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1.
Quant Imaging Med Surg ; 13(10): 7304-7337, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37869282

RESUMEN

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

2.
Reprod Fertil ; 3(2): 77-89, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35514541

RESUMEN

Sperm motility varies between ejaculates from different men and from individual men. We studied normozoospermic and asthenozoospermic ejaculates after density-gradient centrifugation washing (DCG, 80/40%) and compared high- (80%) and low (40%)-motility sperm populations within the same sample. Our objective was to identify differences in endogenous metabolomes and energy metabolism in relation to sperm motility. 1H-Nuclear Magnetic Resonance spectroscopy (NMR) measured the endogenous metabolome of live human sperm. Incubating sperm with 13C-labelled substrates detected energy metabolism by 13C-NMR. The study examined 850 ejaculates and diagnosed asthenozoospermia in 6.1%. DGC was used to wash 160 normozoospermic (N) and 52 asthenozoospermic (A) ejaculates to recover high-motility sperm from the pellet (80N/80A) and low motility from the interface (40N/40A). 1H-NMR spectra, 45(N) and 15(A), were binned and the integrals normalised by sperm concentration. Sperm from 126(N) and 36(A) ejaculates were incubated with either 13C-glucose, 13C-fructose or 13C-pyruvate. 13C-NMR lactate and bicarbonate integrals were normalised by motile or vital sperm concentrations. 1H-NMR spectra choline integrals from the 80A population were significantly lower than the 80N, P < 0.0001. 13C-substrate conversion to lactate was significantly higher for 40A sperm than 80A sperm when normalised by motile sperm concentration. Bicarbonate integrals were sporadically observed. Sperm from asthenozoospermic ejaculates had similar glycolytic requirements to normozoospermic ones, with larger differences observed between 40 and 80% sperm populations. Higher lactate levels produced by 40% sperm may indicate that impaired sperm motility is due to dysregulated energy metabolism. The alteration in choline metabolism provides opportunities to understand the aetiology of asthenozoospermia. Lay summary: How well sperm swim (motility) varies between ejaculates from different men? Normal sperm motility is beneficial to conception and some men diagnosed with infertility have low sperm motility. Sperm metabolise molecules to produce the energy required for motility. We measured concentrations of molecules within sperm and metabolism of molecules given to sperm and related these to the proportion of motile sperm. The study examined 850 sperm samples and found low motility in 6.1%. Metabolism of molecules given to sperm was similar between low and normal motility sperm samples. However, when the most motile sperm were separated from the rest, they were more efficient in metabolising these molecules to achieve motility. Lower concentrations of a molecule called choline were found in low-motility sperm samples compared to normal samples. Choline is associated with cell membranes, energy metabolism and oxidative stress, which may give opportunities to understand the causes of low motility.


Asunto(s)
Astenozoospermia , Bicarbonatos , Colina , Humanos , Lactatos , Espectroscopía de Resonancia Magnética , Masculino , Semen , Motilidad Espermática , Espermatozoides
3.
NMR Biomed ; 35(5): e4650, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34841602

RESUMEN

Dissolution dynamic nuclear polarisation (dDNP) of 13 C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised 13 C-labelled pyruvate (13 C1 -pyruvate) and urea (13 C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, Kip , and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, kpl and klp . An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, Kiu . A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. Kiu equalled Kip , indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (kpo , klo and kuo , respectively) indicated that T1 s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, kavail , most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T1 for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.


