Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility

Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD fMRI CVR measurements based on a BH task with preparatory inspiration, yielding robust estimates of this important physiological parameter. (C) 2016 Elsevier Inc. All rights reserved.

Fourier Analysis of Functional Time Series, with Applications to DNA Dynamics

Shahin Tavakoli

This work is about time series of functional data (functional time series), and consists of three main parts. In the first part (Chapter 2), we develop a doubly spectral decomposition for functional time series that generalizes the Karhunen–Loève expansion. In the second part (Chapter 3), we develop the theory of estimation for the spectral density operators, which are the main tool involved in the doubly spectral decomposition. The third part (Chapter 4) is concerned with the problem of understanding and comparing the dynamics of DNA. It proposes a methodology for comparing the dynamics of DNA minicircles that are vibrating in solution, using tools developed in this thesis. In the first part, we develop a doubly spectral representation of a stationary functional time series that generalizes the Karhunen–Loève expansion to the functional time series setting. The representation decomposes the time series into an integral of uncorrelated frequency components (Cramér representation), each of which is in turn expanded in a Karhunen-Loève series, thus yielding a Cramér–Karhunen–Loève decomposition of the series. The construction is based on the spectral density operators—whose Fourier coefficients are the lag-t autocovariance operators—which characterise the second-order dynamics of the process. The spectral density operators are the functional analogues of the spectral density matrices, whose eigenvalues and eigenfunctions at different frequencies provide the building blocks of the representation. By truncating the representation at a finite level, we obtain a harmonic principal component analysis of the time series, an optimal finite dimensional reduction of the time series that captures both the temporal dynamics of the process, and the within-curve dynamics, and dominates functional PCA. The proofs rely on the construction of a stochastic integral of operator-valued functions, whose construction is similar to that of the Itô integral. In practice, the spectral density operators are unknown. In the second part, we therefore develop the basic theory of a frequency domain framework for drawing statistical inferences on the spectral density operators of a stationary functional time series. Our main tool is the functional Discrete Fourier Transform(fDFT).We derive an asymptotic Gaussian representation of the fDFT, thus allowing the transformation of the original collection of dependent random functions into a collection of approximately independent complex-valued Gaussian random functions. Our results are then employed in order to construct estimators of the spectral density operators based on smoothed versions of the periodogram kernel, the functional generalisation of the periodogram matrix. The consistency and asymptotic law of these estimators are studied in detail. As immediate consequences, we obtain central limit theorems for the mean and the long-run covariance operator of a stationary functional time series. Our results do not depend on structural modeling assumptions, but only functional versions of classical cumulant mixing conditions. The effect of discrete noisy observations on the consistency of the estimators is studied in a framework general enough to apply to a wide range of smoothing techniques for converting discrete noisy observations into functional data. We also perform a simulation study to assess the finite sample performance of our estimators, and give a discussion of the technical assumptions of our results, and at what cost our weak dependence assumptions could be changed or weakened, and provide examples of processes satisfying the technical assumptions of our asymptotic results. As an application, we consider in the third part the problem of comparing the dynamics of the trajectories of two DNA minicircles that are vibrating in solution, which are obtained via Molecular Dynamics simulations. The approach we take is to view and compare the dynamics through their spectral density operators, which contain the entire second-order structure of the trajectories. As a first step, we compare the spectral density operators of the two DNA minicircles using a new test we develop, which allows us to compare the spectral density operators at a fixed frequencies. Using multiple testing procedures, we are able to localize in frequencies the differences in spectral density operators of the two DNA minicircles, while controlling a type-I error, and conduct numerical simulations to assess the performance of our method. We further investigate the differences between the two minicircles by comparing their spectral density operators within frequencies. This allows us to localize their differences both in frequencies and on the minicircles, while controlling the averaged false discovery rate over the selected frequencies. Our methodology is general enough to be applied to the comparison of the dynamics of any pair of stationary functional time series.

EPFL2014

Signal Processing in Space and Time

Francisco Pereira Correia Pinto

Sound waves propagate through space and time by transference of energy between the particles in the medium, which vibrate according to the oscillation patterns of the waves. These vibrations can be captured by a microphone and translated into a digital signal, representing the amplitude of the sound pressure as a function of time. The signal obtained by the microphone characterizes the time-domain behavior of the acoustic wave field, but has no information related to the spatial domain. The spatial information can be obtained by measuring the vibrations with an array of microphones distributed at multiple locations in space. This allows the amplitude of the sound pressure to be represented not only as a function of time but also as a function of space. The use of microphone arrays creates a new class of signals that is somewhat unfamiliar to Fourier analysis. Current paradigms try to circumvent the problem by treating the microphone signals as multiple "cooperating" signals, and applying the Fourier analysis to each signal individually. Conceptually, however, this is not faithful to the mathematics of the wave equation, which expresses the acoustic wave field as a single function of space and time, and not as multiple functions of time. The goal of this thesis is to provide a formulation of Fourier theory that treats the wave field as a single function of space and time, and allows it to be processed as a multidimensional signal using the theory of digital signal processing (DSP). We base this on a physical principle known as the Huygens principle, which essentially says that the wave field can be sampled at the surface of a given region in space and subsequently reconstructed in the same region, using only the samples obtained at the surface. To translate this into DSP language, we show that the Huygens principle can be expressed as a linear system that is both space- and time-invariant, and can be formulated as a convolution operation. If the input signal is transformed into the spatio-temporal Fourier domain, the system can also be analyzed according to its frequency response. In the first half of the thesis, we derive theoretical results that express the 4-D Fourier transform of the wave field as a function of the parameters of the scene, such as the number of sources and their locations, the source signals, and the geometry of the microphone array. We also show that the wave field can be effectively analyzed on a small scale using what we call the space/time-frequency representation space, consisting of a Gabor representation across the spatio-temporal manifold defined by the microphone array. These results are obtained by treating the signals as continuous functions of space and time. The second half of the thesis is dedicated to processing the wave field in discrete space and time, using Nyquist sampling theory and multidimensional filter banks theory. In particular, we show examples of orthogonal filter banks that effectively represent the wave field in terms of its elementary components while satisfying the requirements of critical sampling and perfect reconstruction of the input. We discuss the architecture of such filter banks, and demonstrate their applicability in the context of real applications, such as spatial filtering and wave field coding.

EPFL2010

Signal Processing in Space and Time

Francisco Pereira Correia Pinto

EPFL2010

Fourier Analysis of Functional Time Series, with Applications to DNA Dynamics

Shahin Tavakoli

EPFL2014