61 research outputs found

    Cerebrovascular dysfunction in cerebral small vessel disease

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    INTRODUCTION: Cerebral small vessel disease (SVD) is the cause of a quarter of all ischaemic strokes and is postulated to have a role in up to half of all dementias. SVD pathophysiology remains unclear but cerebrovascular dysfunction may be important. If confirmed many licensed medications have mechanisms of action targeting vascular function, potentially enabling new treatments via drug repurposing. Knowledge is limited however, as most studies assessing cerebrovascular dysfunction are small, single centre, single imaging modality studies due to the complexities in measuring cerebrovascular dysfunctions in humans. This thesis describes the development and application of imaging techniques measuring several cerebrovascular dysfunctions to investigate SVD pathophysiology and trial medications that may improve small blood vessel function in SVD. METHODS: Participants with minor ischaemic strokes were recruited to a series of studies utilising advanced MRI techniques to measure cerebrovascular dysfunction. Specifically MRI scans measured the ability of different tissues in the brain to change blood flow in response to breathing carbon dioxide (cerebrovascular reactivity; CVR) and the flow and pulsatility through the cerebral arteries, venous sinuses and CSF spaces. A single centre observational study optimised and established feasibility of the techniques and tested associations of cerebrovascular dysfunctions with clinical and imaging phenotypes. Then a randomised pilot clinical trial tested two medications’ (cilostazol and isosorbide mononitrate) ability to improve CVR and pulsatility over a period of eight weeks. The techniques were then expanded to include imaging of blood brain barrier permeability and utilised in multi-centre studies investigating cerebrovascular dysfunction in both sporadic and monogenetic SVDs. RESULTS: Imaging protocols were feasible, consistently being completed with usable data in over 85% of participants. After correcting for the effects of age, sex and systolic blood pressure, lower CVR was associated with higher white matter hyperintensity volume, Fazekas score and perivascular space counts. Lower CVR was associated with higher pulsatility of blood flow in the superior sagittal sinus and lower CSF flow stroke volume at the foramen magnum. Cilostazol and isosorbide mononitrate increased CVR in white matter. The CVR, intra-cranial flow and pulsatility techniques, alongside blood brain barrier permeability and microstructural integrity imaging were successfully employed in a multi-centre observational study. A clinical trial assessing the effects of drugs targeting blood pressure variability is nearing completion. DISCUSSION: Cerebrovascular dysfunction in SVD has been confirmed and may play a more direct role in disease pathogenesis than previously established risk factors. Advanced imaging measures assessing cerebrovascular dysfunction are feasible in multi-centre studies and trials. Identifying drugs that improve cerebrovascular dysfunction using these techniques may be useful in selecting candidates for definitive clinical trials which require large sample sizes and long follow up periods to show improvement against outcomes of stroke and dementia incidence and cognitive function

    An evaluation of the role of biomarkers in Alzheimer’s disease and age-related cognitive decline

