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The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'.
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Encéfalo , Imagen de Difusión por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Neuroimagen/métodos , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , HumanosRESUMEN
OBJECTIVES: To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). METHODS: Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T1 was measured. Dynamic series of T1-weighted volumes were then obtained while breathing oxygen. T1-parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO2max), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. RESULTS: Mean CF-CT was 24.1±17.1. Mean ΔPO2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO2max: r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO2max: r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). CONCLUSIONS: Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. KEY POINTS: ⢠Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. ⢠Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. ⢠Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.
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Fibrosis Quística/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Pulmón/fisiopatología , Imagen por Resonancia Magnética/métodos , Oxígeno/administración & dosificación , Tomografía Computarizada por Rayos X/métodos , Adulto , Estudios de Casos y Controles , Fibrosis Quística/fisiopatología , Femenino , Voluntarios Sanos , Humanos , Imagenología Tridimensional , Enfermedades Pulmonares/fisiopatología , Masculino , Pruebas de Función Respiratoria , Adulto JovenRESUMEN
The original version of this article, published on 13 April 2018, unfortunately contained a mistake.
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BACKGROUND: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. OBJECTIVE: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients' Paced-Auditory-Serial-Addition-Test (PASAT) scores. METHODS: Relapsing-remitting MS (RRMS) patients (n = 25) and controls (n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. RESULTS: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. CONCLUSIONS: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.
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Trastornos del Conocimiento/patología , Imagen de Difusión Tensora/métodos , Esclerosis Múltiple Recurrente-Remitente/patología , Vías Nerviosas/patología , Adulto , Anisotropía , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Vías Nerviosas/fisiopatología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases. METHODS: Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan. RESULTS: In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (v(e)), tumour enhancing fraction (E(F)), and microvascular uniformity (assessed with the fractal measure box dimension, d(0)) (R(2)=0.86, P<0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan. CONCLUSION: Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers.
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Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Medios de Contraste , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamiento farmacológico , Imagen por Resonancia Magnética , Anciano , Anticuerpos Monoclonales Humanizados , Bevacizumab , Biomarcadores de Tumor , Neoplasias Colorrectales/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Gadolinio DTPA , Humanos , Leucovorina/uso terapéutico , Neoplasias Hepáticas/secundario , Masculino , Compuestos Organoplatinos/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Dynamic contrast-enhanced MRI (DCE-MRI) is frequently used to provide response biomarkers in clinical trials of novel cancer therapeutics but assessment of their physiological accuracy is difficult. DCE-CT provides an independent probe of similar pharmacokinetic processes and may be modeled in the same way as DCE-MRI to provide purportedly equivalent physiological parameters. In this study, DCE-MRI and DCE-CT were directly compared in subjects with primary bladder cancer to assess the degree to which the model parameters report modeled physiology rather than artefacts of the measurement technique and to determine the interchangeability of the techniques in a clinical trial setting. The biomarker K(trans) obtained by fitting an extended version of the Kety model voxelwise to both DCE-MRI and DCE-CT data was in excellent agreement (mean across subjects was 0.085 ± 0.030 min(-1) for DCE-MRI and 0.087 ± 0.033 min(-1) for DCE-CT, intermodality coefficient of variation 9%). The parameter v(p) derived from DCE-CT was significantly greater than that derived from DCE-MRI (0.018 ± 0.006 compared to 0.009 ± 0.008, P = 0.0007) and v(e) was in reasonable agreement only for low values. The study provides evidence that the biomarker K(trans) is a robust parameter indicative of the underlying physiology and relatively independent of the method of measurement.
