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Introduction: Dynamic contrast-enhanced (DCE) MRI and arterial spin labeling (ASL) MRI enable non-invasive measurement of renal blood flow (RBF), whereas blood oxygenation level-dependent (BOLD) MRI enables non-invasive measurement of the apparent relaxation rate (R2*), an indicator of oxygenation. This study was conducted to evaluate the potential role of these MRI modalities in assessing RBF and oxygenation in dogs. The correlation between contrast-enhanced ultrasound (CEUS) and the MRI modalities was examined and also the ability of the MRI modalities to detect pharmacologically induced changes. Methods: RBF, using CEUS, ASL- and DCE-MRI, as well as renal oxygenation, using BOLD-MRI of eight adult beagles were assessed at two time-points, 23 weeks apart. During each time point, the anesthetized dogs received either a control (0.9% sodium chloride) or a dopamine treatment. For each time point, measurements were carried out over 2 days. An MRI scan at 3 T was performed on day one, followed by CEUS on day two. Results: Using the model-free model with caudal placement of the arterial input function (AIF) region of interest (ROI) in the aorta, the DCE results showed a significant correlation with ASL measured RBF and detected significant changes in blood flow during dopamine infusion. Additionally, R2* negatively correlated with ASL measured RBF at the cortex and medulla, as well as with medullary wash-in rate (WiR) and peak intensity (PI). ASL measured RBF, in its turn, showed a positive correlation with cortical WiR, PI, area under the curve (AUC) and fall time (FT), and with medullary WiR and PI, but a negative correlation with medullary rise time (RT). During dopamine infusion, BOLD-MRI observed a significant decrease in R2* at the medulla and entire kidney, while ASL-MRI demonstrated a significant increase in RBF at the cortex, medulla and the entire kidney. Conclusion: ASL- and BOLD-MRI can measure pharmacologically induced changes in renal blood flow and renal oxygenation in dogs and might allow detection of changes that cannot be observed with CEUS. However, further research is needed to confirm the potential of ASL- and BOLD-MRI in dogs and to clarify which analysis method is most suitable for DCE-MRI in dogs.
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Arterial spin labeling (ASL) MRI allows non-invasive quantification of renal blood flow (RBF) and shows great potential for renal assessment. To our knowledge, renal ASL-MRI has not previously been performed in dogs. The aim of this pilot study was to determine parameters essential for ALS-MRI-based quantification of RBF in dogs: T1, blood (longitudinal relaxation time), λ (blood tissue partition coefficient) and TI (inversion time). A Beagle was scanned at 3T with a multi-TI ASL sequence, with TIs ranging from 250 to 2500 ms, to determine the optimal TI value. The T1 of blood for dogs was determined by scanning a blood sample with a 2D IR TSE sequence. The water content of the dog's kidney was determined by analyzing kidney samples from four dogs with a moisture analyzer and was subsequently used to calculate λ. The optimal TI and the measured values for T1,blood, and λ were 2000 ms, 1463 ms and 0.91 mL/g, respectively. These optimized parameters for dogs resulted in lower RBF values than those obtained from inline generated RBF maps. In conclusion, this study determined preliminary parameters essential for ALS-MRI-based RBF quantification in dogs. Further research is needed to confirm these values, but it may help guide future research.
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Background: Elevated tumor tissue interstitial fluid pressure (IFP) is an adverse biomechanical biomarker that predicts poor therapy response and an aggressive phenotype. Advances in functional imaging have opened the prospect of measuring IFP non-invasively. Image-based estimation of the IFP requires knowledge of the tissue hydraulic conductivity (K), a measure for the ease of bulk flow through the interstitium. However, data on the magnitude of K in human cancer tissue are not available. Methods: We measured the hydraulic conductivity of tumor tissue using modified Ussing chambers in surgical resection specimens. The effect of the tumor microenvironment (TME) on K was investigated by quantifying the collagen content, cell density, and fibroblast density of the tested samples using quantitative immune histochemistry. Also, we developed a computational fluid dynamics (CFD) model to evaluate the role of K on interstitial fluid flow and drug transport in solid tumors. Results: The results show that the hydraulic conductivity of human tumor tissues is very limited, ranging from approximately 10-15 to 10-14 m2/Paâs. Moreover, K values varied significantly between tumor types and between different samples from the same tumor. A significant inverse correlation was found between collagen fiber density and hydraulic conductivity values. However, no correlation was detected between K and cancer cell or fibroblast densities. The computational model demonstrated the impact of K on the interstitial fluid flow and the drug concentration profile: higher K values led to a lower IFP and deeper drug penetration. Conclusions: Human tumor tissue is characterized by a very limited hydraulic conductivity, representing a barrier to effective drug transport. The results of this study can inform the development of realistic computational models, facilitate non-invasive IFP estimation, and contribute to stromal targeting anticancer therapies.
