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1.
Geohealth ; 8(7): e2024GH001033, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979060

RESUMO

The increasing frequency and severity of wildfires due to climate change pose health risks to migrant farm workers laboring in wildfire-prone regions. This study focuses on Sonoma County, California, investigating the effectiveness of air monitoring and safety protections for farmworkers. The analysis employs AirNow and PurpleAir PM2.5 data acquired during the 2020 wildfire season, comparing spatial variability in air pollution. Results show significant differences between the single Sonoma County AirNow station data and the PurpleAir data in the regions directly impacted by wildfire smoke. Three distinct wildfire pollution episodes with elevated PM2.5 levels are identified to examine the regional variations. This study also examines the system used to exempt farmworkers from wildfire mandatory evacuation orders, finding incomplete information, ad hoc decision-making, and scant enforcement. In response, we make policy recommendations that include stricter requirements for employers, real-time air quality monitoring, post-exposure health screenings, and hazard pay. Our findings underscore the need for significant consideration of localized air quality readings and the importance of equitable disaster policies for protecting the health of farmworkers (particularly those who are undocumented migrants) in the face of escalating wildfire risks.

2.
Metallomics ; 15(10)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37715341

RESUMO

The gadolinium-based contrast agent Gadoxetic acid and the platinum-based antitumor agent Cisplatin were quantitatively imaged in liver and liver cancer (hepatocellular carcinoma, HCC) tissue of rats by means of laser ablation-inductively coupled plasma-mass spectrometry. HCC bearing rats simultaneously received a tail vein injection of the hepatocyte-specific magnetic resonance imaging contrast agent Gadoxetic acid and a transarterial injection of Cisplatin 15 min before sacrifice and liver removal. Resecting HCC with adjacent liver tissue allows the comparison of Gd, Pt, and endogenous elements like Fe, Cu, and Zn in the various tissue types. Region of interest analysis reveals lower concentrations of Gd in HCC and higher Gd content in the adjacent liver, fitting the selective uptake of Gadoxetic acid into hepatocytes. Furthermore, two malignancy grades and their possible impact on the Gadoxetic acid and Cisplatin uptake are compared. For this, four high grade (G3) and two moderate grade (G2) HCCs were analysed, including a control sample each. Gd concentrations were lower in HCC irrespective of the grade of dedifferentiation (G2, G3) compared to adjacent liver. Despite local arterial Cisplatin injection, concentrations of Pt were similar or also reduced in HCC compared to liver tissue. In addition, endogenous Fe, Cu, and Zn were quantified. While Zn was homogenously distributed, higher Fe concentrations were determined in liver tissue compared to HCC. Hotspots of Cu suggest a deregulated copper homeostasis in certain liver lesions. The Gd and Fe distributions are compared in detail with cellular alterations examined by hematoxylin and eosin staining.

3.
Sci Adv ; 9(19): eadg1213, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37163592

RESUMO

The climate response to biomass burning emissions from the 2019-2020 Australian wildfire season is estimated from two 30-member ensembles using CESM2: one of which incorporates observed wildfire emissions and one that does not. In response to the fires, an increase in biomass aerosol burdens across the southern hemisphere is simulated through late 2019 and early 2020, accompanied by an enhancement of cloud albedo, particularly in the southeastern subtropical Pacific Ocean. In turn, the surface cools, the boundary layer dries, and the moist static energy of the low-level flow into the equatorial Pacific is reduced. In response, the intertropical convergence zone migrates northward and sea surface temperature in the Niño3.4 region cools, with coupled feedbacks amplifying the cooling. A subsequent multiyear ensemble mean cooling of the tropical Pacific is simulated through the end of 2021, suggesting an important contribution to the 2020-2022 strong La Niña events.

4.
Cancers (Basel) ; 14(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35740575

RESUMO

Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.

