A discriminative feature selection approach for shape analysis: Application to fetal brain cortical folding.

The development of post-processing reconstruction techniques has opened new possibilities for the study of in-utero fetal brain MRI data. Recent cortical surface analysis have led to the computation of quantitative maps characterizing brain folding of the developing brain. In this paper, we describe a novel feature selection-based approach that is used to extract the most discriminative and sparse set of features of a given dataset. The proposed method is used to sparsely characterize cortical folding patterns of an in-utero fetal MR dataset, labeled with heterogeneous gestational age ranging from 26 weeks to 34 weeks. The proposed algorithm is validated on a synthetic dataset with both linear and non-linear dynamics, supporting its ability to capture deformation patterns across the dataset within only a few features. Results on the fetal brain dataset show that the temporal process of cortical folding related to brain maturation can be characterized by a very small set of points, located in anatomical regions changing across time. Quantitative measurements of growth against time are extracted from the set selected features to compare multiple brain regions (e.g. lobes and hemispheres) during the considered period of gestation.

Update on Efinaconazole 10% Topical Solution for the Treatment of Onychomycosis.

Efinaconazole 10% nail solution is a novel topical antifungal drug for the treatment of onychomycosis. Two Phase III trials were completed using efinaconazole 10% nail solution, where 17.8% and 15.2% of patients achieved complete cure, and 55.2% and 53.4% achieved mycological cure. Several post hoc analyses were carried out using data from Phase III trials to determine the efficacy of efinaconazole with respect to disease duration, disease progression, and comorbidities of diabetes or tinea pedis with onychomycosis. Efinaconazole produced higher efficacy rates with patients presenting onychomycosis in a small portion of the toenail (≤25%) for a shorter duration of time (<1 year and 1-5 years). When patients presenting with both onychomycosis and tinea pedis underwent concurrent treatment, efficacy of efinaconazole increased from 16.1% to 29.4%, suggesting combination therapy improved results. Most interestingly, there was no difference in efinaconazole efficacy between diabetic and non-diabetic groups, indicating efinaconazole could be a safe and effective form of treatment for diabetics. Overall, efinaconazole 10% nail solution shows potential as an antifungal therapy for the treatment of onychomycosis.

Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa.

Adalimumab (Humira®) is a novel therapy approved by the US Food and Drug Administration, Health Canada, and the European Commission for the treatment of hidradenitis suppurativa (HS). Results of two Phase III trials of adalimumab demonstrate significantly higher efficacies compared to placebo. Primary efficacy outcome of 50% reduction in abscess and inflammatory nodule count was seen in 41.8% and 58.9% of participants receiving adalimumab in PIONEER I and PIONEER II studies, respectively, showing substantial improvement compared with placebo groups in both trials (26.0% and 27.6%, respectively). Although the significance of secondary efficacy measures of adalimumab every week treatment (EW) was not consistent between PIONEER I and PIONEER II studies, participants achieving abscess and inflammatory nodule counts of 0, 1, or 2 were significant (EW 51.8%) compared to placebo (32.2%) in the PIONEER II trial. Participants also demonstrated a marked decrease in skin pain measurements from baseline between EW patients (45.7%) and placebo (20.7%) in the PIONEER II trial. Modified Sartorius scores were decreased from baseline in both PIONEER I (-24.4) and PIONEER II (-28.9) trials versus placebo (-15.7 and -9.5, respectively). Adverse events were mild to moderate and comparable between all treatment groups including placebo. Taken together, these data conclude that treatment of HS with adalimumab is a safe and effective therapy resulting in a significant decrease in abscess and inflammatory nodule counts within the first 12 weeks of treatment.

Probabilistic tractography using Q-ball imaging and particle filtering: application to adult and in-utero fetal brain studies.

By assuming that orientation information of brain white matter fibers can be inferred from Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) measurements, tractography algorithms provide an estimation of the brain connectivity in vivo. The two key ingredients of tractography are the diffusion model (tensor, high-order tensor, Q-ball, etc.) and the means to deal with uncertainty during the tracking process (deterministic vs probabilistic mathematical framework). In this paper, we investigate the use of an analytical Q-ball model for the diffusion data within a well-formalized particle filtering framework. The proposed method is validated and compared to other tracking algorithms on the MICCAI'09 contest Fiber Cup phantom. Tractographies of in vivo adult and fetal brain Diffusion-Weighted Images (DWIs) are also shown to illustrate the robustness of the algorithm.

Diffusion-weighted imaging in fetuses with severe congenital heart defects.

