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1.
Magn Reson Imaging ; 65: 15-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629075

RESUMO

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images.

3.
J Appl Clin Med Phys ; 20(11): 95-103, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587520

RESUMO

OBJECT: The purpose of this study was to compare two methods of stereotactic localization in Gamma Knife treatment planning: cone beam computed tomography (CBCT) or fiducial. While the fiducial method is the traditional method of localization, CBCT is now available for use with the Gamma Knife Icon. This study seeks to determine whether a difference exists between the two methods and then whether one is better than the other regarding accuracy and workflow optimization. METHODS: Cone beam computed tomography was used to define stereotactic space around the Elekta Film Pinprick phantom and then treated with film in place. The same phantom was offset known amounts from center and then imaged with CBCT and registered with the reference CBCT image to determine if measured offsets matched those known. Ten frameless and 10 frame-based magnetic resonance imaging (MRI) to CBCT patient fusions were retrospectively evaluated using the TG-132 TRE method. The stereotactic coordinates defined by CBCT and traditional fiducials were compared on the Elekta 8 cm Ball phantom, an anthropomorphic phantom, and actual patient data. Offsets were introduced to the anthropomorphic phantom in the stereotactic frame and CBCT's ability to detect those offsets was determined. RESULTS: Cone beam computed tomography defines stereotactic space well within the established limits of the mechanical alignment system. The CBCT to CBCT registration can detect offsets accurately to within 0.1 mm and 0.5°. In all cases, some disagreement existed between fiducial localization and that of CBCT which in some cases was small, but also was as high as 0.43 mm in the phantom domain and as much as 1.54 mm in actual patients. CONCLUSION: Cone beam computed tomography demonstrates consistent accuracy in defining stereotactic space. Since both localization methods do not agree with each other consistently, the more reliable method must be identified. Cone beam computed tomography can accurately determine offsets occurring within stereotactic space that would be nondiscernible utilizing the fiducial method and seems to be more reliable. Using CBCT localization offers the opportunity to streamline workflow both from a patient and clinic perspective and also shows patient position immediately prior to treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31499213

RESUMO

The leukodystrophies are a heterogeneous group of inherited diseases characterized by progressive demyelination of the central nervous system leading to devastating neurologic symptoms and premature death. Hematopoietic stem cell transplantation (HSCT) has been successfully used to treat certain leukodystrophies, including adrenoleukodystrophy, globoid leukodystrophy (Krabbe disease), and metachromatic leukodystrophy, over the past 30 years. To date, these complex patients have primarily been transplanted at a limited number of pediatric centers. As the number of cases identified through pregnancy and newborn screening is increasing, additional centers will be required to treat these children. Hunter's Hope created the Leukodystrophy Care Network in part to create and standardize high-quality clinical practice guidelines to guide the care of affected patients. In this report the clinical guidelines for the care of pediatric patients with leukodystrophies undergoing treatment with HSCT are presented. The initial transplant evaluation, determination of patient eligibility, donor selection, conditioning, supportive care, and post-transplant follow-up are discussed. Throughout these guidelines the need for early detection and treatment and the role of the partnership between families and multidisciplinary providers are emphasized.

6.
Med Phys ; 46(11): 4983-4991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419312

RESUMO

BACKGROUND AND PURPOSE: Appropriate images extracted from the MRI of mothers' wombs can be of great help in the medical diagnosis of fetal abnormalities. As maternal tissue may appear in such images, affecting visualization of myelination of the fetal brain, it is not possible to use methods routinely used for extraction of adult brains for fetal brains. The aim of the present study was to use a variational level set approach to extract fetal brain from T2-weighted MR images of the womb. METHODS: Coronal T2-weighted images were acquired using fast MRI protocols (to avoid artifacts). The database includes 105 MR images from eight subjects. After correcting the inhomogeneity of the images, the fetal eyes were located, and from that information, the location of the fetus brain was automatically determined. Then, the variational level set was used for fetus brain extraction. The results were analyzed by a clinical specialist (radiologist) and the similarity (Dice and Jaccard coefficients), sensitivity and specificity were calculated. RESULTS AND CONCLUSIONS: The means of the statistical analysis for the Dice and Jaccard coefficients, sensitivity and specificity, were 99.56%, 96.89%, 95.71%, and 97.96%, respectively. Thus, extraction of fetal brain from MR images was confirmed, both statistically and visually through cross-validation.

