by “in vivo” detection of the neuro pathological substrate, as Aβ deposition, nigrostriatal dopaminergic depletion or tau inclusions. This concise review will dis cuss the potential of PET and SPECT imaging as a solid guide to better characterize atypical phenotypes of neurodegeneration in the clinical routine, with the potential to drive personalized interventions, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies. Material and methods. Literature search was performed focusing on the role of PET and SPECT imaging in assessing atypical phenotypes of neurodegeneration, using the electronic source of database PubMed/MEDLINE and the web-based search engines Google, Google Scholar. Analysis of the literature. New disease-modifying drugs may increase their effect with early initiation, which is especially im portant in working persons and younger subjects presenting atypical symptoms. In older individuals, the coexistence of neu rodegeneration, age-related changes, cerebrovascular lesions, or depression makes challenging a definitive diagnosis. Quantitative tools able to measure tracer distribution increase the accuracy of molecular neuroimaging creating topographic maps that compare subject’s data with healthy controls databases. Conclusion. Atypical phenotypes may be associated with quantitative key-pattern allowing a more precise and early diagnosis of the neurodegenerative disorder. Finally, quantitative assessment of the pathological substrates allows us to track the disease process and measure treatment response.

Evaluating the Model Representation of Asian Summer Monsoon Upper Troposphere and Lower Stratosphere Transport and Composition Using Airborne In Situ Observations

AbstractChemistry Climate Models (CCMs) are essential tools for characterizing and predicting the role of atmospheric composition and chemistry in Earth's climate system. This study demonstrates the use of airborne in situ observations to diagnose the representation of chemical composition and transport by CCMs. Process‐based diagnostics using dynamical and chemical coordinates are presented which minimize the spatial and temporal sampling differences between airborne in situ measurements and CCM grid points. The chosen process is the chemical impact of the Asian summer monsoon (ASM), where deep convection serves as a rapid transport pathway for surface emissions to reach the upper troposphere and lower stratosphere (UTLS). We examine two CCM configurations for their representation of the ASM UTLS using a set of airborne observations from south Asia. The diagnostics reveal good model performance at representing tropospheric tracer distribution throughout the troposphere and lower stratosphere, and excellent representation of chemical aging in the lower stratosphere when chemical loss is dominated by photolysis. Identified model limitations include the use of zonally averaged mole fraction boundary conditions for species with sufficiently short tropospheric lifetimes, which may obscure enhanced regional emissions sources. Overall, the diagnostics underscore the skill of current‐generation models at representing pollution transport from the boundary layer to the stratosphere via the ASM mechanism, and demonstrate the strength of airborne in situ observations toward characterizing this representation.

Seasonal Study of the Kako River Discharge Dynamics into Harima Nada Using a Coupled Atmospheric–Marine Model

This study developed a coupled atmospheric–marine model using the COAWST model system for the Harima Nada area between spring 2010 and winter 2011 to evaluate the seasonal influence of the Kako River’s discharge in the sea. The Kako River is one of the largest rivers in southwest Japan, contributing almost half of the freshwater discharged in the Harima Nada region in the Seto Inland Sea. Validation was conducted for the entire period, showing a good performance for the atmospheric and marine variables selected. Multiple experiments injecting an inert tracer in the Kako River estuary were performed to simulate the seasonal river water distribution from the estuary into the sea and to analyze the seasonal differences in concentration patterns and mean residence times in Harima Nada. Because the study area is shallow, the results were evaluated at the surface and 10 m depth layers and showed significant seasonal differences in tracer distribution, circulation patterns, and mean residence times for the region. On the other hand, differences seemed to not be significant during the same season at different depths. The obtained results also agreed with the area’s natural water circulation, showing that the Kako River waters tend to distribute towards the west coast of Harima Nada in the warmer seasons but shift towards the east in winter. The influence of the Kako River in the center of the study area is seasonal and strongly dependent on the direction of the horizontal velocities more than their magnitude. The mean residence times varied seasonally from approximately 30 days in spring to 12 days in fall. The magnitude of the horizontal velocity was found to be maximum during summer when circulation patterns at the surface and 10 m depth in the central part of Harima Nada also seem to promote the strongest horizontal and vertical mixes.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature

BackgroundInside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.MethodsBlood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg−1 min−1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg−1 min−1) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy.ResultsNicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (− 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes.ConclusionsThis is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid flow.

