Phenomenological model of diffuse global and regional atrophy using finite-element methods

The main goal of this work is the generation of ground-truth data for the validation of atrophy measurement techniques, commonly used in the study of neurodegenerative diseases such as dementia. Several techniques have been used to measure atrophy in cross-sectional and longitudinal studies, but it is extremely difficult to compare their performance since they have been applied to different patient populations. Furthermore, assessment of performance based on phantom measurements or simple scaled images overestimates these techniques' ability to capture the complexity of neurodegeneration of the human brain. We propose a method for atrophy simulation in structural magnetic resonance (MR) images based on finite-element methods. The method produces cohorts of brain images with known change that is physically and clinically plausible, providing data for objective evaluation of atrophy measurement techniques. Atrophy is simulated in different tissue compartments or in different neuroanatomical structures with a phenomenological model. This model of diffuse global and regional atrophy is based on volumetric measurements such as the brain or the hippocampus, from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions and tissues. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on biomechanical tissue properties and simulating plausible tissue deformations with finite-element methods. A thermoelastic model of tissue deformation is employed, controlling the rate of progression of atrophy by means of a set of thermal coefficients, each one corresponding to a different type of tissue. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh that will be introduced to a finite-element solver to create the simulated deformations. Preliminary work on the simulation of acquisition artefa- - cts is also presented. Cross-sectional and

Evaluation of local and global atrophy measurement techniques with simulated Alzheimer's disease data

The main goal of this work was to evaluate several well-known methods which provide global (BSI and SIENA) or local (Jacobian integration) estimates of atrophy in brain structures using Magnetic Resonance images. For that purpose, we have generated realistic simulated Alzheimer's disease images in which volume changes are modelled with a Finite Element thermoelastic model, which mimic the patterns of change obtained from a cohort of 19 real controls and 27 probable Alzheimer's disease patients. SIENA and BSI results correlate very well with gold standard data (BSI mean absolute error <0.29%; SIENA <0.44%). Jacobian integration was guided by both fluid and FFD-based registration techniques and resulting deformation fields and associated Jacobians were compared, region by region, with gold standard ones. The FFD registration technique provided more satisfactory results than the fluid one. Mean absolute error differences between volume changes given by the FFD-based technique and the gold standard were: sulcal CSF <2.49%; lateral ventricles 2.25%; brain <0.36%; hippocampi <0.42%

Accuracy assessment of global and local atrophy measurement techniques with realistic simulated longitudinal data

The main goal of this work was to assess the accuracy of several well-known methods which provide global (BSI and SIENA) or local (Jacobian integration) estimates of longitudinal atrophy in brain structures using Magnetic Resonance images. For that purpose, we have generated realistic simulated images which mimic the patterns of change obtained from a cohort of 19 real controls and 27 probable Alzheimer's disease patients. SIENA and BSI results correlate very well with gold standard data (BSI mean absolute error < 0.29%; SIENA < 0.44%). Jacobian integration was guided by both fluid and FFD-based registration techniques and resulting deformation fields and associated Jacobians were compared, region by region, with gold standard ones. The FFD registration technique provided more satisfactory results than the fluid one. Mean absolute error differences between volume changes given by the FFD-based technique and the gold standard were: sulcal CSF < 2.49%; lateral ventricles < 2.25%; brain < 0.36%; hippocampi < 1.42%

Pathological and Biomedical Characteristics of Spinal Cord Injury Determined Using Diffusion Tensor Imaging

Traumatic spinal cord injury: SCI) is the most devastating injury that often causes the victim permanent paralysis and undergo a lifetime of therapy and care. It is caused by a mechanical impact that ultimately causes pathophysiological consequences which at this moment in time are an unresolved scientific challenge of great social impact. Scientists have long used animal contusion models to study the pathophysiology of SCI in the discovery of progressive secondary tissue degeneration, demyelination, and apoptosis. More importantly, most therapies that have gone to human clinical trial were first validated in spinal cord contusion models. Magnetic resonance imaging: MRI) is the modality of choice to noninvasively detect the soft tissue injury, particularly suitable for assessing the tissue integrity in SCI. However, the convention MRI lacks capability of detecting and evaluating the injury severity acutely, probably resulting in lost opportunities of effective prognostication or treatment stratification for SCI patients. Diffusion Tensor Magnetic Resonance Imaging: DTMRI, DTI) is an emerging technique known to provide dynamic contrast reflecting the progression of the underlying pathology in CNS tissues. In this study, we hypothesized that axial: ||) and radial: λ^) diffusivity derived from DTI is sensitive to the pathological alteration in spinal cord white matter: WM) tract and could be used as potential biomarkers detecting and characterizing the axonal and myelin damage in SCI. A mouse model of contusion SCI was examined using DTI, behavioral assessment, and histology to test our hypothesis. Techniques employed including the simplification of diffusion weighting scheme, the implementation of diffusion weighted multiple spin-echo sequence, and verified for setting up the experimental protocol and data processing procedures. Secondly, the hypothesis was test on the projects comparing the change of these biomarkers on both the myelinated and dysmyelinated shiverer mice cooperating with histological analysis, and behavioral assessment. Finally, a finite element analysis: FEA) of contusion SCI was deployed to provide evidences of injury mechanics correlated with the injury patterns detected by diffusion MRI for a better characterized animal model of contusion SCI

