The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism

INTRODUCTION: We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. METHODS: We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. RESULTS: Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. DISCUSSION: Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent

Evaluating Small Airways Disease in Asthma and COPD using the Forced Oscillation Technique and Magnetic Resonance Imaging

Obstructive lung disease, including asthma and chronic obstructive pulmonary disease (COPD), is characterized by heterogeneous ventilation. Unfortunately, the underlying structure-function relationships and the relationships between measurements of heterogeneity and patient quality-of-life in obstructive lung disease are not well understood. Hyperpolarized noble gas MRI is used to visualize and quantify ventilation distribution and the forced oscillation technique (FOT) applies a multi-frequency pressure oscillation at the mouth to measure respiratory impedance to airflow (including resistance and reactance). My objective was to use FOT, ventilation MRI and computational airway tree modeling to better understand ventilation heterogeneity in asthma and COPD. FOT-measured respiratory system impedance was correlated with MRI ventilation heterogeneity and both were related to quality-of-life in asthma and COPD. FOT-measurements and model-predictions of reactance and small-airways resistance were correlated in asthma and COPD respectively. This study is the first to demonstrate the relationships between FOT-measured impedance, MRI ventilation heterogeneity, and patient quality-of-life

Management of COPD:Is there a role for quantitative imaging?

While the recent development of quantitative imaging methods have led to their increased use in the diagnosis and management of many chronic diseases, medical imaging still plays a limited role in the management of chronic obstructive pulmonary disease (COPD). In this review we highlight three pulmonary imaging modalities: computed tomography (CT), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) imaging and the COPD biomarkers that may be helpful for managing COPD patients. We discussed the current role imaging plays in COPD management as well as the potential role quantitative imaging will play by identifying imaging phenotypes to enable more effective COPD management and improved outcomes

Parkinsoǹs disease and emerging of imaging tools for prognosis and diagnosis applications

Parkinson's disease (PD) is a chronicdegenerative neurological disease, characterized by a range of motor (bradykinesia, rigidity, and tremor) and non-motor (fatigue and depression) symptoms in PD, each of which will affect a particular patient to varying degrees in the limbs resulting in the postural instability. A clearer explanation of the association of nondopaminergic structures with PD, could potentially provide valuable insight into non-motor symptoms experienced by subgroups of cases and hopefully rationalize the therapeutic options for the management of these disabling complications

Imaging Genetics and Biomarker Variations of Clinically Diagnosed Alzheimer's Disease

Indiana University-Purdue University Indianapolis (IUPUI)Neuroimaging biomarkers play a crucial role in our understanding of Alzheimer’s disease. Beyond providing a fast and accurate in vivo picture of the neuronal structure and biochemistry, these biomarkers make up a research framework, defined in a 2018 as the A(amyloid)/T(tau)/N(neurodegeneration) framework after three of the hallmarks of Alzheimer’s disease. I first used imaging measures of amyloid, tau and neurodegeneration to study clinically diagnosed Alzheimer’s disease. After dividing subjects into early (onset younger than 65) and late-onset (onset of 65 and older) amyloid-positive (AD) and amyloid-negative (nonAD) groups, I saw radically differing topographical distribution of tau and neurodegeneration. AD subjects with an early disease onset had a much more severe amyloid, tau and neurodegeneration than lateonset AD. In the nonAD group, neurodegeneration was found only in early-onset FDG PET data and in a nonAlzheimer’s-like MRI and FDG pattern for late-onset. The late-onset nonAD resembled that of limbic-predominant age-related TDP-43 encephalopathy. I next utilized an imaging genetics approach to associate genome-wide significant Alzheimer’s risk variants to structural (MRI), metabolic (FDG PET) and tau (tau PET) imaging biomarkers. Linear regression was used to select variants for each of the models and included a pooled sample, cognitively normal, mild cognitive impairment and dementia groups in order to fully capture the cognitive spectrum from normal cognition to the most severely impaired. Model selected variants were replicated using voxelwise regression in an exploratory analysis of spatial associations for each modality. For each imaging type, I replicated some associations to the biomarkers previously seen, as well as identified several novel associations. Several variants identified with crucial Alzheimer’s biomarkers may be potential future targets for drug interventions

Role of diffusion tensor imaging as an imaging biomarker and theranostic tool in structural imaging of traumatic brain injury

Neuroimaging technology is at a "newborn" stage in the evaluation of TBI. While additional literature are obviously required to decide whether these modalities and progress in knowledge with noninvasive monitors will allow early and consistent recognition of revocable secondary brain damages, the final query is whether these new modalities will help in treatment plans that will absolutely mark result. DTI is an influential instrument for assessing white matter anatomy and related anomalies. DTI was formerly an investigation tool, but is using clinical practice. Accepting the terms and basic ideas of this method can aid in the clinical implementation and interpretation of this blend of structural and physiologic white matter evaluation. In conclusion, although DTI is as a diagnostic tool for severity of TBI and as an outcome predictor, but severe preclinical and clinical validation of each imaging method should be a top importance

In Vivo Imaging Biomarkers in Mouse Models of Alzheimer's Disease: Are We Lost in Translation or Breaking Through?

Identification of biomarkers of Alzheimer's Disease (AD) is a critical priority to efficiently diagnose the patients, to stage the progression of neurodegeneration in living subjects, and to assess the effects of disease-modifier treatments. This paper addresses the development and usefulness of preclinical neuroimaging biomarkers of AD. It is today possible to image in vivo the brain of small rodents at high resolution and to detect the occurrence of macroscopic/microscopic lesions in these species, as well as of functional alterations reminiscent of AD pathology. We will outline three different types of imaging biomarkers that can be used in AD mouse models: biomarkers with clear translational potential, biomarkers that can serve as in vivo readouts (in particular in the context of drug discovery) exclusively for preclinical research, and finally biomarkers that constitute new tools for fundamental research on AD physiopathogeny

From joint anatomy to clinical outcomes in osteoarthritis and cartilage repair: summary of the fifth annual osteoarthritis imaging workshop

SummaryObjectiveThis white paper constitutes an overview of presentations and discussions from the fifth Annual Workshop on Imaging in Osteoarthritis (OA) held in Salzburg June eighth to eleventh 2011.DesignThis workshop brought together the communities of basic OA researchers, orthopedists and rheumatologists, imaging scientists, instrument manufacturers, and pharmaceutical representatives to focus on three overlapping themes of joint anatomy, cartilage repair and clinical validation of imaging biomarkers.ResultsThe workshop was held on the campus of the Paracelsus Medical University in Salzburg, Austria from June 8–11, 2011; 133 attendees participated, representing 17 countries. The meeting was successful in facilitating discussion, raising awareness and consolidating knowledge about application of imaging in OA research studies and cartilage repair.ConclusionsThe OA research communities need to work alongside the regulatory, pharmaceutical, and MRI industries to support the new ideas and engage in the positive reinforcement of resources to further the new studies. A number of new initiatives were discussed to further break down obstacles to clinical trial utility of imaging biomarkers