Physiological noise modeling in fMRI based on the pulsatile component of photoplethysmograph.

The blood oxygenation level-dependent (BOLD) contrast mechanism allows the noninvasive monitoring of changes in deoxyhemoglobin content. As such, it is commonly used in functional magnetic resonance imaging (fMRI) to study brain activity since levels of deoxyhemoglobin are indirectly related to local neuronal activity through neurovascular coupling mechanisms. However, the BOLD signal is severely affected by physiological processes as well as motion. Due to this, several noise correction techniques have been developed to correct for the associated confounds. The present study focuses on cardiac pulsatility fMRI confounds, aiming to refine model-based techniques that utilize the photoplethysmograph (PPG) signal. Specifically, we propose a new technique based on convolution filtering, termed cardiac pulsatility model (CPM) and compare its performance with the cardiac-related RETROICOR (Card-RETROICOR), which is a technique commonly used to model fMRI fluctuations due to cardiac pulsatility. Further, we investigate whether variations in the amplitude of the PPG pulses (PPG-Amp) covary with variations in amplitude of pulse-related fMRI fluctuations, as well as with the systemic low frequency oscillations (SLFOs) component of the fMRI global signal (GS - defined as the mean signal across all gray matter voxels). Capitalizing on 3T fMRI data from the Human Connectome Project, CPM was found to explain a significantly larger fraction of the fMRI signal variance compared to Card-RETROICOR, particularly for subjects with larger heart rate variability during the scan. The amplitude of the fMRI pulse-related fluctuations did not covary with PPG-Amp; however, PPG-Amp explained significant variance in the GS that was not attributed to variations in heart rate or breathing patterns. Our results suggest that the proposed approach can model high-frequency fluctuations due to pulsation as well as low-frequency physiological fluctuations more accurately compared to model-based techniques commonly employed in fMRI studies.

Evaluation of different cerebrospinal fluid and white matter fMRI filtering strategies-Quantifying noise removal and neural signal preservation.

This study examines the impact of using different cerebrospinal fluid (CSF) and white matter (WM) nuisance signals for data-driven filtering of functional magnetic resonance imaging (fMRI) data as a cleanup method before analyzing intrinsic brain fluctuations. The routinely used temporal signal-to-noise ratio metric is inappropriate for assessing fMRI filtering suitability, as it evaluates only the reduction of data variability and does not assess the preservation of signals of interest. We defined a new metric that evaluates the preservation of selected neural signal correlates, and we compared its performance with a recently published signal-noise separation metric. These two methods provided converging evidence of the unfavorable impact of commonly used filtering approaches that exploit higher numbers of principal components from CSF and WM compartments (typically 5 + 5 for CSF and WM, respectively). When using only the principal components as nuisance signals, using a lower number of signals results in a better performance (i.e., 1 + 1 performed best). However, there was evidence that this routinely used approach consisting of 1 + 1 principal components may not be optimal for filtering resting-state (RS) fMRI data, especially when RETROICOR filtering is applied during the data preprocessing. The evaluation of task data indicated the appropriateness of 1 + 1 principal components, but when RETROICOR was applied, there was a change in the optimal filtering strategy. The suggested change for extracting WM (and also CSF in RETROICOR-corrected RS data) is using local signals instead of extracting signals from a large mask using principal component analysis.

Physiology recording with magnetic field probes for fMRI denoising.

Physiological noise originating in cardiovascular and respiratory processes is a substantial confound in BOLD fMRI. When unaccounted for it reduces the temporal SNR and causes error in inferred brain activity and connectivity. Physiology correction typically relies on auxiliary measurements with peripheral devices such as ECG, pulse oximeters, and breathing belts. These require direct skin contact or at least a tight fit, impairing subject comfort and adding to the setup time. In this work, we explore a touch-free alternative for physiology recording, using magnetic detection with NMR field probes. Placed close to the chest such probes offer high sensitivity to cardiovascular and respiratory dynamics without mechanical contact. This is demonstrated by physiology regression in a typical fMRI scenario at 7T, including validation against standard devices. The study confirms essentially equivalent performance of noise models based on conventional recordings and on field probes. It is shown that the field probes may be positioned in the subject's back such that they could be readily integrated in the patient table.

Mapping dependencies of BOLD signal change to end-tidal CO2: Linear and nonlinear modeling, and effect of physiological noise correction.

BACKGROUND: Disentangling physiological noise and signal of interest is a major issue when evaluating BOLD-signal changes in response to breath holding. Currently-adopted approaches for retrospective noise correction are general-purpose, and have non-negligible effects in studies on hypercapnic challenges. NEW METHOD: We provide a novel approach to the analysis of specific and non-specific BOLD-signal changes related to end-tidal CO2 (PETCO2) in breath-hold fMRI studies. Multiple-order nonlinear predictors for PETCO2 model a region-dependent nonlinear input-output relationship hypothesized in literature and possibly playing a crucial role in disentangling noise. We explore Retrospective Image-based Correction (RETROICOR) effects on the estimated BOLD response, applying our analysis both with and without RETROICOR and analyzing the linear and non-linear correlation between PETCO2 and RETROICOR regressors. RESULTS: The RETROICOR model of noise related to respiratory activity correlated with PETCO2 both linearly and non-linearly. The correction affected the shape of the estimated BOLD response to hypercapnia but allowed to discard spurious activity in ventricles and white matter. Activation clusters were best detected using non-linear components in the BOLD response model. COMPARISON WITH EXISTING METHOD: We evaluated the side-effects of standard physiological noise correction procedure, tailoring our analysis on challenging understudied brainstem and subcortical regions. Our novel approach allowed to characterize delays and non-linearities in BOLD response. CONCLUSIONS: RETROICOR successfully avoided false positives, still broadly affecting the estimated non-linear BOLD responses. Non-linearities in the model better explained CO2-related BOLD signal fluctuations. The necessity to modify the standard procedure for physiological-noise correction in breath-hold studies was addressed, stating its crucial importance.

The PhysIO Toolbox for Modeling Physiological Noise in fMRI Data.

BACKGROUND: Physiological noise is one of the major confounds for fMRI. A common class of correction methods model noise from peripheral measures, such as ECGs or pneumatic belts. However, physiological noise correction has not emerged as a standard preprocessing step for fMRI data yet due to: (1) the varying data quality of physiological recordings, (2) non-standardized peripheral data formats and (3) the lack of full automatization of processing and modeling physiology, required for large-cohort studies. NEW METHODS: We introduce the PhysIO Toolbox for preprocessing of physiological recordings and model-based noise correction. It implements a variety of noise models, such as RETROICOR, respiratory volume per time and heart rate variability responses (RVT/HRV). The toolbox covers all intermediate steps - from flexible read-in of data formats to GLM regressor/contrast creation - without any manual intervention. RESULTS: We demonstrate the workflow of the toolbox and its functionality for datasets from different vendors, recording devices, field strengths and subject populations. Automatization of physiological noise correction and performance evaluation are reported in a group study (N=35). COMPARISON WITH EXISTING METHODS: The PhysIO Toolbox reproduces physiological noise patterns and correction efficacy of previously implemented noise models. It increases modeling robustness by outperforming vendor-provided peak detection methods for physiological cycles. Finally, the toolbox offers an integrated framework with full automatization, including performance monitoring, and flexibility with respect to the input data. CONCLUSIONS: Through its platform-independent Matlab implementation, open-source distribution, and modular structure, the PhysIO Toolbox renders physiological noise correction an accessible preprocessing step for fMRI data.

Sensitivity of PPI analysis to differences in noise reduction strategies.

BACKGROUND: In some fields of fMRI data analysis, using correct methods for dealing with noise is crucial for achieving meaningful results. This paper provides a quantitative assessment of the effects of different preprocessing and noise filtering strategies on psychophysiological interactions (PPI) methods for analyzing fMRI data where noise management has not yet been established. METHODS: Both real and simulated fMRI data were used to assess these effects. Four regions of interest (ROIs) were chosen for the PPI analysis on the basis of their engagement during two tasks. PPI analysis was performed for 32 different preprocessing and analysis settings, which included data filtering with RETROICOR or no such filtering; different filtering of the ROI "seed" signal with a nuisance data-driven time series; and the involvement of these data-driven time series in the subsequent PPI GLM analysis. The extent of the statistically significant results was quantified at the group level using simple descriptive statistics. Simulated data were generated to assess statistical improvement of different filtering strategies. RESULTS: We observed that different approaches for dealing with noise in PPI analysis yield differing results in real data. In simulated data, we found RETROICOR, seed signal filtering and the addition of data-driven covariates to the PPI design matrix significantly improves results. CONCLUSIONS: We recommend the use of RETROICOR, and data-driven filtering of the whole data, or alternatively, seed signal filtering with data-driven signals and the addition of data-driven covariates to the PPI design matrix.

GLMdenoise: a fast, automated technique for denoising task-based fMRI data.

In task-based functional magnetic resonance imaging (fMRI), researchers seek to measure fMRI signals related to a given task or condition. In many circumstances, measuring this signal of interest is limited by noise. In this study, we present GLMdenoise, a technique that improves signal-to-noise ratio (SNR) by entering noise regressors into a general linear model (GLM) analysis of fMRI data. The noise regressors are derived by conducting an initial model fit to determine voxels unrelated to the experimental paradigm, performing principal components analysis (PCA) on the time-series of these voxels, and using cross-validation to select the optimal number of principal components to use as noise regressors. Due to the use of data resampling, GLMdenoise requires and is best suited for datasets involving multiple runs (where conditions repeat across runs). We show that GLMdenoise consistently improves cross-validation accuracy of GLM estimates on a variety of event-related experimental datasets and is accompanied by substantial gains in SNR. To promote practical application of methods, we provide MATLAB code implementing GLMdenoise. Furthermore, to help compare GLMdenoise to other denoising methods, we present the Denoise Benchmark (DNB), a public database and architecture for evaluating denoising methods. The DNB consists of the datasets described in this paper, a code framework that enables automatic evaluation of a denoising method, and implementations of several denoising methods, including GLMdenoise, the use of motion parameters as noise regressors, ICA-based denoising, and RETROICOR/RVHRCOR. Using the DNB, we find that GLMdenoise performs best out of all of the denoising methods we tested.