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1.
PLoS One ; 19(5): e0302623, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38776318

RESUMO

Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) of the human placenta is potentially a sensitive marker of in vivo oxygenation. This methodological study shows that full coverage of the placenta is possible using 3D mapping of the change in longitudinal relaxation rate (ΔR1), in a group of healthy pregnant subjects breathing elevated levels of oxygen. Twelve pregnant subjects underwent a comparison of 2D and 3D OE-MRI. ΔR1 was mapped for a single 2D slice (ss-2D), a single matched-slice from the 3D volume (ss-3D) and the full 3D volume (vol-3D). The group-average median ΔR1 values for ss-3D (0.023 s-1) and vol-3D (0.022 s-1) do not differ significantly from ss-2D (0.020 s-1), when compared using a two-tailed paired t-test (ss-3D (p = 0.58) and vol-3D (p = 0.70)). However, median baseline T1 (T1b) for ss-2D was higher (1603 ms) than T1b for ss-3D (1540 ms, p = 0.07) and significantly higher than vol-3D (1515 ms, p = 0.02), when compared using a two-tailed paired t-test. In contrast with previous studies, no correlation of median ΔR1 with gestation age at scan for the normal group (N = 10) was observed for ss-2D, likely due to the smaller gestational range. Full volume OE-MRI maps reveal sensitivity to changes in ΔR1, with some participants showing an enhanced gradient in the intermediate space between the fetal and maternal sides of the placenta in the 3D data. This study shows that it is feasible to acquire whole placental volume OE-MRI data in women with healthy pregnancy.


Assuntos
Imageamento Tridimensional , Imageamento por Ressonância Magnética , Oxigênio , Placenta , Humanos , Feminino , Gravidez , Imageamento por Ressonância Magnética/métodos , Placenta/diagnóstico por imagem , Oxigênio/metabolismo , Adulto , Imageamento Tridimensional/métodos
2.
Magn Reson Med ; 91(5): 1803-1821, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38115695

RESUMO

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética , Humanos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Software , Algoritmos
3.
Magn Reson Med ; 90(3): 1130-1136, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37222226

RESUMO

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Espectroscopia de Ressonância Magnética , Biomarcadores
4.
Phys Med ; 101: 165-182, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36055125

RESUMO

PURPOSE: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice. METHODS: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK. RESULTS: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions. CONCLUSIONS: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard.


Assuntos
Biomarcadores , Humanos , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética/métodos
5.
Magn Reson Med ; 84(3): 1250-1263, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32057115

RESUMO

PURPOSE: MRI biomarkers of tumor response to treatment are typically obtained from parameters derived from a model applied to pre-treatment and post-treatment data. However, as tumors are spatially and temporally heterogeneous, different models may be necessary in different tumor regions, and model suitability may change over time. This work evaluates how the suitability of two diffusion-weighted (DW) MRI models varies spatially within tumors at the voxel level and in response to radiotherapy, potentially allowing inference of qualitatively different tumor microenvironments. METHODS: DW-MRI data were acquired in CT26 subcutaneous allografts before and after radiotherapy. Restricted and time-independent diffusion models were compared, with regions well-described by the former hypothesized to reflect cellular tissue, and those well-described by the latter expected to reflect necrosis or oedema. Technical and biological validation of the percentage of tissue described by the restricted diffusion microstructural model (termed %MM) was performed through simulations and histological comparison. RESULTS: Spatial and radiotherapy-related variation in model suitability was observed. %MM decreased from a mean of 64% at baseline to 44% 6 days post-radiotherapy in the treated group. %MM correlated negatively with the percentage of necrosis from histology, but overestimated it due to noise. Within MM regions, microstructural parameters were sensitive to radiotherapy-induced changes. CONCLUSIONS: There is spatial and radiotherapy-related variation in different models' suitability for describing diffusion in tumor tissue, suggesting the presence of different and changing tumor sub-regions. The biological and technical validation of the proposed %MM cancer imaging biomarker suggests it correlates with, but overestimates, the percentage of necrosis.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias , Difusão , Humanos , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Microambiente Tumoral
6.
Mater Sci Eng C Mater Biol Appl ; 101: 217-227, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029314

