A clinical system for the measurement of regional metabolic rates in the brain.

The study of the chemical events that regulate the function of the human brain is particularly difficult. The introduction by Hounsfield, in 1973, of a tomographic technique based on the attenuation of X-rays by tissues has proved invaluable in the study of the morphology of the brain. An extension of this technique, employing the concepts of computerised tomography in combination with the use of specific molecules labelled with positron emitters, is now making the direct regional measurement of metabolic rates during life possible. Although some positron tomography systems are available commercially, they do not necessarily fulfil the specific needs of all researchers. Faced with the problem of quantitating the regional distribution of the essential neurotransmitter, dopamine, in the human brain a positron tomography system, which forms the basis of this work, was designed and built based on a series of experiments aimed at optimizing spatial resolution and detection efficiency. The performance of the tomograph has been evaluated through a series of phantom studies; and the system has been used to measure the local cerebral metabolic rate of glucose and the local distribution of dopamine in the healthy and diseased brain. It is felt that the ability of this tomograph to resolve metabolic structures in the brain as small as 10[3] mm[3] will only be surpassed at the cost of unduly increasing the radiation dose to the subject. The results of positron tomographic studies performed using different positron labelled molecules and those obtained using X-ray computerized tomographic techniques and magnetic resonance techniques in the same subject have been compared. The results have been found to be complementary, each technique providing a clue to the proper understanding of the functioning of the brain

2013 IMSAloquium, Student Investigation Showcase

This year, we are proudly celebrating the twenty-fifth anniversary of IMSA’s Student Inquiry and Research (SIR) Program. Our first IMSAloquium, then called Presentation Day, was held in 1989 with only ten presentations; this year we are nearing two hundred.https://digitalcommons.imsa.edu/archives_sir/1005/thumbnail.jp

Pathophysiology of normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH), a CSF circulation disorder, is important as a reversible cause of gait and cognitive disturbance in an aging population. The inconsistent response to CSF shunting is usually attributed to difficulties in differential diagnosis or co-morbidity. Improving outcome depends on an increased understanding of the pathophysiology of NPH. Specifically, this thesis examines the contribution of, and inter-relationship between, the brain parenchyma and CSF circulation in the pathophysiology of NPH. Of the four core studies of the thesis, the first quantifies the characteristics of the CSF circulation and parenchyma in NPH using CSF infusion studies to measure the resistance to CSF absorption and brain compliance. The second study assesses cerebral blood flow (CBF) was using O15-labelled positron emission tomography (PET) with MR co-registration. By performing CSF infusion studies in the PET scanner, CBF at baseline CSF pressure and at a higher equilibrium pressure is measured. Regional changes and autoregulatory capacity are assessed. The final study examines the microstructural integrity of the parenchyma using MR diffusion tensor imaging. These studies confirm the importance of the inter-relationship of the brain parenchyma and CSF circulation. NPH symptomatology and its relationship to the observed regional CBF reductions in the basal ganglia and thalamus are discussed. Regional CBF reductions with increased CSF pressure and the implications for autoregulatory capacity in NPH are considered. The reduction in CBF when CSF was increased was most striking in the periventricular regions. In addition, periventricular structures demonstrated increased diffusivity and decreased anisotropy. The relationship between these changes and mechanisms such as transependymal CSF passage are reviewed. The findings of this thesis support a role of both the CSF circulation and the brain parenchyma in the pathophysiology of NPH. The results have implications for the approach to the management of patients with NPH

Pathophysiology of normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH), a CSF circulation disorder, is important as a reversible cause of gait and cognitive disturbance in an aging population. The inconsistent response to CSF shunting is usually attributed to difficulties in differential diagnosis or co-morbidity. Improving outcome depends on an increased understanding of the pathophysiology of NPH. Specifically, this thesis examines the contribution of, and inter-relationship between, the brain parenchyma and CSF circulation in the pathophysiology of NPH. Of the four core studies of the thesis, the first quantifies the characteristics of the CSF circulation and parenchyma in NPH using CSF infusion studies to measure the resistance to CSF absorption and brain compliance. The second study assesses cerebral blood flow (CBF) was using O15-labelled positron emission tomography (PET) with MR co-registration. By performing CSF infusion studies in the PET scanner, CBF at baseline CSF pressure and at a higher equilibrium pressure is measured. Regional changes and autoregulatory capacity are assessed. The final study examines the microstructural integrity of the parenchyma using MR diffusion tensor imaging. These studies confirm the importance of the inter-relationship of the brain parenchyma and CSF circulation. NPH symptomatology and its relationship to the observed regional CBF reductions in the basal ganglia and thalamus are discussed. Regional CBF reductions with increased CSF pressure and the implications for autoregulatory capacity in NPH are considered. The reduction in CBF when CSF was increased was most striking in the periventricular regions. In addition, periventricular structures demonstrated increased diffusivity and decreased anisotropy. The relationship between these changes and mechanisms such as transependymal CSF passage are reviewed. The findings of this thesis support a role of both the CSF circulation and the brain parenchyma in the pathophysiology of NPH. The results have implications for the approach to the management of patients with NPH

Oscillatory activity in the basal ganglia - is it relevant to movement disorders therapy?