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In 2010, the National Institute of Neurological Disorders and Stroke (NINDS) created a set of common data elements (CDEs) to help standardize the assessment and reporting of imaging findings in traumatic brain injury (TBI). However, as opposed to other standardized radiology reporting systems, a visual overview and data to support the proposed standardized lexicon are lacking. We used over 4000 admission computed tomography (CT) scans of patients with TBI from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study to develop an extensive pictorial overview of the NINDS TBI CDEs, with visual examples and background information on individual pathoanatomical lesion types, up to the level of supplemental and emerging information (e.g., location and estimated volumes). We documented the frequency of lesion occurrence, aiming to quantify the relative importance of different CDEs for characterizing TBI, and performed a critical appraisal of our experience with the intent to inform updating of the CDEs. In addition, we investigated the co-occurrence and clustering of lesion types and the distribution of six CT classification systems. The median age of the 4087 patients in our dataset was 50 years (interquartile range, 29-66; range, 0-96), including 238 patients under 18 years old (5.8%). Traumatic subarachnoid hemorrhage (45.3%), skull fractures (37.4%), contusions (31.3%), and acute subdural hematoma (28.9%) were the most frequently occurring CT findings in acute TBI. The ranking of these lesions was the same in patients with mild TBI (baseline Glasgow Coma Scale [GCS] score 13-15) compared with those with moderate-severe TBI (baseline GCS score 3-12), but the frequency of occurrence was up to three times higher in moderate-severe TBI. In most TBI patients with CT abnormalities, there was co-occurrence and clustering of different lesion types, with significant differences between mild and moderate-severe TBI patients. More specifically, lesion patterns were more complex in moderate-severe TBI patients, with more co-existing lesions and more frequent signs of mass effect. These patients also had higher and more heterogeneous CT score distributions, associated with worse predicted outcomes. The critical appraisal of the NINDS CDEs was highly positive, but revealed that full assessment can be time consuming, that some CDEs had very low frequencies, and identified a few redundancies and ambiguity in some definitions. Whilst primarily developed for research, implementation of CDE templates for use in clinical practice is advocated, but this will require development of an abbreviated version. In conclusion, with this study, we provide an educational resource for clinicians and researchers to help assess, characterize, and report the vast and complex spectrum of imaging findings in patients with TBI. Our data provides a comprehensive overview of the contemporary landscape of TBI imaging pathology in Europe, and the findings can serve as empirical evidence for updating the current NINDS radiologic CDEs to version 3.0.
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An MRI protocol tree on a clinical MRI system is a large database containing hundreds of protocols, each containing multiple sequences, and up to 900 parameters per sequence. Protocol variation between scan sessions or patients must be avoided as much as possible, as it may lead to financial loss and less than optimal outcomes for the patient. Without proper management, protocol variation and errors in MRI protocol trees are easily introduced and may remain undetected, leading to a cluttered protocol tree. This in turn reduces the efficiency of the radiological MRI workflow. We introduce a method and open-source software tools for managing MRI protocols on a sequence parameter level, which can detect deviations and variations in the protocol tree. It can be used offline, away from the scanner console, without disturbing the clinical workflow. These tools help to create a standardized protocol library across multiple MRI scanners, reducing variation and errors, enabling radiology departments to create optimal value for the patient and institution.
