Functional MRI of sentence comprehension in children with dyslexia: beyond word recognition.

Sentence comprehension (SC) studies in typical and impaired readers suggest that reading for meaning involves more extensive brain activation than reading isolated words. Thus far, no reading disability/dyslexia (RD) studies have directly controlled for the word recognition (WR) components of SC tasks, which is central for understanding comprehension processes beyond WR. This experiment compared SC to WR in 29, 9-14 year olds (15 typical and 14 impaired readers). The SC-WR contrast for each group showed activation in left inferior frontal and extrastriate regions, but the RD group showed significantly more activation than Controls in areas associated with linguistic processing (left middle/superior temporal gyri), and attention and response selection (bilateral insula, right cingulate gyrus, right superior frontal gyrus, and right parietal lobe). Further analyses revealed this overactivation was driven by the RD group's response to incongruous sentences. Correlations with out-of-scanner measures showed that better word- and text-level reading fluency was associated with greater left occipitotemporal activation, whereas worse performance on WR, fluency, and comprehension (reading and oral) were associated with greater right hemisphere activation in a variety of areas, including supramarginal and superior temporal gyri. Results provide initial foundations for understanding the neurobiological correlates of higher-level processes associated with reading comprehension.

Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (NC) mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed. METHODS: We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (FA) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE). RESULTS: Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable. CONCLUSIONS: Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression.

Sex differences in cerebral laterality of language and visuospatial processing.

Sex differences on language and visuospatial tasks are of great interest, with differences in hemispheric laterality hypothesized to exist between males and females. Some functional imaging studies examining sex differences have shown that males are more left lateralized on language tasks and females are more right lateralized on visuospatial tasks; however, findings are inconsistent. Here we used functional magnetic resonance imaging to study thirty participants, matched on task performance, during phonological and visuospatial tasks. For each task, region-of-interest analyses were used to test differences in cerebral laterality. Results indicate that lateralization differences exist, with males more left lateralized during the phonological task and showing greater bilateral activity during the visuospatial task, whereas females showed greater bilateral activity during the phonological task and were more right lateralized during the visuospatial task. Our data provide clear evidence for differences in laterality between males and females when processing language versus visuospatial information.

Retrospective radiation dosimetry using electron paramagnetic resonance in canine dental enamel.

Electron paramagnetic resonance (EPR) biodosimetry of human tooth enamel has been widely used for measuring radiation doses in various scenarios. We have now developed EPR dosimetry in tooth enamel extracted from canines. Molars and incisors from canines were cleaned by processing in supersaturated aqueous potassium hydroxide solution. The dosimetric signal in canine tooth enamel was found to increase linearly as a function of laboratory added dose from 0.44+/-0.02 to 4.42+/-0.22 Gy. The gamma radiation sensitivity of the canine molar enamel was found to be comparable to that of human tooth enamel. The dosimetric signal in canine enamel has been found to be stable up to at least 6 weeks after in vitro irradiation. A dosimetric signal variation of 10-25% was observed for canines ranging from in age 3 years to 16 year old.

19F magnetic resonance imaging of cerebral blood flow with 0.4-cc resolution.

19F magnetic resonance imaging techniques were used to determine "wash-in" and "wash-out" curves of the inert, diffusible gas CHF3 from 0.4-cc voxels in the cat brain, and mass spectrometer gas detection was used to determine the CHF3 concentration in expired air. These two sets of data were used to calculate cerebral blood flow values in the 0.4-cc voxels, and the blood flow images were registered with high-resolution 1H magnetic resonance images. Data were collected both during the wash-in and wash-out phases of the experiment, but the two sets of data were analyzed separately to obtain independent estimates of the blood flow during the two phases, i.e., Qin and Qout. Repeated determinations of cerebral blood flow images were performed in individual animals, and the entire protocol was repeated on five different animals. The average values of Qin and Qout for a typical 0.4-cc voxel in the parietal cortex were 83 ml 100 g-1 min-1 and 72 ml 100 g-1 min-1, respectively. Monte Carlo calculations utilizing the noise in the 19F NMR signal from this voxel predict an average standard deviation for Qin and Qout of +/- 10%. The average standard deviation for repeated measurements (in the same animal) of Qin and Qout in this voxel was +/- 14%. We conclude that 19F magnetic resonance imaging approaches have the potential to image cerebral blood flow in humans.