Chronic high frequency stimulation of the basal ganglia can be a highly effective intervention for movement disorders in patients. In the past decade, therapeutic benefits have been seen with stimulation of the subthalamic nucleus and globus pallidus interna for Parkinson's disease (PD) and dystonia, respectively. These procedures have allowed direct recording of basal ganglia activity and have suggested that abnormal synchronisation of neurons in these nuclei may contribute to motor impairment. This thesis explores the possible correlation between synchronised activity in the basal ganglia, as evidenced by oscillations in local field potentials, and movement disorders. In Chapter 3, we demonstrate the correlation between synchronization at frequencies under 10 Hz in the globus pallidus interna and dystonic EMG. This low frequency activity is shown to be locked to neuronal activity within GPi in patients with dystonia (Chapter 4). Deep brain stimulation is thought to suppress spontaneous pathological activity in the basal ganglia. Equally, however, it must also suppress any residual physiological activity in these nuclei. In Chapter 5, we demonstrate that the basal ganglia are involved in the processing of simple limb movements in the human, by separating the effects of deep brain stimulation on pathological and physiological activities based on baseline task performance. An impairment of motor performance was seen during high frequency stimulation in those patients with the best task performance at baseline. This deleterious effect, however, should be distinguished from the effect of direct stimulation at 20 Hz in Parkinson's disease. Oscillatory activity at around 20 Hz is thought to be a core feature in Parkinson's disease. In Chapter 6, we demonstrate that the excessive synchronization imposed by stimulation of the subthalamic nucleus at 20 Hz slows movement, in those patients with the best task performance at baseline. This supports the notion that synchronization around 20 Hz may be causally linked to bradykinesia. Last, the therapeutic effectiveness of DBS therapy for patients with PD partially relies on the accurate localisation of the motor region of the subthalamic nucleus. In Chapter 7, we propose an alternative method for the localization of this region using the spontaneous pathological 20 Hz activity to be found in this nucleus. The findings of these studies provide evidence that basal ganglia oscillatory activities of differing frequencies contribute to movement disorders

Computational methods toward early detection of neuronal deterioration

In today's world, because of developments in medical sciences, people are living longer, particularly in the advanced countries. This increasing of the lifespan has caused the prevalence of age-related diseases like Alzheimer’s and dementia. Researches show that ion channel disruptions, especially the formation of permeable pores to cations by Aβ plaques, play an important role in the occurrence of these types of diseases. Therefore, early detection of such diseases, particularly using non-invasive tools can aid both patients and those scientists searching for a cure. To achieve the goal toward early detection, the computational analysis of ion channels, ion imbalances in the presence of Aβ pores in neurons and fault detection is done. Any disruption in the membrane of the neuron, like the formation of permeable pores to cations by Aβ plaques, causes ionic imbalance and, as a result, faults occur in the signalling of the neuron.The first part of this research concentrates on ion channels, ion imbalances and their impacts on the signalling behaviour of the neuron. This includes investigating the role of Aβ channels in the development of neurodegenerative diseases. Results revealed that these types of diseases can lead to ionic imbalances in the neuron. Ion imbalances can change the behaviour of neuronal signalling. Therefore, by identifying the pattern of these changes, the disease can be detected in the very early stages. Then the role of coupling and synchronisation effects in such diseases were studied. After that, a novel method to define minimum requirements for synchronicity between two coupled neurons is proposed. Further, a new computational model of Aβ channels is proposed and developed which mimics the behaviour of a neuron in the course of Alzheimer's disease. Finally, both fault computation and disease detection are carried out using a residual generation method, where the residuals from two observers are compared to assess their performance

Unveiling the impact of neuromotor disorders on speech: a structured approach combining biomechanical fundamentals and statistical machine learning

Speech has been shown to convey clinically useful information in the study of Neurodegenerative Disorders (NDs), such as Parkinson’s Disease (PD). Traditionally the use of speech as an exploratory tool in People with Parkinson’s (PwP) has focused on the estimation of acoustic characteristics and their study at face value, analysing the physio-acoustical markers and using them as features for the differentiation between Healthy Controls (HC) and PwP. The present work takes a step further, given the intricate interoperation between neuromotor activity, responsible for both planning and driving the system, and the production of the acoustic speech signal; by the study of speech, this relationship may be properly exploited and analysed, providing a non-invasive method for the diagnosis, analysis, and observation of NDs. This work aims to introduce a working model that is capable of linking both domains and serves as a projection tool to provide insights about a speaker’s neuromotor state. This is based on a review of the neurophysiological background of the structure and function of the nervous system, and a review of the main nervous system dysfunctions involved in PD and other related neuromotor disorders. The role of the respiratory, phonatory, and articulatory systems is reviewed in the production of voice and speech under normal and pathological circumstances. This setting might allow for speech to be considered a useful trait within the precision medicine framework, as it provides a personal biometric marker that is innate and easy to elicit, can be recorded remotely with inexpensive equipment, is non-invasive, cost-effective, and easy to process. The problem can be divided into two main categories: firstly, a binary detection task distinguishing between healthy controls and individuals with NDs based on the projection model and phonatory estimates; secondly, a progression and tracking task providing a set of quantitative indices that enable clinically interpretable scores. This study aims to define a set of features and models that help to characterise hypokinetic dysarthria (HD). These incorporate the neuroscientific knowhow semantically and quantitatively to be used in clinical decision support tools that provide mechanistic insight on the processes involved in speech production, incorporating into the algorithmic element neuromotor considerations that add to better interpretability, consequently leading to improved clinical decisions and diagnosis. An overview of the acoustic signal processing algorithms for use in speech articulation and phonation system inversion regarding neuromotor disorder assessment is provided. An algorithmic methodology for model inversion and exploration has been proposed for the functional characterization and system inversion of each subsystem involved under the neuro-biomechanical foundations exposed before. A description of the vocal fold biomechanics using the glottal source, and formant dynamics provides the base for specific mapping to articulation kinematics. The statistical methods used in performance evaluation are based on three-way comparisons and transversal and longitudinal assessment by classical hypothesis testing. Three related experimental studies are shown to empirically illustrate the potential of phonation and articulation analysis: the characterization of PD from glottal biomechanics based on the amplitude distributions of the glottal flow and on the vocal fold body stiffness in assessing the efficiency of transcranial magnetic stimulation, and the description of PD dysarthria through an articulation projection model. The results from the biomechanical analysis of phonation showed that the behaviour of glottal source amplitude distributions from PD and healthy controls using three-way comparisons and hierarchical clustering were essentially distinguishable from those from normative young participants with the best accuracy scores produced by SVM classifiers of 94.8% (males) and 92.2% (females). Nevertheless, PD participants were barely separable from age-matched controls, possibly pointing to confounding factors due to age. The outcomes from using vocal fold stiffness in assessing the efficiency of transcranial magnetic stimulation showed mixed results, as some PD participants reflected clear improvements in phonation stability after stimulation, whereas some others did not. Some cases of sham controls experienced also minor improvements of unknown origin, possibly expressing a placebo effect. The overall results on the efficiency of stimulation showed an accuracy global score of 67% over the 18 cases studied. The results from articulation projection modelling showed the possibility of formulating personalised models for PD and control participants to transform acoustic formant dynamics into articulation kinematics. This might open the possibility of characterising PD dysarthria based on speech audio records. The most remarkable findings of the study include the determination of the glottal source amplitude distribution behaviour of normative and PD participants; the impact of age effects in phonation as a confounding factor in neuromotor disorder characterization; the importance of ensuring that the classification of speech dysarthria is based on principles that can be explained and interpreted; the need of taking into account the effects of medication when framing new classification experiments; the potential of using EEG-band decomposition to analyse vocal fold stiffness correlates, as well as the possibility of using these descriptions in longitudinal monitoring of treatment efficiency; the feasibility of establishing a relationship between acoustic and kinematic variables by projection model inversion; and the potential of these descriptions for estimating neuromotor activities in midbrain related to phonation and articulation activity. The most important outcome to be brought forth from the thesis is that the methodology used throughout the project uses a bottom-up approach based on speech model inversion at the acoustical, biomechanical, and neuromotor levels allowing to estimate glottal signals, biomechanical correlates, and neuromotor activity from speech alone, establishing a common neuromechanical characterisation framework on its own

Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies