Structural Imaging Methods Research Articles

The Effects of Psychosis Risk Variants on Brain Connectivity: A Review

In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e., functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e., Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d = 0.76) and structural connectivity (mean d = 1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation.

P-246 - The neuroimaging of dissociative disorders

Introduction Dissociative disorders are characterized by disturbances of integration of memory, perception, consciousness or identity. They were linked to psychological stress or trauma across various cultures. Dissociative amnesia and fugue, depersonalization disorder, dissociative identity disorder and dissociative disorder not otherwise specified (such as Ganser syndrome) belong to dissociative disorders in DSM-IV-TR. In contrast to DSM-IV-TR, ICD-10 also subsumes the conversion disorder under the category of dissociative (conversion) disorders. Objectives This work's objective is establishing greater recognition of the neural correlates of dissociative disorders. Aims We review neuroimaging data pertaining to dissociative amnesia and fugue, depersonalization disorder, dissociative identity disorder (multiple personality disorder), Ganser syndrome and various forms of conversion disorder, which were obtained with functional and structural imaging techniques, including diffusion tensor imaging or magnetization transfer ratio measurements. Methods In addition to own imaging data from patients with dissociative amnesia and fugue, a comprehensive review of the scientific literature on the neuroimaging of dissociative disorders was performed. Results Neuroimaging research data point to metabolic and sometimes even structural brain alterations in dissociative disorders, involving regions that are agreed upon to play roles in mnemonic processing, self referential processing (including body schema), perception, consciousness and/or emotional processing. Conclusions The use of functional and newer structural brain imaging methods has improved and will continue to further our understanding of the neural correlates of dissociative disorders and has provided evidence that environmentally-driven (stress-related) alterations of cognition, identity, body schema, perception, affectivity and behavior are accompanied by metabolic and even structural brain changes.

Frontotemporal Dementia

The behavioral variant of frontotemporal dementia (bvFTD) slowly undermines emotion, social behavior, personal conduct, and decision making. These deficits occur in concert with focal neurodegeneration that can be quantified with modern structural and functional imaging and neuropathological methods. As a result, studies of bvFTD have helped to clarify brain structures, networks, and neurons that prove critical for normal social-emotional functioning. In this article, the authors review the evolving bvFTD literature and propose a simple, testable network-based working model for understanding bvFTD.

Fluorescence Molecular Tomography: Principles and Potential for Pharmaceutical Research

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue's optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development.

Neurodynamic measures of functional connectivity and cognition

Exploring the structure and function of the human brainrelies on a range of non-invasive measures and computa-tional approaches. Neurodynamic functional brain imagingmethods offer unique insight into the human brain pro-cesses by capturing neuronal activity in real time. Mea-surements of scalp potential differences of spontaneous andevoked activity were the first electrophysiological measurethat revealed differences in the measured waveforms whichwere state, stimulus, task, context etc. dependant. Fourdecades ago the application of ultrasensitive supercon-ducting quantum interference device (SQUID) for themeasurements of extremely week magnetic fields of thehuman brain led to a dynamic development of magnetoe-cephalography (MEG) research [2]. Development of thisnew functional brain imaging method resulted in openingnew questions and furthering the analysis of the EEG/ERPas well since the interest of MEG researchers moved fromthe analysis based on the evaluations of the measuredwaveforms to explore the approaches to identify and trackcortical activations in space and time. Spatio-temporalsource localization models and inverse bio-electro-mag-netic problem estimation approaches were developed toestimate the underlying neuronal substrates of the evokedactivity related to sensory perception, movement, andcognition. Exploration of the underlying dynamic corticalnetworks of the working human brain was made possiblenot only in the measurement space but also at the func-tional source level.During the 1990s, The Decade of the Brain, non-inva-sive structural and functional brain imaging methods wereregarded as revolutionary in exploring the structure andfunction of the human brain in healthy and diseased states.The wealth of data regarding sensory, motor, and cognitiveprocesses provided initially by positron emission tomog-raphy (PET) is dominated during the last two decades by anexplosion of research using functional magnetic resonanceimaging (fMRI). fMRI is often reported to offer superbmillimeter spatial resolution, almost uniform throughoutthe brain. EEG and MEG were, however, regarded asmodel dependent and consequently prone to erroneoussource location estimation. Multi-modal integrationappeared in mid 1990’ as a solution to overcome ill-posednature of the bio-electro-magnetic problem and a low, 2 sand even 40 s, temporal resolutions of fMRI and PET,respectively. The initial confidence that PET or fMRIidentified functional foci could be used to constrain EEG orMEG solution was soon reconsidered.Unlike in EEG and MEG, there is a great degree ofstandardization regarding preprocessing and statisticalapproaches in fMRI. During a rather intensive data gath-ering period since its discovery important questions such asthe reliability of the fMRI results remain almost uncon-sidered and unanswered [3]. Another open question is therelationship of the hemodynamic and/or metabolicresponse and the neuronal activity of interest. Despite awidely used terminology referring to PET and fMRI data asneuroimaging their data represent only correlates of theneuronal activity. Consequently, there is an increasingawareness that all noninvasive functional brain imagingmethods are in fact subject to solving inverse problems tomove from the measurement space to the source space in

Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11C-D-deprenyl is a promising tracer for these purposes.

Three dimensional digital articulator labeled atlas.

There is an increased use of both dynamic and structural magnetic resonance imaging (MRI) methods on studies in normal and disordered speeches. However, due to the anatomical variation among subjects, it has been a challenge to obtain quantitative results from a series of subjects or patients. To compare inter- and intrasubjects’ MRI data a 3-D digital articulator labeled atlas is presented. Experts, head and neck surgeons and speech language pathologists, manually segmented the tongue, soft and hard palate, lips, pharyngeal walls, and larynx from three sets of MRI of healthy volunteers. Then, 30 naïve raters segmented the same articulators with a multiple-structure semiautomated approach for rapid delineation. Concept, application, and comparison with multiple raters and fully manual delineation are provided. [Work supported by NIH-NIDCD Grant No. R00-DC009279.]

Strukturelle und funktionelle Bildgebung zur Pathophysiologie der Apraxie

A better understanding of the neural bases of apraxia is an important prerequisite to develop new therapeutic strategies for the disabling apraxic deficits after left-hemisphere stroke, like disturbed imitation of gestures, deficient pantomime, and object use deficits. Recently, functional and structural imaging methods allowed deeper insights into the pathophysiology of apraxia: While apraxic object use deficits result from the dysfunction of an extended fronto-parietal network within the left hemisphere, pantomime deficits are caused by impaired functioning of the left inferior frontal cortex. Further apraxia-related, motor cognitive processes (i.e., gesture imitation, integration of temporal and spatial movement information, and intentional movement planning) depend on the integrity of the left parietal cortex. Newly developed functional and structural imaging methods, like dynamic causal modelling (DCM) and diffusion tensor imaging (DTI), promise to further elucidate the pathophysiology of apraxia at the network level.

11C]PIB-, [ 18F]FDG-PET and MRI imaging in patients with Parkinson’s disease with and without dementia

The objective of this study was to identify possible group differences between PD patients with dementia and without dementia by combining different functional and structural imaging methods in vivo, which might provide an opportunity to disentangle the pathophysiological correlates of cognitive impairment and dementia in PD. We performed a neuropsychological evaluation, structural brain MRI, [ 18F]FDG PET and [ 11C]PIB PET in 19 PD patients [eight non-demented (PD), eleven demented (PDD)] and 24 healthy elderly volunteers. [ 11C]PIB region-to-cerebellum ratios did not differ significantly between the groups in any brain region ( p > 0.05). PDD patients showed impaired glucose metabolism in cortical brain regions and this reduction was associated with the degree of cognitive impairment. PDD patients had more atrophy both in the hippocampus and the frontal cortex compared with PD patients and controls, and hippocampal atrophy was associated with impaired memory. This cross-sectional data suggests that development of dementia in PD is associated with extensive spread of hypometabolism beyond the occipital cortex, and with hippocampal and frontal atrophy but not beta-amyloid deposition consistent with a unique biological process related to PD rather than co-incidental development of AD in persons with PD.