The interhemispheric gradient of SF6 in the upper troposphere

Abstract. Anthropogenic trace gases often exhibit interhemispheric gradients because of larger emissions in the Northern Hemisphere. Depending on a tracer's emission pattern and sink processes, trace gas observations can thus be used to investigate interhemispheric transport in the atmosphere. Vice versa, understanding interhemispheric transport is important for interpreting spatial tracer distributions and for inferring emissions. We combine several data sets from the upper troposphere (UT) to investigate the interhemispheric gradient of sulfur hexafluoride (SF6) covering latitudes from ∼ 80∘ N to ∼ 60∘ S: canister sampling based measurements from the IAGOS-CARIBIC infrastructure and data from the in-flight gas chromatography instruments GhOST (Gas chromatograph for Observational Studies using Tracers) and UCATS (Unmanned aircraft systems Chromatograph for Atmospheric Trace Species). The interhemispheric gradient of SF6 in the UT is found to be weaker than near the surface. Using the concept of a lag time removes the increasing trend from the time series. At the most southern latitudes, a lag time of over 1 year with respect to the northern mid-latitude surface is derived, and lag times decrease over the period 2006–2020 in the extra-tropics and the southern tropics. Observations are compared to results from the two-dimensional Advanced Global Atmospheric Gases Experiment (AGAGE) 12-box model. Based on Emissions Database for Global Atmospheric Research (EDGAR 7) emissions, fair agreement of lag times is obtained for the Northern Hemisphere, but southern hemispheric air appears too “old”. This is consistent with earlier findings that transport from the northern extra-tropics into the tropics is too slow in many models. The influence of the emission scenario and the model transport scheme are evaluated in sensitivity runs. It is found that EDGAR 7 underestimates emissions of SF6 globally and in the Southern Hemisphere, whereas northern extra-tropical emissions seem overestimated. Faster southward transport from the northern extra-tropics would be needed in the model, but transport from the southern tropics into the southern extra-tropics appears too fast.

Postnatal meningeal CSF transport is primarily mediated by the arachnoid and pia maters and is not altered after intraventricular hemorrhage-posthemorrhagic hydrocephalus

BackgroundCSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine, is less understood. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to meningeal CSF solute distribution in a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF solute interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles.Methods1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 min post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 h post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also evaluated.ResultsThere was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH.ConclusionsDifferential CSF tracer handling by the meninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border.

Tracer Stirring and Variability in the Antarctic Circumpolar Current Near the Southwest Indian Ridge

AbstractOceanic macroturbulence is efficient at stirring and transporting tracers. The dynamical properties of this stirring can be characterized by statistically quantifying tracer structures. Here, we characterize the macroscale (1–100 km) tracer structures observed by two Seagliders downstream of the Southwest Indian Ridge in the Antarctic Circumpolar Current (ACC). These are some of the first glider observations in an energetic standing meander of the ACC, a region associated with enhanced ventilation. The small‐scale density variance in the mixed layer (ML) was relatively enhanced near the surface and base of the ML, while being muted at mid‐depth in the ML, suggesting the formation mechanism to be associated with ML instabilities and eddies. In addition, ML density fronts were formed by comparable contributions from temperature and salinity gradients. In the interior, along‐isopycnal spectra and structure functions of spice indicated that there is relatively lower variance at smaller scales than would be expected based on non‐local stirring, suggesting that flows smaller than the deformation radius play a role in the cascade of tracers to small scales. These interior spice anomalies spanned across isopycnals, and were found to be about 3–5 times flatter than the aspect ratio that would be expected for O(1) Burger number flows like interior QG dynamics, suggesting the ratio of vertical shear to horizontal strain is greater than N/f. This further supports that small‐scale flows, with high‐mode vertical structures, impact tracer distributions.

In vivo distribution of cerebrospinal fluid tracer in human upper spinal cord and brain stem.

BACKGROUNDIntrathecal injection is an attractive route through which drugs can be administered and directed to the spinal cord, restricted by the blood-spinal cord barrier. However, in vivo data on the distribution of cerebrospinal fluid (CSF) substances in the human spinal cord are lacking. We conducted this study to assess the enrichment of a CSF tracer in the upper cervical spinal cord and the brain stem.METHODSAfter lumbar intrathecal injection of a magnetic resonance imaging (MRI) contrast agent, gadobutrol, repeated blood samples and MRI of the upper cervical spinal cord, brain stem, and adjacent subarachnoid spaces (SAS) were obtained through 48 hours. The MRI scans were then analyzed for tracer distribution in the different regions and correlated to age, disease, and amounts of tracer in the blood to determine CSF-to-blood clearance.RESULTSThe study included 26 reference individuals and 35 patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH). The tracer enriched all analyzed regions. Moreover, tracer enrichment in parenchyma was associated with tracer enrichment in the adjacent SAS and with CSF-to-blood clearance. Clearance from the CSF was delayed in patients with iNPH compared with younger reference patients.CONCLUSIONA CSF tracer substance administered to the lumbar thecal sac can access the parenchyma of the upper cervical spinal cord and brain stem. Since CSF-to-blood clearance is highly individual and is associated with tracer level in CSF, clearance assessment may be used to tailor intrathecal treatment regimes.FUNDINGSouth-Eastern Norway Regional Health and Østfold Hospital Trust supported the research and publication of this work.

Dose reduction in dynamic synaptic vesicle glycoprotein 2A PET imaging using artificial neural networks

Objective. Reducing dose in positron emission tomography (PET) imaging increases noise in reconstructed dynamic frames, which inevitably results in higher noise and possible bias in subsequently estimated images of kinetic parameters than those estimated in the standard dose case. We report the development of a spatiotemporal denoising technique for reduced-count dynamic frames through integrating a cascade artificial neural network (ANN) with the highly constrained back-projection (HYPR) scheme to improve low-dose parametric imaging. Approach. We implemented and assessed the proposed method using imaging data acquired with 11C-UCB-J, a PET radioligand bound to synaptic vesicle glycoprotein 2A (SV2A) in the human brain. The patch-based ANN was trained with a reduced-count frame and its full-count correspondence of a subject and was used in cascade to process dynamic frames of other subjects to further take advantage of its denoising capability. The HYPR strategy was then applied to the spatial ANN processed image frames to make use of the temporal information from the entire dynamic scan. Main results. In all the testing subjects including healthy volunteers and Parkinson’s disease patients, the proposed method reduced more noise while introducing minimal bias in dynamic frames and the resulting parametric images, as compared with conventional denoising methods. Significance. Achieving 80% noise reduction with a bias of −2% in dynamic frames, which translates into 75% and 70% of noise reduction in the tracer uptake (bias, −2%) and distribution volume (bias, −5%) images, the proposed ANN+HYPR technique demonstrates the denoising capability equivalent to a 11-fold dose increase for dynamic SV2A PET imaging with 11C-UCB-J.

A tracer model nowcast/forecast study of the Tampa Bay, Piney Point effluent plume: Rapid response to an environmental hazard

An emergency discharge of nutrient-rich effluent from the defunct Piney Point fertilizer stack into Tampa Bay at Port Manatee occurred from 30 March–8 April 2021. This resulted in a pollutant plume that evolved over time and space across the entire bay, including its environmentally sensitive marine preserves, and out onto the adjacent continental shelf. As a rapid response to environmental concerns, the plume evolution was simulated using the high resolution, unstructured grid, Tampa Bay Coastal Ocean Model (TBCOM) nowcast/forecast system, with an embedded tracer module that included realistic point discharge rates. Normalized tracer distributions were automatically updated each day, providing 1-day hindcasts and 3.5-day forecasts. Due to mixing and advection, tracer concentration was quickly reduced by two or more orders of magnitude as the plume spread out. Highest tracer concentrations hugged the southeastern Tampa Bay shoreline during the first week. Lower tracer concentrations were gradually advected to the western side of Tampa Bay, and the tracer was slowly flushed out of the bay to be transported primarily northward along the coast. The modeled plume evolution served as principal guidance for coordinating environmental monitoring by state, local and academic personnel. The model results also provide a basis for future multidisciplinary studies.