Asunto(s)
Neoplasias , Ácido Pirúvico , Animales , Isótopos de Carbono , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Neoplasias/diagnóstico por imagen , Ácido Pirúvico/metabolismo , Ratas , Solubilidad , Urea
4.
Magn Reson Imaging ; 79: 76-84, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33753137

RESUMEN

The optic nerve is known to be one of the largest nerve bundles in the human central nervous system. There have been many studies of optic nerve imaging and post-processing that have provided insights into pathophysiology of optic neuritis related to multiple sclerosis and neuromyelitis optica spectrum disorder, glaucoma, and Leber's hereditary optic neuropathy. There are many challenges in optic nerve imaging, due to the morphology of the nerve through its course to the optic chiasm, its mobility due to eye movements and the high signal from cerebrospinal fluid and orbital fat surrounding the optic nerve. Recently, many advanced and fast imaging sequences have been used with post-processing techniques in attempts to produce higher resolution images of the optic nerve for evaluating various diseases. Magnetic resonance imaging (MRI) is one of the most common imaging methodologies for the optic nerve. This review paper will focus on recent MRI advances in optic nerve imaging and explain several post-processing techniques being used for analysis of optic nerve images. Finally, some challenges and potential for future optic nerve studies will be discussed.


Asunto(s)
Esclerosis Múltiple , Neuritis Óptica , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Quiasma Óptico , Nervio Óptico/diagnóstico por imagen , Neuritis Óptica/diagnóstico por imagen
5.
Eur Radiol ; 28(10): 4438-4446, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29713778

RESUMEN

OBJECTIVES: MR imaging of neonates is difficult for many reasons and a major factor is safe transport to the MR facilities. In this article we describe the use of a small, investigational 3-T MR customised for brain imaging and sited on a neonatal unit of a tertiary centre in the UK, which is in contrast to a 300-m journey to the whole-body MR scanner used at present for clinical cases. METHODS: We describe our methods for preparing babies for safe transport and scanning on an investigational 3-T MR scanner on a neonatal unit and the development of appropriate MR sequences. The MR scanner does not have CE marking at present so this early development work was undertaken on normal neonates whose parents consented to a research examination. RESULTS: Fifty-two babies were scanned and there were no serious adverse events. The MR examinations were considered to be diagnostically evaluable in all 52 cases and in 90% the imaging was considered to be at least as good as the quality obtained on the 1.5-T scanner currently used for clinical cases. CONCLUSION: We have shown that this investigational 3-T MR scanner can be used safely on a neonatal unit and we have refined the MR sequences to a point that they are clinically usable. KEY POINTS: • Access to neonatal MR imaging is limited. • We describe an investigational 3-T MR scanner site on a neonatal unit. • The scanner produces images suitable for clinical practice.


Asunto(s)
Encéfalo/diagnóstico por imagen , Unidades Hospitalarias , Imagen por Resonancia Magnética/instrumentación , Diseño de Equipo , Humanos , Recién Nacido , Imagen por Resonancia Magnética/métodos , Transporte de Pacientes , Reino Unido
6.
Sci Rep ; 7(1): 4322, 2017 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-28659585

RESUMEN

Poor sperm motility is a common cause of male infertility for which there are no empirical therapies. Sperm motility is powered by adenosine triphosphate but the relative importance of lactate fermentation and Oxidative Phosphorylation (OxPhos) is debated. To study the relationship between energy metabolism and sperm motility we used dissolution Dynamic Nuclear Polarization (dDNP) for the first time to show the rapid conversion of 13C1-pyruvate to lactate and bicarbonate, indicating active glycolytic and OxPhos metabolism in sperm. The magnitude of both lactate and bicarbonate signals were positively correlated with the concentration of progressively motile sperm. After controlling for sperm concentration, increased progressive sperm motility generated more pyruvate conversion to lactate and bicarbonate. The technique of dDNP allows 'snapshots' of sperm metabolism to be tracked over the different stages of their life. This may provide help to uncover the causes of poor sperm motility and suggest new approaches for novel treatments or therapies.