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Biomarcadores , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Neoplasias de la Vejiga Urinaria/diagnóstico por imagenRESUMEN
BACKGROUND: Patients with recurrent ovarian cancer often achieve partial response following chemotherapy, resulting in persistent small volume disease. After completion of treatment, the dilemma of when to initiate subsequent chemotherapy arises. Identification of biomarkers that could be used to predict when subsequent treatment is needed would be of significant benefit. DESIGN: Twenty-three patients with advanced ovarian cancer and residual asymptomatic disease following chemotherapy underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at study entry, 4, 8, 12, 18 and 26 weeks or disease progression. A subgroup of patients provided plasma samples within which a panel of angiogenic biomarkers was quantified. RESULTS: By 4 weeks, significant differences in whole tumour volume, enhancing fraction and Ca125 were observed between patients whose disease progressed by 26 weeks and those who remained stable. Significant correlations between plasma soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2 concentrations, and blood volume and tumour endothelial permeability surface area product measured by DCE-MRI were observed. CONCLUSIONS: Imaging markers have a potential role in early prediction of disease progression in patients with residual ovarian cancer and may supplement current measures of progression. The correlation of DCE-MRI and serological biomarkers suggests that tumour angiogenesis affects these markers through common biological means and warrants further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Cistadenocarcinoma Seroso/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias Peritoneales/diagnóstico , Antígeno Ca-125/sangre , Medios de Contraste , Cistadenocarcinoma Seroso/sangre , Cistadenocarcinoma Seroso/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Imagen por Resonancia Magnética , Proteínas de la Membrana/sangre , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estadificación de Neoplasias , Neoplasia Residual/sangre , Neoplasia Residual/tratamiento farmacológico , Neovascularización Patológica , Neoplasias Ováricas/sangre , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/tratamiento farmacológico , Pronóstico , Tasa de Supervivencia , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
PURPOSE: To assess the feasibility of multiple-bolus dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the pancreas; to optimize the analysis; and to investigate application of the method to a glucose challenge in type 2 diabetes. MATERIALS AND METHODS: A 4-bolus DCE-MRI protocol was performed on five patients with type 2 diabetes and 11 healthy volunteers during free-breathing. Motion during the dynamic time series was corrected for using a model-driven nonlinear registration. A glucose challenge was administered intravenously between the first and second DCE-MRI acquisition in all patients and in seven of the healthy controls. RESULTS: Image registration improved the reproducibility of the DCE-MRI model parameters across the repeated bolus-acquisitions in the healthy controls with no glucose challenge (eg, coefficient of variation for K(trans) improved from 38% to 28%). Native tissue T(1) was significantly lower in patients (374 +/- 68 msec) compared with volunteers (519 +/- 41 msec) but there was no significant difference in any of the baseline DCE-MRI parameters. No effect of glucose challenge was observed in either the patients or healthy volunteers. CONCLUSION: Multiple bolus DCE-MRI is feasible in the pancreas and is improved by nonlinear image registration but is not sensitive to the effects of an intravenous glucose challenge.
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Medios de Contraste , Diabetes Mellitus Tipo 2/diagnóstico , Gadolinio DTPA , Imagen por Resonancia Magnética/métodos , Páncreas/anatomía & histología , Adulto , Anciano , Glucemia/análisis , Estudios de Casos y Controles , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Quimioterapia por Pulso , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T(1)-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24-43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was -15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24-47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was -11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection.
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Lobectomía Temporal Anterior/efectos adversos , Epilepsia del Lóbulo Temporal/cirugía , Trastornos de la Visión/etiología , Campos Visuales , Vías Visuales/patología , Adolescente , Adulto , Mapeo Encefálico/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Estudios de Factibilidad , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Lóbulo Temporal/patología , Trastornos de la Visión/patología , Vías Visuales/lesiones , Adulto JovenRESUMEN
Characterization of porous media is essential in a wide range of biomedical and industrial applications. Microstructural features can be probed non-invasively by diffusion magnetic resonance imaging (dMRI). However, diffusion encoding in conventional dMRI may yield similar signatures for very different microstructures, which represents a significant limitation for disentangling individual microstructural features in heterogeneous materials. To solve this problem, we propose an augmented multidimensional diffusion encoding (MDE) framework, which unlocks a novel encoding dimension to assess time-dependent diffusion specific to structures with different microscopic anisotropies. Our approach relies on spectral analysis of complex but experimentally efficient MDE waveforms. Two independent contrasts to differentiate features such as cell shape and size can be generated directly by signal subtraction from only three types of measurements. Analytical calculations and simulations support our experimental observations. Proof-of-concept experiments were applied on samples with known and distinctly different microstructures. We further demonstrate substantially different contrasts in different tissue types of a post mortem brain. Our simultaneous assessment of restriction size and shape may be instrumental in studies of a wide range of porous materials, enable new insights into the microstructure of biological tissues or be of great value in diagnostics.
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Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR.
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Lobectomía Temporal Anterior/efectos adversos , Trastornos del Lenguaje/diagnóstico , Trastornos del Lenguaje/etiología , Adulto , Edad de Inicio , Mapeo Encefálico , Electroencefalografía , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Lóbulo Frontal/patología , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
In a patient with refractory temporal lobe epilepsy, EEG-fMRI showed activation in association with left anterior temporal interictal discharges, in the left temporal, parietal and occipital lobes. Dynamic causal modelling suggested propagation of neural activity from the temporal focus to the area of occipital activation. Tractography showed connections from the site of temporal lobe activation to the site of occipital activation. This demonstrates the principle of combining EEG-fMRI and tractography to delineate the pathways of propagation of epileptic activity.