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Imageamento por Ressonância Magnética , Árvores , Humanos , SoftwareRESUMO
Inadequate uptake of therapeutic agents by tumor cells is still a major barrier in clinical cancer therapy. Mathematical modeling is a powerful tool to describe and investigate the transport phenomena involved. However, current models for interstitial flow and drug delivery in solid tumors have not yet embedded the existing heterogeneity of tumor biomechanical properties. The purpose of this study is to introduce a novel and more realistic methodology for computational models of solid tumor perfusion and drug delivery accounting for these regional heterogeneities as well as lymphatic drainage effects. Several tumor geometries were studied using an advanced computational fluid dynamics (CFD) modeling approach of intratumor interstitial fluid flow and drug transport. Hereby, the following novelties were implemented: (i) the heterogeneity of tumor-specific hydraulic conductivity and capillary permeability; (ii) the effect of lymphatic drainage on interstitial fluid flow and drug penetration. Tumor size and shape both have a crucial role on the interstitial fluid flow regime as well as drug transport illustrating a direct correlation with interstitial fluid pressure (IFP) and an inverse correlation with drug penetration, except for large tumors having a diameter larger than 50 mm. The results also suggest that the interstitial fluid flow and drug penetration in small tumors depend on tumor shape. A parameter study on the necrotic core size illustrated that the core effect (i.e. fluid flow and drug penetration alteration) was only profound in small tumors. Interestingly, the impact of a necrotic core on drug penetration differs depending on the tumor shape from having no effect in ideally spherical tumors to a clear effect in elliptical tumors with a necrotic core. A realistic presence of lymphatic vessels only slightly affected tumor perfusion, having no substantial effect on drug delivery. In conclusion, our findings illustrated that our novel parametric CFD modeling strategy in combination with accurate profiling of heterogeneous tumor biophysical properties can provide a powerful tool for better insights into tumor perfusion and drug transport, enabling effective therapy planning.
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Neoplasias , Humanos , Neoplasias/patologia , Transporte Biológico , Modelos Teóricos , Sistemas de Liberação de Medicamentos , Líquido ExtracelularRESUMO
BACKGROUND: Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally, we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline. METHODS: High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test-Revised (HVLT-R). RESULTS: HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory. CONCLUSIONS: HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.
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Lesões Encefálicas , Neoplasias Encefálicas , Neoplasias Pulmonares , Intervenção Coronária Percutânea , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/prevenção & controle , Irradiação Craniana/efeitos adversos , Hipocampo/efeitos da radiação , Transtornos da MemóriaRESUMO
The physical microenvironment of cancer is characterized by elevated stiffness and tissue pressure, the main component of which is the interstitial fluid pressure (IFP). Elevated IFP is an established negative predictive and prognostic parameter, directly affecting malignant behavior and therapy response. As such, measurement of the IFP would allow to develop strategies aimed at engineering the physical microenvironment of cancer. Traditionally, IFP measurement required the use of invasive methods. Recent progress in dynamic and functional imaging methods such as dynamic contrast enhanced (DCE) magnetic resonance imaging and elastography, combined with numerical models and simulation, allows to comprehensively assess the biomechanical landscape of cancer, and may help to overcome physical barriers to drug delivery and immune cell infiltration. Here, we provide a comprehensive overview of the origin of elevated IFP, and its role in the malignant phenotype. Also, we review the methods used to measure IFP using invasive and imaging based methods, and highlight remaining obstacles and potential areas of progress in order to implement IFP measurement in clinical practice.
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Líquido Extracelular , Neoplasias , Biomarcadores , Líquido Extracelular/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias/patologia , Pressão , Microambiente TumoralRESUMO
PURPOSE: Thiel embalming followed by freezing in the desired position and acquiring CTâ¯+ MRI scans is expected to be the ideal approach to obtain accurate, enhanced CT data for delineation guideline development. The effect of Thiel embalming and freezing on MRI image quality is not known. This study evaluates the above-described process to obtain enhanced CT datasets, focusing on the integration of MRI data obtained from frozen, Thiel-embalmed specimens. METHODS: Three Thiel-embalmed specimens were frozen in prone crawl position and MRI scanning protocols were evaluated based on contrast detail and structural conformity between 3D renderings from corresponding structures, segmented on corresponding MRI and CT scans. The measurement error of the dataset registration procedure was also assessed. RESULTS: Scanning protocol T1 VIBE FS enabled swift differentiation of soft tissues based on contrast detail, even allowing a fully detailed segmentation of the brachial plexus. Structural conformity between the reconstructed structures on CT and MRI was excellent, with nerves and blood vessels imported into the CT scan never intersecting with the bones. The mean measurement error for the image registration procedure was consistently in the submillimeter range (range 0.77-0.94â¯mm). CONCLUSION: Based on the excellent MRI image quality and the submillimeter error margin, the procedure of scanning frozen Thiel-embalmed specimens in the treatment position to obtain enhanced CT scans is recommended. The procedure can be used to support the postulation of delineation guidelines, or for training deep learning algorithms, considering automated segmentations.