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    An ageing population will lead to an increase in age-related cognitive decline and dementia syndromes such as Alzheimer’s disease (AD), which can seriously limit an individual’s independence and quality of life. Identifying biomarkers associated with cognitive impairment in both ageing and AD are needed as they will improve our understanding of underlying pathophysiology and may eventually improve prognoses via the identification of at-risk individuals and the development of novel therapeutics. Several pathological changes in the brain which are typically seen in AD can be detected in the cerebrospinal fluid (CSF) and plasma of middle- and late-life adults without dementia. Previous work has identified associations between CSF markers and cognitive functions, although a synthesis of the large number of studies is needed. Furthermore CSF marker levels may also differ with AD risk factors, however evidence is mixed. Increasingly, research has shifted to focus on blood-based biomarkers which provide the benefit of being less invasive and more accessible. Several plasma biomarkers have been associated with cognitive functions in ageing, although few studies use appropriate cognitive tests, and even fewer have examined these proteins in the brain. There remains no gold-standard biomarkers associated with cognitive functions in either AD or age-related cognitive decline, therefore additional approaches are needed to fully understand their relationship. The aims of the current thesis are to: investigate CSF biomarkers associated with cognition in dementia and ageing; assess the relationship between CSF biomarkers and AD risk factors; examine whether plasma biomarkers are associated with age-related cognitive decline; and lastly, to examine the level of proteins (which have previously been investigated as biomarkers) in post-mortem brain tissue. Cerebrospinal fluid biomarkers associated with cognition have been investigated across a range of dementia syndromes and age-related cognitive decline. While much of the work has focused on tau and amyloid-beta (Aβ), there is burgeoning research around markers such as neurogranin and neurofilament-light. Due to a wide range of markers investigated across several dementia syndromes and ageing, the roles of each marker are less clear. Therefore, a systematic review was conducted examining the association between CSF synaptic/axonal markers, and cognitive functions across dementia syndromes and typical ageing. Sixty-seven studies were included in the review in Chapter 3. Despite substantial heterogeneity in the field, there was evidence for an association between CSF neurofilament-light and cognition in AD, frontotemporal dementia, and typical cognitive ageing. Cerebrospinal fluid neurogranin tended to be associated with cognition in those with CSF tau and CSF Aβ profiles indicative of AD. Chapter 4 focuses on the interaction between Apolipoprotein E (APOE) and sex on CSF tau levels in a middle-life cohort without dementia. Females account for an estimated 60% of those diagnosed with AD and the APOE4 allele is widely recognised to be the strongest genetic risk factor for late-onset AD. However, evidence for the interaction between these two risk factors is mixed. In this chapter, a significant interaction between APOE, sex, and CSF AD biomarkers was found, suggesting that tau accumulation may be independent of Ab in females, but not males. This has potential implications for the implementation of CSF AD biomarkers in clinical practice and pharmacological interventions which target cortical Ab. Chapter 5 focuses on the relationship between plasma biomarkers and cognitive functions in typical ageing. Previous studies have focused on this relationship, however, few use appropriate cognitive tests for a sample without dementia. In this chapter, the association between cognitive ability and plasma phosphor-tau 181 (ptau181), Ab, neurofilament-light (NfL), and glial fibrillary acidic protein (GFAP) were investigated in the Lothian Birth Cohort 1936. A significant relationship was observed between baseline p-tau181, NfL, GFAP and cognitive decline up to ~ 10-years later. Further, increasing levels of p-tau181 over time were associated with steeper cognitive decline. The results of this chapter suggest that plasma p-tau181, NfL, and GFAP may be useful biomarkers of age-related cognitive decline. In Chapter 6, several of the aforementioned markers that were previously investigated in the CSF and plasma are examined in post-mortem brain tissue. While previous work has focused on these markers in the CSF and plasma, few studies have investigated them in post-mortem tissue and how levels differ between AD and typically ageing participants. Relative differences in neurogranin, p-tau181, p-tau231, total tau, and SNAP-25 were examined by western blot in AD cases, healthy ageing cases, and mid-life cases. The results of this chapter provide evidence of a reduction of neurogranin and SNAP-25 at the synapse in AD, as well as an increase of p-tau231. This suggests that the elevations of CSF neurogranin, SNAP-25, and p-tau231 seen in AD may reflect both the loss of neurogranin/SNAP-25 and the accumulation of ptau231 in synapses. The final chapter of the thesis summarise the findings of the previous chapters, their limitations, and the impact of this work on the field

    Characterising Shape Variation in the Human Right Ventricle Using Statistical Shape Analysis: Preliminary Outcomes and Potential for Predicting Hypertension in a Clinical Setting

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    Variations in the shape of the human right ventricle (RV) have previously been shown to be predictive of heart function and long term prognosis in Pulmonary Hypertension (PH), a deadly disease characterised by high blood pressure in the pulmonary arteries. The extent to which ventricular shape is also affected by non-pathological features such as sex, body mass index (BMI) and age is explored in this thesis. If fundamental differences in the shape of a structurally normal RV exist, these might also impact the success of a predictive model. This thesis evaluates the extent to which non-pathological features affect the shape of the RV and determines the best ways, in terms of procedure and analysis, to adapt the model to consistently predict PH. It also identifies areas where the statistical shape analysis procedure is robust, and considers the extent to which specific, non-pathological, characteristics impact the diagnostic potential of the statistical shape model. Finally, recommendations are made on next steps in the development of a classification procedure for PH. The dataset was composed of clinically-obtained, cardiovascular magnetic resonance images (CMR) from two independent sources; The University of Pittsburgh Medical Center and Newcastle University. Shape change is assessed using a 3D statistical shape analysis technique, which topologically maps heart meshes through an harmonic mapping approach to create a unique shape function for each shape. Proper Orthogonal Decomposition (POD) was applied to the complete set of shape functions in order to determine and rank a set of shape features (i.e. modes and corresponding coefficients from the decomposition). MRI scanning protocol produced the most significant difference in shape; a shape mode associated with detail at the RV apex and ventricular length from apex to base strongly correlated with the MRI sequence used to record each subject. Qualitatively, a protocol which skipped slices produced a shorter RV with less detail at the apex. Decomposition of sex, age and BMI also derives unique RV shape descriptors which correspond to anatomically meaningful features. The shape features are shown to be able to predict presence of PH. The predictive model can be improved by including BMI as a factor, but these improvements are mainly concentrated in identification of healthy subjects

