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BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). METHODS: Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. RESULTS: QSM visualized two renal calcifications measuring 9 and 10 mm and three pelvic phleboliths measuring 2 mm but missed 24 calcifications measuring 1 mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. CONCLUSION: Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.
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Hemorragia , Cálculos Renales , Imagen por Resonancia Magnética , Riñón Poliquístico Autosómico Dominante , Humanos , Femenino , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/complicaciones , Masculino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto , Hemorragia/diagnóstico por imagen , Cálculos Renales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Estudios de Factibilidad , Diagnóstico Diferencial , Interpretación de Imagen Asistida por Computador/métodos , AncianoRESUMEN
PURPOSE: To develop a tissue field-filtering algorithm, called maximum spherical mean value (mSMV), for reducing shadow artifacts in QSM of the brain without requiring brain-tissue erosion. THEORY AND METHODS: Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field-magnitude values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. RESULTS: Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke, and multiple sclerosis. CONCLUSION: The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Algoritmos , ArtefactosRESUMEN
Quantification of the myelin content of the white matter is important for studying demyelination in neurodegenerative diseases such as Multiple Sclerosis (MS), particularly for longitudinal monitoring. A novel noninvasive MRI method, called Microstructure-Informed Myelin Mapping (MIMM), is developed to quantify the myelin volume fraction (MVF) by utilizing a multi gradient echo sequence (mGRE) and a detailed biophysical model of tissue microstructure. Myelin is modeled as anisotropic negative susceptibility source based on the Hollow Cylindrical Fiber Model (HCFM), and iron as isotropic positive susceptibility source in the extracellular region. Voxels with a range of biophysical parameters are simulated to create a dictionary of MR echo time magnitude signals and total susceptibility values. MRI signals measured using a mGRE sequence are then matched voxel-by-voxel to the created dictionary to obtain the spatial distributions of myelin and iron. Three different MIMM versions are presented to deal with the fiber orientation dependent susceptibility effects of the myelin sheaths: a basic variation, which assumes fiber orientation is an unknown to fit, two orientation informed variations, which assume the fiber orientation distribution is available either from a separate diffusion tensor imaging (DTI) acquisition or from a DTI atlas based fiber orientation map. While all showed a significant linear correlation with the reference method based on T2-relaxometry (p < 0.0001), DTI orientation informed and atlas orientation informed variations reduced overestimation at white matter tracts compared to the basic variation. Finally, the implications and usefulness of attaining an additional iron susceptibility distribution map are discussed. Highlights: novel stochastic matching pursuit algorithm called microstructure-informed myelin mapping (MIMM) is developed to quantify Myelin Volume Fraction (MVF) using Magnetic Resonance Imaging (MRI) and microstructural modeling.utilizes a detailed biophysical model to capture the susceptibility effects on both magnitude and phase to quantify myelin and iron.matter fiber orientation effects are considered for the improved MVF quantification in the major fiber tracts.acquired myelin and iron maps may be utilized to monitor longitudinal disease progress.
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Magnetic materials in tissue, such as iron, calcium, or collagen, can be studied using quantitative susceptibility mapping (QSM). To date, QSM has been overwhelmingly applied in the brain, but is increasingly utilized outside the brain. QSM relies on the effect of tissue magnetic susceptibility sources on the MR signal phase obtained with gradient echo sequence. However, in the body, the chemical shift of fat present within the region of interest contributes to the MR signal phase as well. Therefore, correcting for the chemical shift effect by means of water-fat separation is essential for body QSM. By employing techniques to compensate for cardiac and respiratory motion artifacts, body QSM has been applied to study liver iron and fibrosis, heart chamber blood and placenta oxygenation, myocardial hemorrhage, atherosclerotic plaque, cartilage, bone, prostate, breast calcification, and kidney stone.