7.
Am J Hum Genet ; 105(2): 413-424, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31327508

RESUMO

WD40 repeat-containing proteins form a large family of proteins present in all eukaryotes. Here, we identified five pediatric probands with de novo variants in WDR37, which encodes a member of the WD40 repeat protein family. Two probands shared one variant and the others have variants in nearby amino acids outside the WD40 repeats. The probands exhibited shared phenotypes of epilepsy, colobomas, facial dysmorphology reminiscent of CHARGE syndrome, developmental delay and intellectual disability, and cerebellar hypoplasia. The WDR37 protein is highly conserved in vertebrate and invertebrate model organisms and is currently not associated with a human disease. We generated a null allele of the single Drosophila ortholog to gain functional insights and replaced the coding region of the fly gene CG12333/wdr37 with GAL4. These flies are homozygous viable but display severe bang sensitivity, a phenotype associated with seizures in flies. Additionally, the mutant flies fall when climbing the walls of the vials, suggesting a defect in grip strength, and repeat the cycle of climbing and falling. Similar to wall clinging defect, mutant males often lose grip of the female abdomen during copulation. These phenotypes are rescued by using the GAL4 in the CG12333/wdr37 locus to drive the UAS-human reference WDR37 cDNA. The two variants found in three human subjects failed to rescue these phenotypes, suggesting that these alleles severely affect the function of this protein. Taken together, our data suggest that variants in WDR37 underlie a novel syndromic neurological disorder.

9.
Ultrasound Med Biol ; 45(7): 1799-1813, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31053427

RESUMO

Clutter in echocardiography hinders the visualization of the heart and reduces the diagnostic value of the images. The detailed mechanisms that generate clutter are, however, not well understood. We present five different hypotheses for generation of clutter based on reverberation artifact with a focus on apical four-chamber view echocardiograms. We demonstrate the plausibility of our hypotheses by in vitro experiments and by comparing the results with in vivo recordings from four volunteers. The results show that clutter in echocardiography can be originated both at structures that lie in the ultrasound beam path and at those that are outside the imaging plane. We show that reverberations from echogenic structures outside the imaging plane can make clutter over the image if the ultrasound beam gets deflected out of its intended path by specular reflection at the ribs. Different clutter types in the in vivo examples show that the appearance of clutter varies, depending on the tissue from which it originates. The results of this work can be applied to improve clutter reduction techniques or to design ultrasound transducers that give higher quality cardiac images. The results can also help cardiologists have a better understanding of clutter in echocardiograms and acquire better images based on the type and the source of the clutter.

10.
Neurotherapeutics ; 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077039

RESUMO

X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260.

11.
Brain Struct Funct ; 224(5): 1815-1829, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31011813

RESUMO

Diffusion tensor imaging (DTI) is increasingly utilized as a sensitive tool for studying brain maturation and injuries during the neonatal period. In this study, we acquired high resolution in vivo DTI data from neonatal rat brains from postnatal day 2 (P2) to P10 and correlated temporal changes in DTI derived markers with microstructural organization of glia, axons, and dendrites during this critical period of brain development. Group average images showed dramatic temporal changes in brain morphology, fractional anisotropy (FA) and mean diffusivity (MD). Most cortical regions showed a monotonous decline in FA and an initial increase in MD from P2 to P8 that declined slightly by P10. Qualitative histology revealed rapid maturation of the glial and dendritic networks in the developing cortex. In the cingulate and motor cortex, the decreases in FA over time significantly correlated with structural anisotropy values computed from histological sections stained with glial and dendritic markers. However, in the sensory and visual cortex, other factors probably contributed to the observed decreases in FA. We did not observe any significant correlations between FA and structural anisotropy computed from the axonal histological marker.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30990429

