BACKGROUND: Phase-contrast MRI (PC MRI) can be used to assess blood flow dynamics noninvasively inside the human body. The acquired images can be reconstructed into flow vector fields. Traditionally, streamlines can be computed based on the vector fields to visualize flow patterns and particle trajectories. OBJECTIVES: The traditional methods may give a false impression of precision, as they do not consider the measurement uncertainty in the PC MRI images. In our prior work, we incorporated the uncertainty of the measurement into the computation of particle trajectories. METHODS: As a major part of the contribution, a novel numerical scheme for solving the anisotropic Fast Marching problem is presented. A computing time comparison to state-of-the-art methods is conducted on artificial tensor fields. A visual comparison of healthy to pathological blood flow patterns is given. RESULTS: The comparison shows that the novel anisotropic Fast Marching solver outperforms previous schemes in terms of computing time. The visual comparison of flow patterns directly visualizes large deviations of pathological flow from healthy flow. CONCLUSIONS: The novel anisotropic Fast Marching solver efficiently resolves even strongly anisotropic path costs. The visualization method enables the user to assess the uncertainty of particle trajectories derived from PC MRI images.
Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without schizophrenia to a group of matched healthy controls using Tract-Based-Spatial-Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity) were observed. Of note, studies in chronic schizophrenia patients report reduced FA, no changes in AD, and increases in RD in WM. Our findings suggest different WM microstructural pathology in 22q11.2DS than in patients with schizophrenia.
CONTEXT: Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. OBJECTIVE: The aim of the study was to understand whether neurobiological factors predict hot flashes. DESIGN: [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. OUTCOME MEASURES: We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET.
Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, however underlying neural circuitry contributing to the comorbidity remain understudied. Our aim was to investigate functional brain circuitry during working memory in a group of participants who meet criteria for both disorders (ADHD + BPD), and to explore the relationship of symptoms of each disorder to brain function. We used fMRI to image brain activity in 18 male adults with both ADHD and BPD, and 18 healthy control participants matched one-to-one on age, sex, and handedness, while they performed a sequential letter N-back task. We investigated differences in activation between these groups, and also correlations of brain activity during the task to symptoms of ADHD and BPD independently. We found significant hypoactivity in the subjects with ADHD + BPD vs. controls across frontal and parietal regions, and further, found that BPD and ADHD symptoms related to activity in anatomically distinct regions that were respectively characterized by activation and suppression during task. We conclude that comorbid ADHD + BPD is associated with alterations across anterior and posterior nodes of the working memory network, and symptoms of each disorder are related to anatomically and functionally distinct brain regions.
BACKGROUND: Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. METHODS: We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. RESULTS: We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. LIMITATIONS: Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. CONCLUSION: Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food’s reward value and integration of these with interoceptive signalling of one’s internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.
Although Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) frequently co-occur and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this comorbidity is scarce. Our aim was to evaluate cortical thickness in ADHD and BPD, testing the hypothesis that comorbid subjects (ADHD+BPD) would have neuroanatomical correlates of both disorders. Magnetic Resonance Imaging (MRI) findings were compared between 31 adults with ADHD+BPD, 18 with BPD, 26 with ADHD, and 23 healthy controls. Cortical thickness analysis of regions of interest was estimated as a function of ADHD and BPD status, using linear regression models. BPD was associated with significantly thicker cortices in 13 regions, independently of ADHD status and ADHD was associated with significantly thinner neocortical gray matter in 28 regions, independent of BPD. In the comorbid state of ADHD plus BPD, the profile of cortical abnormalities consisted of structures that are altered in both disorders individually. Results support the hypothesis that ADHD and BPD independently contribute to cortical thickness alterations of selective and distinct brain structures, and that the comorbid state represents a combinatory effect of the two. Attention to comorbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.
Many axons follow wave-like undulating courses. This is a general feature of extracranial nerve segments, but is also found in some intracranial nervous tissue. The importance of axonal undulation has previously been considered, for example, in the context of biomechanics, where it has been shown that posture affects undulation properties. However, the importance of axonal undulation in the context of diffusion MR measurements has not been investigated. Using an analytical model and Monte Carlo simulations of water diffusion, this study compared undulating and straight axons in terms of diffusion propagators, diffusion-weighted signal intensities and parameters derived from diffusion tensor imaging, such as the mean diffusivity (MD), the eigenvalues and the fractional anisotropy (FA). All parameters were strongly affected by the presence of undulation. The diffusivity perpendicular to the undulating axons increased with the undulation amplitude, thus resembling that of straight axons with larger diameters. Consequently, models assuming straight axons for the estimation of the axon diameter from diffusion MR measurements might overestimate the diameter if undulation is present. FA decreased from approximately 0.7 to 0.5 when axonal undulation was introduced into the simulation model structure. Our results indicate that axonal undulation may play a role in diffusion measurements when investigating, for example, the optic and sciatic nerves and the spinal cord. The simulations also demonstrate that the stretching or compression of neuronal tissue comprising undulating axons alters the observed water diffusivity, suggesting that posture may be of importance for the outcome of diffusion MRI measurements.
BACKGROUND: There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. CONCLUSIONS/SIGNIFICANCE: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.
Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.
