Electroencephalography and functional magnetic resonance are two different methods for measuring of neural activity. EEG signals have excellent time resolution, fMRI scans capture records of brain activity in excellent spatial resolution. It is assumed that the joint analysis can take advantage of both methods simultaneously. Statistical Parametric Mapping (SPM8) is freely available software which serves to automatic analysis of fMRI data estimated with general linear model. It is not possible to estimate automatic EEG–fMRI analysis with it. Therefore software EEG Regressor Builder was created during master thesis. It preprocesses EEG signals into EEG regressors which are loaded with program SPM8 where joint EEG–fMRI analysis is estimated in general linear model. EEG regressors consist of vectors of temporal changes in absolute or relative power values of EEG signal in the specified frequency bands from selected electrodes due to periods of fMRI acquisition of individual images. The software is tested on the simultaneous EEG-fMRI data of a visual oddball experiment. EEG regressors are calculated for temporal changes in absolute and relative EEG power values in three frequency bands of interest ( 8-12Hz, 12-20Hz a 20-30Hz) from the occipital electrodes (O1, O2 and Oz). Three types of test analyzes is performed. Data from three individuals is examined in the first. Accuracy of results is evaluated due to the possibilities of setting of calculation method of regressor. Group analysis of data from twenty-two healthy patients is performed in the second. Group EEG regressors analysis is realized in the third through the correlation matrix due to the specified type of power and frequency band outside of the general linear model.

The master thesis deals with the joint EEG-fMRI analysis based on a heuristic model that describes the relationship between changes in blood flow in active brain areas and in the electrical activity of neurons. This work also discusses various methods of extracting of useful information from the EEG and their influence on the final result of joined analysis. There were tested averaging methods of electrodes interest, decomposition by principal components analysis and decomposition by independent component analysis. Methods of averaging and decomposition by PCA give similar results, but information about a stimulus vector can not be extracted. Using ICA decomposition, we are able to obtain information relating to the certain stimulation, but there is the problem in the final interpretation and selection of the right components in a blind search for variability coupled with the experiment. It was found out that although components calculated from the time sequence EEG are independent for each to other, their spectrum shifts are correlated. This spectral dependence was eliminated by PCA / ICA decomposition from vectors of spectrum shifts. For this method, each component brings new information about brain activity. The results of the heuristic approach were compared with the results of the joined analysis based on the relative and absolute power approach from frequency bands of interest. And the similarity between activation maps was founded, especially for the heuristic model and the relative power from the gamma band (20-40Hz).

Zobrazení funkční magnetickou rezonancí (fMRI) využívající "blood-oxygen-level-dependent" efekt jako indikátor lokální aktivity je velmi užitečnou technikou k identifikaci oblastí mozku, které jsou aktivní během percepce, kognice, akce, ale také během klidového stavu. V poslední době také roste zájem o studium konektivity mezi těmito oblastmi, zejména v klidovém stavu. Tato práce předkládá nový a originální přístup k problému nepřímého vztahu mezi měřenou hemodynamickou odezvou a její příčinou, tj. neuronálním signálem. Zmíněný nepřímý vztah komplikuje odhad efektivní konektivity (kauzálního ovlivnění) mezi různými oblastmi mozku z dat fMRI. Novost prezentovaného přístupu spočívá v použití (zobecněné nelineární) techniky slepé dekonvoluce, což dovoluje odhad endogenních neuronálních signálů (tj. vstupů systému) z naměřených hemodynamických odezev (tj. výstupů systému). To znamená, že metoda umožňuje "data-driven" hodnocení efektivní konektivity na neuronální úrovni i v případě, že jsou měřeny pouze zašumělé hemodynamické odezvy. Řešení tohoto obtížného dekonvolučního (inverzního) problému je dosaženo za použití techniky nelineárního rekurzivního Bayesovského odhadu, který poskytuje společný odhad neznámých stavů a parametrů modelu. Práce je rozdělena do tří hlavních částí. První část navrhuje metodu k řešení výše uvedeného problému. Metoda využívá odmocninové formy nelineárního kubaturního Kalmanova filtru a kubaturního Rauch-Tung-Striebelova vyhlazovače, ovšem rozšířených pro účely řešení tzv. problému společného odhadu, který je definován jako simultánní odhad stavů a parametrů sekvenčním přístupem. Metoda je navržena především pro spojitě-diskrétní systémy a dosahuje přesného a stabilního řešení diskretizace modelu kombinací nelineárního (kubaturního) filtru s metodou lokální linearizace. Tato inverzní metoda je navíc doplněna adaptivním odhadem statistiky šumu měření a šumů procesu (tj. šumů neznámých stavů a parametrů). První část práce je zaměřena na inverzi modelu pouze jednoho časového průběhu; tj. na odhad neuronální aktivity z fMRI signálu. Druhá část generalizuje navrhovaný přístup a aplikuje jej na více časových průběhů za účelem umožnění odhadu parametrů propojení neuronálního modelu interakce; tj. odhadu efektivní konektivity. Tato metoda představuje inovační stochastické pojetí dynamického kauzálního modelování, což ji činí odlišnou od dříve představených přístupů. Druhá část se rovněž zabývá metodami Bayesovského výběru modelu a navrhuje techniku pro detekci irelevantních parametrů propojení za účelem dosažení zlepšeného odhadu parametrů. Konečně třetí část se věnuje ověření navrhovaného přístupu s využitím jak simulovaných tak empirických fMRI dat, a je významných důkazem o velmi uspokojivých výsledcích navrhovaného přístupu.

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Introduction : L’évaluation hémodynamique des patients critiques est difficile et l'estimation du débit cardiaque par le clinicien est peu fiable. La chaleur des extrémités est utilisée pour évaluer la perfusion périphérique mais reste très subjective. Un gradient thermique élevé entre la température centrale et la température périphérique a été corrélé à une augmentation des résistances vasculaires systémiques et une diminution du débit cardiaque. L'objectif de cette étude est d'évaluer la relation entre le gradient thermique, obtenu par thermographie infra-rouge (TIR), et le ratio d'extraction d'oxygène (O2ER) chez les enfants de 0 à 18 ans ayant eu une chirurgie cardiaque avec circulation extracorporelle. Méthode : Étude observationnelle prospective portant sur les enfants en post opératoire de chirurgie cardiaque avec une circulation extracorporelle. Le gradient thermique entre la température centrale (cantus interne de l’oeil) et périphérique (hallux) obtenue par TIR a été comparé à l’O2ER concomitant dans les 24 premières heures post opératoires. Résultats : 41 patients ont été inclus. Une corrélation faible a été retrouvée entre le gradient thermique et l’O2ER (r = 0.25 p = 0.016). Cette corrélation augmentait pour des niveaux d’O2ER plus élevés. La spectroscopie par proche infra-rouge (NIRS) cérébrale avait aussi une corrélation significative avec le gradient thermique (r = -28 p=0.001). Seul l’âge influençait significativement le gradient thermique. Les agents vasopresseurs et vasodilatateurs n’exerçaient aucune influence. Conclusion : Une corrélation significative mais faible a été retrouvée entre le gradient thermique par thermographie infrarouge et l’O2ER après une chirurgie cardiaque pédiatrique. Une caméra thermique plus sensible et l’acquisition de mesures plus précises du gradient thermique à partir d’un plus grand effectif pourraient améliorer nos résultats. / Introduction: Hemodynamic assessment of critical patients is challenging, and clinician estimation of cardiac output is unreliable. Extremity heat is used to assess peripheral perfusion but remains highly subjective. A high thermal gradient between core and the peripheral temperature has been correlated with increased systemic vascular resistance and decreased cardiac output. The objective of this study was to evaluate the relationship between the thermal gradient obtained by infrared thermography (IRT) and the oxygen extraction ratio (O2ER) in children aged 0 to 18 years, after cardiac surgery with cardiopulmonary bypass. Method: Prospective observational study of children undergoing postoperative cardiac surgery with cardio-pulmonary bypass. The thermal gradient between the central (inner eye cantus) and peripheral (hallux) temperatures obtained by IRT was compared with concomitant O2ER in the first 24 hours postoperatively. Results: 41 patients were included. A weak correlation was found between the thermal gradient and O2ER (r = 0.25 p = 0.016). This correlation increased for higher O2ER levels. Cerebral near infrared spectroscopy (NIRS) also correlated significantly with thermal gradient (r = -28 p=0.001). Only age significantly influenced the thermal gradient. Vasopressor and vasodilator agents had no influence. Conclusion: A significant but weak correlation was observed between thermal gradient by IRT and O2ER after pediatric cardiac surgery. A more sensitive thermal camera and acquiring of more accurate thermal gradient measurements from a larger population could improve our results.