    Physiological underpinnings of healthy brain ageing

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    Changes in cerebral perfusion or metabolism can occur as a result of healthy ageing, and in conditions of impaired ageing such as mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Overarchingly, this thesis aimed to explore physiological magnetic resonance imaging (MRI) measures to study both cerebral perfusion and metabolism in the healthy ageing brain. Specifically, arterial spin labelling (ASL) and functional magnetic resonance spectroscopy (1H-fMRS) were employed in the elucidation of healthy ageing. Investigation of cerebral functionality is clinically important, enabling understanding of healthy ageing and disease pathology beyond that provided by structural measures. Given the necessity for tightly-regulated tissue perfusion in the delivery of oxygen to the brain, assessment of brain perfusion can enable elucidation of related brain health. Firstly, this thesis focused on changes in brain perfusion within a cross-sectional retrospective cohort of healthy subjects. This study aimed to assess the utility of univariate and multivariate pattern analysis (MVPA) techniques, and determine whether spatial coefficient of variation (sCoV) measures – which provide a method for inferring spatial heterogeneity of blood flow from single post-label delay (PLD) ASL data – are more significantly associated with age than standard perfusion metrics (ml/100g/min values). The impact of data processing steps on quantification of perfusion was initially assessed. Particularly, the influence of partial volume effect (PVE) correction and how this affected quantification of cerebral perfusion was of interest. The relationship between measures of cerebral perfusion – in regions of interest, vascular territories, and grey matter – and age were assessed, before grey matter (GM) spatial covariance patterns were identified, with MVPA hypothesised to elucidate more subtle age-related change than univariate, voxel-wise methodology. The executive control network (ECN) was the only network exhibiting a significant decline in perfusion with age, after controlling for relevant covariates. Interestingly, whilst the PCA approach resulted in a pattern of both positive and negative associations with age across cerebral GM, the surviving clusters in voxel-wise approaches were deemed spurious. Five-fold cross validation of PCA findings was used to assess whether the resultant spatial covariance patterns were able to predict subject age. This prediction was successful, with related r2 values of between 0.5316 and 0.7297 (p < 0.001 for all), however validation of these findings in an unseen dataset is required. The utility of the sCoV metric was also compared with standard tissue perfusion values, finding that sCoV may be more closely associated with ageing than ml/100g/min in certain regions. Particularly, a significant increase in whole GM sCoV with age was notable, given the absence of significant changes in perfusion with age in the same region. Additionally, a MVPA approach was used to establish the complex unknown relationship between cerebral perfusion and the Montreal Cognitive Assessment (MoCA), before graph visualisation was used to further understand the regional relatedness of the spatial covariance pattern. PCA resulted in a model which provided a moderate explanation of the aforementioned relationship, but this may be improved by inclusion of additional covariates in subsequent work, such as those pertaining to genetic status, such as apolipoprotein E (APOE). This study also replicates an FDG PET cognitive resilience signature in an ASL cohort for the first time, with a trend towards declining perfusion with age found (p = .08). Lastly, as ageing is associated with metabolic failure in the brain, which is often investigated using methodology which employs ionising radiation, the final study was motivated to investigate possible metabolic markers of brain ageing which can be measured using MRI. Metabolic-functional coupling can be studied using functional stimulation, and functional magnetic resonance spectroscopy (fMRS) is perfectly poised to elucidate certain metabolic behaviour. Given the close relationship between glucose (Glc) – the key fuel for cerebral functionality – and lactate (Lac) metabolism, an optimised long echo time (TE) semi-localized by adiabatic selective refocusing (semi-LASER) sequence (TE=144ms) with optimised J-modulation selection at 7T was employed to assess the effects of age on the dynamic behaviour of Lac, and determine its absolute concentrations throughout the time course, whilst a visual stimulation paradigm was viewed. Successful quantification of metabolite concentrations – including Lac, tCr and tNAA – was achieved in both the young and old cohorts, and their Lac peaks clearly visually identifiable throughout the time course. A significant increase in Lac concentration was observed between rest and stimulation, but not stimulation and recovery, in the young cohort. No significant Lac time course changes were identified in the full old cohort. This thesis concluded by summarising and contextualising the key findings herein, and discussion of possible directions for further associated research. The findings of this thesis broaden the field of knowledge around healthy ageing, and therefore may contribute to subsequent translation efforts for both clinical diagnostics and treatment approaches