Simultaneous measurement of cerebral oxygen consumption and blood flow using 17O and 19F magnetic resonance imaging.

17O and 19F magnetic resonance (MR) imaging were used to determine simultaneously the concentrations of H2 17O and CHF3 in 0.8-cc voxels in the cat brain during inhalation of a gas mixture containing both 17O2 and CHF3. The arterial time course of CHF3 was determined by "on-line" mass spectrometer detection of expired CHF3, and the arterial time course of H2 17O was determined by 17O MR analysis of arterial samples withdrawn during the inhalation period. The brain data and the arterial data for the two tracers were combined to calculate the cerebral oxygen consumption (CMRO2) and the CBF. The protocol was repeated on seven cats, using pentobarbital anesthesia. The average values of CMRO2 and CBF for a 0.8-cc voxel in the parietal cortex were 1.5 +/- 0.5 mmol kg-1 min-1 and 38 +/- 15 ml 100 g-1 min-1, respectively. In individual animals the average uncertainty in CMRO2 and CBF, calculated from Monte Carlo approaches, was +/- 9%.

Anatomical and functional imaging of the auditory cortex in awake mustached bats using magnetic resonance technology.

The auditory cortex of mustached bats, Pteronotus parnellii, has been studied extensively using neuroanatomical tract-tracing and electrophysiological techniques to elucidate the functional organization and neural mechanisms important for auditory processing. While these techniques have identified several cortical maps involved in processing auditory information, there has been no direct observation of the dynamics of simultaneous activation of several discrete areas. We applied magnetic resonance (MR) imaging techniques for visualizing brain structures in awake bats using a 7-Tesla magnet system; we also investigated functional MR imaging by measuring changes in stimulus-correlated blood oxygenation levels to detect cortical areas exhibiting evoked neural activity. High resolution (100 microm) anatomical images were successfully acquired without any motion artifacts. It was possible to reconstruct the whole brain image and analyze brain surface structures with three dimensional (3D) MR imaging data. These data provide detailed morphometric measurements that will allow localization of stimulus specific neural activity patterns using modified functional magnetic-resonance-imaging (fMRI) protocols. Motion artifacts is the primary disadvantage of using awake bats; our study shows that fMRI of a bat's brain is feasible and may prove to be an important advancement for a further understanding of auditory processing in this species.Themes: Sensory systems, Neural basis of behavior.

An investigation of the toxicity of gadolinium based MRI contrast agents using neutron activation analysis.

The toxicity of gadolinium (Gd) based MRI contrast agents, is based upon the amount of Gd that dissociates from its chelate and deposits in tissues. In this study, the toxicities of two contrast agents were tested using different injection strategies in two animal models. Following a bolus injection of 0.2 mmol/kg of Gd-DTPA in a pilot study with a single canine, Gd levels were as high as 2.05 +/- 0.17 ppm and 0.47 +/- 0.11 ppm 2 weeks post injection in the kidney and liver tissues, respectively. To evaluate the role that the injection strategy plays in toxicity, 0.8 mmol/kg of Gd-(HP-DO3A) was injected into rats, in a second study, via bolus and constant infusion techniques. Gd was only detected in the kidney in the bolus injected rats but in the lung as well in the constant infusion injected rats. Concentrations detected in the kidney for both strategies, were comparable within error: 1.37 +/- 0.46 ppm for the bolus and 1.24 +/- 0.39 ppm for the bolus/constant infusion strategy and 0.16 +/- 0.14 ppm in the lung for the constant infusion technique. The contrast infusion technique does not appear to present an increased risk of toxicity over the bolus technique except perhaps to a small degree in the lung.