Fetal diffusion MR imaging was performed in 3 fetuses with CHD. ADC values in the periatrial WM, thalamus, and basal ganglia were compared with those in a control population of fetuses. Diffusivity in the periatrial WM and thalamus was higher for the fetuses with CHD compared with controls. These observations support the finding of abnormal in utero brain development in fetuses with CHD.

Brain atrophy associated with baseline and longitudinal measures of cognition.

The overall goal was to identify patterns of brain atrophy associated with cognitive impairment and future cognitive decline in non-demented elders. Seventy-one participants were studied with structural MRI and neuropsychological testing at baseline and 1-year follow-up. Deformation-based morphometry was used to examine the relationship between regional baseline brain tissue volume with baseline and longitudinal measures of delayed verbal memory, semantic memory, and executive function. Smaller right hippocampal and entorhinal cortex (ERC) volumes at baseline were associated with worse delayed verbal memory performance at baseline while smaller left ERC volume was associated with greater longitudinal decline. Smaller left superior temporal cortex at baseline was associated with worse semantic memory at baseline, while smaller left temporal white and gray matter volumes were associated with greater semantic memory decline. Increased CSF and smaller frontal lobe volumes were associated with impaired executive function at baseline and greater longitudinal executive decline. These findings suggest that baseline volumes of prefrontal and temporal regions may underlie continuing cognitive decline due to aging, pathology, or both in non-demented elderly individuals.

3D global and regional patterns of human fetal subplate growth determined in utero.

The waiting period of subplate evolution is a critical phase for the proper formation of neural connections in the brain. During this time, which corresponds to 15 to 24 postconceptual weeks (PCW) in the human fetus, thalamocortical and cortico-cortical afferents wait in and are in part guided by molecules embedded in the extracellular matrix of the subplate. Recent advances in fetal MRI techniques now allow us to study the developing brain anatomy in 3D from in utero imaging. We describe a reliable segmentation protocol to delineate the boundaries of the subplate from T2-W MRI. The reliability of the protocol was evaluated in terms of intra-rater reproducibility on a subset of the subjects. We also present the first 3D quantitative analyses of temporal changes in subplate volume, thickness, and contrast from 18 to 24 PCW. Our analysis shows that firstly, global subplate volume increases in proportion with the supratentorial volume; the subplate remained approximately one-third of supratentorial volume. Secondly, we found both global and regional growth in subplate thickness and a linear increase in the median and maximum subplate thickness through the waiting period. Furthermore, we found that posterior regions--specifically the occipital pole, ventral occipito-temporal region, and planum temporale--of the developing brain underwent the most statistically significant increases in subplate thickness. During this period, the thickest region was the developing somatosensory/motor cortex. The subplate growth patterns reported here may be used as a baseline for comparison to abnormal fetal brain development.

On super-resolution for fetal brain MRI.

Super-resolution techniques provide a route to studying fine scale anatomical detail using multiple lower resolution acquisitions. In particular, techniques that do not depend on regular sampling can be used in medical imaging situations where imaging time and resolution are limited by subject motion. We investigate in this work the use of a super-resolution technique for anisotropic fetal brain MR data reconstruction without modifying the data acquisition protocol. The approach, which consists of iterative motion correction and high resolution image estimation, is compared with a previously used scattered data interpolation-based reconstruction method. To optimize acquisition time, an evaluation of the influence of the number of input images and image noise is also performed. Evaluation on simulated MR images and real data show significant improvements in performance provided by the super-resolution approach.

Diffusion-weighted imaging in fetuses with unilateral cortical malformations and callosal agenesis.

DWI was performed in fetuses with callosal agenesis and unilateral cortical malformations. ADC values were retrospectively measured in the developing white matter underlying the cortical malformation and compared with the corresponding contralateral white matter. In all 3 patients, ADC values were lower under the areas of cortical malformation compared with the normal contralateral side. Our findings suggest that there are structural differences in the developing white matter underlying areas of cortical malformation.

Normative apparent diffusion coefficient values in the developing fetal brain.

BACKGROUND AND PURPOSE: Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses. MATERIALS AND METHODS: DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed. RESULTS: Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus. CONCLUSIONS: Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.

Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy.

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P<.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI).

Distributions of proton MR-detected metabolites have been mapped throughout the brain in a group of normal subjects using a volumetric MR spectroscopic imaging (MRSI) acquisition with an interleaved water reference. Data were processed with intensity and spatial normalization to enable voxel-based analysis methods to be applied across a group of subjects. Results demonstrate significant regional, tissue, and gender-dependent variations of brain metabolite concentrations, and variations of these distributions with normal aging. The greatest alteration of metabolites with age was observed for white-matter choline and creatine. An example of the utility of the normative metabolic reference information is then demonstrated for analysis of data acquired from a subject who suffered a traumatic brain injury. This study demonstrates the ability to obtain proton spectra from a wide region of the brain and to apply fully automated processing methods. The resultant data provide a normative reference for subsequent utilization for studies of brain injury and disease.