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Algoritmos , Imagen por Resonancia Magnética , Masculino , Humanos , Imagen por Resonancia Magnética/métodos , Hígado , Hierro , Abdomen , Encéfalo , Mapeo EncefálicoRESUMEN
BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of separating magnetic sources in quantitative susceptibility mapping (QSM) by incorporating magnitude decay rates R 2 ∗ $R_2^{\rm{*}}$ in gradient echo (GRE) MRI. METHODS: Magnetic susceptibility source separation was developed using R 2 ∗ $R_2^{\rm{*}}$ and compared with a prior method using R 2 ' = R 2 ∗ - R 2 ${R^{\prime}_2} = R_2^* - {R_2}$ that required an additional sequence to measure the transverse relaxation rate R2 . Both susceptibility separation methods were compared in multiple sclerosis (MS) patients (n = 17). Susceptibility values of negative sources estimated with R 2 ∗ $R_2^{\rm{*}}$ -based source separation in a set of enhancing MS lesions (n = 44) were correlated against longitudinal myelin water fraction (MWF) changes. RESULTS: In in vivo data, linear regression of the estimated χ + ${\chi}^{+}$ and χ - ${\chi}^{-}$ susceptibility values between the R 2 ∗ $R_2^*$ - and the R 2 ' ${R^{\prime}_2}$ -based separation methods performed across 182 segmented lesions revealed correlation coefficient r = .96 and slope close .99. Correlation analysis in enhancing lesions revealed a significant positive association between the χ - ${\chi}^{-}$ increase at 1-year post-onset relative to 0 year and the MWF increase at 1 year relative to 0 year (ß = -0.144, 95% confidence interval: [-0.199, -0.1], p = .0008) and good agreement between R 2 ' ${R^{\prime}_2}$ and R 2 ∗ $R_2^*$ methods (r = .79, slope = .95). CONCLUSIONS: Separation of magnetic sources based solely on GRE complex data is feasible by combining magnitude decay rate modeling and phase-based QSM and χ - ${\chi}^{-}$ change may serve as a biomarker for myelin recovery or damage in acute MS lesions.
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Imagen por Resonancia Magnética , Esclerosis Múltiple , Biomarcadores , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Vaina de Mielina/patología , AguaRESUMEN
Quantitative susceptibility mapping (QSM) facilitates mapping of the bulk magnetic susceptibility of tissue from the phase of complex gradient echo (GRE) MRI data. QSM phase processing combined with an R2* model of magnitude of multiecho gradient echo data (R2*QSM) allows separation of dia- and para-magnetic components (e.g., myelin and iron) that contribute constructively to R2* value but destructively to the QSM value of a voxel. This R2*QSM technique is validated against quantitative histologyoptical density of myelin basic protein and Perls' iron histological stains of rim and core of 10 ex vivo multiple sclerosis lesions, as well as neighboring normal appearing white matter. We found that R2*QSM source maps are in good qualitative agreement with histology, e.g., showing increased iron concentration at the edge of the rim+ lesions and myelin loss in the lesions' core. Furthermore, our results indicate statistically significant correlation between paramagnetic and diamagnetic tissue components estimated with R2*QSM and optical densities of Perls' and MPB stains. These findings provide direct support for the use of R2*QSM magnetic source separation based solely on GRE complex data to characterize MS lesion composition.
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Esclerosis Múltiple , Sustancia Blanca , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Hierro/metabolismo , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismo , Sustancia Blanca/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro. METHODS: This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared. RESULTS: Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro. DISCUSSION: Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.
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Dimetilfumarato/farmacología , Acetato de Glatiramer/farmacología , Inmunosupresores/farmacología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Adulto , Células Cultivadas , Femenino , Humanos , Células Madre Pluripotentes Inducidas , Masculino , Microglía , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Enfermedades Neuroinflamatorias/patología , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Excessive brain iron deposition is involved in Parkinson's disease (PD) pathogenesis. However, the correlation of iron accumulation in various brain nuclei is not well-established in different stages of the disease. This cross-sectional study aims to evaluate quantitative susceptibility mapping (QSM) as an imaging technique to measure brain iron accumulation in PD patients in different stages compared to healthy controls. METHODS: Ninety-six PD patients grouped by their Hoehn and Yahr (H&Y) stages and 31 healthy controls were included in this analysis. The magnetic susceptibility values of the substantia nigra (SN), red nucleus (RN), caudate, putamen, and globus pallidus were obtained and compared. RESULTS: Iron level was increased in the SN of PD patients in all stages versus controls (p < .001), with no significant difference within stages. Iron in the RN was significantly increased in stage II versus controls (p = .013) and combined stages III and IV versus controls (p < .001). The iron levels in caudate, putamen, and globus pallidus were not different between any groups. CONCLUSIONS: Our data suggest iron accumulation occurs early in the disease course and only in the SN and RN of these patients. This is a large cross-sectional study of brain iron deposition in PD patients according to H&Y staging. Prospective studies are warranted to further validate QSM as a method to follow brain iron, which could serve as a disease biomarker and a therapeutic target.