Background: Diabetic kidney disease is the leading cause of end-stage renal disease. Administration of ACE inhibitors or/and SGLT2 inhibitors show renoprotective effects in diabetic and other kidney diseases. The underlying renoprotective mechanisms of SGLT2 inhibition, especially in combination with ACE inhibition, are incompletely understood. We used longitudinal intravital microscopy to directly elucidate glomerular hemodynamics on a single nephron level in response to the ACE inhibitor enalapril or/and the SGLT2 inhibitor empagliflozin. Methods: Five weeks after the induction of diabetes by streptozotocin, male C57BL/6 mice were treated with enalapril, empagliflozin, enalapril/empagliflozin or placebo for 3 days. To identify hemodynamic regulation mechanisms, longitudinal intravital multiphoton microscopy was employed to measure single nephron glomerular filtration rate (snGFR) and afferent/efferent arteriole width. Results: Diabetic mice presented a significant hyperfiltration. Compared to placebo treatment, snGFR was reduced in response to enalapril, empagliflozin, or enalapril/empagliflozin administration under diabetic conditions. While enalapril treatment caused significant dilation of the efferent arteriole (12.55 ± 1.46 µm vs. control 11.92 ± 1.04 µm, p < 0.05), empagliflozin led to a decreased afferent arteriole diameter (11.19 ± 2.55 µm vs. control 12.35 ± 1.32 µm, p < 0.05) in diabetic mice. Unexpectedly under diabetic conditions, the combined treatment with enalapril/empagliflozin had no effects on both afferent and efferent arteriole diameter change. Conclusion: SGLT2 inhibition, besides ACE inhibition, is an essential hemodynamic regulator of glomerular filtration during diabetes mellitus. Nevertheless, additional mechanisms—independent from hemodynamic regulation—are involved in the nephroprotective effects especially of the combination therapy and should be further explored in future studies.

While task-based functional magnetic resonance imaging (fMRI) has helped us understand the functional role of many regions in the human brain, many diseases and complex behaviors defy explanation. Alternatively, if no task is performed, the fMRI signal between distant, anatomically connected, brain regions is similar over time. These correlations in “resting state” fMRI have been strongly linked to behavior and disease. Previous work primarily calculated correlation in entire fMRI runs of six minutes or more, making understanding the neural underpinnings of these fluctuations difficult. Recently, coordinated dynamic activity on shorter time scales has been observed in resting state fMRI: correlation calculated in comparatively short sliding windows and quasi-periodic (periodic but not constantly active) spatiotemporal patterns. However, little relevance to behavior or underlying neural activity has been demonstrated. This dissertation addresses this problem, first by using 12.3 second windows to demonstrate a behavior-fMRI relationship previously only observed in entire fMRI runs. Second, simultaneous recording of fMRI and electrical signals from the brains of anesthetized rats is used to demonstrate that both types of dynamic activity have strong correlates in electrophysiology. Very slow neural signals correspond to the quasi-periodic patterns, supporting the idea that low-frequency activity organizes large scale information transfer in the brain. This work both validates the use of dynamic analysis of resting state fMRI, and provides a starting point for the investigation of the systemic basis of many neuropsychiatric diseases.

Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.