Biomechanics of foetal movement.

© 2015, AO Research Institute. All rights reserved.Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements, breathing movements, head and neck movements, jaw movements (including yawning, sucking and swallowing) and hiccups by ten weeks of gestational age. There are two key biomechanical aspects to gross foetal movements; the first being that the foetus moves in a dynamically changing constrained physical environment in which the freedom to move becomes increasingly restricted with increasing foetal size and decreasing amniotic fluid. Therefore, the mechanical environment experienced by the foetus affects its ability to move freely. Secondly, the mechanical forces induced by foetal movements are crucial for normal skeletal development, as evidenced by a number of conditions and syndromes for which reduced or abnormal foetal movements are implicated, such as developmental dysplasia of the hip, arthrogryposis and foetal akinesia deformation sequence. This review examines both the biomechanical effects of the physical environment on foetal movements through discussion of intrauterine factors, such as space, foetal positioning and volume of amniotic fluid, and the biomechanical role of gross foetal movements in human skeletal development through investigation of the effects of abnormal movement on the bones and joints. This review also highlights computational simulations of foetal movements that attempt to determine the mechanical forces acting on the foetus as it moves. Finally, avenues for future research into foetal movement biomechanics are highlighted, which have potential impact for a diverse range of fields including foetal medicine, musculoskeletal disorders and tissue engineering

Finite element analysis for normal pressure hydrocephalus: The effects of the integration of sulci.

Finite element analysis (FEA) is increasingly used to investigate the brain under various pathological changes. Although FEA has been used to study hydrocephalus for decades, previous studies have primarily focused on ventriculomegaly. The present study aimed to investigate the pathologic changes regarding sulcal deformation in normal pressure hydrocephalus (NPH). Two finite element (FE) models-an anatomical brain geometric (ABG) model and the conventional simplified brain geometric (SBG) model-of NPH were constructed. The models were constructed with identical boundary conditions but with different geometries. The ABG model contained details of the sulci geometry, whereas these details were omitted from the SBG model. The resulting pathologic changes were assessed via four biomechanical parameters: pore pressure, von Mises stress, pressure, and void ratio. NPH was induced by increasing the transmantle pressure gradient (TPG) from 0 to a maximum of 2.0 mmHg. Both models successfully simulated the major features of NPH (i.e., ventriculomegaly and periventricular lucency). The changes in the biomechanical parameters with increasing TPG were similar between the models. However, the SBG model underestimated the degree of stress across the cerebral mantle by 150% compared with the ABG model. The SBG model also overestimates the degree of ventriculomegaly (increases of 194.5% and 154.1% at TPG = 2.0 mmHg for the SBG and ABG models, respectively). Including the sulci geometry in a FEA for NPH clearly affects the overall results. The conventional SBG model is inferior to the ABG model, which accurately simulated sulcal deformation and the consequent effects on cortical or subcortical structures. The inclusion of sulci in future FEA for the brain is strongly advised, especially for models used to investigate space-occupying lesions.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1004827).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.media.2015.05.00

