Dafna Ben Bashat

Accelerated maturation of white matter in young children with autism: A high b value DWI study

The goal of this work was to study white matter maturation in young children with autism following previous reports of increased cerebral volume during early development, as well as arguments for abnormal neural growth patterns and regulation at this critical developmental period. We applied diffusion tensor imaging (DTI) and high b value diffusion-weighted imaging (DWI) to young children diagnosed with autism and to a typically developing (TD) control group. Fractional anisotropy (FA), probability and displacement were measured in overall analysis as well as in regions of interest (ROI). Individual data points of children with autism were compared to the developmental curves obtained from typically developing children. Increased restriction, reflected in significantly increased FA and probability along with reduced displacement values, was detected in overall analysis as well as in several brain regions. Increased restriction, suggesting an early and accelerated abnormal maturation of white matter, was more dominant in the left hemisphere and was mainly detected in the frontal lobe. No changes were detected in the occipital lobes. These results support previous claims of abnormal brain overgrowth in young children with autism and are in contrast to the decreased restricted diffusion reported in previous studies in adolescent with autism.

Abnormal White Matter Integrity in Young Children with Autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty‐two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract‐based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS–VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid‐body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism. Hum Brain Mapp, 2011.

Vase or Face? A Neural Correlate of Shape-Selective Grouping Processes in the Human Brain

Recent neuroimaging studies have described a differential activation pattern associated with specific object images (e.g., face-related and building-related activation) in human occipito-temporal cortex. However, it is as yet unclear to what extent this selectivity is due to differences in the statistics of local object features present in the different object categories, and to what extent it reflects holistic grouping processes operating across the entire object image. To resolve this question it is essential to use images in which identical sets of local features elicit the perception of different object categories. The classic Rubin vase-face illusion provides an excellent experimental set to test this question. In the illusion, the same local contours lead to the perception of different objects (vase or face). Here we employed a modified Rubin vase-face illusion to explore to what extent the activation in face-related regions is attributable to the presence of local face features, or is due to a more holistic grouping process that involves the entire face figure. Biasing cues (gratings and color) were used to control the perceptual state of the observer. We found enhanced activation in face-related regions during the face profile perceptual state compared to the vase perceptual state. Control images ruled out the involvement of the biasing cues in the effect. Thus, object-selective activation in human face-related regions entails global grouping processes that go beyond the local processing of stimulus features.

Compressed sensing for longitudinal MRI: An adaptive-weighted approach

PURPOSE Repeated brain MRI scans are performed in many clinical scenarios, such as follow up of patients with tumors and therapy response assessment. In this paper, the authors show an approach to utilize former scans of the patient for the acceleration of repeated MRI scans. METHODS The proposed approach utilizes the possible similarity of the repeated scans in longitudinal MRI studies. Since similarity is not guaranteed, sampling and reconstruction are adjusted during acquisition to match the actual similarity between the scans. The baseline MR scan is utilized both in the sampling stage, via adaptive sampling, and in the reconstruction stage, with weighted reconstruction. In adaptive sampling, k-space sampling locations are optimized during acquisition. Weighted reconstruction uses the locations of the nonzero coefficients in the sparse domains as a prior in the recovery process. The approach was tested on 2D and 3D MRI scans of patients with brain tumors. RESULTS The longitudinal adaptive compressed sensing MRI (LACS-MRI) scheme provides reconstruction quality which outperforms other CS-based approaches for rapid MRI. Examples are shown on patients with brain tumors and demonstrate improved spatial resolution. Compared with data sampled at the Nyquist rate, LACS-MRI exhibits signal-to-error ratio (SER) of 24.8 dB with undersampling factor of 16.6 in 3D MRI. CONCLUSIONS The authors presented an adaptive method for image reconstruction utilizing similarity of scans in longitudinal MRI studies, where possible. The proposed approach can significantly reduce scanning time in many applications that consist of disease follow-up and monitoring of longitudinal changes in brain MRI.

A multi-site study of functional outcomes following a themed approach to hand-arm bimanual intensive therapy for children with hemiplegia.

This study investigated the effects of a theme‐based (‘magic’) variation of the hand–arm bimanual intensive therapy programme, in two different countries, in improving activity performance for children with hemiplegia, including those with severe movement restrictions.

Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

BACKGROUND Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T2-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. METHODS AND MATERIALS Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. RESULTS The non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T1-weighted (58 ± 10%) and hyperintense FLAIR (53 ± 9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r=-0.86, p=0.003, week 16: r=-0.99, p=0.001). CONCLUSION Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

T1 Mapping using variable flip angle SPGR data with flip angle correction

To improve the calculation of T1 relaxation time from a set of variable flip‐angle (FA) spoiled gradient recalled echo images.

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

BACKGROUND Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. MATERIALS AND METHODS FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. RESULTS FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. CONCLUSION This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

Hemodynamic response imaging: a potential tool for the assessment of angiogenesis in brain tumors.

Blood oxygenation level dependence (BOLD) imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI)). Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors) and one with atypical-meningioma. Maps of percent signal intensity changes (ΔS) during hyperoxia (carbogen; 95%O2+5%CO2) and hypercapnia (95%air+5%CO2) challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2) were calculated. VRM values were measured in white matter (WM) and gray matter (GM) areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3), increased response to carbogen was detected with substantially increased VRM response (compared to threshold values) within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors.

Cognitive Decline After Stroke Relation to Inflammatory Biomarkers and Hippocampal Volume

Background and Purpose— Inflammation may contribute to cognitive impairment after stroke. Inflammatory markers are associated with hippocampal atrophy. We tested whether markers of inflammation, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein are associated with reduced hippocampal volume and poor cognitive performance among stroke survivors. Methods— We analyzed 368 consecutive cases from our prospective study of first-ever mild–moderate stroke patients. MRI, cognitive tests, and inflammatory markers were determined. Patients were reevaluated 6 and 12 months after the event. Results— ESR remained unchanged in follow-up examinations, suggesting a chronic inflammation background in some patients. Higher levels of C-reactive protein and ESR were associated with worse performance in cognitive tests, particularly memory scores. This association was maintained for ESR (but not C-reactive protein) after adjustment for confounders (P=0.002). Patients with smaller hippocampi had inferior cognitive results. Moreover, in a multivariate regression model, higher ESR values (but not C-reactive protein) were related to reduced hippocampal volume (P=0.049). Conclusions— This report shows a strong relationship between ESR and hippocampal volume, as well as with cognitive performance among poststroke patients. This could plausibly relate to incipient cognitive decline via hippocampal pathways.