RESUMO

Diffusion magnetic resonance imaging (dMRI) is considered as a useful tool to study solid tumours. However, the interpretation of dMRI signal and validation of quantitative measurements of is challenging. One way to address these challenges is by using a standard reference material that can mimic tumour cell microstructure. There is a growing interest in using hollow polymeric microspheres, mainly prepared by multiple steps, as mimics of cells in healthy and diseased tissue. The present work reports on tumour cell-mimicking materials composed of hollow microspheres for application as a standard material in dMRI. These microspheres were prepared via one-step co-electrospraying process. The shell material was poly(d,l-lactic-co-glycolic acid) (PLGA) polymers with different molecule weights and/or ratios of glycolic acid-to-lactic, while the core was polyethylene glycol (PEG) or ethylene glycol. The resultant co-electrosprayed products were characterised by optical microscopy, scanning electron microscopy (SEM) and synchrotron X-ray micro-CT. These products were found to have variable structures and morphologies, e.g. from spherical particles with/without surface hole, through beaded fibres to smooth fibres, which mainly depend on PLGA composition and core materials. Only the shell material of PLGA polymer with ester terminated, Mw 50,000-75,000 g mol-1, and lactide:glycolide 85:15 formed hollow microspheres via the co-electrospraying process using the core material of 8 wt% PEG/chloroform as the core. A water-filled test object (or phantom) was designed and constructed from samples of the material generated from co-electrosprayed PLGA microspheres and tested on a 7 T MRI scanner. The preliminary MRI results provide evidence that hollow PLGA microspheres can restrict/hinder water diffusion as cells do in tumour tissue, implying that the phantom may be suitable for use as a quantitative validation and calibration tool for dMRI.


Assuntos
Imagem de Difusão por Ressonância Magnética , Eletroquímica/métodos , Microesferas , Polímeros/química , Linhagem Celular Tumoral , Humanos , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Síncrotrons , Tomografia Computadorizada por Raios X
7.
Magn Reson Med ; 81(4): 2288-2301, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30338871

RESUMO

PURPOSE: To determine the feasibility of extracting sufficiently precise estimates of cell radius, R, and intracellular volume fraction, fi , from DW-MRI data in order to distinguish between specific microstructural changes tissue may undergo, specifically focusing on cell death in tumors. METHODS: Simulations with optimized and non-optimized clinical acquisitions were performed for a range of microstructures, using a two-compartment model. The ability to distinguish between (i) cell shrinkage with cell density constant, mimicking apoptosis, and (ii) cell size constant with cell density decreasing, mimicking loss of cells, was evaluated based on the precision of simulated parameter estimates. Relationships between parameter precision, SNR, and the magnitude of specific parameter changes, were used to infer SNR requirements for detecting changes. RESULTS: Accuracy and precision depended on microstructural properties, SNR, and the acquisition protocol. The main benefit of optimized acquisitions tended to be improved accuracy and precision of R, particularly for small cells. In most cases considered, higher SNR was required for detecting changes in R than for changes in fi . CONCLUSIONS: Given the relative changes in R and fi due to apoptosis, simulations indicate that, for a range of microstructures, detecting changes in R require higher SNR than detecting changes in fi , and that such SNR is typically not achieved in clinical data. This suggests that if apoptotic cell size decreases are to be detected in clinical settings, improved SNR is required. Comparing measurement precision with the magnitude of expected biological changes should form part of the validation process for potential biomarkers.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Algoritmos , Apoptose , Axônios/patologia , Biomarcadores/metabolismo , Simulação por Computador , Estudos de Viabilidade , Humanos , Distribuição Normal , Reprodutibilidade dos Testes , Razão Sinal-Ruído
8.
Neuroimage ; 181: 395-402, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29936312

RESUMO

Grey and white matter mimicking phantoms are important for assessing variations in diffusion MR measures at a single time point and over an extended period of time. This work investigates the stability of brain-mimicking microfibre phantoms and reproducibility of their MR derived diffusion parameters. The microfibres were produced by co-electrospinning and characterized by scanning electron microscopy (SEM). Grey matter and white matter phantoms were constructed from random and aligned microfibres, respectively. MR data were acquired from these phantoms over a period of 33 months. SEM images revealed that only small changes in fibre microstructure occurred over 30 months. The coefficient of variation in MR measurements across all time-points was between 1.6% and 3.4% for MD across all phantoms and FA in white matter phantoms. This was within the limits expected for intra-scanner variability, thereby confirming phantom stability over 33 months. These specialised diffusion phantoms may be used in a clinical environment for intra and inter-site quality assurance purposes, and for validation of quantitative diffusion biomarkers.


Assuntos
Imagem de Difusão por Ressonância Magnética/normas , Substância Cinzenta/diagnóstico por imagem , Microscopia Eletrônica de Varredura , Imagens de Fantasmas/normas , Substância Branca/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Controle de Qualidade , Reprodutibilidade dos Testes , Fatores de Tempo
9.
Invest Radiol ; 53(9): 563-570, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29771727

RESUMO

OBJECTIVES: The aim of this study was to model the in vivo transporter-mediated uptake and efflux of the hepatobiliary contrast agent gadoxetate in the liver. The efficacy of the proposed technique was assessed for its ability to provide quantitative insights into drug-drug interactions (DDIs), using rifampicin as inhibitor. MATERIALS AND METHODS: Three groups of C57 mice were scanned twice with a dynamic gadoxetate-enhanced magnetic resonance imaging protocol, using a 3-dimensional spoiled gradient-echo sequence for approximately 72 minutes. Before the second magnetic resonance imaging session, 2 of the groups received a rifampicin dose of 20 (n = 7) or 40 (n = 7) mg/kg, respectively. Data from regions of interest in the liver were analyzed using 2 simplifications of a 2-compartment uptake and efflux model to provide estimates for the gadoxetate uptake rate (ki) into the hepatocytes and its efflux rate (kef) into the bile. Both models were assessed for goodness-of-fit in the group without rifampicin (n = 9), and the appropriate model was selected for assessing the ability to monitor DDIs in vivo. RESULTS: Seven of 9 mice from the group without rifampicin were assessed for model implementation and reproducibility. A simple 3 parameter model (ki, kef, and extracellular space, vecs) adequately described the observed liver concentration time series with mean ki = 0.47 ± 0.11 min and mean kef = 0.039 ± 0.016 min. Visually, the area under the liver concentration time profile was reduced for the groups receiving rifampicin. Furthermore, tracer kinetic modeling demonstrated a significant dose-dependent decrease in the uptake (5.9- and 17.3-fold decrease for 20 mg/kg and 40 mg/kg, respectively) and efflux rates (2.2- and 7.9-fold decrease) compared with the first scan for each group. CONCLUSIONS: This study presents the first in vivo implementation of a 2-compartment uptake and efflux model to monitor DDIs at the transporter-protein level, using the clinically relevant organic anion transporting polypeptide inhibitor rifampicin. The technique has the potential to be a novel alternative to other methods, allowing real-time changes in transporter DDIs to be measured directly in vivo.


Assuntos
Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Fígado/diagnóstico por imagem , Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , Animais , Interações Medicamentosas , Imageamento Tridimensional , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Reprodutibilidade dos Testes
10.
Mater Des ; 137: 394-403, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29307950

RESUMO

Highly hydrophilic hollow polycaprolactone (PCL) microfibres were developed as building elements to create tissue-mimicking test objects (phantoms) for validation of diffusion magnetic resonance imaging (MRI). These microfibres were fabricated by the co-electrospinning of PCL-polysiloxane-based surfactant (PSi) mixture as shell and polyethylene oxide as core. The addition of PSi had a significant effect on the size of resultant electrospun fibres and the formation of hollow microfibres. The presence of PSi in both co-electrospun PCL microfibre surface and cross-section, revealed by X-ray energy dispersive spectroscopy (EDX), enabled water to wet these fibres completely (i.e., zero contact angle) and remained active for up to 12 months after immersing in water. PCL and PCL-PSi fibres with uniaxial orientation were constructed into water-filled phantoms. MR measurement revealed that water molecules diffuse anisotropically in the PCL-PSi phantom. Co-electrospun hollow PCL-PSi microfibres have desirable hydrophilic properties for the construction of a new generation of tissue-mimicking dMRI phantoms.

11.
Magn Reson Med ; 80(1): 147-158, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29154442

RESUMO

PURPOSE: To develop a biomimetic tumor tissue phantom which more closely reflects water diffusion in biological tissue than previously used phantoms, and to evaluate the stability of the phantom and its potential as a tool for validating diffusion-weighted (DW) MRI measurements. METHODS: Coaxial-electrospraying was used to generate micron-sized hollow polymer spheres, which mimic cells. The bulk structure was immersed in water, providing a DW-MRI phantom whose apparent diffusion coefficient (ADC) and microstructural properties were evaluated over a period of 10 months. Independent characterization of the phantom's microstructure was performed using scanning electron microscopy (SEM). The repeatability of the construction process was investigated by generating a second phantom, which underwent high resolution synchrotron-CT as well as SEM and MR scans. RESULTS: ADC values were stable (coefficients of variation (CoVs) < 5%), and varied with diffusion time, with average values of 1.44 ± 0.03 µm2 /ms (Δ = 12 ms) and 1.20 ± 0.05 µm2 /ms (Δ = 45 ms). Microstructural parameters showed greater variability (CoVs up to 13%), with evidence of bias in sphere size estimates. Similar trends were observed in the second phantom. CONCLUSION: A novel biomimetic phantom has been developed and shown to be stable over 10 months. It is envisaged that such phantoms will be used for further investigation of microstructural models relevant to characterizing tumor tissue, and may also find application in evaluating acquisition protocols and comparing DW-MRI-derived biomarkers obtained from different scanners at different sites. Magn Reson Med 80:147-158, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.


Assuntos
Biomimética , Imagem de Difusão por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Imagens de Fantasmas , Algoritmos , Biomarcadores , Eletroquímica , Desenho de Equipamento , Humanos , Funções Verossimilhança , Teste de Materiais , Microscopia Eletrônica de Varredura , Polímeros , Síncrotrons , Tomografia Computadorizada por Raios X , Água
12.
Langmuir ; 33(46): 13262-13271, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-28901145

RESUMO

We describe the co-electrospraying of hollow microspheres from a polycaprolactone (PCL) shell solution and various core solutions including water, cyclohexane, poly(ethylene oxide) (PEO), and polyethylene glycol (PEG), using different collectors. The morphologies of the resultant microspheres were characterized by scanning electron microscopy (SEM), confocal microscopy, and nano-X-ray computed tomography (nano-XCT). The core/shell solution miscibility played an important role in the co-electrospraying process and the formation of microsphere structures. Spherical particles were more likely to be produced from miscible combinations of core/shell solutions than from immiscible ones. Hollow PCL microspheres with a single hole in their surfaces were produced when an ethanol bath was used as the collector. The mechanism by which the core/shell structure is transformed into single-hole hollow microspheres is proposed to be primarily based on the evaporation through the shell and extraction by ethanol of the core solution and is described in detail. Additionally, we present a 3D macroscopic tubular structure composed of hollow PCL microspheres, directly assembled on a copper wire collector during co-electrospraying. SEM and nano-XCT confirm that microspheres in the 3D bulk structure remain hollow.