1H-MR Spectroscopy in Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients' outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome.

Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: A voxel-based morphometry study

Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain.

MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz

Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer's disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes.

Neural mechanisms and development of reasoning ability

Event Abstract Back to Event Neural mechanisms and development of reasoning ability Elizabeth OHare1* 1 University of California at Berkeley, United States The capacity to reason with complex information and to solve novel problems, or fluid reasoning, is a core component of human cognition. During childhood, the emerging capacity to reason is thought to serve as a scaffold for the development of other cognitive functions. Understanding this most complex of human abilities provides a daunting but compelling challenge. Brain imaging studies in adults have gained some traction on this problem by examining the neural underpinnings of a key component of fluid reasoning: relational integration, or the process by which multiple mental representations are compared or combined. Drawing on research employing behavioral, and functional and structural imaging methods to investigate longitudinal changes in fluid reasoning development, this talk will provide an overview of the neural substrates of fluid reasoning in adults, as well as the maturational changes brain structure and function that support the development of relational integration during childhood and adolescence. Conference: Conference on Neurocognitive Development, Berkeley, CA, United States, 12 Jul - 14 Jul, 2009. Presentation Type: Oral Presentation Topic: Higher cognition Citation: OHare E (2009). Neural mechanisms and development of reasoning ability. Conference Abstract: Conference on Neurocognitive Development. doi: 10.3389/conf.neuro.09.2009.10.032 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Jul 2009; Published Online: 07 Jul 2009. * Correspondence: Elizabeth OHare, University of California at Berkeley, Berkeley, United States, edohare@berkeley.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elizabeth OHare Google Elizabeth OHare Google Scholar Elizabeth OHare PubMed Elizabeth OHare Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Brain Imaging in Intensive Care Medicine

The management of severe brain injury requires a comprehensive approach in which imaging is an indispensable complement to the clinical and physiological information acquired at the bedside. Neuroimaging methods are routinely used in the diagnosis and prognosis of a broad spectrum of patients with acute neurological dysfunction. With incremental theoretical and technological refinements, imaging modalities are helping to unravel fundamental questions regarding the pathophysiology and neuroplasticity associated with critical neurological injury, and it is anticipated that this knowledge will lead to new and effective therapeutic interventions. We review some of the established and emerging structural and physiological imaging methods, and discuss their applications in patients with critical injuries including trauma and encephalopathy due to anoxia, liver failure, and sepsis.

Diagnostic accuracy of 201Thallium-SPECT and 18F-FDG-PET in the clinical assessment of glioma recurrence

Reliable differential diagnosis between tumour recurrence and treatment-induced lesions is required to take advantage of new therapeutic approaches to recurrent gliomas. Structural imaging methods offer a high sensitivity but a low specificity, which might be improved by neurofunctional imaging. This study aimed to test the hypothesis that incorporation of 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) increases the accuracy of this differential diagnosis obtained with 201Tl chloride-single-photon emission computed tomography (201Tl-SPECT). Seventy-six patients (mean age 47.72 +/- 16.19 years) under suspicion of glioma recurrence, 42% with low-grade and 58% with high-grade lesions, were studied by (201)Tl-SPECT and FDG-PET, reporting results under blinded conditions using visual analysis. Tumour was confirmed by histological confirmation (23 patients) or clinical and structural neuroimaging follow-up (mean of 2.6 years). This population had a high disease prevalence (72%). Globally, highest sensitivity was obtained using 201Tl-SPECT assessed with MRI (96%) and highest specificity using FDG-PET + MRI (95%). FDG-PET appeared slightly better for confirming tumour recurrence, whereas 201Tl-SPECT was superior for ruling out possible recurrence (disease present in 38% of FDG-PET negative explorations). In the high-grade subgroup, there were no false-positive examinations (specificity: 100%), but sensitivity differed among techniques (201Tl-SPECT : 94%; 201Tl-SPECT + MRI: 97%; FDG-PET + MRI: 83%). In the low-grade subgroup, 201Tl-SPECT + MRI showed highest sensitivity (95%) and lowest posttest negative probability (9%); FDG-PET + MRI offered highest specificity (92%) with a posttest negative probability of 35%. FDG-PET does not clearly improve the diagnostic accuracy of (201)Tl-SPECT, which appears to be a more appropriate examination for the diagnosis of possible brain tumour recurrence, especially for ruling it out.

