800 research outputs found
Dynamic Assessment of Cerebral Metabolic Rate of Oxygen (cmro2) With Magnetic Resonance Imaging
The brain is almost entirely dependent on oxidative metabolism to meet its energy requirements. As such, the cerebral metabolic rate of oxygen (CMRO2) is a direct measure of brain energy use. CMRO2 provides insight into brain functional architecture and has demonstrated potential as a clinical tool for assessing many common neurological disorders.
Recent developments in magnetic resonance imaging (MRI)-based CMRO2 quantification have shown promise in spatially resolving CMRO2 in clinically feasible scan times. However, brain energy requirements are both spatially heterogeneous and temporally dynamic, responding to rapid changes in oxygen supply and demand in response to physiologic stimuli and neuronal activation.
Methods for dynamic quantification of CMRO2 are lacking, and this dissertation aims to address this gap. Given the fundamental tradeoff between spatial and temporal resolution in MRI, we focus initially on the latter. Central to each proposed method is a model-based approach for deriving venous oxygen saturation (Yv) – the critical parameter for CMRO2 quantification – from MRI signal phase using susceptometry-based oximetry (SBO).
First, a three-second-temporal-resolution technique for whole-brain quantification of Yv and CMRO2 is presented. This OxFlow method is applied to measure a small but highly significant increase in CMRO2 in response to volitional apnea.
Next, OxFlow is combined with a competing approach for Yv quantification based on blood T2 relaxometry (TRUST). The resulting interleaved-TRUST (iTRUST) pulse sequence greatly improves T2-based CMRO2 quantification, while allowing direct, simultaneous comparison of SBO- and T2-based Yv. iTRUST is applied to assess the CMRO2 response to hypercapnia – a topic of great interest in functional neuroimaging – demonstrating significant biases between SBO- and T2-derived Yv and CMRO2.
To address the need for dynamic and spatially resolved CMRO2 quantification, we explore blood-oxygen-level-dependent (BOLD) calibration, introducing a new calibration model and hybrid pulse sequence combining OxFlow with standard BOLD/CBF measurement. Preliminary results suggest Ox-BOLD provides improved calibration “M-maps” for converting BOLD signal to CMRO2.
Finally, OxFlow is applied clinically to patients with obstructive sleep apnea (OSA). A small clinical pilot study demonstrates OSA-associated reductions in CMRO2 at baseline and in response to apnea, highlighting the potential utility of dynamic CMRO2 quantification in assessing neuropathology
Oral application of L-menthol in the heat: From pleasure to performance
When menthol is applied to the oral cavity it presents with a familiar refreshing sensation and cooling mint flavour. This may be deemed hedonic in some individuals, but may cause irritation in others. This variation in response is likely dependent upon trigeminal sensitivity toward cold stimuli, suggesting a need for a menthol solution that can be easily personalised. Menthol’s characteristics can also be enhanced by matching colour to qualitative outcomes; a factor which can easily be manipulated by practitioners working in athletic or occupational settings to potentially enhance intervention efficacy.