Plantar Fasciitis: Biomechanics, Atrophy and Muscle Energetics

Purpose: The purpose of this dissertation was to determine the effects of chronic plantar fasciitis on intrinsic foot structures with respect to biomechanics, muscle atrophy and muscle energetics. This was accomplished in three parts. Methods: In Part I, a three-dimensional motion capture system with a synchronized force platform quantified multi-segment foot model kinematics and ground reaction forces associated with walking. Healthy individuals were compared to individuals with chronic plantar fasciitis feet. Typical kinematic variables, measures of coupling, phase and variability were examined in rearfoot, forefoot and hallux segments. In Part II, foot and leg magnetic resonance images were taken in subjects with unilateral plantar fasciitis so that within each subject, the healthy limb could be compared to the plantar fasciitis limb. Cross sectional areas (CSA) of the plantar intrinsic foot muscles (PIFM) and tibialis posterior muscle were computed from user-digitized images. In Part III, the metabolic demands of the PIFM were evaluated using phosphorous magnetic resonance spectroscopy at rest and after barefoot walking. Muscle pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) were compared in healthy and plantar fasciitis feet. Results: In comparison to healthy feet, plantar fasciitis feet exhibited significantly (p \u3c 0.05): 1) greater rearfoot motion, 2) greater sagittal plane forefoot motion, 3) fewer rearfoot-forefoot frontal anti-phase movements, 4) reduced rearfoot-forefoot transverse coordinative variability, 5) greater first metatarsophalangeal (FMPJ) joint dorsiflexion, 6) greater FMPJ-medial longitudinal arch (MLA) coupling variability, and 7) decreased vertical ground reaction forces at propulsion. Also, plantar fasciitis feet had 5.2% smaller PIFM CSA at the forefoot compared to contralateral healthy feet. No CSA differences were seen in the rearfoot PIFM or at the tibialis posterior muscle. The PIFM of healthy and PF feet were not significantly different in resting intracellular levels of pH or Pi/PCr, and there were no significant differences in the increase of Pi/PCr from rest to postwalking. Conclusions: In Part I, it was concluded that plantar fasciitis feet exhibit kinematics which are consistent with theoretical causation of the plantar fasciitis injury, that is, the plantar fasciitis foot exhibits excessive motion. Fewer number of anti-phase movements exhibited by plantar fasciitis feet may be an indication of pathology. The ground reaction force results suggested a compensatory pain response. In Part II, it was concluded that atrophy of the forefoot PIFM may destabilize the medial longitudinal arch and prolong the healing process. Lastly in Part III, it was concluded that resting energetics were consistent with muscle free of systemic disease or neuromuscular pathology. The presence of plantar fasciitis did not elicit systematic asymmetries in the metabolic response in comparison to healthy feet. Clinical Relevance: These kinematic results provided some evidence to support the clinical assertion that excessive motion is related to plantar fasciitis. These results also support treatment modalities which clinicians currently use to reduce rearfoot eversion, flattening of the medial longitudinal arch and dorsiflexion of the FMPJ (e.g. foot orthoses, insoles, taping, rocker soles). When treating plantar fasciitis patients, clinicians should assess for PIFM and tibialis posterior muscle atrophy and prescribe targeted exercises when appropriate

Multi-scale interaction of flow and the artery wall

We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying their widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of flow, and proceed to propose, then validate (in practical, qualitative terms, at least) a multiply coupled, multi-scale modeling strategy, which, eventually, aims at a quantitative, patient-specific understanding of the coupling between the flow and the endothelial state

Advancing imaging technologies for patients with spinal pain : with a focus on whiplash injury

Background: Radiological observations of soft-tissue changes that may relate to clinical symptoms in patients with traumatic and non-traumatic spinal disorders are highly controversial. Studies are often of poor quality and findings are inconsistent. A plethora of evidence suggests some pathoanatomical findings from traditional imaging applications are common in asymptomatic participants across the life span, which further questions the diagnostic, prognostic, and theranostic value of traditional imaging. Although we do not dispute the limited evidence for the clinical importance of most imaging findings, we contend that the disparate findings across studies may in part be due to limitations in the approaches used in assessment and analysis of imaging findings. Purpose: This clinical commentary aimed to (1) briefly detail available imaging guidelines, (2) detail research-based evidence around the clinical use of findings from advanced, but available, imaging applications (eg, fat and water magnetic resonance imaging and magnetization transfer imaging), and (3) introduce how evolving imaging technologies may improve our mechanistic understanding of pain and disability, leading to improved treatments and outcomes. Study Design/Setting: A non-systematic review of the literature is carried out. Methods: A narrative summary (including studies from the authors' own work in whiplash injuries) of the available literature is provided. Results: An emerging body of evidence suggests that the combination of existing imaging sequences or the use of developing imaging technologies in tandem with a good clinical assessment of modifiable risk factors may provide important diagnostic information toward the exploration and development of more informed and effective treatment options for some patients with traumatic neck pain. Conclusions: Advancing imaging technologies may help to explain the seemingly disconnected spectrum of biopsychosocial signs and symptoms of traumatic neck pain