Asunto(s)
Ácido Láctico/metabolismo , Fosforilación Oxidativa , Motilidad Espermática , Espermatozoides/fisiología , Metabolismo de los Hidratos de Carbono , Espectroscopía de Resonancia Magnética con Carbono-13 , Fermentación , Humanos , Masculino , Ácido Pirúvico/metabolismo
7.
Magn Reson Med ; 78(6): 2116-2126, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28191664

RESUMEN

PURPOSE: A rat model was developed to enable direct administration of hyperpolarized 13 C-labeled molecules into a tumor-supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism. METHODS: Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized 13 C-molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein. Spectroscopic data were obtained on a 7 Tesla preclinical scanner. RESULTS: Intra-arterial infusion of hyperpolarized 13 C-pyruvate increased the pyruvate tumor signal by a factor of 4.6, compared with intravenous infusion, despite an approximately 7 times smaller total dose to the rat. Hyperpolarized glucose signal was detected at near-physiological systemic blood concentration. Pyruvate to lactate but not glucose to lactate metabolism was detected in the tumor. Hyperpolarized 13 C-labeled combretastatin A1 diphosphate, a tumor vascular disrupting agent, showed an in vivo signal in the tumor. CONCLUSIONS: The model maximizes tumor substrate/drug delivery and minimizes T1 relaxation signal losses in addition to systemic toxicity. Therefore, it permits metabolic studies of hyperpolarized substrates with relatively short T1 and opens up the possibility for preclinical studies of hyperpolarized drug molecules. Magn Reson Med 78:2116-2126, 2017. © 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.


Asunto(s)
Isótopos de Carbono/química , Espectroscopía de Resonancia Magnética , Neoplasias/diagnóstico por imagen , Animales , Arterias/diagnóstico por imagen , Sistemas de Liberación de Medicamentos , Arterias Epigástricas/diagnóstico por imagen , Femenino , Vena Femoral/diagnóstico por imagen , Gadolinio/química , Masculino , Metástasis de la Neoplasia , Neoplasias/metabolismo , Imagen Óptica , Perfusión , Fosforilación , Ácido Pirúvico/química , Ratas , Espectrofotometría , Estilbenos/química
8.
Metabolomics ; 12: 67, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27065760

RESUMEN

INTRODUCTION: Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. OBJECTIVES: We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. METHODS: A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20-22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20-22 g.w., n = 71, and 26-28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24-36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. RESULTS: Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p < 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20-22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20-22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61-0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64-1) in the SYM women, whilst other metabolites were not. CONCLUSION: High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.

9.
Radiother Oncol ; 116(3): 392-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25824978

RESUMEN

PURPOSE: To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised (13)C1-pyruvate and magnetic resonance spectroscopy. METHODS AND MATERIALS: Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised (13)C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised (13)C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. RESULTS: MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p<0.01) from 0.029±0.002s(-1) to 0.049±0.006s(-1) (mean±SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. CONCLUSION: The rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation.


Asunto(s)
Fibrosarcoma/metabolismo , Hipoxia/metabolismo , Espectroscopía de Resonancia Magnética , Ácido Pirúvico/metabolismo , Animales , Isótopos de Carbono , Modelos Animales de Enfermedad , Ácido Láctico/metabolismo , Ratas
10.
Proteomics ; 14(7-8): 890-903, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24520073

RESUMEN

Tumour vasculature is notoriously sinusoidal and leaky, and is hence susceptible to vascular disruption. Microtubule destabilising drugs such as the combretastatins form the largest group of tumour vascular disrupting agents and cause selective shutdown of tumour blood flow within minutes to hours, leading to secondary tumour cell death. Targeting the tumour vasculature is a proven anticancer strategy but early treatment response biomarkers are required for personalising treatment planning. Protein induction following treatment with combretastatin A4-phosphate was examined in a mouse fibrosarcoma model (fs188), where tumour cells express only the matrix-bound isoform of vascular endothelial growth factor A (VEGF188). These tumours are relatively resistant to vascular disruption by combretastatin A4-phosphate and hence a study of protein induction following treatment could yield insights into resistance mechanisms. The distribution of a number of proteins induced following treatment were visualised by MALDI-mass spectrometry imaging. Responses identified were validated by LC-ESI-MS/MS and immunohistochemical staining. Significant changes in proteins connected with necrosis, cell structure, cell survival and stress-induced molecular chaperones were identified. Protein-protein interactions were identified using STRING 9.0 proteomic network software. These relationship pathways provided an insight into the activity of the active tumour milieu and a means of linking the identified proteins to their functional partners.


Asunto(s)
Fibrosarcoma/genética , Neovascularización Patológica/genética , Proteómica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Neovascularización Patológica/tratamiento farmacológico , Mapas de Interacción de Proteínas , Estilbenos/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/biosíntesis
11.
J Magn Reson ; 239: 1-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24355621

RESUMEN

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100µl to 10.000ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7µl for 100µl and 20µl for 10.000ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3-4s post-injection trigger signal and at 9-12s in tumor tissue. The pH of the injected pyruvate was 7.1±0.3 (mean±S.D., n=10). For small injection volumes, e.g. less than 100µl, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump.


Asunto(s)
Metabolómica/instrumentación , Metabolómica/métodos , Resonancia Magnética Nuclear Biomolecular/instrumentación , Resonancia Magnética Nuclear Biomolecular/métodos , Animales , Calibración , Isótopos de Carbono , Concentración de Iones de Hidrógeno , Procesamiento de Imagen Asistido por Computador , Marcaje Isotópico , Imagen por Resonancia Magnética , Ratones , Neoplasias Experimentales/patología , Fantasmas de Imagen , Ácido Pirúvico/química , Conejos , Ratas , Reproducibilidad de los Resultados , Sarcoma Experimental/patología , Hidróxido de Sodio/química , Programas Informáticos
12.
Sensors (Basel) ; 13(9): 11271-9, 2013 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-23979479

RESUMEN

We have developed a Magnetic Resonance Imaging (MRI)-compatible system to enable gating of a scanner to the heartbeat of a foetus for cardiac, umbilical cord flow and other possible imaging applications. We performed radiofrequency safety testing prior to a fetal electrocardiogram (fECG) gated imaging study in pregnant volunteers (n = 3). A compact monitoring device with advanced software capable of reliably detecting both the maternal electrocardiogram (mECG) and fECG simultaneously was modified by the manufacturer (Monica Healthcare, Nottingham, UK) to provide an external TTL trigger signal from the detected fECG which could be used to trigger a standard 1.5 T MR (GE Healthcare, Milwaukee, WI, USA) gating system with suitable attenuation. The MR scanner was tested by triggering rapidly during image acquisition at a typical fetal heart rate (123 beats per minute) using a simulated fECG waveform fed into the gating system. Gated MR images were also acquired from volunteers who were attending for a repeat fetal Central Nervous System (CNS) examination using an additional rapid cardiac imaging sequence triggered from the measured fECG. No adverse safety effects were encountered. This is the first time fECG gating has been used with MRI and opens up a range of new possibilities to study a developing foetus.


Asunto(s)
Técnicas de Imagen Sincronizada Cardíacas/instrumentación , Electrocardiografía/instrumentación , Feto/anatomía & histología , Feto/fisiología , Imagen por Resonancia Magnética/instrumentación , Diagnóstico Prenatal/instrumentación , Imagen de Cuerpo Entero/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
13.
PLoS One ; 8(6): e66186, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23762480

RESUMEN

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm², P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference -0.56IU/L, P = 0.006; osteocalcin, mean difference -3.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference -5%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P>0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease.


Asunto(s)
Prótesis de Cadera , Prótesis Articulares de Metal sobre Metal , Osteoartritis de la Cadera/cirugía , Biomarcadores/sangre , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/sangre , Factores de Tiempo , Resultado del Tratamiento
14.
Interface Focus ; 3(2): 20120065, 2013 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-24427520

RESUMEN

We construct the components for a family of computational models of the electrophysiology of the human foetal heart from 60 days gestational age (DGA) to full term. This requires both cell excitation models that reconstruct the myocyte action potentials, and datasets of cardiac geometry and architecture. Fast low-angle shot and diffusion tensor magnetic resonance imaging (DT-MRI) of foetal hearts provides cardiac geometry with voxel resolution of approximately 100 µm. DT-MRI measures the relative diffusion of protons and provides a measure of the average intravoxel myocyte orientation, and the orientation of any higher order orthotropic organization of the tissue. Such orthotropic organization in the adult mammalian heart has been identified with myocardial sheets and cleavage planes between them. During gestation, the architecture of the human ventricular wall changes from being irregular and isotropic at 100 DGA to an anisotropic and orthotropic architecture by 140 DGA, when it has the smooth, approximately 120° transmural change in myocyte orientation that is characteristic of the adult mammalian ventricle. The DT obtained from DT-MRI provides the conductivity tensor that determines the spread of potential within computational models of cardiac tissue electrophysiology. The foetal electrocardiogram (fECG) can be recorded from approximately 60 DGA, and RR, PR and QT intervals between the P, R, Q and T waves of the fECG can be extracted by averaging from approximately 90 DGA. The RR intervals provide a measure of the pacemaker rate, the QT intervals an index of ventricular action potential duration, and its rate-dependence, and so these intervals constrain and inform models of cell electrophysiology. The parameters of models of adult human sinostrial node and ventricular cells that are based on adult cell electrophysiology and tissue molecular mapping have been modified to construct preliminary models of foetal cell electrophysiology, which reproduce these intervals from fECG recordings. The PR and QR intervals provide an index of conduction times, and hence propagation velocities (approx. 1-10 cm s(-1), increasing during gestation) and so inform models of tissue electrophysiology. Although the developing foetal heart is small and the cells are weakly coupled, it can support potentially lethal re-entrant arrhythmia.

15.
Radiology ; 257(3): 802-9, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20876389

RESUMEN

PURPOSE: To establish whether fetal exposure to the operating noise of 1.5-T magnetic resonance (MR) imaging is associated with cochlear injury and subsequent hearing loss in neonates. MATERIALS AND METHODS: The study was performed with local research ethics committee approval and written informed parental consent. Neonatal hearing test results, including otoacoustic emission (OAE) data, were sought for all neonates delivered in Sheffield who had previously undergone in utero MR imaging between August 1999 and September 2007. The prevalence of hearing impairment in these neonates was determined, with corresponding 95% confidence intervals calculated by using the binomial exact method, and mean OAE measurements were compared with anonymized local audiometric reference data by using the t test. RESULTS: One hundred three neonates who had undergone in utero MR imaging were identified; 96 of them had completed hearing screening assessment. Thirty-four of these babies were admitted to the neonatal intensive care unit (NICU), and one of them had bilateral hearing impairment. The prevalence of hearing impairment was 1% (one of 96; 95% confidence interval: 0.03%, 5.67%), which is in accordance with the prevalence expected, given the high proportion of babies in this study who had been in the NICU (ie, NICU graduates). In addition, for the well babies, there was no significant difference in mean OAE cochlear response compared with that for a reference data set of more than 16,000 OAE results. When NICU graduates were included in the comparison, a significant difference (P = .002) was found in one of four frequency bands used to analyze the cochlear response; however, this difference was small compared with the normal variation in OAE measurements. CONCLUSION: The findings in this study provide some evidence that exposure of the fetus to 1.5-T MR imaging during the second and third trimesters of pregnancy is not associated with an increased risk of substantial neonatal hearing impairment.


Asunto(s)
Estimulación Acústica , Cóclea/fisiología , Trastornos de la Audición/diagnóstico , Imagen por Resonancia Magnética/efectos adversos , Tamizaje Neonatal/métodos , Ruido , Femenino , Edad Gestacional , Trastornos de la Audición/epidemiología , Trastornos de la Audición/fisiopatología , Humanos , Recién Nacido , Masculino , Emisiones Otoacústicas Espontáneas , Embarazo , Prevalencia , Factores de Riesgo
16.
Dev Med Child Neurol ; 52(7): 652-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20132141

RESUMEN

AIM: The aim of this study was to determine if apparent diffusion coefficients (ADCs) generated with diffusion-weighted imaging of cerebral white matter and the cerebellum are affected by white matter damage. METHOD: Seventy-two preterm infants (32 males, 40 females; mean gestational age at birth 30.3 wks, SD 3.0 wks; mean birthweight 1458g, SD 534g) underwent magnetic resonance imaging of the brain around term-equivalent age and were categorized into three groups: normal, overt abnormality, and diffuse excessive high signal intensity (DEHSI). ADC values were calculated from cerebral white matter, cerebellar hemispheres, and cerebellar midline, and were compared between groups. Regression analysis identified clinical parameters correlated with ADC values. RESULTS: Imaging was normal in 27 infants, and revealed overt abnormalities in 14 and DEHSI in 31. ADC values did not differ between groups. ADC values from cerebral white matter were negatively correlated with the number of episodes of postnatal sepsis (p=0.002). ADC values from cerebellar hemispheres (p=0.007) and cerebellar midline (p=0.036) correlated with gestational age at birth. INTERPRETATION: ADC values from white matter are not altered in preterm infants with DEHSI but are negatively correlated with the number of episodes of postnatal sepsis. ADC values in the cerebellum are not altered by white matter damage, but are affected by preterm birth itself.


Asunto(s)
Encéfalo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Recien Nacido Prematuro , Sepsis/patología , Encéfalo/anomalías , Cerebelo/anomalías , Cerebelo/patología , Femenino , Humanos , Recién Nacido , Masculino , Fibras Nerviosas Mielínicas/patología , Nacimiento Prematuro , Análisis de Regresión
17.
Magn Reson Med ; 60(5): 1147-54, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18956466

RESUMEN

Direct-MR neuronal detection (DND) of transient magnetic fields has recently been investigated as a novel imaging alternative to the conventional BOLD functional MRI (fMRI) technique. However, there remain controversial issues and debate surrounding this methodology, and this study attempts clarification by comparing BOLD responses in the human visual system with those of DND. BOLD relies on indirectly measuring blood oxygenation and flow changes as a result of neuronal activity, whereas the putative DND method is based on the hypothesis that the components of the in vivo neuronal magnetic fields, which lie parallel to the B(0) field, can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. Block paradigms of checkerboard patterns were used for visual stimulation in both DND and BOLD experiments, allowing detection based on different frequency responses. This study shows colocalization of some voxels with slow BOLD responses and putative fast DND responses using General Linear Model (GLM) analysis. Frequency spectra for the activated voxel cluster are also shown for both stimulated and control data. The mean percentage signal change for the DND responses is 0.2%, corresponding to a predicted neuronal field of 0.14 nT.


Asunto(s)
Mapeo Encefálico/métodos , Potenciales Evocados Visuales/fisiología , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Neuronas/fisiología , Corteza Visual/fisiología , Adulto , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/citología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Corteza Visual/citología
18.
J Magn Reson Imaging ; 28(5): 1061-7, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18972346

RESUMEN

PURPOSE: To estimate the levels of basal ganglia iron levels in Parkinson's disease (PD) using the PRIME MR sequence at 3.0 Tesla, in relation to patients' motor symptom severity. MATERIALS AND METHODS: Seventy patients with PD and 10 healthy controls underwent assessment of movement and MR imaging. Mean R2' relaxation rates were recorded in the substantia nigra, frontal white matter and in the rostral, mid, and caudal putamen. RESULTS: R2' relaxation rates were significantly higher in patients with PD than in healthy controls. R2' in the most affected substantia nigra correlated with PD patients' motor symptom severity, but not with disease duration. Neuroradiological observation revealed a rostral to caudal "gradient" of putaminal hypointensity. This was substantiated by the finding that the mid and caudal putamen showed significantly higher R2' relaxation rates, consistent with higher iron levels in PD relative to the healthy controls. CONCLUSION: MRI at 3.0 Tesla suggests that substantia nigra iron levels are increased and linked to the severity of motor symptoms experienced in PD. Findings consistent with increased iron levels in the PD putamen are shown, in a region-specific rostral to caudal gradient.