Structural cerebellar abnormalities in antipsychotic-naive schizophrenia: Evidence for cognitive dysmetria

Byline: Rashmi. Arasappa, Naren. Rao, G. Venkatasubramanian, P. Jayakumar, B. Gangadhar Background: Cognitive has been proposed as a unifying model to explain the pathogenesis of schizophrenia. Most of the previous studies examining structural cerebellar abnormalities in schizophrenia were confounded by various factors like antipsychotic treatment, comorbid alcohol dependence, and low-resolution imaging procedure with manual morphometric analysis. In this study, we describe the first report of structural cerebellar abnormalities in antipsychotic-naive schizophrenia patients using high-resolution imaging (3.0 Tesla MRI). Aim: This study was aimed at examining the structural cerebellar abnormalities in antipsychotic-naive schizophrenia patients and its correlation with psychopathology. Methods: Brain imaging of 20 antipsychotic-naive schizophrenia patients and their age, gender, and years of education matched 20 healthy controls was done using 3.0 Tesla MRI machine. Image analysis was done using the optimized Voxel Based Morphometry (VBM), an automated unbiased technique. Results: Antipsychotic-naive schizophrenia patients had significant cerebellar gray matter volume deficits compared to healthy controls. The Scale for the Assessment of Negative Symptoms (SANS) score in patients had negative correlation with cerebellar gray matter volume. Conclusion: Structural cerebellar abnormalities and their negative correlation with negative syndrome in antipsychotic-naive schizophrenia patients support the cognitive dysmetria. Introduction Cerebellum, well known for its motor coordination, has been suggested in recent times to have an important role in cognition.[sup] [1] The motor coordination is brought about by the feedback between sensory motor cortex and the cerebellum, mediated through thalamus. Similar circuit (where the feedback is between cerebellum and prefrontal cortex, mediated through thalamus - the corticocerebellar thalamic cortical circuit (CCTCC)) has been implicated in the function of monitoring and coordinating the smooth execution of mental activity, that is, synchrony. Disruption in this circuit has been proposed as to cause cognitive dysmetria leading on to disordered cognition and symptoms of schizophrenia.[sup] [2] Some of the earlier studies in patients with schizophrenia, using structural and functional imaging methods, have shown abnormalities in the cerebellum. CT scan study[sup] [3] showed degeneration of cerebellar vermis and enlargement of third ventricle and on magnetic resonance imaging (MRI) small cerebellar volume, smaller vermian and its subregions volume, and reversed cerebellar asymmetry in males were seen.[sup] [4],[5],[6] In addition, a proton magnetic resonance spectroscopy (MRS) study[sup] [7] showed lower N-acetylaspartate in cerebellar cortex and vermis in schizophrenia patients. Similar abnormalities have been noted in functional MRI (fMRI) study.[sup] [8] On positron emission tomography (PET) scan, decreased blood flow was seen in right anterior cingulate, right thalamus, and bilateral cerebellum during novel memory task.[sup] [9] Another study[sup] [10] showed absence of normal activation of prefrontal thalamic circuit in schizophrenia patients. However, there are few studies with conflicting results - In one study, there was no difference between patients and controls in cerebellar vermis and height of fourth ventricle.[sup] [11] In another study, no abnormality in posterior fossa structures size was found in patients with schizophrenia.[sup] [12] These discrepancies in findings could potentially be due to some of the methodological factors like selection of patients and image acquisition. *One of the important confounding factors is effect of drugs on brain volume, and only a few studies have been conducted on drug-naive patients.[sup] [13],[5] *Effect of comorbid conditions like alcohol dependence syndrome (ADS) can confound the results due to the effect of alcohol on cerebellum. …

Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon?