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Electroencefalografía , Epilepsia del Lóbulo Temporal/fisiopatología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Vías Nerviosas/fisiopatología , Lóbulo Occipital/fisiopatología , Lóbulo Parietal/fisiopatología , Transmisión Sináptica/fisiología , Lóbulo Temporal/fisiopatología , Adulto , Algoritmos , Ritmo Delta , Dominancia Cerebral/fisiología , Potenciales Evocados/fisiología , Humanos , Masculino , Modelos Estadísticos , Neuronas/fisiología , Oxígeno/sangreRESUMEN
PURPOSE: Specific blocking of vascular endothelial growth factor receptor 2 (VEGFR-2) is a novel therapeutic approach. Here, we report the first phase I clinical trial evaluation of CDP791, a PEGylated di-Fab' conjugate that binds VEGFR-2. EXPERIMENTAL DESIGN: Cohorts of patients received CDP791 at doses between 0.3 and 30 mg/kg every 3 weeks for the initial two doses. RESULTS: The compound was well tolerated with no dose-limiting toxicity. Dose-related hypertension was observed in patients receiving CDP791 10 mg/kg or more and several patients on the higher doses developed infusion-related cutaneous hemangiomata arising 28 to 106 days after the first drug administration and resolving 3 weeks after cessation. Biopsy and histologic evaluation showed that CDP791-bound VEGFR-2 is non-phosphorylated, suggesting that the drug is biologically active. Concentrations of CDP791 considered biologically relevant were sustained for 3 weeks when doses of 10 mg/kg or more were administered. Although no reductions in vascular permeability were recorded using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), there was a significant dose level-related reduction in tumor growth. While challenging the recent dogma that active VEGF inhibitors should modulate DCE-MRI measurements of vascular permeability, this highlights the potential of serial three-dimensional tumor measurements to detect tumor growth arrest. Twelve patients received drug for more than two treatments, although no partial or complete responses were seen. CONCLUSION: The data show that CDP791 is biologically active and well tolerated, achieving appropriate plasma concentrations when administered at 10 mg/kg or more every 3 weeks.
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Inhibidores de la Angiogénesis/administración & dosificación , Inmunoconjugados/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Neoplasias/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacocinética , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/farmacocinética , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Fragmentos Fab de Inmunoglobulinas/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias/irrigación sanguínea , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacocinética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
Magnetic resonance imaging (MRI) is a highly versatile imaging modality that can be used to measure features of the tumour microenvironment including cell death, proliferation, metabolism, angiogenesis, and hypoxia. Mapping and quantifying these pathophysiological features has the potential to alter the use of adaptive radiotherapy planning. Although these methods are available for use on diagnostic machines, several challenges exist for implementing these functional MRI methods on the MRI-linear accelerators (linacs). This review considers these challenges and potential solutions.
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Imagen por Resonancia Magnética/métodos , Aceleradores de Partículas , Planificación de la Radioterapia Asistida por Computador/métodos , HumanosRESUMEN
PURPOSE: CDP860 is an engineered Fab' fragment-polyethylene glycol conjugate, which binds to and blocks the activity of the beta-subunit of the platelet-derived growth factor receptor (PDGFR-beta). Studies in animals have suggested that PDGFR-beta inhibition reduces tumor interstitial fluid pressure, and thus increases the uptake of concomitantly administered drugs. The purpose of this study was to determine whether changes in tumor vascular parameters could be detected in humans, and to assess whether CDP860 would be likely to increase the uptake of a concurrently administered small molecule in future studies. PATIENTS AND METHODS: Patients with advanced ovarian or colorectal cancer and good performance status received intravenous infusions of CDP860 on days 0 and 28. Patients had serial dynamic contrast-enhanced magnetic resonance imaging studies to measure changes in tumor vascular parameters. RESULTS: Three of eight patients developed significant ascites, and seven of eight showed evidence of fluid retention. In some patients, the ratio of vascular volume to total tumor volume increased significantly (P < .001) within 24 hours following CDP860 administration, an effect suggestive of recruitment of previously non-functioning vessels. CONCLUSION: These observations suggest that inhibition of PDGFR-beta might improve delivery of a concurrently administered therapy. However, in cancer patients, further exploration of the dosing regimen of CDP860 is required to dissociate adverse effects from beneficial effects. The findings challenge the view that inhibition of PDGF alone is beneficial, and confirm that effects of PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in patients treated with mixed tyrosine kinase inhibitors.
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Neoplasias del Colon/irrigación sanguínea , Líquido Extracelular/metabolismo , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Neoplasias Ováricas/irrigación sanguínea , Polietilenglicoles/uso terapéutico , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Neoplasias del Recto/irrigación sanguínea , Adulto , Anciano , Ascitis/etiología , Permeabilidad Capilar/fisiología , Medios de Contraste , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Derrame Pleural/etiología , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Flujo Sanguíneo Regional/fisiología , Carga TumoralRESUMEN
BACKGROUND AND PURPOSE: A number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI-derived parameters and histologic features in glioblastoma multiforme. MATERIALS AND METHODS: Twenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined. RESULTS: High values of contrast transfer coefficient were associated with the presence of frank necrosis (P = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern (P < .01) and with increased mitotic activity (P < .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern. CONCLUSIONS: A correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Adulto , Neoplasias Encefálicas/patología , Medios de Contraste , Espacio Extracelular/diagnóstico por imagen , Femenino , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Diffusion-weighted MR images provide information that is present in no other imaging modality. Whilst some of this information may be appreciated visually in diffusion weighted images, much of it may be extracted only with the aid of data post-processing. This review summarizes the methods available for interpreting diffusion weighted imaging (DWI) information using the diffusion tensor and other models of the DWI signal. This is followed by an overview of methods that allow the estimation of fibre tract orientation and that provide estimates of the routes and degree of anatomical cerebral white matter connectivity.
