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1.
NMR Biomed ; : e5139, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38465729

RESUMO

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r2 : 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B0  of 3 T or higher with no additional time cost, when standard T2 *-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

2.
J Magn Reson Imaging ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308397

RESUMO

BACKGROUND: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. PURPOSE: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R2 */R2 ' /QSM. STUDY TYPE: Longitudinal, prospective. SUBJECTS: Twenty relapsing-remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years). FIELD STRENGTH/SEQUENCE: Three-dimensional multiple echo gradient echo (QSM and R2 * mapping), two-dimensional dual echo fast spin echo (R2 mapping), T2 -weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T. ASSESSMENT: Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R2 * or separated into positive/negative components from χ separation. STATISTICAL TESTS: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R2 */R2 ' /QSM. Significant level: P < 0.005. RESULTS: A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R2 */R2 ' . When lesions were grouped based on changes in QSM and R2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and χ separation. DATA CONCLUSION: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R2 * and QSM alone. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

3.
Magn Reson Imaging ; 92: 224-231, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35772582

RESUMO

PURPOSE: To optimize quantitative susceptibility-weighted imaging also known as true susceptibility-weighted imaging (tSWI) for strong susceptibility sources like hemorrhage and compare to standard susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM). METHODS: Ten patients with known intracerebral hemorrhage (ICH) were scanned using a 3D SWI sequence. The magnitude and phase images were utilized to compute QSM, tSWI and SWI images. tSWI parameters including the upper threshold for creating susceptibility-weighted masks and the multiplication factor were optimized for hemorrhage depiction. Combined tSWI was also computed with independent optimized parameters for both veins and hemorrhagic regions. tSWI results were compared to SWI and QSM utilizing region-of-interest measurements, Pearson's correlation and Kruskal-Wallis test. RESULTS: Fifteen hemorrhages were found, with mean susceptibility 0.81 ± 0.37 ppm. Unlike SWI which utilizes a phase mask, tSWI uses a mask computed from QSM. In tSWI, the weighted mask required an extended upper threshold far beyond the standard level for more effective visualization of hemorrhage texture. The upper threshold was set to the mean maximum susceptibility in the hemorrhagic region (3.24 ppm) with a multiplication factor of 2. The blooming effect, seen in SWI, was observed to be larger in hemorrhages with higher susceptibility values (r = 0.78, p < 0.001) with reduced blooming on tSWI. On SWI, 4 out of 15 hemorrhages showed phase wrap artifacts in the hemorrhagic region and all patients showed some phase wraps in the air-tissue interface near the auditory and frontal sinuses. These phase wrap artifacts were absent on tSWI. In hemorrhagic regions, a higher correlation was observed between the actual susceptibility values and mean gray value for tSWI (r = -0.93, p < 0.001) than SWI (r = -0.87, p < 0.001). CONCLUSION: In hemorrhage, tSWI minimizes both blooming effects and phase wrap artifacts observed in SWI. However, unlike SWI, tSWI requires an altered upper threshold for best hemorrhage depiction that greatly differs from the standard value. tSWI can be used as a complementary technique for visualizing hemorrhage along with SWI.


Assuntos
Artefatos , Imageamento por Ressonância Magnética , Hemorragia Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Veias
4.
J Magn Reson Imaging ; 51(3): 712-718, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31276278

RESUMO

BACKGROUND: Quantitative susceptibility mapping (QSM) offers a means to track iron evolution in hemorrhage. However, standard QSM sequences have long acquisition times and are prone to motion artifact in hemorrhagic patients. PURPOSE: To minimize motion artifact and acquisition time by performing rapid QSM in intracerebral hemorrhage (ICH) using single-shot echo planar imaging (EPI). STUDY TYPE: Prospective method evaluation. POPULATION/SUBJECTS: Forty-five hemorrhages were analyzed from 35 MRI exams obtained between February 2016 and March 2019 from 27 patients (14 male / 13 female, age: 71 ± 12 years) with confirmed primary ICH. FIELD STRENGTH/SEQUENCE: 3T; susceptibility-weighted imaging (SWI) with 4.54-minute acquisition and 2D single-shot gradient EPI with 0.45-minute acquisition. ASSESSMENT: Susceptibility maps were constructed from both methods. Measurement of ICH area and mean magnetic susceptibility were made manually by three independent observers. Motion artifacts were quantified using the magnitude signal ratio of artifact-to-brain tissue to classify into three categories: mild or no artifact, moderate artifact, or severe artifact. The cutoff for each category was determined by four observers. STATISTICAL TESTS: Pearson's correlation coefficient and paired t-test using α = 0.05 were used to compare results. Inter- and intraclass correlation was used to assess observer variability. RESULTS: Using 45 hemorrhages, the ICH regions measured on susceptibility maps obtained from EPI and SWI sequences had high correlation coefficients for area (R2 ≥ 0.97) and mean magnetic susceptibility (R2 ≥ 0.93) for all observers. The artifact-to-tissue ratio was significantly higher (P < 0.01) for SWI vs. EPI, and the standard deviation for the SWI method (SD = 0.05) was much larger than EPI (SD = 0.01). All observers' measurements showed high agreement. DATA CONCLUSION: Single-shot EPI-QSM enabled rapid measurement of ICH area and mean magnetic susceptibility, with reduced motion as compared with more standard SWI. EPI-QSM requires minimal additional acquisition time and could be incorporated into iron tracking studies in ICH. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:712-718.