Indirect evidence for disturbed structural connectivity of subcortical fiber tracts in schizophrenia has been obtained from functional neuroimaging and electrophysiologic studies. During the past few years, new structural imaging methods have become available. Diffusion tensor imaging and magnetization transfer imaging (MTI) have been used to investigate directly whether fiber tract abnormalities are indeed present in schizophrenia. To date, findings are inconsistent that may express problems related to methodological issues and sample size. Also, pathological processes detectable with these new techniques are not yet well understood. Nevertheless, with growing evidence of disturbed structural connectivity, myelination has been in the focus of postmortem investigations. Several studies have shown a significant reduction of oligodendroglial cells and ultrastructural alterations of myelin sheats in schizophrenia. There is also growing evidence for abnormal expression of myelin-related genes in schizophrenia: Neuregulin (NRG1) is important for oligodendrocyte development and function, and altered expression of erbB3, one of the NRG1 receptors, has been shown in schizophrenia patients. This is consistent with recent genetic studies suggesting that NRG1 may contribute to the genetic risk for schizophrenia. In conclusion, there is increasing evidence from multiple sides that structural connectivity might be pathologically changed in schizophrenia illness. Up to the present, however, it has not been possible to decide whether alterations of structural connectivity are intrinsically linked to the primary risk factors for schizophrenia or to secondary downstream effects (ie, degeneration of fibers secondarily caused by cortical neuronal dysfunction)-an issue that needs to be clarified by future research.

Contributions of functional Magnetic Resonance Imaging (fMRI) to sport concussion evaluation

Mild traumatic brain injury (mTBI) in contact sport is a problem of such magnitude that improved approaches to diagnosis, investigation and management are urgent. Concussion has traditionally been described as a transient, fully reversible, cerebral dysfunction. However, this seemingly 'mild' injury sometimes results in long-lasting and disabling post-concussion symptoms (PCS) and abnormal neuropsychological profiles characteristic of frontal and/or temporal lobe dysfunction. At present, the pathological changes following concussion remain unclear, but it is now widely accepted that concussion results mainly in functional disturbance rather than structural damage. Therefore, functional imaging techniques can help in demonstrating brain abnormalities undetectable by structural imaging methods. This paper will review the use of functional magnetic resonance imaging (fMRI) in studies of concussion. Our existing and ongoing fMRI studies will be described as examples to highlight the potential and contribution of this non-invasive functional neuroimaging technique in the assessment of sports-related concussion and its management.

The Opportunities and Challenges of Developing Imaging Biomarkers to Study Lung Function and Disease

Recent advances in imaging offer exciting opportunities to develop and validate lung-specific biomarkers as valuable adjuncts to diagnosis, tests of treatment efficacy, and/or treatment monitoring. State-of-the-art structural, functional, and molecular imaging methods allow the lungs to be visualized noninvasively in vivo at submillimeter and subsecond spatial and temporal scales. However, the development and validation of imaging biomarkers present some special challenges, including the following: equipment evaluation, procedure standardization, data regarding reproducibility and replication, interrater variability, the production and measurement of reference standards, sensitivity to interventions or disease progression, intersubject variance, choice of image reconstruction and segmentation algorithms, automated versus observer-dependent image analysis, data acquisition during conditions of standardized lung volume, whether a reliable association can be demonstrated between the imaging biomarker and a clinical endpoint, and whether its use will have a favorable cost-effective impact on drug development or disease management. Establishing such performance characteristics, especially for single investigators at single institutions, can be daunting if not impossible for costly biomarkers such as imaging. Therefore, to take full advantage of the opportunities presented by state-of-the-art imaging methods, new approaches to analytic and clinical validation must be developed in collaboration with industry, foundation, and federal funding agencies.

Incorporating PET information into radiation therapy planning

PET scanning, because of its impressive sensitivity and accuracy, is being incorporated into the standard staging workup for many cancers. These include lung cancer, lymphomas, head and neck cancers, and oesophageal cancers. PET often provides incremental information about the patient’s disease status, adding to the data obtained from structural imaging methods, such as, CT scan or MRI. PET commonly upstages patients into more advanced disease categories. Incorporation of PET information into the radiotherapy planning process has the potential to reduce the risks of geographic miss and can help minimise unnecessary irradiation of normal tissues. The best means of incorporating PET information into radiotherapy planning is uncertain, and considerable effort is being expended in this area of research.