    Deep Interpretability Methods for Neuroimaging

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    Brain dynamics are highly complex and yet hold the key to understanding brain function and dysfunction. The dynamics captured by resting-state functional magnetic resonance imaging data are noisy, high-dimensional, and not readily interpretable. The typical approach of reducing this data to low-dimensional features and focusing on the most predictive features comes with strong assumptions and can miss essential aspects of the underlying dynamics. In contrast, introspection of discriminatively trained deep learning models may uncover disorder-relevant elements of the signal at the level of individual time points and spatial locations. Nevertheless, the difficulty of reliable training on high-dimensional but small-sample datasets and the unclear relevance of the resulting predictive markers prevent the widespread use of deep learning in functional neuroimaging. In this dissertation, we address these challenges by proposing a deep learning framework to learn from high-dimensional dynamical data while maintaining stable, ecologically valid interpretations. The developed model is pre-trainable and alleviates the need to collect an enormous amount of neuroimaging samples to achieve optimal training. We also provide a quantitative validation module, Retain and Retrain (RAR), that can objectively verify the higher predictability of the dynamics learned by the model. Results successfully demonstrate that the proposed framework enables learning the fMRI dynamics directly from small data and capturing compact, stable interpretations of features predictive of function and dysfunction. We also comprehensively reviewed deep interpretability literature in the neuroimaging domain. Our analysis reveals the ongoing trend of interpretability practices in neuroimaging studies and identifies the gaps that should be addressed for effective human-machine collaboration in this domain. This dissertation also proposed a post hoc interpretability method, Geometrically Guided Integrated Gradients (GGIG), that leverages geometric properties of the functional space as learned by a deep learning model. With extensive experiments and quantitative validation on MNIST and ImageNet datasets, we demonstrate that GGIG outperforms integrated gradients (IG), which is considered to be a popular interpretability method in the literature. As GGIG is able to identify the contours of the discriminative regions in the input space, GGIG may be useful in various medical imaging tasks where fine-grained localization as an explanation is beneficial