Assuntos
Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
5.
J Am Heart Assoc ; 8(11): e010904, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31131671

RESUMO

Background Subacute ischemic lesions in intracerebral hemorrhage ( ICH ) have been hypothesized to result from hypoperfusion. Although studies of cerebral blood flow ( CBF ) indicate modest hypoperfusion in ICH , these investigations have been limited to early time points. Arterial spin labeling ( ASL ), a magnetic resonance imaging technique, can be used to measure CBF without a contrast agent. We assessed CBF in patients with ICH using ASL and tested the hypothesis that CBF is related to systolic blood pressure ( SBP ). Methods and Results In this cross-sectional study, patients with ICH were assessed with ASL at 48 hours, 7 days, and/or 30 days after onset. Relative CBF ( rCBF ; ratio of ipsilateral/contralateral perfusion) was measured in the perihematomal regions, hemispheres, border zones, and the perilesional area in patients with diffusion-weighted imaging hyperintensities. Twenty-patients (65% men; mean± SD age, 68.5±12.7 years) underwent imaging with ASL at 48 hours (N=12), day 7 (N=6), and day 30 (N=11). Median (interquartile range) hematoma volume was 13.1 (6.3-19.3) mL. Mean± SD baseline SBP was 185.4±25.5 mm Hg. Mean perihematomal rCBF was 0.9±0.2 at 48 hours at all time points. Baseline SBP and other SBP measurements were not associated with a decrease in rCBF in any of the regions of interest ( P≥0.111). r CBF did not differ among time points in any of the regions of interest ( P≥0.097). Mean perilesional rCBF was 1.04±0.65 and was unrelated to baseline SBP ( P=0.105). Conclusions ASL can be used to measure rCBF in patients with acute and subacute ICH . Perihematomal CBF was not associated with SBP changes at any time point. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.


Assuntos
Pressão Sanguínea , Hemorragia Cerebral/diagnóstico por imagem , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Imagem de Perfusão/métodos , Marcadores de Spin , Idoso , Idoso de 80 Anos ou mais , Alberta , Hemorragia Cerebral/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
6.
Neurorehabil Neural Repair ; 33(1): 59-69, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30595088

RESUMO

BACKGROUND: Dysfunction of corticospinal pathways has been implicated in motor impairments in people with bilateral spastic cerebral palsy (CP). While structural damage to corticospinal pathways in people with CP is known, its impact on the activation of these pathways is not. OBJECTIVE: To provide the first, complete activation profile of corticospinal pathways in adults with CP using a full range of transcranial magnetic stimulation (TMS) intensities and voluntary contractions. METHODS: TMS targeted the soleus muscle of 16 adults with bilateral spastic CP and 15 neurologically intact (NI) control participants. Activation profiles were generated using motor-evoked potentials (MEPs) produced by varying both stimulation intensity and degree of voluntary muscle activity. Anatomical integrity of corticospinal pathways was also measured with diffusion tractography. RESULTS: Participants with CP had smaller MEPs produced by TMS at 1.2× active motor threshold during submaximal (20%) muscle activity and smaller maximal MEPs produced under any combination of stimulation intensity and voluntary muscle activity. At a fixed stimulation intensity, increasing voluntary muscle activity facilitated MEP amplitudes to a lesser degree in the participants with CP. Consistent differences in diffusion tractography suggested structural abnormalities in the corticospinal pathways of participants with CP that correlated with maximal MEPs. CONCLUSION: People with bilateral spastic CP have impaired activation of low and high-threshold corticospinal pathways to soleus motoneurons by TMS and reduced facilitation by voluntary activity that may be associated with structural damage to these pathways. These impairments likely contribute to impaired voluntary movement.