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Enfermedad de Parkinson , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios Transversales , Humanos , Hierro , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/patologíaRESUMEN
PURPOSE: To improve accuracy and speed of quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) -based oxygen extraction fraction (OEF) mapping using a deep neural network (QQ-NET). METHODS: The 3D multi-echo gradient echo images were acquired in 34 ischemic stroke patients and 4 healthy subjects. Arterial spin labeling and diffusion weighted imaging (DWI) were also performed in the patients. NET was developed to solve the QQ model inversion problem based on Unet. QQ-based OEF maps were reconstructed with previously introduced temporal clustering, tissue composition, and total variation (CCTV) and NET. The results were compared in simulation, ischemic stroke patients, and healthy subjects using a two-sample Kolmogorov-Smirnov test. RESULTS: In the simulation, QQ-NET provided more accurate and precise OEF maps than QQ-CCTV with 150 times faster reconstruction speed. In the subacute stroke patients, OEF from QQ-NET had greater contrast-to-noise ratio (CNR) between DWI-defined lesions and their unaffected contralateral normal tissue than with QQ-CCTV: 1.9 ± 1.3 vs 6.6 ± 10.7 (p = 0.03). In healthy subjects, both QQ-CCTV and QQ-NET provided uniform OEF maps. CONCLUSION: QQ-NET improves the accuracy of QQ-based OEF with faster reconstruction.
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Aprendizaje Profundo , Oxígeno , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Circulación Cerebrovascular , Sustancia Gris , Humanos , Imagen por Resonancia Magnética , Consumo de Oxígeno , Saturación de OxígenoRESUMEN
BACKGROUND AND PURPOSE: The objective ofthis study was to demonstrate a global cerebrospinal fluid (CSF) method for a consistent and automated zero referencing of brain quantitative susceptibility mapping (QSM). METHODS: Whole brain CSF mask was automatically segmented by thresholding the gradient echo transverse relaxation ( R2∗) map, and regularization was employed to enforce uniform susceptibility distribution within the CSF volume in the field-to-susceptibility inversion. This global CSF regularization method was compared with a prior ventricular CSF regularization. Both reconstruction methods were compared in a repeatability study of 12 healthy subjects using t-test on susceptibility measurements, and in patient studies of 17 multiple sclerosis (MS) and 10 Parkinson's disease (PD) patients using Wilcoxon rank-sum test on radiological scores. RESULTS: In scan-rescan experiments, global CSF regularization provided more consistent CSF volume as well as higher repeatability of QSM measurements than ventricular CSF regularization with a smaller bias: -2.7 parts per billion (ppb) versus -0.13 ppb (t-test p<0.05) and a narrower 95% limits of agreement: [-7.25, 6.99] ppb versus [-16.60, 11.19 ppb] (f-test p<0.05). In PD and MS patients, global CSF regularization reduced smoothly varying shadow artifacts and significantly improved the QSM quality score (p<0.001). CONCLUSIONS: The proposed whole brain CSF method for QSM zero referencing improves repeatability and image quality of brain QSM compared to the ventricular CSF method.
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Algoritmos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.
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Biomarcadores/metabolismo , Diagnóstico por Imagen de Elasticidad/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Ultrasonografía/métodos , Trombosis de la Vena/patología , Fibrinolíticos/administración & dosificación , Humanos , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/metabolismoRESUMEN
BACKGROUND: Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron. OBJECTIVE: To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions. METHODS: MS brain slabs were imaged with MRI and QSM, and processed for histology. Immunolabeled cells were quantified in the lesion rim, center, and adjacent normal-appearing white matter (NAWM). Iron+ myeloid cell densities at the rims were correlated with susceptibilities. Human-induced pluripotent stem cell (iPSC)-derived microglia were used to determine the effect of iron on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. RESULTS: QSM hyperintensity at the lesion perimeter correlated with activated iron+ myeloid cells in the rim and NAWM. Lesions with high punctate or homogenous QSM signal contained no or minimally activated iron- myeloid cells. In vitro, iron accumulation was highest in M1-polarized human iPSC-derived microglia, but it did not enhance ROS or cytokine production. CONCLUSION: A high QSM signal outlining the lesion rim but not punctate signal in the center is a biomarker for chronic inflammation in white matter lesions.