5.
Metallomics ; 14(6)2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35482657

RESUMO

Gadolinium (Gd) deposition has been found in both animal and human tissues after injections of Gd-based contrast agents (GBCAs). Without the knowledge of which tissues are most affected, it is difficult to determine whether Gd accumulation could lead to any pathological changes. The current study aims at investigating histological sections of three patients who were exposed to GBCAs during their lifetime, and identify areas of Gd accumulation. Tissue sections of three autopsy cases were investigated by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to assess the distribution of Gd, and the deposition within tissue sections was quantified. Additional application of laser ablation-inductively coupled plasma-optical emission spectroscopy (LA-ICP-OES) enabled a sensitive detection of calcium (Ca) in the vessel walls, which is usually impeded in LA-ICP-MS due to the isobaric interference with argon. Complementary LA-ICP-MS and LA-ICP-OES analysis revealed that Gd was co-localized with zinc and Ca, in the area where smooth muscle actin was present. Notably, high levels of Gd were found in the tunica media of arterial walls, which requires further research into potential Gd-related toxicity in this specific location.


Assuntos
Meios de Contraste , Gadolínio , Animais , Meios de Contraste/química , Humanos , Imageamento por Ressonância Magnética/métodos , Coloração e Rotulagem , Túnica Média/química
6.
Nat Commun ; 13(1): 2043, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440561

RESUMO

Rising emissions from wildfires over recent decades in the Pacific Northwest are known to counteract the reductions in human-produced aerosol pollution over North America. Since amplified Pacific Northwest wildfires are predicted under accelerating climate change, it is essential to understand both local and transported contributions to air pollution in North America. Here, we find corresponding increases for carbon monoxide emitted from the Pacific Northwest wildfires and observe significant impacts on both local and down-wind air pollution. Between 2002 and 2018, the Pacific Northwest atmospheric carbon monoxide abundance increased in August, while other months showed decreasing carbon monoxide, so modifying the seasonal pattern. These seasonal pattern changes extend over large regions of North America, to the Central USA and Northeast North America regions, indicating that transported wildfire pollution could potentially impact the health of millions of people.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Incêndios Florestais , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monóxido de Carbono , Humanos , América do Norte , Estações do Ano
7.
Metallomics ; 14(3)2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35294013

RESUMO

A rapid and cost-efficient tissue preparation protocol for laser ablation-inductively coupled plasma-mass spectrometry imaging (LA-ICP-MSI) has been developed within this study as an alternative to the current gold standard using fresh-frozen samples or other preparation techniques such as formalin fixation (FFix) and formalin-fixed paraffin-embedding (FFPE). Samples were vacuum dried at room temperature (RT) and stored in sealed vacuum containers for storage and shipping between collaborating parties. We compared our new protocol to established methods using prostate tissue sections investigating typical endogenous elements such as zinc, iron, and phosphorous with LA-ICP-MSI. The new protocol yielded comparable imaging results as fresh-frozen sections. FFPE sections were also tested due to the wide use and availability of FFPE tissue. However, the FFPE protocol and the FFix alone led to massive washout of the target elements on the sections tested in this work. Therefore, our new protocol presents an easy and rapid alternative for tissue preservation with comparable results to fresh-frozen sections for LA-ICP-MSI. It overcomes washout risks of commonly used tissue fixation techniques and does not require expensive and potentially unstable and time-critical shipping of frozen material on dry ice. Additionally, this protocol is likely applicable for several bioimaging approaches, as the dry condition may act comparable to other dehydrating fixatives, such as acetone or methanol, preventing degradation while avoiding washout effects.


Assuntos
Formaldeído , Terapia a Laser , Formaldeído/química , Espectrometria de Massas/métodos , Inclusão em Parafina/métodos , Fixação de Tecidos/métodos
8.
ACS Infect Dis ; 8(2): 360-372, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35045258

RESUMO

Staphylococcus aureus-induced infective endocarditis (IE) is a life-threatening disease. Differences in virulence between distinct S. aureus strains, which are partly based on the molecular mechanisms during bacterial adhesion, are not fully understood. Yet, distinct molecular or elemental patterns, occurring during specific steps in the adhesion process, may help to identify novel targets for accelerated diagnosis or improved treatment. Here, we use laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of post-mortem tissue slices of an established mouse model of IE to obtain fingerprints of element distributions in infected aortic valve tissue. Three S. aureus strains with different virulence due to deficiency in distinct adhesion molecules (fibronectin-binding protein A and staphylococcal protein A) were used to assess strain-specific patterns. Data analysis was performed by t-distributed stochastic neighbor embedding (t-SNE) of mass spectrometry imaging data, using manual reference tissue classification in histological specimens. This procedure allowed for obtaining distinct element patterns in infected tissue for all three bacterial strains and for comparing those to patterns observed in healthy mice or after sterile inflammation of the valve. In tissue from infected mice, increased concentrations of calcium, zinc, and magnesium were observed compared to noninfected mice. Between S. aureus strains, pronounced variations were observed for manganese. The presented approach is sensitive for detection of S. aureus infection. For strain-specific tissue characterization, however, further improvements such as establishing a database with elemental fingerprints may be required.