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Embalsamamento , Imageamento por Ressonância Magnética , Cadáver , Embalsamamento/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: MRI is the imaging modality of choice for soft tissue-related spine disease. However, CT is superior to MRI in providing clear visualization of bony morphology. The purpose of this study is to test equivalency of MRI-based synthetic CT to conventional CT in quantitatively assessing bony morphology of the lumbar spine. METHOD: A prospective study with an equivalency design was performed. Adult patients who had undergone MRI and CT of the lumbar spine were included. Synthetic CT images were generated from MRI using a deep learning-based image synthesis method. Two readers independently measured pedicle width, spinal canal width, neuroforamen length, anterior and posterior vertebral body height, superior and inferior vertebral body length, superior and inferior vertebral body width, maximal disc height, lumbar curvature and spinous process length on synthetic CT and CT. The agreement among CT and synthetic CT was evaluated using equivalency statistical testing. RESULTS: Thirty participants were included (14 men and 16 women, range 20-60 years). The measurements performed on synthetic CT of pedicle width, spinal canal width, vertebral body height, vertebral body width, vertebral body length and spinous process length were statistically equivalent to CT measurements at the considered margins. Excellent inter- and intra-reader reliability was found for both synthetic CT and CT. CONCLUSIONS: Equivalency of MRI-based synthetic CT to CT was demonstrated on geometrical measurements in the lumbar spine. In combination with the soft tissue information of the conventional MRI, this provides new possibilities in diagnosis and surgical planning without ionizing radiation.
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Vértebras Lombares , Imageamento por Ressonância Magnética , Adulto , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.
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To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.
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Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/tendências , Nefrologia/tendências , Pesquisa Translacional Biomédica/tendências , Consenso , Técnica Delphi , Humanos , Comunicação Interdisciplinar , Imageamento por Ressonância Magnética/instrumentação , Inquéritos e QuestionáriosRESUMO
PURPOSE: The potential of renal MRI biomarkers has been increasingly recognised, but clinical translation requires more standardisation. The PARENCHIMA consensus project aims to develop and apply a process for generating technical recommendations on renal MRI. METHODS: A task force was formed in July 2018 focused on five methods. A draft process for attaining consensus was distributed publicly for consultation and finalised at an open meeting (Prague, October 2018). Four expert panels completed surveys between October 2018 and March 2019, discussed results and refined the surveys at a face-to-face meeting (Aarhus, March 2019) and completed a second round (May 2019). RESULTS: A seven-stage process was defined: (1) formation of expert panels; (2) definition of the context of use; (3) literature review; (4) collection and comparison of MRI protocols; (5) consensus generation by an approximate Delphi method; (6) reporting of results in vendor-neutral and vendor-specific terms; (7) ongoing review and updating. Application of the process resulted in 166 consensus statements. CONCLUSION: The process generated meaningful technical recommendations across very different MRI methods, while allowing for improvement and refinement as open issues are resolved. The results are likely to be widely supported by the renal MRI community and thereby promote more harmonisation.
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Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/normas , Nefrologia/normas , Pesquisa Translacional Biomédica/normas , Biomarcadores/metabolismo , Consenso , Técnica Delphi , Europa (Continente) , Prova Pericial , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/tendências , Nefrologia/tendências , Padrões de Referência , Inquéritos e Questionários , Pesquisa Translacional Biomédica/tendências , Estados UnidosRESUMO
OBJECTIVES: Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization. MATERIALS AND METHODS: Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement. RESULTS: Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65-74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided. DISCUSSION: The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.
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Biomarcadores/metabolismo , Imagem de Difusão por Ressonância Magnética , Rim/diagnóstico por imagem , Pesquisa Translacional Biomédica , Algoritmos , Consenso , Técnica Delphi , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Rim/metabolismo , Modelos Estatísticos , Movimento (Física) , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Observer variability in local radiological reading is a major concern in large-scale multi-center traumatic brain injury (TBI) studies. A central review process has been advocated to minimize this variability. The aim of this study is to compare central with local reading of TBI imaging datasets and to investigate the added value of central review. A total of 2050 admission computed tomography (CT) scans from subjects enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were analyzed for seven main CT characteristics. Kappa statistics were used to calculate agreement between central and local evaluations and a center-specific analysis was performed. The McNemar test was used to detect whether discordances were significant. Central interobserver and intra-observer agreement was calculated in a subset of patients. Good agreement was found between central and local assessment for the presence or absence of structural pathology (CT+, CT-, κ = 0.73) and most CT characteristics (κ = 0.62 to 0.71), except for traumatic axonal injury lesions (κ = 0.37). Despite good kappa values, discordances were significant in four of seven CT characteristics (i.e., midline shift, contusion, traumatic subarachnoid hemorrhage, and cisternal compression; p = 0.0005). Central reviewers showed substantial to excellent interobserver and intra-observer agreement (κ = 0.73 to κ = 0.96), contrasted by considerable variability in local radiological reading. Compared with local evaluation, a central review process offers a more consistent radiological reading of acute CT characteristics in TBI. It generates reliable, reproducible data and should be recommended for use in multi-center TBI studies.