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Imagen por Resonancia Magnética , Microglía , Esclerosis Múltiple , Enfermedades Neuroinflamatorias , Sustancia Blanca , Adulto , Biomarcadores , Células Cultivadas , Femenino , Humanos , Células Madre Pluripotentes Inducidas , Hierro/metabolismo , Masculino , Microglía/inmunología , Microglía/metabolismo , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/inmunología , Sustancia Blanca/patologíaRESUMEN
PURPOSE: In the present study, we investigated the potential of QSM to assess the physiological state of cortical tissue in the middle cerebral artery occlusion canine model of a cerebral ischemia. METHODS: Experiments were performed in 8 anesthetized canines. Gradient echo, perfusion, and DWI data of brains at normal and ischemic states were acquired. In the postprocessed susceptibility and quantitative cerebral blood flow maps, changes in values within the middle cerebral artery-fed cortical territories were quantified both on the ischemic and normal contralateral hemisphere side. RESULTS: QSM values in critically ischemic tissue were significantly different from contralateral values-namely, susceptibility increase was observed in the cases in which cerebral perfusion was maintained above the threshold of neuronal death. Furthermore, the data indicates presence of a significant correlation between the changes in susceptibility values, cerebral perfusion, and the infarct volume and pial collateral scores. Additionally, our data suggests that difference in cortical susceptibility is prospectively indicative of the infarct growth rate. CONCLUSION: In an experimental permanent middle cerebral artery occlusion model, QSM was shown to correlate with the functional parameters characterizing viability of ischemic tissue, thus warranting further research on its ability to provide complementary information during acute stroke MRI examinations in humans.
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Isquemia Encefálica , Accidente Cerebrovascular , Animales , Isquemia Encefálica/diagnóstico por imagen , Circulación Cerebrovascular , Perros , Humanos , Imagen por Resonancia Magnética , Proyectos PilotoRESUMEN
BACKGROUND: This study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke. METHODS: Twenty mongrel canines (20-30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1-1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation. RESULTS: Differences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome. CONCLUSION: Our results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.
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Circulación Colateral/efectos de los fármacos , Quimioterapia Combinada/métodos , Hidralazina/farmacología , Infarto de la Arteria Cerebral Media , Accidente Cerebrovascular Isquémico , Norepinefrina/farmacología , Animales , Imagen de Difusión por Resonancia Magnética/métodos , Perros , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Angiografía por Resonancia Magnética/métodos , Resultado del Tratamiento , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: padj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: padj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain. Graphical abstract.
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Hemangioma Cavernoso del Sistema Nervioso Central , Transcriptoma , Anciano , Envejecimiento/genética , Encéfalo/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Humanos , Plasma , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative permeability (DCEQP) on magnetic resonance (MR) have been shown to correlate with neurovascular disease progression as markers of vascular leakage and hemosiderin deposition. Applying these techniques as monitoring biomarkers in clinical trials will be necessary; however, their validation across multiple MR platforms and institutions has not been rigorously verified. PURPOSE: To validate quantitative measurement of MR biomarkers on multiple instruments at different institutions. STUDY TYPE: Phantom validation between platforms and institutions. PHANTOM MODEL: T1 /susceptibility phantom, two-compartment dynamic flow phantom. FIELD STRENGTH/SEQUENCE: 3T/QSM, T1 mapping, dynamic 2D SPGR. ASSESSMENT: Philips Ingenia, Siemens Prisma, and Siemens Skyra at three different institutions were assessed. A QSM phantom with concentrations of gadolinium, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8 ppm was assayed. DCEQP was assessed by measuring a MultiHance bolus as the consistency of the width ratio of the curves at the input and outputs over a range of flow ratios between outputs. STATISTICAL TESTS: Each biomarker was assessed by measures of accuracy (Pearson correlation), precision (paired t-test between repeated measurements), and reproducibility (analysis of covariance [ANCOVA] between instruments). RESULTS: QSM accuracy of r2 > 0.997 on all three platforms was measured. Precision (P = 0.66 Achieva, P = 0.76 Prisma, P = 0.69 Skyra) and reproducibility (P = 0.89) were good. T1 mapping of accuracy was r2 > 0.98. No significant difference between width ratio regression slopes at site 2 (P = 0.669) or site 3 (P = 0.305), and no significant difference between width ratio regression slopes between sites was detected by ANCOVA (P = 0.48). DATA CONCLUSION: The phantom performed as expected and determined that MR measures of QSM and DCEQP are accurate and consistent across repeated measurements and between platforms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1192-1199.