    Impact of arterial stiffness on white matter microstructure in the elderly

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    La rigidité artérielle fait référence à la perte d'élasticité principalement dans les grandes artères telles que l'aorte et les carotides. On sait que la rigidité artérielle chroniquement élevée contribue à des modifications vasculaires cérébrales telles que des lésions parenchymateuses de la substance blanche cérébrale via une modification du flux sanguin cérébral. En particulier, parmi les structures perfusées par les artérioles fournies par les artères cérébrales antérieure et moyenne, le corps calleux, la capsule interne, la corona radiata et le faisceau longitudinal supérieur sont les plus vulnérables à l’hypoperfusion. Des études antérieures ont montré que l'augmentation de la rigidité artérielle évaluée par la vitesse de l'onde de pouls carotide-fémorale (cfPWV) est associée à une diminution de l'anisotropie fractionnelle (FA) et à une augmentation de la diffusivité radiale (RD). On a émis l'hypothèse que les altérations au niveau des régions vulnérables de la substance blanche (par exemple, le corps calleux, la capsule interne) seraient probablement liées à la démyélinisation axonale. Cependant, bien que la RD a auparavant été corrélée avec la démyélinisation axonale, l'imagerie de diffusion est principalement aveugle à la myéline. En revanche, l'imagerie par transfert de magnétisation (MT) est une métrique adaptée pour estimer la fraction volumique de myéline. De plus, malgré leur sensibilité à l'organisation des fibres axonales, les métriques de tenseur de diffusion (DTI) telles que les FA et RD manquent de spécificité pour la microstructure tissulaire individuelle. Des modèles microstructuraux plus avancés tels que l’imagerie dispersion et de l'orientation des neurites (NODDI) fournissent des outils pour disséquer les changements microstructuraux derrière les mesures DTI. Dans l'article 1, nous avons utilisé les métriques de DTI et basé sur le MT pour examiner de plus près l'interaction entre la rigidité artérielle et la microstructure de la substance blanche chez les personnes âgées de plus de 65 ans. Nous avons constaté que la mesure de référence absolue de la rigidité artérielle, la mesure de la vitesse de l'onde de pouls entre l’artère fémorale et carotidienne (cfPWV) était associée à l'organisation axonale des fibres telle que reflétée par FA et RD plutôt qu'à la démyélinisation dans les régions de la substance blanche qui ont été précédemment désignées comme vulnérables à rigidité artérielle. Dans notre deuxième article, nous avons utilisé le modèle NODDI pour approfondir la relation entre le cfPWV et l'organisation axonale. Nos résultats ont montré que la cfPWV est positivement associée à la diffusion extracellulaire de l'eau (ISOVF), ce qui signifie que la rigidité artérielle peut entraîner une dispersion axonale, diminuant la contrainte de directionnalité de l'eau le long des axones. En outre, nous avons constaté que la rigidité artérielle est associée à une augmentation de la densité des fibres dans le corps calleux tel que mesuré par l’ICVF, ce qui pourrait suggérer que les personnes à risque plus élevé de déclin cognitif présentent des mécanismes compensatoires précoces avant l'apparition de signes cliniques de déclin cognitif. Compte tenu de la forte interaction entre la rigidité artérielle et le déclin à la fois de la structure du cerveau et des fonctions cérébrales, on peut envisager un avenir meilleur où la rigidité artérielle sera mesurée dans la pratique clinique de routine afin d'identifier les personnes à risque plus élevé d’altérations de la substance blanche et de déclin cognitif. Ces personnes pourraient bénéficier de programmes multi-interventionnels visant à préserver la structure et la fonction cérébrale. Un seuil de rigidité artérielle est donc nécessaire pour identifier ces individus. L'article 3 présente la première estimation d'une valeur seuil de cfPWV à laquelle la rigidité artérielle affecte la microstructure de la substance blanche chez les personnes âgées. Nos résultats suggèrent que le seuil actuel de 10 m / s de cfPWV adopté par la Société européenne d'hypertension n'est peut-être pas le seuil optimal pour diviser les individus en groupes à risque neurovasculaire élevé et faible. Au lieu de cela, nos résultats suggèrent que le seuil de cfPWV est plus susceptible d’être autour de 8,5 m / s. Bien que le cfPWV offre une excellente valeur pronostique chez les adultes, il reste malheureusement principalement utilisé dans la recherche en raison du besoin d'experts formés pour cette mesure. À l'inverse, la mesure de l'indice de rigidité artérielle (ASI) à l'aide de la pléthysmographie suscite un intérêt croissant ces dernières années en raison de son approche simple à utiliser. Dans l'article 4, nous avons étudié la relation entre l'ASI et la pression pulsée (PP) qui est une mesure indirecte de la rigidité artérielle, avec la FA et les lésions de la substance blanche chez les participants du UK Biobank. Nous avons constaté que la PP prédit mieux l'intégrité de la substance blanche que l'ASI chez les participants de moins de 75 ans. Cette constatation implique que l'ASI de la pléthysmographie ne semble pas être une mesure fiable de la rigidité artérielle chez les personnes âgées. Des études futures sont évidemment nécessaires pour valider nos résultats, en particulier notre seuil de cfPWV. Une fois ce seuil validé, nous envisageons un avenir radieux où la mesure du cfPWV sera non seulement utilisée pour aider à sélectionner les personnes qui bénéficieraient le plus d'un programme multi-interventionnel visant à préserver l'intégrité cérébrale, mais pourrait également être utilisée pour surveiller l’effet d’une telle intervention.Arterial stiffness refers to the loss of elasticity mainly in large arteries such as the aorta and carotids. Chronically elevated arterial stiffness contributes to cerebrovascular changes such as cerebral white matter parenchymal damage via an alteration of cerebral blood flow. In particular, among the areas perfused by arterioles supplied by the anterior and middle cerebral arteries, the corpus callosum, the internal capsule, the corona radiata, and the superior longitudinal fasciculus are more vulnerable to cerebral hypoperfusion. Previous studies have shown that increased arterial stiffness as assessed by carotid-femoral pulse wave velocity (cfPWV) is associated with a decrease in fractional anisotropy (FA) and increase in radial diffusivity (RD). It was hypothesized that alterations in vulnerable white matter tracts (e.g. corpus callosum, internal capsule) are likely to be related to axonal demyelination. However, while RD was previously correlated with axonal demyelination, diffusion imaging is mostly blind to myelin. In contrast magnetization transfer (MT) imaging is a tailored metric to estimate myelin volume fraction. Moreover, despite their sensitivity to axon fiber organization, diffusion tensor metrics (DTI) such as FA and RD lack specificity for individual tissue microstructure. More advanced microstructural model such as neurite orientation dispersion and density imaging (NODDI) give tools to disecate the microstructural changes behind DTI metrics. In Article 1 we used DTI and MT based metric to look more closely at the interplay between arterial stiffness and white matter microstructure in older adults > 65 years old. We found that the gold standard measure of arterial stiffness, the measure of carotid femoral pulse wave velocity (cfPWV) was associated with axonal fiber organization as reflected by FA and RD rather than demyelination in the white matter regions that have been previously denoted as vulnerable to arterial stiffness. In our second Article, we used the NODDI model to take a further look at the relationship between cfPWV and axonal organization. Our results showed that cfPWV is positively associated with the extracellular water diffusion (ISOVF) which means that arterial stiffness may result in axonal dispersion, lessening the constraint of water directionality along axons. In addition, we found that arterial stiffness is associated with increased fibers density in the corpus callosum as measured by ICVF which could suggest that individuals at higher risk for cognitive decline demonstrate early compensatory mechanisms before the appearance of clinical signs of cognitive decline. Considering the strong interplay between arterial stiffness and decline both in brain structure and function, one can envision a bright future where arterial stiffness would be measured in routine clinical practice in order to identify individuals at higher risk for white matter changes and cognitive decline. Such individuals could benefit from multi-interventions programs aiming to preserve brain structure and function. A cut-off arterial stiffness is thus needed to identify these individuals. Article 3 presents the first estimation of an cfPWV cut-off value at which arterial stiffness impacts the white matter microstructure in older adults. Our results suggested that the current 10 m/s cfPWV cut-off adopted by the European Society of Hypertension may not be the optimal threshold to split individuals into high and low neurovascular risk groups. Instead, our findings suggest that the cfPWV cut-off is more likely to fall around 8.5 m/s. While cfPWV provides excellent prognostic value in adults, it remains unfortunately mainly used in research due to the need of trained experts. Conversely, measure of arterial stiffness index (ASI) using plethysmography is getting increased interest in the last few years due to its simple-to-use approach. In article 4, we investigated the relationship between ASI and pulse pressure (PP), an indirect measure of arterial stiffness, with FA and white matter lesions in participants of the UK Biobank. We found that PP better predicts white matter integrity compared to ASI in participants younger than 75 years old. This finding implies that ASI from plethysmography may not be a reliable measure of arterial stiffness in older adults. Future studies are obviously needed to validate our results, in particular our cfPWV cut-off. Once such cut-off will be validated, the present author envision a bright future where measure of cfPWV will not only be used to help selecting individuals that would most benefit from a multi intervention program aiming to preserve brain integrity, but could also be used to monitor the effect of such intervention

    Case series of breast fillers and how things may go wrong: radiology point of view

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    INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

    Pursuit of precision medicine: Systems biology approaches in Alzheimer\u27s disease mouse models.

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    Alzheimer\u27s disease (AD) is a complex disease that is mediated by numerous factors and manifests in various forms. A systems biology approach to studying AD involves analyses of various body systems, biological scales, environmental elements, and clinical outcomes to understand the genotype to phenotype relationship that potentially drives AD development. Currently, there are many research investigations probing how modifiable and nonmodifiable factors impact AD symptom presentation. This review specifically focuses on how imaging modalities can be integrated into systems biology approaches using model mouse populations to link brain level functional and structural changes to disease onset and progression. Combining imaging and omics data promotes the classification of AD into subtypes and paves the way for precision medicine solutions to prevent and treat AD
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