Assuntos
Endocardite Bacteriana , Endocardite , Infecções Estafilocócicas , Animais , Endocardite Bacteriana/microbiologia , Espectrometria de Massas/métodos , Camundongos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo
9.
Ann Rev Mar Sci ; 14: 303-330, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34416126

RESUMO

A key Earth system science question is the role of atmospheric deposition in supplying vital nutrients to the phytoplankton that form the base of marine food webs. Industrial and vehicular pollution, wildfires, volcanoes, biogenic debris, and desert dust all carry nutrients within their plumes throughout the globe. In remote ocean ecosystems, aerosol deposition represents an essential new source of nutrients for primary production. The large spatiotemporal variability in aerosols from myriad sources combined with the differential responses of marine biota to changing fluxes makes it crucially important to understand where, when, and how much nutrients from the atmosphere enter marine ecosystems. This review brings together existing literature, experimental evidence of impacts, and new atmospheric nutrient observations that can be compared with atmospheric and ocean biogeochemistry modeling. We evaluate the contribution and spatiotemporal variability of nutrient-bearing aerosols from desert dust, wildfire, volcanic, and anthropogenic sources, including the organic component, deposition fluxes, and oceanic impacts.


Assuntos
Ecossistema , Vento , Aerossóis/análise , Atmosfera , Nutrientes , Oceanos e Mares
10.
Biology (Basel) ; 10(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34827210

RESUMO

Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm3 and 1000 mm3) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity (p > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica-van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma-mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa.

11.
Contrast Media Mol Imaging ; 2021: 9999847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007253

RESUMO

Background: Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods: Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results: In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (p=0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R 2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion: The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Apolipoproteínas E/genética , Doxiciclina/farmacologia , Angiotensina II/genética , Animais , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Modelos Animais de Doenças , Gadolínio/farmacologia , Humanos , Imageamento por Ressonância Magnética , Camundongos , Compostos Organometálicos/farmacologia
14.
Invest Radiol ; 56(9): 591-598, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787536

RESUMO

OBJECTIVES: Macrophages accumulating in the periablational rim play a pivotal role in initiating and sustaining the perifocal inflammatory reaction, which has been shown to be at least 1 of the mechanisms responsible for the systemic pro-oncogenic effects of focal hepatic radiofrequency ablation (RFA). Herein, we tested the hypothesis to use superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI) for noninvasive quantification of iron-loaded macrophages in the periablational rim of VX2 tumor-bearing rabbits. MATERIALS AND METHODS: Twelve VX2 tumor-bearing rabbits underwent MRI immediately after and up to 3 weeks after focal hepatic RFA. For noninvasive quantification of macrophage accumulation in the periablational rim, animals were scanned before and 24 hours after SPION injection. T2*-weighted images were analyzed and correlated with histopathological and immunohistochemical findings. Furthermore, correlations with quantitative measurements (ICP-MS [inductively coupled plasma-mass spectrometry] and LA-ICP-MS [laser ablation-ICP-MS]) were performed. RESULTS: SPION-enhanced T2*-weighted MRI scans displayed a progressive increase in the areas of signal intensity (SI) loss within the periablational rim peaking 3 weeks after RFA. Accordingly, quantitative analysis of SI changes demonstrated a significant decline in the relative SI ratio reflecting a growing accumulation of iron-loaded macrophages in the rim. Histological analyses confirmed a progressive accumulation of iron-loaded macrophages in the periablational rim. The ICP-MS and LA-ICP-MS confirmed a progressive increase of iron concentration in the periablational rim. CONCLUSIONS: SPION-enhanced MRI enables noninvasive monitoring and quantification of ablation-induced macrophage recruitment in the periablational rim. Given the close interplay between ablation-induced perifocal inflammation and potential unwanted tumorigenic effects of RFA, SPION-enhanced MRI may serve as a valuable tool to guide and modulate adjuvant therapies after hepatic RFA.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Animais , Modelos Animais de Doenças , Macrófagos , Imageamento por Ressonância Magnética , Coelhos
15.
Sci Rep ; 11(1): 6814, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767303

RESUMO

Hepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x - 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.