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Permeabilidad , Fantasmas de Imagen , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The objective of this study was to investigate the relationship between iron and white matter connectivity in the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) of the STN for treatment of Parkinson's disease. METHODS: Nine Parkinson's disease patients underwent preoperative 3T MRI imaging which included acquisition of T1-weighted anatomical images along with diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM). MR tractography was performed for the seed voxels located within the STN, and the correlations between normalized QSM values and the STN's connectivity to a set of a priori chosen regions of interest were assessed. RESULTS: A strong negative correlation was found between STN connectivity and QSM intensity for the thalamus, premotor, motor, and sensory regions, while a strong positive correlation was found for frontal, putamen, and brain stem areas. CONCLUSIONS: Quantitative susceptibility mapping not only accurately delineates the STN borders but is also able to provide functional information about the STN functional subdivisions. The observed iron-to-connectivity correlation patterns may aid in planning DBS surgery to avoid unwanted side effects associated with DBS.
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OBJECTIVE: To introduce quantitative susceptibility mapping (QSM), a novel magnetic resonance imaging sequence, to the field of neurosurgery. METHODS: QSM is introduced both in its historical context and by providing a brief overview of the physics behind the technique tailored to a neurosurgical audience. Its application to clinical neurosurgery is then highlighted using case examples. RESULTS: QSM offers a quantitative assessment of susceptibility (previously considered as an artifact) via a single, straightforward gradient echo acquisition. QSM differs from standard susceptibility weighted imaging in its ability to both quantify and precisely localize susceptibility effects. Clinical applications of QSM are wide reaching and include precise localization of the deep nuclei for deep brain stimulation electrode placement, differentiation between blood products and calcification within brain lesions, and enhanced sensitivity of cerebral micrometastasis identification. CONCLUSIONS: We present this diverse range of QSM's clinical applications to neurosurgical care via case examples. QSM can be obtained in all patients able to undergo magnetic resonance imaging and is easily integratable into busy neuroradiology programs because of its short acquisition time and straightforward, automated offline postprocessing workflow. Clinical integration of QSM may help clinicians better identify and characterize neurosurgical lesions, thereby improving patient care.
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Imagen por Resonancia Magnética/métodos , Procedimientos Neuroquirúrgicos , Cirugía Asistida por Computador , Adolescente , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Encefalopatías/diagnóstico por imagen , Encefalopatías/cirugía , Niño , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Faithful depiction of the subthalamic nucleus (STN) is critical for planning deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD). Quantitative susceptibility mapping (QSM) has been shown to be superior to traditional T2-weighted spin echo imaging (T2w). The aim of the study was to describe submillimeter QSM for preoperative imaging of the STN in planning of DBS. METHODS: Seven healthy volunteers were included in this study. T2w and QSM were obtained for all healthy volunteers, and images of different resolutions were reconstructed. Image quality and visibility of STN anatomical features were analyzed by a radiologist using a 5-point scale, and contrast properties of the STN and surrounding tissue were calculated. Additionally, data from 10 retrospectively and randomly selected PD patients who underwent 3-T MRI for DBS were analyzed for STN size and susceptibility gradient measurements. RESULTS: Higher contrast-to-noise ratio (CNR) values were observed in both high-resolution and low-resolution QSM images. Inter-resolution comparison demonstrated improvement in CNR for QSM, but not for T2w images. QSM provided higher inter-quadrant contrast ratios (CR) within the STN, and depicted a gradient in the distribution of susceptibility sources not visible in T2w images. CONCLUSIONS: For 3-T MRI, submillimeter QSM provides accurate delineation of the functional and anatomical STN features for DBS targeting.