RESUMO

Many adaptive beamformers claim to produce images with increased contrast, a feature that could enable a better detection of lesions and anatomical structures. Contrast is often quantified using the contrast ratio (CR) and the contrast-to-noise ratio (CNR). The estimation of CR and CNR can be affected by dynamic range alterations (DRAs), such as those produced by a trivial gray-level transformation. Thus, we can form the hypothesis that contrast improvements from adaptive beamformers can, partly, be due to DRA. In this paper, we confirm this hypothesis. We show evidence on the influence of DRA on the estimation of CR and CNR and on the fact that several methods in the state of the art do alter the DR. To study this phenomenon, we propose a DR test (DRT) to estimate the degree of DRA and we apply it to seven beamforming methods. We show that CR improvements correlate with DRT with [Formula: see text] in simulated data and [Formula: see text] in experiments. We also show that DRA may lead to increased CNR values, under some circumstances. These results suggest that claims on lesion detectability, based on CR and CNR values, should be revised.

13.
Neuropsychobiology ; 78(1): 7-13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970364

RESUMO

BACKGROUND: Recent investigations have highlighted significant differences in verbal recall between patients with panic disorder (PD) and controls. These studies have highlighted that verbal memory and working memory could be impaired in PD. OBJECTIVES: The objective of the present meta-analysis is to confirm this hypothesis, reviewing the studies that have investigated neurocognitive testing in PD. METHODS: We performed a systematic literature search for studies published between 1980 and 2015 that reported cognitive measurements in PD patients and controls. Effect size estimates were computed using the restricted maximum likelihood model. Only case-control studies were selected for this meta-analysis. We included studies that made a direct comparison between PD subjects and healthy controls. The diagnostic group consisted of adult patients aged over 18 years diagnosed with PD. We excluded the studies that did not employ a case-control design. All statistical analyses were carried out on R using the "metafor" package version 1.9-8. The effect size for each study neuropsychological test was calculated using the mean and SD of performance results, and p values < 0.05 were considered significant. RESULTS: We identified few studies that tested verbal memory and executive functions in PD patients and controls, and this difference was not significant. On the other hand, there are several studies that have used the emotional Stroop task to assess cognitive functions in PD. There is no robust evidence of impairment of memory function in PD; however, when considering the emotional Stroop task, it was found that PD patients performed slower (p < 0.01) than healthy controls for all three types of stimuli (neutral, negative, positive). CONCLUSION: This meta-analysis included a small number of studies, which may have introduced bias into the analysis. However, there is some evidence of impairment of neurocognitive functions in PD when performing the emotional Stroop task. Furthermore, the paucity of studies evaluating neurocognition in PD suggests the need for further research in this field in order to draw meaningful conclusions.


Assuntos
Atenção , Emoções , Transtorno de Pânico/psicologia , Humanos , Teste de Stroop
14.
Tomography ; 5(1): 77-89, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30854445

RESUMO

Accurate, patient-specific measurement of arterial input functions (AIF) may improve model-based analysis of vascular permeability. This study investigated factors affecting AIF measurements from magnetic resonance imaging (MRI) magnitude (AIFMAGN) and phase (AIFPHA) signals, and compared them against computed tomography (CT) (AIFCT), under controlled conditions relevant to clinical protocols using a multimodality flow phantom. The flow phantom was applied at flip angles of 20° and 30°, flow rates (3-7.5 mL/s), and peak bolus concentrations (0.5-10 mM), for in-plane and through-plane flow. Spatial 3D-FLASH signal and variable flip angle T1 profiles were measured to investigate in-flow and radiofrequency-related biases, and magnitude- and phase-derived Gd-DTPA concentrations were compared. MRI AIF performance was tested against AIFCT via Pearson correlation analysis. AIFMAGN was sensitive to imaging orientation, spatial location, flip angle, and flow rate, and it grossly underestimated AIFCT peak concentrations. Conversion to Gd-DTPA concentration using T1 taken at the same orientation and flow rate as the dynamic contrast-enhanced acquisition improved AIFMAGN accuracy; yet, AIFMAGN metrics remained variable and significantly reduced from AIFCT at concentrations above 2.5 mM. AIFPHA performed equivalently within 1 mM to AIFCT across all tested conditions. AIFPHA, but not AIFMAGN, reported equivalent measurements to AIFCT across the range of tested conditions. AIFPHA showed superior robustness.