Assuntos
Elastina/metabolismo , Matriz Extracelular/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Imageamento por Ressonância Magnética , Animais , Ablação por Cateter/métodos , Modelos Animais de Doenças , Feminino , Gadolínio , Humanos , Neoplasias Hepáticas/terapia , Masculino , Espectrometria de Massas , Imagem Molecular/métodos , Cuidados Pós-Operatórios , Coelhos , Ablação por Radiofrequência/métodos
16.
Anal Chem ; 93(4): 2135-2143, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416303

RESUMO

Lipids, such for example the multifaceted category of glycerophospholipids (GP), play a major role in many biological processes. High-resolution mass spectrometry is able to identify these highly diverse lipid species in combination with fragmentation experiments (MS/MS) on the basis of the accurate m/z and fragmentation pattern. However, for the differentiation of isomeric lipids or isobaric interferences, more elaborate separation methods are required. Especially for imaging techniques, such as matrix-assisted laser desorption/ionization (MALDI)-MS imaging, the identification is often exclusively based on the accurate m/z. Fragmentation via MS/MS increases the confidence in lipid annotation in imaging approaches. However, this is sometimes not feasible due to insufficient sensitivity and significantly prolonged analysis time. The use of a separation dimension such as trapped ion mobility spectrometry (TIMS) after ionization strengthens the confidence of the identification based on the collision cross section (CCS). Since CCS libraries are limited, a tissue-specific database was initially generated using hydrophilic interaction liquid chromatography-TIMS-MS. Using this database, the identification of isomeric lipid classes as well as isobaric interferences in a lipid class was performed using a mouse spleen sample in a workflow described in this study. Besides a CCS-based identification as an additional identification criterion for GP in general, the focus was on the distinction of the isomeric GP classes phosphatidylglycerol and bis(monoacylglycero)phosphate, as well as the differentiation of possible isobaric interferences based on the formation of adducts by MALDI-TIMS-MS imaging on a molecular level.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Mobilidade Iônica/métodos , Fosfolipídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Camundongos
17.
Mol Imaging ; 19: 1536012120961875, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216687

RESUMO

BACKGROUND: Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1ß (IL-1ß) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1ß-therapy on AAA-formation in a mouse-model. METHODS: Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1ß-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg). RESULTS: Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1ß-expression. CONCLUSIONS: Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1ß-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.


Assuntos
Aneurisma da Aorta Abdominal , Angiotensina II , Animais , Anti-Inflamatórios , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Modelos Animais de Doenças , Interleucina-1beta , Imageamento por Ressonância Magnética , Camundongos
18.
Sci Rep ; 10(1): 20785, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247185

RESUMO

To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14-28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.


Assuntos
Elastina/metabolismo , Matriz Extracelular/metabolismo , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/metabolismo , Animais , Linhagem Celular Tumoral , Meios de Contraste , Matriz Extracelular/patologia , Feminino , Gadolínio , Neoplasias Hepáticas Experimentais/patologia , Imageamento por Ressonância Magnética , Sondas Moleculares , Compostos Organometálicos , Coelhos
19.
Sci Rep ; 10(1): 15206, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939002

RESUMO

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p < 0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Colágeno/análise , Matriz Extracelular/metabolismo , Compostos Férricos/análise , Inflamação/diagnóstico por imagem , Animais , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/metabolismo , Ruptura Aórtica/complicações , Ruptura Aórtica/imunologia , Ruptura Aórtica/metabolismo , Colágeno/química , Modelos Animais de Doenças , Estudos de Viabilidade , Compostos Férricos/administração & dosagem , Compostos Férricos/química , Gadolínio/administração & dosagem , Gadolínio/química , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Camundongos , Análise de Sobrevida
20.
Sci Rep ; 10(1): 12410, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709967

RESUMO

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls'-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Espectroscopia de Ressonância Magnética/métodos , Angiotensina II/toxicidade , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/imunologia , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/patologia , Modelos Animais de Doenças , Progressão da Doença , Estudos de Viabilidade , Humanos , Inflamação , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Knockout para ApoE
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