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Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Anisotropía , Encéfalo/anatomía & histología , Encéfalo/fisiología , Humanos , Modelos BiológicosRESUMEN
We report on a pilot study of dynamic lung electrical impedance tomography (EIT) at the University of Manchester. Low-noise EIT data at 100 frames per second were obtained from healthy male subjects during controlled breathing, followed by magnetic resonance imaging (MRI) subsequently used for spatial validation of the EIT reconstruction. The torso surface in the MR image and electrode positions obtained using MRI fiducial markers informed the construction of a 3D finite element model extruded along the caudal-distal axis of the subject. Small changes in the boundary that occur during respiration were accounted for by incorporating the sensitivity with respect to boundary shape into a robust temporal difference reconstruction algorithm. EIT and MRI images were co-registered using the open source medical imaging software, 3D Slicer. A quantitative comparison of quality of different EIT reconstructions was achieved through calculation of the mutual information with a lung-segmented MR image. EIT reconstructions using a linear shape correction algorithm reduced boundary image artefacts, yielding better contrast of the lungs, and had 10% greater mutual information compared with a standard linear EIT reconstruction.
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Imagenología Tridimensional/métodos , Pulmón/fisiología , Tomografía/métodos , Algoritmos , Impedancia Eléctrica , Electrodos , Análisis de Elementos Finitos , Humanos , Imagenología Tridimensional/instrumentación , Imagen por Resonancia Magnética , Masculino , Reproducibilidad de los Resultados , Tomografía/instrumentaciónRESUMEN
BACKGROUND: Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers. METHODS: Sixty patients were randomised to receive two single doses of cediranib in either fed/fasted or fasted/fed state (Part A). In continual dosage phase (Part B), patients were randomised to a fixed-dose or dose-escalation arm. Exploratory pharmacodynamic assessments were performed using DCE-MRI and CT enhancing fraction (EnF). RESULTS: In part A, plasma AUC and C (max) of cediranib were lower in the presence of food by a mean of 24 and 33%, respectively (94% CI: AUC, 12-34% and C (max), 20-43%), indicating food reduces cediranib plasma exposure. In part B, cediranib 30 mg/day appeared to be the most sustainable for chronic dosing. Continuous cediranib therapy was associated with sustained antivascular effects up to 16 weeks, with significant reductions in DCE-MRI parameters and CT EnF. CONCLUSIONS: It is recommended that cediranib be administered at least 1 h before or 2 h after food. Evidence of antitumour activity was observed, with significant sustained effects upon imaging vascular parameters.
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Neoplasias/tratamiento farmacológico , Quinazolinas/farmacocinética , Quinazolinas/uso terapéutico , Adulto , Anciano , Área Bajo la Curva , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Electrocardiografía/efectos de los fármacos , Ayuno/metabolismo , Femenino , Interacciones Alimento-Droga , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias/patología , Quinazolinas/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: ADC measurements have been shown to have an inverse relationship with tumor cell density. DCE-MR imaging modeling techniques can produce a measurement of the v(e), which would also be expected to have an inverse relationship with cell density. The objective of this study was to test the hypothesis that areas of increased cellularity, and therefore low ADC, would be expected to have a small EES (low v(e)). MATERIALS AND METHODS: Nineteen patients with GBM were recruited. All imaging was performed before surgery on a 3T MR imaging scanner. Imaging included diffusion tensor imaging, T1-weighted DCE-MR imaging, and anatomic sequences. Tumor VOIs were defined on the anatomic images and modified to contain only enhancing voxels. Parametric maps of ADC and v(e) were generated. Statistical analysis of ADC and v(e) was performed on both a voxel-by-voxel basis and comparison of median values. RESULTS: No correlation was demonstrated between ADC and v(e) in either a voxel-by-voxel analysis or comparison of median values (P = .124). CONCLUSIONS: This study failed to demonstrate a correlation between ADC and v(e). This is important because it suggests that though the mechanisms underlying these parameters are theoretically similar, they actually reflect different aspects of tumor microenvironment. Consequently ADC and v(e) should be considered to provide independent information about the properties of the EES.