Assuntos
Paralisia Cerebral/patologia , Paralisia Cerebral/fisiopatologia , Potencial Evocado Motor/fisiologia , Neurônios Motores , Músculo Esquelético , Tratos Piramidais/patologia , Tratos Piramidais/fisiopatologia , Adulto , Imagem de Tensor de Difusão , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/patologia , Neurônios Motores/fisiologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Estimulação Magnética Transcraniana , Adulto Jovem
7.
Radiology ; 288(3): 830-839, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29916778

RESUMO

Purpose To follow the evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM). Materials and Methods Thirty-six patients with ICH confirmed at CT were enrolled to follow ICH evolution on day 2, 7, and 30 after symptom onset between August 2013 and April 2017. QSM was reconstructed from MRI gradient-echo phase images acquired at 1.5 T or 3.0 T. ICH regions were manually drawn on two-dimensional sections of co-registered CT and MR images independently by two raters. The ICH areas and mean values were compared between CT and MRI by using Bland-Altman plots and Pearson correlation. QSM time evolution of ICH was assessed by using paired t tests and was compared with conventional T2-weighted fluid-attenuated inversion recovery, or T1-weighted or T2*-weighted magnitude intensities. Results Significant reductions in ICH susceptibility were found between day 2 and day 7 (P < .001) and between day 7 and day 30 (P = .003), corresponding to different disease stages. The ICH areas measured at CT and QSM were linearly correlated (r2 = 0.98). The mean CT attenuation and mean susceptibility of ICH were linearly correlated (r2 = 0.29). Excellent intra- and interobserver reproducibility were found for QSM (intraclass correlation coefficient, 0.987 and 0.966, respectively). Conclusion Longitudinal evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM) demonstrated susceptibility differences in different disease stages, which was not found at conventional MRI; therefore, QSM may assist in quantitatively following ICH iron content.


Assuntos
Mapeamento Encefálico/métodos , Processamento de Imagem Assistida por Computador/métodos , Hemorragias Intracranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos
8.
J Stroke Cerebrovasc Dis ; 25(7): 1696-1704, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27068775

RESUMO

BACKGROUND: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis (AAV; ANCA denotes antineutrophil cytoplasmic antibody) that causes necrotizing inflammation of small blood vessels. Renal and pulmonary manifestations are common whereas central nervous system (CNS) involvement, and in particular spinal disease, is rare. METHODS: We reviewed a case of MPA presenting with spinal intradural hemorrhage and intracerebral hemorrhage. We also summarized all reported cases of AAV with spinal cord involvement in the literature (database search included MEDLINE, Embase, Scopus, and Proquest with no date or language restriction). RESULTS: We reviewed 20 cases of AAV with spinal cord involvement (12 granulomatosis with polyangiitis [GPA], 4 eosinophilic granulomatosis with polyangiitis, 2 MPA, and 2 cases diagnosed as AAV only) and reported demographic information, clinical features, methods of diagnosis, treatment, and patient outcome. Although CNS involvement has been associated with a poor prognosis, 14 of 18 cases that reported outcome data achieved remission during follow-up. Death occurred in 3 patients diagnosed with GPA and in 1 patient with MPA. Our patient with MPA deteriorated rapidly despite use of prednisone and died. CONCLUSIONS: AAV can present with brain and spinal cord involvement, even in the absence of systemic disease. CNS disease may be responsive to immunosuppressive therapy (e.g., steroids and cyclophosphamide) in several of the cases reviewed.


Assuntos
Poliangiite Microscópica , Adulto , Idoso , Biópsia , Hemorragia Cerebral/etiologia , Progressão da Doença , Evolução Fatal , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Laminectomia , Imageamento por Ressonância Magnética , Masculino , Poliangiite Microscópica/complicações , Poliangiite Microscópica/diagnóstico por imagem , Poliangiite Microscópica/terapia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Fatores de Risco , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/terapia , Hemorragia Subaracnóidea/etiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Magn Reson Med ; 76(3): 781-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26414757