13.
Clin Exp Rheumatol ; 35(6): 954-958, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28850028

RESUMO

OBJECTIVES: To investigate the association of novel non-contrast MRI biomarkers with standard measurements of renal function and renal disease activity in lupus. METHODS: A pilot study of lupus nephritis (LN) and lupus non-nephritis (LNN) patients, and healthy volunteers (HV), was undertaken. Multi-modal renal MRI was performed including sequences for arterial spin labelling (ASL) measuring blood flow, diffusion tensor imaging (DTI), measuring microstructural disruption, and effective transverse relaxation time (T2*) which is a biomarker of micro-haemorrhage. MRI measurements were compared with urinary protein creatinine ratio (uPCR) and estimated glomerular filtration rate (eGFR) measurements in the whole study population, then differences in imaging measurements between the groups were explored. RESULTS: 21 patients (6 LN, 8 LNN and 7 HV) completed the study, although ASL data were not available in 4 subjects. In the whole cohort, eGFR correlated significantly with the apparent diffusion coefficient measurement from DTI in the medulla (r=0.47, p=0.03). uPCR correlated strongly with the fractional anisotropy (FA) DTI measurement in the cortex and moderately with T2* measurements (rho=-0.71, p<0.001 and rho=-0.53, p=0.013, respectively). Delayed blood flow to the medulla was found in LN subjects and there was a trend towards lower FA values in the cortex, suggesting micro-structural disruption (p=0.04 and p=0.07, respectively). CONCLUSIONS: This preliminary study demonstrates that non-contrast renal MRI biomarkers are associated with standard measures of disease activity in lupus. The potential utility of these non-invasive biomarkers warrants further investigation, as there is an unmet need for reliable biomarkers of disease activity in lupus nephritis.


Assuntos
Nefrite Lúpica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Biomarcadores , Estudos de Coortes , Creatinina/urina , Imagem de Tensor de Difusão , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Rim/ultraestrutura , Nefrite Lúpica/fisiopatologia , Masculino , Projetos Piloto
14.
Invest Radiol ; 52(2): 111-119, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28002117

RESUMO

OBJECTIVE: The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. MATERIALS AND METHODS: Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. RESULTS: Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. CONCLUSIONS: This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions.


Assuntos
Meios de Contraste , Gadolínio DTPA , Aumento da Imagem/métodos , Fígado/fisiologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Estudos de Avaliação como Assunto , Feminino , Voluntários Saudáveis , Humanos , Fígado/diagnóstico por imagem , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Adulto Jovem
15.
Aerosol Sci Technol ; 50(11): 1201-1215, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27928195

RESUMO

The ability to reproducibly produce and effectively collect electrosprayed polymeric microspheres with controlled morphology and size in bulk form is challenging. In this study, microparticles were produced by electrospraying polycaprolactone (PCL) of various molecular weights and solution concentrations in chloroform, and by collecting materials on different substrates. The resultant PCL microparticles were characterized by optical and electron microscopy to investigate the effect of molecular weight, solution concentration, applied voltage, working distance, and flow rate on their morphology and size. The work demonstrates the key role of a moderate molecular weight and/or solution concentration in the formation of spherical PCL particles via an electrospraying process. Increasing the applied voltage was found to produce smaller and more uniform PCL microparticles. There was a relatively low increase in the particle average size with an increase in the working distance and flow rate. Four types of substrates were adopted to collect electrosprayed PCL particles: a glass slide, aluminium foil, liquid bath, and copper wire. Unlike 2D bulk structures collected on the other substrates, a 3D tubular structure of microspheres was formed on the copper wire which could find application in the construction of 3D tumor mimics.

16.
PLoS One ; 11(3): e0149760, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26958856

RESUMO

PURPOSE: Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers. MATERIALS AND METHODS: Lung T1 measurements from 35 subjects, 23 never smokers and 12 current smokers were retrospectively analyzed from an institutional review board approved study. All 35 subjects underwent pulmonary function test (PFT) measurements and lung T1, with similar T1 measurement protocols. A backward linear model of T1 as a function of FEV1, FVC, weight, height, age and PY was tested. RESULTS: A significant correlation between lung T1 and PY was found with a negative slope of -3.2 ms/year (95% confidence interval [CI] [-5.8, -0.6], p = 0.02), when adjusted for age and height. Lung T1 shortens with ageing among all subjects, -4.0 ms/year (95%CI [-6.3, -1.7], p = 0.001), and among the never smokers, -3.7 ms/year (95%CI [-6.0, -1.3], p = 0.003). CONCLUSIONS: A correlation between lung T1 and PY when adjusted for both age and height was found, and T1 of the lung shortens with ageing. Accordingly, PY and age can be significant confounding factors when T1 is used as a biomarker in lung MRI studies that must be taken into account to detect underlying patterns of disease.


Assuntos
Pulmão/fisiopatologia , Imageamento por Ressonância Magnética , Fumar/efeitos adversos , Adulto , Envelhecimento/fisiologia , Demografia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fatores de Tempo , Adulto Jovem
17.
COPD ; 13(2): 153-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26488310

RESUMO

Magnetic resonance imaging (MRI) may provide attractive biomarkers for assessment of pulmonary disease in clinical trials as it is free from ionizing radiation, minimally invasive and allows regional information. The aim of this study was to characterize lung MRI T1 relaxation time as a biomarker of chronic obstructive pulmonary disease (COPD); and specifically its relationship to smoking history, computed tomography (CT), and pulmonary function test (PFT) measurements in comparison to healthy age-matched controls. Lung T1 and inter-quartile range (IQR) of T1 maps from 24 COPD subjects and 12 healthy age-matched non-smokers were retrospectively analyzed from an institutional review board approved study. The subjects underwent PFTs and two separate MR imaging sessions at 1.5 tesla to test T1 repeatability. CT scans were performed on the COPD subjects. T1 repeatability (intraclass correlation coefficient) was 0.72 for repeated scans acquired on two visits. The lung T1 was significantly shorter (p < 0.0001) and T1 IQR was significantly larger (p = 0.0002) for the COPD subjects compared to healthy controls. Lung T1 significantly (p = 0.001) correlated with lung density assessed with CT. Strong significant correlations (p < 0.0001) between lung T1 and all PFT measurements were observed. Cigarette exposure did not correlate with lung T1 in COPD subjects. In conclusion, lung MRI T1 mapping shows potential as a repeatable, radiation free, non-invasive imaging technique in the evaluation of COPD.


Assuntos
Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X/métodos
18.
J Magn Reson Imaging ; 43(3): 594-600, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26213152

RESUMO

PURPOSE: Diffusion magnetic resonance imaging (MRI) is increasingly used to characterize cardiac tissue microstructure, necessitating the use of physiologically relevant phantoms for methods development. Existing phantoms are generally simplistic and mostly simulate diffusion in the brain. Thus, there is a need for phantoms mimicking diffusion in cardiac tissue. MATERIALS AND METHODS: A biomimetic phantom composed of hollow microfibers generated using co-electrospinning was developed to mimic myocardial diffusion properties and fiber and sheet orientations. Diffusion tensor imaging was carried out at monthly intervals over 4 months at 9.4T. 3D fiber tracking was performed using the phantom and compared with fiber tracking in an ex vivo rat heart. RESULTS: The mean apparent diffusion coefficient and fractional anisotropy of the phantom remained stable over the 4-month period, with mean values of 7.53 ± 0.16 × 10(-4) mm(2) /s and 0.388 ± 0.007, respectively. Fiber tracking of the 1st and 3rd eigenvectors generated analogous results to the fiber and sheet-normal direction respectively, found in the left ventricular myocardium. CONCLUSION: A biomimetic phantom simulating diffusion in the heart was designed and built. This could aid development and validation of novel diffusion MRI methods for investigating cardiac microstructure, decrease the number of animals and patients needed for methods development, and improve quality control in longitudinal and multicenter cardiac diffusion MRI studies.


Assuntos
Biomimética , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Coração/diagnóstico por imagem , Miocárdio/patologia , Imagens de Fantasmas , Animais , Anisotropia , Encéfalo , Desenho de Equipamento , Ventrículos do Coração/patologia , Microscopia Eletrônica de Varredura , Ratos
19.
Mater Charact ; 109: 25-35, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26702249

RESUMO

The development of co-electrospun (co-ES) hollow microfibrous assemblies of an appreciable thickness is critical for many practical applications, including filtration membranes and tissue-mimicking scaffolds. In this study, thick uniaxially aligned hollow microfibrous assemblies forming fiber bundles and strips were prepared by co-ES of polycaprolactone (PCL) and polyethylene oxide (PEO) as shell and core materials, respectively. Hollow microfiber bundles were deposited on a fixed rotating disc, which resulted in non-controllable cross-sectional shapes on a macroscopic scale. In comparison, fiber strips were produced with tuneable thickness and width by additionally employing an x-y translation stage in co-ES. Scanning electron microscopy (SEM) images of cross-sections of fiber assemblies were analyzed to investigate the effects of production time (from 0.5 h to 12 h), core flow rate (from 0.8 mL/h to 2.0 mL/h) and/or translation speed (from 0.2 mm/s to 5 mm/s) on the pores and porosity. We observed significant changes in pore size and shape with core flow rate but the influence of production time varied; five strips produced under the same conditions had reasonably good size and porosity reproducibility; pore sizes didn't vary significantly from strip bottom to surface, although the porosity gradually decreased and then returned to the initial level.

20.
Radiology ; 275(2): 579-88, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25575114

RESUMO

PURPOSE: To compare magnetic resonance (MR) quantitative equilibrium signal (qS0) mapping with quantitative computed tomography (CT) in the estimation of emphysema in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Written informed consent of the original study permitted future reanalysis of data. This study was a retrospective analysis of data from an institutional review board-approved study. Twenty-four patients with COPD and 12 healthy patients who did not smoke underwent spirometry and two separate 1.5-T MR imaging examinations. All patients with COPD underwent additional chest CT. Lung MR qS0 maps were generated from MR images obtained with multiple inversion times by fitting the inversion recovery signal equation. Mean, 15th percentile, and standard deviation of whole-lung qS0 and relative lung area with a qS0 value below 0.20 (RA0.20) were measured and compared between groups with an unpaired t test. Reproducibility between two examinations was tested with intraclass correlation coefficients (ICCs), and their associations with spirometry and CT measurements of 15th percentile attenuation (PA15) and relative lung area with attenuation below -950 HU (RA-950) were assessed with the Pearson correlation coefficient. RESULTS: Whole-lung mean qS0 and 15th percentile of qS0 were significantly lower, whereas RA0.20 and standard deviation of qS0 were significantly higher in patients with COPD than in healthy control subjects (P = .014, P = .002, P = .005, and P < .001, respectively). Whole-lung mean qS0, the 15th percentile of qS0, and RA0.20 strongly correlated with RA-950 (r = -0.78, r = -0.81, and r = 0.86, respectively; P < .001) and PA15 (r = 0.78, r = 0.79, and r = -0.71, respectively; P < .001) and moderately correlated with the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (r = 0.63, r = 0.67, and r = -0.60, respectively; P < .001) and percentage predicted FEV1 (r = 0.54, r = 0.62, and r = -0.56, respectively; P ≤ .001). Good reproducibility of qS0 readouts was found in both groups (ICC range, 0.89-0.98). CONCLUSION: Lung MR qS0 mapping may be a reliable noncontrast nonradiation alternative to CT in the assessment of emphysema in patients with COPD.


Assuntos
Imageamento por Ressonância Magnética , Enfisema Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/complicações , Reprodutibilidade dos Testes , Estudos Retrospectivos
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