Sculpting the developing brain.

The developing brain experiences major construction during fetal life and for at least the first decade of childhood. Many more neurons and synoptic connections are produced than are needed for later function, and the mature brain is what remains after these excess building materials are "sculpted" away. This process is thought to be the basis for the developing brain's plasticity, or the capacity to adapt its behavior and circuitry to stimulation from the external environment. Plastic reorganization of the brain is now being studied in children and adults with new noninvasive tools such as functional brain magnetic resonance imaging. This exploratory tool and other new clinical methods demonstrate how the brain's functional "maps" undergo major reorganization in response to early environmental changes. The neurobiology of brain reorganization during development is also being studied with use of new insights into the molecular mechanisms for activity-dependent neuronal plasticity. Clinical disorders such as lead poisoning, metabolic and epileptic encephalopathies, and psychosocial deprivation may arise from disrupted brain plasticity. Several mental retardation syndromes and cognitive disorders recently recognized as being secondary to genetic disruption of intracellular signaling cascades may also disrupt this process. Understanding how the brain's circuitry is sculpted during development provides an important perspective for thinking about neurodevelopmental disorders.

Specific features of the influence of high-energy electron beams on the luminescent properties of undoped and Nb, Fe-doped Al2O3 crystals.

The influence of 10 MeV high-current electron beams accelerated by the M-30 microtron on the luminescent properties of the α-Al2O3, Al2O3:Nb and Al2O3:Fe crystals has been studied. The effect of the long-term phosphorescence at room temperature has been found that can be used to monitor electron and gamma accelerator beams.

Poster - Thur Eve - 10: Long term stability of VMAT quality assurance parameters using an EPID.

The rapidly growing use of volumetric modulated arc therapy (VMAT) treatments in radiation therapy calls for a quantitative, automated, and reliable quality assurance (QA) procedure that can be used routinely in the clinical setting. In this work, we present a series VMAT QA procedures used to assess dynamic multi-leaf collimator (MLC) positional accuracy, variable dose-rate accuracy, and MLC leaf speed accuracy. The QA procedures were performed using amorphous silicon electronic portal imaging devices (EPID) to determine the long term stability of the measured parameters on two Varian linear accelerators. The measurements were repeated weekly on both linear accelerators for a period of three months and the EPID images were analyzed using custom Matlab software. The results of the picket fence tests indicate that MLC leaf positions can be identified to within 0.11 mm and 0.15 mm for static gantry delivery and VMAT delivery respectively. In addition, the dose-rate, gantry speed and MLC leaf speed tests both show very good stability over the measurement period. The measurements thus far, suggest that a number of the dosimetry tests may be suitable for quarterly QA for Varian iX and Trilogy linacs. However, additional measurements are required to confirm the frequency with which each test is required for safe and reliable VMAT delivery at our centre.

Method for multimodal analysis of independent source differences in schizophrenia: combining gray matter structural and auditory oddball functional data.

The acquisition of both structural MRI (sMRI) and functional MRI (fMRI) data for a given study is a very common practice. However, these data are typically examined in separate analyses, rather than in a combined model. We propose a novel methodology to perform independent component analysis across image modalities, specifically, gray matter images and fMRI activation images as well as a joint histogram visualization technique. Joint independent component analysis (jICA) is used to decompose a matrix with a given row consisting of an fMRI activation image resulting from auditory oddball target stimuli and an sMRI gray matter segmentation image, collected from the same individual. We analyzed data collected on a group of schizophrenia patients and healthy controls using the jICA approach. Spatially independent joint-components are estimated and resulting components were further analyzed only if they showed a significant difference between patients and controls. The main finding was that group differences in bilateral parietal and frontal as well as posterior temporal regions in gray matter were associated with bilateral temporal regions activated by the auditory oddball target stimuli. A finding of less patient gray matter and less hemodynamic activity for target detection in these bilateral anterior temporal lobe regions was consistent with previous work. An unexpected corollary to this finding was that, in the regions showing the largest group differences, gray matter concentrations were larger in patients vs. controls, suggesting that more gray matter may be related to less functional connectivity in the auditory oddball fMRI task.