RESUMO

PURPOSE: To investigate gradient-echo phase errors caused by intracranial hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts from phase errors in quantitative susceptibility mapping (QSM) of ICH. METHODS: Two QSM methods are proposed: (1) mask-inversion that masks the phase of low signal magnitude regions, and (2) ICH magnetic dipole field isolation followed by susceptibility superposition using multiple boundaries for background field removal. The reconstruction methods were tested in eight subjects with ICH using standard single-echo susceptibility-weighted imaging at 1.5 Tesla with 40 ms echo time. Different phase unwrapping algorithms were also compared. RESULTS: Significant phase errors were evident inside ICHs with low signal magnitude. The mask-inversion method recovered susceptibility of ICH in numerical simulation and minimized phase error propagation in patients with ICH. The additional superposed dipole inversion process substantially suppressed and constrained streaking artifacts in all subjects. Using the proposed superposition method, ICH susceptibilities measured from long and short echo times were similar. Laplacian based phase unwrapping substantially underestimated the ICH dipole field as compared to a path-based method. CONCLUSION: The proposed methods of mask-inversion as well as ICH isolation and superposition can substantially reduce artifacts in QSM of ICH. Magn Reson Med 76:781-791, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Algoritmos , Artefatos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Hemorragias Intracranianas/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
BMC Neurol ; 15: 61, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25899600

RESUMO

BACKGROUND: Decision-making is an essential function of everyday life. Decision-making under explicit risk requires developing advantageous decision strategies based on fixed outcomes (e.g., probabilities of winning or losing a bet). Decision-making and its neural substrates have been rarely studied in MS. We expected performance in decision-making under risk to be lowered in MS patients, and negatively correlated with disease-related disability, cognition, and ventricular width. METHODS: Three groups were included: 32 MS patients and 20 healthy controls were examined with conventional neuropsychological tests and the Game-of-Dice Task (GDT) assessing decision-making under explicit risk. Linear 2-D ventricular width was assessed on MS patients' clinical MRIs and compared to a third group, 20 non-MS neurological control patients. RESULTS: Compared to healthy controls, MS patients showed impaired GDT and neuropsychological performance, depending on the MS-subtype (relapsing-remitting (RR), n = 22; secondary progressive, n = 10) and disability severity among RR-MS patients. In MS patients, GDT performance correlated with processing speed, intercaudate ratio, and third ventricle ratio (p's < 0.05). Mediation analysis showed that the link between GDT performance and processing speed was fully explained by ventricular size. CONCLUSION: Decision-making under explicit risk was reduced in MS patients, but only those with more pronounced disability. Independent of processing speed, decision-making under explicit risk correlates inversely with central atrophy in MS.


Assuntos
Ventrículos Cerebrais/patologia , Tomada de Decisões/fisiologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Assunção de Riscos , Análise e Desempenho de Tarefas , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
11.
Neuroimage ; 105: 486-92, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25462797

RESUMO

Quantitative susceptibility mapping (QSM) measures bulk susceptibilities in the brain, which can arise from many sources. In iron-rich subcortical gray matter (GM), non-heme iron is a dominant susceptibility source. We evaluated the use of QSM for iron mapping in subcortical GM by direct comparison to tissue iron staining. We performed in situ or in vivo QSM at 4.7 T combined with Perls' ferric iron staining on the corresponding extracted subcortical GM regions. This histochemical process enabled examination of ferric iron in complete slices that could be related to susceptibility measurements. Correlation analyses were performed on an individual-by-individual basis and high linear correlations between susceptibility and Perls' iron stain were found for the three multiple sclerosis (MS) subjects studied (R(2) = 0.75, 0.62, 0.86). In addition, high linear correlations between susceptibility and transverse relaxation rate (R2*) were found (R(2) = 0.88, 0.88, 0.87) which matched in vivo healthy subjects (R(2) = 0.87). This work validates the accuracy of QSM for brain iron mapping and also confirms ferric iron as the dominant susceptibility source in subcortical GM, by demonstrating high linear correlation of QSM to Perls' ferric iron staining.


Assuntos
Química Encefálica , Substância Cinzenta/metabolismo , Ferro/metabolismo , Fenômenos Magnéticos , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta/química , Substância Cinzenta/patologia , Humanos , Ferro/análise , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia
12.
J Clin Invest ; 124(11): 4877-81, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25250569

RESUMO

Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2-/- mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease.