A framework for in vivo quantification of regional brain folding in premature neonates.

This paper describes and compares novel approaches to in vivo 3D measurement of brain surface folding in clinically acquired neonatal MR image data, which allows regional folding evaluation. Most of the current measures of folding are not independent of the area of the surface they are derived from. Therefore, applying them to whole-brain surfaces or subregions of different sizes results in differences which may or may not reflect true differences in folding. We address this problem by proposing new measures to quantify gyrification and two approaches to normalize previously defined measures. The method was applied to twelve premature infants (age 28-37 weeks) from which cerebrospinal fluid/gray matter and gray matter/white matter interface surfaces were extracted. Experimental results show that previous folding measures are sensitive to the area of the surface of analysis and that the area-independent measures proposed here provide significant improvements. Such a system provides a tool that facilitates the study of structural development in the neonatal brain within specific functional subregions, which may be critical in identifying later neurological impairment.

MR imaging anatomy in neurodegeneration: a robust volumetric parcellation method of the frontal lobe gyri with quantitative validation in patients with dementia.

BACKGROUND AND PURPOSE: Brain volumetry is widely used for evaluating tissue degeneration; however, the parcellation methods are rarely validated and use arbitrary planes to mark boundaries of brain regions. The goal of this study was to develop, validate, and apply an MR imaging tracing method for the parcellation of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to the structures of interest, without the need for global reorientation or the use of dividing planes or lines. METHODS: Studies were performed on 25 subjects--healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer disease--with significant variation in the underlying gyral anatomy and state of atrophy. The protocol was evaluated by using multiple observers tracing scans of subjects diagnosed with neurodegenerative disease and those aging normally, and the results were compared by spatial overlap agreement. To confirm the results, observers marked the same locations in different brains. We illustrated the variabilities of the key boundaries that pose the greatest challenge to defining consistent parcellations across subjects. RESULTS: The resulting gyral volumes were evaluated, and their consistency across raters was used as an additional assessment of the validity of our marking method. The agreement on a scale of 0-1 was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85 spatial and 0.90 volumetric for 2 different raters. The results revealed that the protocol remained consistent across different neurodegenerative conditions. CONCLUSION: Our method provides a simple and reliable way for the volumetric evaluation of frontal lobe neurodegeneration and can be used as a resource for larger comparative studies as well as a validation procedure of automated algorithms.

Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging.

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.

Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes.

BACKGROUND: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. METHODS: High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. RESULTS: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. CONCLUSIONS: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.

A novel approach to high resolution fetal brain MR imaging.

This paper describes a novel approach to forming high resolution MR images of the human fetal brain. It addresses the key problem of motion of the fetus by proposing a registration refined compounding of multiple sets of orthogonal fast 2D MRI slices, that are currently acquired for clinical studies, into a single high resolution MRI volume. A robust multi-resolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between 2D acquisitions. This is combined with an intensity correction step and a super resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions are included. Results indicate the method promises a unique route to acquiring high resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data is highly valuable in allowing a clinically applicable window into the process of normal and abnormal brain development.

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites.

BACKGROUND: The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS: Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS: Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS: Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

Deformation tensor morphometry of semantic dementia with quantitative validation.

High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.

Accurate template-based correction of brain MRI intensity distortion with application to dementia and aging.

This paper examines an alternative approach to separating magnetic resonance imaging (MRI) intensity inhomogeneity from underlying tissue-intensity structure using a direct template-based paradigm. This permits the explicit spatial modeling of subtle intensity variations present in normal anatomy which may confound common retrospective correction techniques using criteria derived from a global intensity model. A fine-scale entropy driven spatial normalisation procedure is employed to map intensity distorted MR images to a tissue reference template. This allows a direct estimation of the relative bias field between template and subject MR images, from the ratio of their low-pass filtered intensity values. A tissue template for an aging individual is constructed and used to correct distortion in a set of data acquired as part of a study on dementia. A careful validation based on manual segmentation and correction of nine datasets with a range of anatomies and distortion levels is carried out. This reveals a consistent improvement in the removal of global intensity variation in terms of the agreement with a global manual bias estimate, and in the reduction in the coefficient of intensity variation in manually delineated regions of white matter.