16.
Pharmacopsychiatry ; 52(5): 217-221, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30669162

RESUMO

INTRODUCTION: Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. METHODS: Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman's rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. RESULTS: The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. DISCUSSION: Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.

18.
J Clin Invest ; 129(3): 1240-1256, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620337

RESUMO

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive. MRI showed hypomyelination, thinning of the corpus callosum, and progressive thalamic and cerebellar atrophy, suggesting a critical role of DEGS1 in myelin development and maintenance. This enzyme converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. We detected a marked increase of the substrate DhCer and DhCer/Cer ratios in patients' fibroblasts and muscle. Further, we used a knockdown approach for disease modeling in Danio rerio, followed by a preclinical test with the first-line treatment for multiple sclerosis, fingolimod (FTY720, Gilenya). The enzymatic inhibition of Cer synthase by fingolimod, 1 step prior to DEGS1 in the pathway, reduced the critical DhCer/Cer imbalance and the severe locomotor disability, increasing the number of myelinating oligodendrocytes in a zebrafish model. These proof-of-concept results pave the way to clinical translation.

19.
Compr Psychiatry ; 89: 28-32, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30579127

RESUMO

BACKGROUND: Treatment resistance is a common issue among schizophrenia patients undergoing antipsychotic treatment. According to the American Psychiatric Association (APA) guidelines, treatment-resistant status is defined as little or no symptom reduction to at least two antipsychotics at a therapeutic dose for a trial of at least six weeks. The aim of the current study is to determine whether ethnicity and migration are associated with treatment resistance. METHODS: In a sample of 251 participants with schizophrenia spectrum disorders, we conducted cross-sectional assessments to collect information regarding self-identified ethnicity, immigration and treatment history. Ancestry was identified using 292 markers overlapping with the HapMap project. Using a regression analysis, we tested whether a history of migration, ethnicity or genetic ancestry were predictive of treatment resistance. RESULTS: Our logistic regression model revealed no significant association between immigration (OR = 0.04; 95%CI = 0.35-3.07; p = 0.93) and treatment resistant schizophrenia. White Europeans did not show significant association with resistance status regardless of whether ethnicity was determined by self-report (OR = 1.89; 95%CI = 0.89-4.20; p = 0.105) or genetic analysis (OR = -0.73; 95%CI = -0.18-2.97; p = 0.667). CONCLUSION: Neither ethnicity nor migrant status was significantly associated with treatment resistance in this Canadian study. However, these conclusions are limited by the small sample size of our investigation.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30149093

RESUMO

BACKGROUND: Approximately 5% of patients with schizophrenia commit suicide, and 20% to 40% of them have at least one suicide attempt during their lifetime. Previous research has identified childhood trauma as a potential risk factor for suicide attempt in schizophrenia. The Psychiatric Genetics Consortium found 108 common genetic risk loci associated with schizophrenia. Moreover, familial, adoption, and twin studies suggested that suicidal behaviour is under genetic influence. OBJECTIVE: Our objective was to determine the effect of childhood trauma and schizophrenia polygenic risk in leading to suicide attempt, as well as to determine any interaction effect between the polygenic scores with childhood trauma. METHODS: The study design was cross-sectional and retrospective considering lifetime suicide attempt as the main dependent variable. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Polygenic Risk Score calculation was done using the genome-analysis toolkit, PLINK. The suicide attempts were recorded using the Columbia Suicide Severity Rating Scale. RESULTS: We included 224 subjects in our sample and 93 attempted suicide at least once in their lifetime. When comparing the weighted scores in attempters and non-attempters, we found no association (p > .05). CONCLUSION: Although our results do not support our hypothesis, the interaction analysis of genetic risk for schizophrenia in combination with the history of childhood trauma requires larger samples with high-quality suicide risk assessment.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Predisposição Genética para Doença , Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/genética , Tentativa de Suicídio , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Estudos Transversais , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Transtornos Psicóticos/psicologia , Estudos Retrospectivos , Psicologia do Esquizofrênico , Tentativa de Suicídio/psicologia
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