Assuntos
Doenças de Pequenos Vasos Cerebrais/genética , Fatores de Transcrição Forkhead/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Animais , Hemorragia Cerebral/genética , Códon sem Sentido , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Leucoencefalopatias/genética , Desequilíbrio de Ligação , Mutação de Sentido Incorreto , Fator de Crescimento Derivado de Plaquetas/fisiologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Transdução de Sinais , Peixe-Zebra , Proteína Homeobox PITX2
13.
Radiology ; 270(1): 186-96, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23925273

RESUMO

PURPOSE: To investigate the relationship between magnetic resonance (MR) imaging markers of iron content and disease severity in patients with multiple sclerosis (MS) over a 2-year period. MATERIALS AND METHODS: This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. Seventeen patients with MS and 17 control subjects were examined twice, 2 years apart, by using phase imaging and transverse relaxation (R2*) mapping at 4.7 T. Quantitative differences in iron content in deep gray matter between patients and control subjects were evaluated with repeated-measures multivariate analysis of variance separately for R2* mapping and phase imaging. Multiple regression analysis was used to evaluate correlations of MR imaging measures, both 2-year-difference and single-time measurements, to baseline disease severity. RESULTS: R2* mapping using 2-year-difference measurements had the highest correlation to disease severity (r = 0.905, P < .001) compared with R2* mapping using single-time measurements (r = 0.560, P = .019) and phase imaging by using either single-time (r = 0.539, P = .026) or 2-year-difference (r = 0.644, P = .005) measurements. Significant increases in R2* occur during 2 years in the substantia nigra (P < .001) and globus pallidus (P = .035), which are both predictors of disease in regression analysis, in patients compared with control subjects. There were group differences in the substantia nigra, globus pallidus, pulvinar thalamus, thalamus, and caudate nucleus, compared with control subjects with R2* mapping (P < .05), and group differences in the caudate nucleus and pulvinar thalamus, compared with control subjects with phase imaging (P < .05). CONCLUSION: There are significant changes in deep gray matter iron content in MS during 2 years measured with MR imaging, changes that are strongly related to physical disability. Longitudinal measurements may produce a higher correlation to disease severity compared with single-time measurements because baseline iron content of deep gray matter is variable among subjects.


Assuntos
Biomarcadores/metabolismo , Encéfalo/metabolismo , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
14.
J Cereb Blood Flow Metab ; 34(1): 81-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24045403

RESUMO

Blood pressure (BP) reduction after intracerebral hemorrhage (ICH) is controversial, because of concerns that this may cause critical reductions in perihematoma perfusion and thereby precipitate tissue damage. We tested the hypothesis that BP reduction reduces perihematoma tissue oxygenation.Acute ICH patients were randomized to a systolic BP target of <150 or <180 mm Hg. Patients underwent CT perfusion (CTP) imaging 2 hours after randomization. Maps of cerebral blood flow (CBF), maximum oxygen extraction fraction (OEF(max)), and the resulting maximum cerebral metabolic rate of oxygen (CMRO2(max)) permitted by local hemodynamics, were calculated from raw CTP data.Sixty-five patients (median (interquartile range) age 70 (20)) were imaged at a median (interquartile range) time from onset to CTP of 9.8 (13.6) hours. Mean OEF(max) was elevated in the perihematoma region (0.44±0.12) relative to contralateral tissue (0.36±0.11; P<0.001). Perihematoma CMRO2(max) (3.40±1.67 mL/100 g per minute) was slightly lower relative to contralateral tissue (3.63±1.66 mL/100 g per minute; P=0.025). Despite a significant difference in systolic BP between the aggressive (140.5±18.7 mm Hg) and conservative (163.0±10.6 mm Hg; P<0.001) treatment groups, perihematoma CBF was unaffected (37.2±11.9 versus 35.8±9.6 mL/100 g per minute; P=0.307). Similarly, aggressive BP treatment did not affect perihematoma OEF(max) (0.43±0.12 versus 0.45±0.11; P=0.232) or CMRO2(max) (3.16±1.66 versus 3.68±1.85 mL/100 g per minute; P=0.857). Blood pressure reduction does not affect perihematoma oxygen delivery. These data support the safety of early aggressive BP treatment in ICH.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hematoma/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Tomografia Computadorizada por Raios X/métodos , Idoso , Anti-Hipertensivos/administração & dosagem , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Feminino , Hematoma/diagnóstico por imagem , Hematoma/tratamento farmacológico , Hematoma/etiologia , Humanos , Hidralazina/administração & dosagem , Hidralazina/uso terapêutico , Labetalol/administração & dosagem , Labetalol/uso terapêutico , Masculino , Resultado do Tratamento
17.
Radiology ; 267(2): 531-42, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23297322

RESUMO

PURPOSE: To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS). MATERIALS AND METHODS: Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images. RESULTS: R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity. CONCLUSION: All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.


Assuntos
Encéfalo/metabolismo , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/metabolismo , Encéfalo/patologia , Cadáver , Causas de Morte , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Análise dos Mínimos Quadrados , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia
18.
J Magn Reson Imaging ; 34(3): 532-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21761489

RESUMO

PURPOSE: To determine the effect of cardiac-related carotid artery motion on the image quality of 3D contrast-enhanced MR angiography (CEMRA) in patients presenting with suspected carotid artery disease. MATERIALS AND METHODS: Twenty patients with suspected carotid artery disease underwent cardiac-gated cinematic steady-state free precession of the carotid arteries followed by standard 3D CEMRA at 1.5 T. Using postprocessing, computer programs determined the degree of vessel wall dilation and translation across the cardiac cycle from the cinematic exam and related this to vessel wall sharpness in 3D CEMRA, which was determined objectively by computer analysis and subjectively by a panel of expert neuroradiologists. RESULTS: In patients, across 40 arteries the average carotid vessel movement due to cardiac pulsation was 0.36 ± 0.17 mm and translation 1.53 ± 0.94 mm. When using computer analysis of sharpness, the mean carotid wall motion had a weak negative correlation with 3D CEMRA vessel sharpness (Pearson's correlation -0.23, P < 0.01). However, the same trend was not present from the radiological review. CONCLUSION: In standard 3D CEMRA in patients with suspected carotid artery disease, cardiac-related carotid movement was a statistically significant source of degradation in vessel sharpness, but did not appear to be clinically significant.


Assuntos
Artefatos , Técnicas de Imagem de Sincronização Cardíaca/métodos , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/patologia , Gadolínio DTPA , Imageamento Tridimensional/métodos , Angiografia por Ressonância Magnética/métodos , Adulto , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Stroke ; 42(4): 1135-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21350210

RESUMO

BACKGROUND AND PURPOSE: Collateral flow augmentation using partial aortic occlusion may improve cerebral perfusion in acute stroke. We assessed the safety and feasibility of partial aortic occlusion immediately after intravenous tissue plasminogen activator. METHODS: We conducted an open-label pilot study of partial aortic occlusion after thrombolysis. The primary end point was all serious adverse events within 30 days of treatment. RESULTS: None of the 22 patients enrolled developed symptomatic parenchymal hemorrhages. Asymptomatic hemorrhagic transformation occurred in 9 patients. Procedure-related adverse events were limited to groin complications (n=13). Seventy-seven percent of patients experienced neurological improvement (≥4-point improvement of the National Institutes of Health Stroke Scale score). CONCLUSIONS: Partial aortic occlusion as an adjunct to thrombolysis in the treatment of acute stroke appears safe. Studies aimed at determining the efficacy of this therapeutic approach are warranted. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01006993.


Assuntos
Oclusão com Balão/métodos , Circulação Cerebrovascular/fisiologia , Terapia Combinada/métodos , Hipóxia-Isquemia Encefálica/terapia , Terapia Trombolítica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/fisiopatologia , Oclusão com Balão/efeitos adversos , Oclusão com Balão/instrumentação , Circulação Cerebrovascular/efeitos dos fármacos , Terapia Combinada/instrumentação , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Hipóxia-Isquemia Encefálica/fisiopatologia , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ativador de Plasminogênio Tecidual/administração & dosagem
20.
Clin Rheumatol ; 30(5): 729-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21210290

RESUMO

To present the clinical and pathological findings in patients presenting with myositis caused by syphilis. The literature is reviewed, and pathophysiologic factors discussed. A 49-year-old Caucasian heterosexual male with a known history of stable human immunodeficiency virus (HIV) and hepatitis C (HCV) co-infection, developed progressive muscle weakness over 10 weeks. He discontinued his medications; however, he had on-going muscle symptoms. A muscle biopsy was performed, consistent with mild myositis. While on prednisone therapy, he developed panuveitis and vertigo. CSF studies were positive for syphilis (Treponema pallidum). He was started on appropriate antibiotic therapy with complete clinical resolution. This patient presented with myositis and panuveitis as a manifestation of acute onset of syphilis. Syphilis is an uncommon cause of myositis. In patients with HIV and/or HCV, the disease itself and side effects of the medications must be considered. As patients with HIV may have co-infections, syphilis must be considered, especially when unresponsive to traditional management.


Assuntos
Miosite/diagnóstico , Miosite/terapia , Sífilis/complicações , Sífilis/diagnóstico , Antibacterianos/uso terapêutico , Antivirais/farmacologia , Progressão da Doença , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Miosite/complicações , Miosite/microbiologia , Sífilis/terapia , Treponema pallidum/metabolismo
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