This presentation will outline the efficacy of oral menthol application for improving time trial performance to date, either via swilling or via co-ingestion with other cooling strategies, with an emphasis upon how menthol can be applied in ecologically valid scenarios. Situations in which performance is not expected to be enhanced will also be discussed. An updated model by which menthol may prove hedonic, satiate thirst and affect ventilation will also be presented, with the potential performance implications of these findings discussed and modelled. Qualitative reflections from athletes that have implemented menthol mouth swilling in competition, training and maximal exercise will also be included
Representation of Somatosensory Afferents in the Cortical Autonomic Network
The relationship between somatosensory stimulation and the autonomic nervous system has been established with effects on heart rate (HR) and sympathetic tone. However, the involvement of the cortical autonomic network (CAN) during muscle sensory afferent stimulation has not been identified. The main objective of the research in this dissertation was to determine the representation of somatosensory afferents in the CAN and their physiologic impact on cardiovascular control. Somatosensory afferent activation was elicited by electrical stimulation of type I and II afferents (sub-motor threshold) and type III and IV afferents (motor threshold), and CAN patterns were assessed using blood-oxygenation level-dependent functional magnetic resonance imaging. Study 1 (Chapter 2) established CAN regions associated with sub-motor stimulation including the ventral medial prefrontal cortex (vMPFC), subgenual anterior cingulate cortex (sACC), and posterior insula, along with a trend towards increased heart rate variability (HRV). Motor threshold stimulation was associated with activation in the posterior insula. Having established the CAN regions affected by sensory afferent input, diffusion tensor imaging was used (Chapter 3) to establish structural connections between the cortical regions associated with functional cardiovascular control. We identified two discrete patterns of white matter connectivity between the anterior insula-sACC and posterior insula-posterior cingulate cortex, suggesting that a structural network may underlie functional roles in autonomic regulation and sensory processing. As somatosensory stimulation had modest impact on cardiovascular control under baseline conditions, Study 3 (Chapter 4) aimed to establish the effects of somatosensory stimulation during baroreceptor unloading (lower-body negative pressure, LBNP) on muscle sympathetic nerve activity (MSNA) and cortical activity. Sensory stimulation during LBNP led to an attenuated increase in MSNA burst frequency, as well as absent activity in the right insula and dorsal ACC, supporting the sympatho-excitatory role of these regions. No effect of somatosensory stimulation during chemoreflex-mediated sympatho-excitation was observed on MSNA, while right insular and dorsal ACC activities were maintained. Overall, the results of these studies provide evidence of somatosensory representation within the CAN regions that are anatomically linked, and highlight a role for type I and II sensory afferents in modulating autonomic outflow in a manner that depends upon baroreceptor loading
Using physiological MRI to estimate dynamic cerebral autoregulation metrics: functional MRI feasibility study
Cerebral autoregulation is the homeostatic mechanism that maintains sufficient cerebral circulation despite changes in the perfusion pressure. Dynamic CA refers to the changes that occur in CBF within the first few seconds after an acute MAP change. Assessment of the CA impairment plays important role in the prognosis of many cerebrovascular diseases such as stroke, sub-arachnoid haemorrhage, as well as traumatic brain injury and neurodegenerative disorders.
This thesis investigates the feasibility of using physiological MRI to estimate dynamic cerebral autoregulation (dCA) metrics. In particular, this thesis has an emphasis on measuring beat-to-beat arterial blood pressure inside the scanner to provide better understanding of the physiological aspects of dCA. Further, continuous blood pressure (BP) measures in response to different non invasive BP fluctuating methods are acquired to evaluate the reliability of these methods to induce response changes.
Blood Oxygen Level Dependent (BOLD) fMRI method was used to estimate the expected variations of tissue oxygenation during induced dCA changes in healthy volunteers. The non invasive arterial blood pressure measurements were acquired using MR compatible arterial blood pressure monitoring device (NIBP-MRI/Caretaker; Biopac®). Further, sudden release of inflated thigh-cuffs (TCR) and inspiratory breath-hold (iBH) methods were used in the scanner to induce dynamic autoregulatory changes. These two methods were investigated in a pilot study, to evaluate the reliability prior to the MR study by comparing BP measurements obtained outside the scanner using non invasive methods. This pilot study included monitoring BP changes in response to four types of non invasive BP fluctuating methods. The reliability of NIBP/MRI Caretaker device was examined by comparing the BP response changes with the simultaneously acquired BP data from Finometer plethysmographic device. The cerebral autoregulation metrics were estimated by calculating the rate of regulation (RoR) following dynamic BP fluctuating events. Rate of regulation defines the rate at which the BOLD signal changes depending on MAP changes at a particular time. Further, the tissue specific regulation parameters were obtained for grey matter (GM), white matter (WM) and water shed areas (WS). The effect of iBH method on cerebral blood flow (CBF) and velocity (CBFV) was explored in a preliminary study by quantitative measures using time resolved 4D PC MRI angiography in two subjects.
The mean arterial blood pressure (MAP) changes in response to TCR and iBH method were comparable. The fMRI data demonstrated BOLD signal amplitude change in response to the induced fast MAP changes. The GM and WS areas showed similar rates of regulation, and these were nominally higher than WM RoR in both TCR and iBH methods. Further, the 4D PC MRI data suggested 29% CBF-increase in response to 33% iBH in four minutes acquisition time.
The acquired non invasive arterial BP measures concurrent with the BOLD signal amplitude response, allowed deriving the rate of regulation as a metric of dCA. It is not known whether this information is clinically relevant to gauge the haemodynamic risk association to cerebrovascular disease. However, BOLD signal change and CBF changes after iBH are confounded by the extent to which the CO2 gradually accumulate in response to iBH and causes an overshoot in the CBF response-change.
In conclusion, the presented study indicates the feasibility of using physiological MRI to measure dCA in response to non-invasively induced MAP changes. Estimation of the dCA metrics could be improved by using advanced data fitting methods as well as controlling for physiological parameters such as PECO2
Using physiological MRI to estimate dynamic cerebral autoregulation metrics: functional MRI feasibility study
Cerebral autoregulation is the homeostatic mechanism that maintains sufficient cerebral circulation despite changes in the perfusion pressure. Dynamic CA refers to the changes that occur in CBF within the first few seconds after an acute MAP change. Assessment of the CA impairment plays important role in the prognosis of many cerebrovascular diseases such as stroke, sub-arachnoid haemorrhage, as well as traumatic brain injury and neurodegenerative disorders.
This thesis investigates the feasibility of using physiological MRI to estimate dynamic cerebral autoregulation (dCA) metrics. In particular, this thesis has an emphasis on measuring beat-to-beat arterial blood pressure inside the scanner to provide better understanding of the physiological aspects of dCA. Further, continuous blood pressure (BP) measures in response to different non invasive BP fluctuating methods are acquired to evaluate the reliability of these methods to induce response changes.
Blood Oxygen Level Dependent (BOLD) fMRI method was used to estimate the expected variations of tissue oxygenation during induced dCA changes in healthy volunteers. The non invasive arterial blood pressure measurements were acquired using MR compatible arterial blood pressure monitoring device (NIBP-MRI/Caretaker; Biopac®). Further, sudden release of inflated thigh-cuffs (TCR) and inspiratory breath-hold (iBH) methods were used in the scanner to induce dynamic autoregulatory changes. These two methods were investigated in a pilot study, to evaluate the reliability prior to the MR study by comparing BP measurements obtained outside the scanner using non invasive methods. This pilot study included monitoring BP changes in response to four types of non invasive BP fluctuating methods. The reliability of NIBP/MRI Caretaker device was examined by comparing the BP response changes with the simultaneously acquired BP data from Finometer plethysmographic device. The cerebral autoregulation metrics were estimated by calculating the rate of regulation (RoR) following dynamic BP fluctuating events. Rate of regulation defines the rate at which the BOLD signal changes depending on MAP changes at a particular time. Further, the tissue specific regulation parameters were obtained for grey matter (GM), white matter (WM) and water shed areas (WS). The effect of iBH method on cerebral blood flow (CBF) and velocity (CBFV) was explored in a preliminary study by quantitative measures using time resolved 4D PC MRI angiography in two subjects.
The mean arterial blood pressure (MAP) changes in response to TCR and iBH method were comparable. The fMRI data demonstrated BOLD signal amplitude change in response to the induced fast MAP changes. The GM and WS areas showed similar rates of regulation, and these were nominally higher than WM RoR in both TCR and iBH methods. Further, the 4D PC MRI data suggested 29% CBF-increase in response to 33% iBH in four minutes acquisition time.
The acquired non invasive arterial BP measures concurrent with the BOLD signal amplitude response, allowed deriving the rate of regulation as a metric of dCA. It is not known whether this information is clinically relevant to gauge the haemodynamic risk association to cerebrovascular disease. However, BOLD signal change and CBF changes after iBH are confounded by the extent to which the CO2 gradually accumulate in response to iBH and causes an overshoot in the CBF response-change.