Asunto(s)
Algoritmos , Ganglios Basales/metabolismo , Interpretación de Imagen Asistida por Computador/métodos , Hierro/análisis , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Ganglios Basales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
Pediatr Dev Pathol ; 11(1): 1-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18237232

RESUMEN

The decline in the postmortem (PM) autopsy rate in the United Kingdom paralleled the change in public perception of this procedure after the organ retention crisis in 2000. The introduction of magnetic resonance imaging (MRI) in the fetal, perinatal, and pediatric autopsy led some investigators to propose that MRI could replace the conventional PM. We assessed the role of MRI in fetal autopsy as an addition or a potential replacement method to the conventional PM and to evaluate the benefits and limitations of each technique. We retrospectively reviewed the PM and MRI examination of 100 fetuses. The MRI was limited to the brain or brain and spinal cord. Forty-six cases involved termination of pregnancy; 30 were intrauterine fetal deaths/stillbirths; 16 were premature deliveries followed by neonatal death; and 8 were miscarriages. The mean gestational age of all cases was 25.54 weeks (range: 13-41 weeks). In 54 of the 90 full PMs, there was a complete agreement between the MRI and autopsy findings on the morphology of the brain and spine. Despite this agreement, the information gained at the PM was relevant to find the cause or mechanism of death in 20 of 54 cases (37%). In 24 autopsies the MRI added valuable information to the autopsy. However, if MRI had been the only investigation, essential information would have been lost in 17 of 24 cases (71%). In 12 cases the PM was clearly superior to the MRI. The integrated result obtained from the traditional autopsy remains crucial in determining the cause or mechanism of the malformation or of the fetal/perinatal death and accordingly is important for the counseling offered to parents regarding the recurrence risk for future pregnancies.


Asunto(s)
Autopsia/métodos , Imagen por Resonancia Magnética , Sistema Nervioso Central/patología , Muerte Fetal/diagnóstico , Feto/patología , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos , Sensibilidad y Especificidad , Mortinato
20.
J Magn Reson Imaging ; 26(2): 265-73, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17654726

RESUMEN

PURPOSE: To investigate the possibility of detecting visually-evoked axonal currents in the splenium of the human corpus callosum using a 3.0T MRI system. MATERIALS AND METHODS: Axonal currents produce weak and transient magnetic fields, and the components of these that lie parallel to the B(0) field of the MRI system can potentially modulate the MR signal, which can be detected as an integrated effect over time. A fast gradient-echo echo-planar imaging (GE-EPI) sequence with short TR and intermediate TE was employed in an attempt to detect such axonal currents using light-emitting diode (LED) visual stimulation paradigms. RESULTS: The mean magnitude signal change, expressed relative to the fully relaxed equilibrium signal calculated from the measured value using the known T1 of white matter, was 0.014 +/- 0.004% at TE = 30 msec. This corresponded to a mean axonal field of 0.11 +/- 0.03 nT, according to the hypothesis that the axonal currents create a Lorentzian field distribution within an imaging voxel. CONCLUSION: Measured frequency spectra and statistical mapping using the general linear model (GLM) showed evidence of the stimulus localized within the splenium of the corpus callosum, which was not thought to be due to motion artifacts or physiological responses.


Asunto(s)
Axones/patología , Cuerpo Calloso/anatomía & histología , Cuerpo Calloso/patología , Imagen Eco-Planar/métodos , Imagen por Resonancia Magnética/métodos , Potenciales de Acción , Adulto , Axones/metabolismo , Campos Electromagnéticos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Luz , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Estimulación Luminosa
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