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Lesões Encefálicas Traumáticas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Pesquisa , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Diffusion kurtosis imaging (DKI) is an advanced magnetic resonance imaging modality that is known to be sensitive to changes in the underlying microstructure of the brain. Image voxels in diffusion weighted images, however, are typically relatively large making them susceptible to partial volume effects, especially when part of the voxel contains cerebrospinal fluid. In this work, we introduce the "Diffusion Kurtosis Imaging with Free Water Elimination" (DKI-FWE) model that separates the signal contributions of free water and tissue, where the latter is modeled using DKI. THEORY AND METHODS: A theoretical study of the DKI-FWE model, including an optimal experiment design and an evaluation of the relative goodness of fit, is carried out. To stabilize the ill-conditioned estimation process, a Bayesian approach with a shrinkage prior (BSP) is proposed. In subsequent steps, the DKI-FWE model and the BSP estimation approach are evaluated in terms of estimation error, both in simulation and real data experiments. RESULTS: Although it is shown that the DKI-FWE model parameter estimation problem is ill-conditioned, DKI-FWE was found to describe the data significantly better compared to the standard DKI model for a large range of free water fractions. The acquisition protocol was optimized in terms of the maximally attainable precision of the DKI-FWE model parameters. The BSP estimator is shown to provide reliable DKI-FWE model parameter estimates. CONCLUSION: The combination of the DKI-FWE model with BSP is shown to be a feasible approach to estimate DKI parameters, while simultaneously eliminating free water partial volume effects. Magn Reson Med 80:802-813, 2018. © 2018 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 NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Imagem de Tensor de Difusão/métodos , Processamento de Imagem Assistida por Computador/métodos , Adulto , Algoritmos , Teorema de Bayes , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Modelos Estatísticos , Água/químicaRESUMO
BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 106 cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI). METHODS: Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 106, 3 × 105, or 5 × 104 ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis. RESULTS: The ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of stroke volumes revealed an increased infarction after injection of 1 × 106 ASCs compared to controls or application of 5 × 104 ASCs (p < 0.05). At 9 days post-MCAo, injection of 3 × 105 ASCs resulted in reduced infarct volumes (p < 0.05). Correspondingly, MRI analysis revealed no changes in cell numbers between both MRI examinations but showed active ASC migration to the site of infarction. CONCLUSION: Our results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 106 cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome.
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Infarto da Artéria Cerebral Média/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Tecido Adiposo/citologia , Animais , Movimento Celular , Rastreamento de Células , Células Cultivadas , Artérias Cerebrais/patologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos Wistar , Células-Tronco/metabolismoRESUMO
PURPOSE: A great need exists for objective biomarkers to assess graft healing following ACL reconstruction to guide the time of return to sports. The purpose of this study was to evaluate the feasibility and reliability of diffusion tensor imaging (DTI) to delineate the anterior cruciate ligament (ACL) graft and to investigate its diffusion properties using a clinical 3T scanner. MATERIALS AND METHODS: DTI of the knee (b = 0, 400, and 800 s/mm2 , 10 diffusion directions, repeated 16 times for a total of 336 diffusion-weighted volumes) was performed at 3T in 17 patients between 3 and 7 months (mean, 4 months) following ACL reconstruction. Tractography was performed by two independent observers to delineate the ACL graft. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated within the graft. Interrater reliability was assessed using the intraclass correlation coefficient (ICC) and the scan-rescan reproducibility was evaluated based on the percentage coefficient of variance (%CV) across 20 repetition bootknife samples. RESULTS: In all subjects, tractography of the ACL graft was feasible. Quantitative evaluation of the diffusion properties of the ACL graft yielded the following mean ± SD values: FA = 0.23 ± 0.04; MD = 1.30 ± 0.11 × 10-3 mm2 /s; AD = 1.61 ± 0.12 × 10-3 mm2 /s, and RD = 1.15 ± 0.11 × 10-3 mm2 /s. Interrater reliability for the DTI parameters was excellent (ICC = 0.91-0.98). Mean %CVs for FA, MD, AD, and RD were 4.6%, 3.5%, 3.7%, and 4.4%, respectively. CONCLUSION: We demonstrated the feasibility and reliability of DTI for the visualization and quantitative evaluation of the ACL graft at 3T. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1423-1432.