In conclusion, the presented study indicates the feasibility of using physiological MRI to measure dCA in response to non-invasively induced MAP changes. Estimation of the dCA metrics could be improved by using advanced data fitting methods as well as controlling for physiological parameters such as PECO2
Ocular rigidity : a previously unexplored risk factor in the pathophysiology of open-angle glaucoma : assessment using a novel OCT-based measurement method
Le glaucome est la première cause de cécité irréversible dans le monde. Bien que sa pathogenèse
demeure encore nébuleuse, les propriétés biomécaniques de l’oeil sembleraient jouer un rôle
important dans le développement et la progression de cette maladie. Il est stipulé que la rigidité
oculaire (RO) est altérée au travers les divers stades de la maladie et qu’elle serait le facteur le
plus influent sur la réponse du nerf optique aux variations de la pression intraoculaire (PIO) au
sein du glaucome. Pour permettre l’investigation du rĂ´le de la RO dans le glaucome primaire Ă
angle ouvert (GPAO), la capacité de quantifier la RO in vivo par l’entremise d’une méthode fiable
et non-invasive est essentielle. Une telle méthode n’est disponible que depuis 2015. Basée sur
l'équation de Friedenwald, cette approche combine l'imagerie par tomographie par cohérence
optique (TCO) et la segmentation choroïdienne automatisée afin de mesurer le changement de
volume choroïdien pulsatile (ΔV), ainsi que la tonométrie dynamique de contour Pascal pour
mesurer le changement de pression pulsatile correspondant.
L’objectif de cette thèse est d’évaluer la validité de cette méthode, et d’en faire usage afin
d’investiguer le rôle de la RO dans les maladies oculaires, particulièrement le GPAO. Plus
spécifiquement, cette thèse vise à : 1) améliorer la méthode proposée et évaluer sa validité ainsi
que sa répétabilité, 2) investiguer l’association entre la RO et le dommage neuro-rétinien chez les
patients glaucomateux, et ceux atteints d’un syndrome de vasospasticité, 3) évaluer l’association
entre la RO et les paramètres biomécaniques de la cornée, 4) évaluer l’association entre la RO et
les pics de PIO survenant suite aux thérapies par injections intravitréennes (IIV), afin de les prédire
et de les prévenir chez les patients à haut risque, et 5) confirmer que la RO est réduite dans les
yeux myopes.
D’abord, nous avons amélioré le modèle mathématique de l’oeil utilisé pour dériver ΔV en le
rendant plus précis anatomiquement et en tenant compte de la choroïde périphérique. Nous
avons démontré la validité et la bonne répétabilité de cette méthodologie. Puis, nous avons
effectué la mesure des coefficients de RO sur un large éventail de sujets sains et glaucomateux
en utilisant notre méthode non-invasive, et avons démontré, pour la première fois, qu'une RO basse est corrélée aux dommages glaucomateux. Les corrélations observées étaient comparables
Ă celles obtenues avec des facteurs de risque reconnus tels que la PIO maximale. Une forte
corrélation entre la RO et les dommages neuro-rétiniens a été observée chez les patients
vasospastiques, mais pas chez ceux atteints d'une maladie vasculaire ischémique. Cela pourrait
potentiellement indiquer une plus grande susceptibilité au glaucome due à la biomécanique
oculaire chez les patients vasospastiques. Bien que les paramètres biomécaniques cornéens aient
été largement adoptés dans la pratique clinique en tant que substitut pour la RO, propriété
biomécanique globale de l'oeil, nous avons démontré une association limitée entre la RO et ces
paramètres, offrant une nouvelle perspective sur la relation entre les propriétés biomécaniques
cornéennes et globales de l’oeil. Seule une faible corrélation entre le facteur de résistance
cornéenne et la RO demeure après ajustement pour les facteurs de confusion dans le groupe des
patients glaucomateux. Ensuite, nous avons présenté un modèle pour prédire l'amplitude des pics
de PIO après IIV à partir de la mesure non-invasive de la RO. Ceci est particulièrement utile pour
les patients à haut risque atteints de maladies rétiniennes exsudatives et de glaucome qui
nécessiteraient des IIV thérapeutiques, et pourrait permettre aux cliniciens d'ajuster ou de
personnaliser le traitement pour Ă©viter toute perte de vision additionnelle. Enfin, nous avons
étudié les différences de RO entre les yeux myopes et les non-myopes en utilisant cette
technique, et avons démontré une RO inférieure dans la myopie axiale, facteur de risque du
GPAO. Dans l'ensemble, ces résultats contribuent à l’avancement des connaissances sur la
physiopathologie du GPAO. Le développement de notre méthode permettra non seulement de
mieux explorer le rĂ´le de la RO dans les maladies oculaires, mais contribuera Ă©galement Ă Ă©lucider
les mécanismes et développer de nouveaux traitements ciblant la RO pour contrer la déficience
visuelle liée à ces maladies.Glaucoma is the leading cause of irreversible blindness worldwide. While its pathogenesis is yet
to be fully understood, the biomechanical properties of the eye are thought to be involved in the
development and progression of this disease. Ocular rigidity (OR) is thought to be altered through
disease processes and has been suggested to be the most influential factor on the optic nerve
head’s response to variations in intraocular pressure (IOP) in glaucoma. To further investigate the
role of OR in open-angle glaucoma (OAG) and other ocular diseases such as myopia, the ability to
quantify OR in living human eyes using a reliable and non-invasive method is essential. Such a
method has only become available in 2015. Based on the Friedenwald equation, the method uses
time-lapse optical coherence tomography (OCT) imaging and automated choroidal segmentation
to measure the pulsatile choroidal volume change (ΔV), and Pascal dynamic contour tonometry
to measure the corresponding pulsatile pressure change.
The purpose of this thesis work was to assess the validity of the methodology, then use it to
investigate the role of OR in ocular diseases, particularly in OAG. More specifically, the objectives
were: 1) To improve the extrapolation of ΔV and evaluate the method’s validity and repeatability,
2) To investigate the association between OR and neuro-retinal damage in glaucomatous
patients, as well as those with concomitant vasospasticity, 3) To evaluate the association between
OR and corneal biomechanical parameters, 4) To assess the association between OR and IOP
spikes following therapeutic intravitreal injections (IVIs), to predict and prevent them in high-risk
patients, and 5) To confirm that OR is lower in myopia.
First, we improved the mathematical model of the eye used to derive ΔV by rendering it more
anatomically accurate and accounting for the peripheral choroid. We also confirmed the validity
and good repeatability of the method. We carried out the measurement of OR coefficients on a
wide range of healthy and glaucomatous subjects using this non-invasive method, and were able
to show, for the first time, that lower OR is correlated with more glaucomatous damage. The
correlations observed were comparable to those obtained with recognized risk factors such as
maximum IOP. A strong correlation between OR and neuro-retinal damage was found in patients with concurrent vasospastic syndrome, but not in those with ischemic vascular disease. This could
perhaps indicate a greater susceptibility to glaucoma due to ocular biomechanics in vasospastic
patients. While corneal biomechanical parameters have been widely adopted in clinical practice
as surrogate measurements for the eye’s overall biomechanical properties represented by OR,
we have shown a limited association between these parameters, bringing new insight unto the
relationship between corneal and global biomechanical properties. Only a weak correlation
between the corneal resistance factor and OR remained in glaucomatous eyes after adjusting for
confounding factors. In addition, we presented a model to predict the magnitude of IOP spikes
following IVIs from the non-invasive measurement of OR. This is particularly useful for high-risk
patients with exudative retinal diseases and glaucoma that require therapeutic IVIs, and could
provide the clinician an opportunity to adjust or customize treatment to prevent further vision
loss. Finally, we investigated OR differences between non-myopic and myopic eyes using this
technique, and demonstrated lower OR in axial myopia, a risk factor for OAG. Overall, these
findings provide new insights unto the pathophysiology of glaucomatous optic neuropathy. The
development of our method will permit further investigation of the role of OR in ocular diseases,
contributing to elucidate mechanisms and provide novel management options to counter vision
impairment caused by these diseases
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