Differential components of sentence comprehension: beyond single word reading and memory.

A number of studies have used functional neuroimaging to examine the neural mechanisms of sentence comprehension; however, few fMRI studies have examined activation patterns associated with sentence comprehension after accounting for activation attributable to single-word-level tasks important for sentence comprehension. To investigate the patterns of activation associated with sentence comprehension after controlling for single word reading and maintaining single words in memory, 20 unimpaired adult readers completed a block design paradigm which included sentence comprehension, single word reading, and short-term memory (for words) tasks. Results indicated that, regardless of the aspect of sentence comprehension being controlled for, activation was observed in bilateral temporal lobes (left > right) as well as bilateral occipital lobes and middle frontal gyri. Additional findings showed that bilateral superior parietal lobe activation was greatest for short-term memory for words, while left anterior inferior frontal gyri activation (centered around Brodmann's area 47) was greatest for single word reading. Results suggest that temporal cortex (left > right) is a core region important for sentence comprehension beyond the short-term memory and semantic requirements inherent in processing sentences.

Semi-blind ICA of fMRI: A method for utilizing hypothesis-derived time courses in a spatial ICA analysis.

Independent component analysis (ICA) is a data-driven approach utilizing high-order statistical moments to find maximally independent sources that has found fruitful application in functional magnetic resonance imaging (fMRI). Being a blind source separation technique, ICA does not require any explicit constraints upon the fMRI time courses. However, for some fMRI data analysis applications, such as for the analysis of an event-related paradigm, it would be useful to flexibly incorporate paradigm information into the ICA analysis. In this paper, we present an approach for constrained or semi-blind ICA (sbICA) analysis of event-related fMRI data by imposing regularization on certain estimated time courses using the paradigm information. We demonstrate the performance of our approach using both simulations and fMRI data from a three-stimulus auditory oddball paradigm. Simulation results suggest that (1) a regression approach slightly outperforms ICA when prior information is accurate and ICA outperforms the general linear model (GLM)-based approach when prior information is not completely accurate, (2) prior information improves the robustness of ICA in the presence of noise, and (3) ICA analysis using prior information with temporal constraints can outperform a regression approach when the prior information is not completely accurate. Using fMRI data, we compare a regression-based conjunction analysis of target and novel stimuli, both of which elicit an orienting response, to an sbICA approach utilizing both the target and novel stimuli to constrain the ICA time courses. Results show similar positive associations for both GLM and sbICA, but sbICA detects additional negative associates consistent with regions implicated in a default mode of brain activity. This suggests that task-related default mode decreases have a more "complex" signal that benefits from a flexible modeling approach. Compared with a traditional GLM approach, the sbICA approach provides a flexible way to analyze fMRI data that reduces the assumptions placed upon the hemodynamic response of the brain. The advantages and limitations of our technique are discussed in detail in the manuscript to provide guidelines to the reader for developing useful applications. The use of prior time course information in a spatial ICA analysis, which combines elements of both a regression approach and a blind ICA approach, may prove to be a useful tool for fMRI analysis.

Challenges in applying autofocus technology to low vision telescopes.

Autofocus (AF) low vision telescopes offer the potential to increase the acceptance and utilization of such low vision aids (LVA) by the visually impaired. Many patients resist conventional manual focus telescopes for a variety of reasons including appearance, field of view, weight, and utility. The elderly who comprise the significant part of the target population may also resist telescopes due to an avoidance of the technical challenge of its use. Although an AF telescope is technically advanced, it may allow for less manipulation by the wearer and hence enable its more effective application to visual tasks, especially in the near- to mid-range where depths of field narrow and the demands for focusing increase. There are many challenges involved in the application of AF technology to LVA including modification of the focusing range, signal processing for physiologically acceptable performance, and power and weight considerations. A preliminary infrared (IR) AF prototype based upon our recent work with the Ocutech Vision Enhancing System (VES) has been produced. Initial findings are presented which address the requirements of a subsequent version as well as the challenges that will be faced to optimize such a device.

On the precision of diffusion/perfusion imaging by gradient sensitization.

Computer simulation is used to assess the precision and accuracy of diffusion and perfusion parameters derived from a set of gradient-sensitized images. Under ideal experimental conditions, a moderate signal-to-noise level (ca. 40) suffices to estimate diffusion coefficients to within 20% relative precision. However, estimation of a typical cerebral perfusion fraction of 5% to within 20% relative precision requires signal-to-noise levels of ca. 400. Simulations also show that systematic errors in perfusion fraction estimation, as well as underestimation of the uncertainties in perfusion parameters (by chi-squared analysis), will be found at moderate signal-to-noise levels.

Determination of cerebral oxygen consumption and blood flow by magnetic resonance imaging.

Simultaneous 17O and 19F magnetic resonance imaging were used to determine the concentrations of H2(17)O and CHF3 in 0.8 cc voxels in the cat brain during in- and exhalation of a gas mixture containing both 17O2 and CHF3. The arterial time course of H2(17)O was determined by 17O MR analysis of arterial samples withdrawn during the inhalation period and the arterial time concentration of CHF3. The brain data and the arterial data for the two tracers were used to calculate the cerebral oxygen consumption (CMRO2) and the cerebral blood flow (CBF). The average values of CMRO2 and CBF for a 0.8 cc voxel in the parietal cortex were 1.5 +/- 0.5 mmol/kg/min and 38 +/- 15 ml/100g/min, respectively. 17O/19F MR imaging approach has the potential to image CMRO2 and CBF simultaneously in humans and might become a strong diagnostic tool.

A method for making group inferences from functional MRI data using independent component analysis.

Independent component analysis (ICA) is a promising analysis method that is being increasingly applied to fMRI data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed models of brain activity are not available. Independent component analysis has been successfully utilized to analyze single-subject fMRI data sets, and an extension of this work would be to provide for group inferences. However, unlike univariate methods (e.g., regression analysis, Kolmogorov-Smirnov statistics), ICA does not naturally generalize to a method suitable for drawing inferences about groups of subjects. We introduce a novel approach for drawing group inferences using ICA of fMRI data, and present its application to a simple visual paradigm that alternately stimulates the left or right visual field. Our group ICA analysis revealed task-related components in left and right visual cortex, a transiently task-related component in bilateral occipital/parietal cortex, and a non-task-related component in bilateral visual association cortex. We address issues involved in the use of ICA as an fMRI analysis method such as: (1) How many components should be calculated? (2) How are these components to be combined across subjects? (3) How should the final results be thresholded and/or presented? We show that the methodology we present provides answers to these questions and lay out a process for making group inferences from fMRI data using independent component analysis.

Dissociation of the neural systems for working memory maintenance of verbal and nonspatial visual information.

Working memory for names and faces was investigated to ascertain whether verbal and nonspatial visual information is maintained in working memory by separate neural systems. The subjects performed a delayed match-to-sample task for famous or unfamous faces and names and a sensorimotor control task. Several occipital, temporal, parietal, and prefrontal areas were activated during all memory delays, in comparison with the control delays. Greater delay activity for unfamous faces than for names was obtained in the right fusiform gyrus, right inferior frontal gyrus (IFG), right IFG/precentral gyrus, and right medial superior frontal gyrus, whereas greater delay activity for unfamous names than for faces was observed in the precuneus, left insula/postcentral gyrus, and left IFG/precentral gyrus. There was no significant difference in the prefrontal activity in the comparison between famous faces and names. Greater delay activity for famous names than for faces was obtained in visual association and parietal areas. The results indicate that there is a functional dissociation based on information type within the neural system that is responsible for working memory maintenance of verbal and nonspatial visual information.

MR color mapping of myelin fiber orientation.

Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders.