Theory of operation
If you’re bored enough or misguided enough to be reading this section, you are my intended audience!
What is rapidtide trying to do?
Rapidtide attempts to separate an fMRI or NIRS dataset into two components - a single timecourse that appears throughout the dataset with varying time delays and intensities in each voxel, and everything else. We and others have observed that a large proportion of the “global mean signal”, commonly referred to as “physiological noise” seen throughout in vivo datasets that quantify time dependant fluctuations in hemodynamic measures can be well modelled by a single timecourse with a range of time shifts. This has been seen in fMRI and NIRS data recorded througout the brain and body, with time lags generally increasing at locations farther from the heart along the vasculature. This appears to be a signal carried by the blood, as changes in blood oxygenation and/or volume that propagate with bulk blood flow. The source of the signal is not known, being variously attributed to cardiac and respiratory changes over time, changes in blood CO2, gastric motility, and other sources (for a survey, see [Tong2019].) As biology is complicated, it’s probably some mixture of these sources and others that we may not have considered. No matter what the source of the signal, this model can be exploited for a number of purposes.
If you’re interested in hemodynamics, using rapidtide to get the time delay in every voxel gives you a lot of information that’s otherwise hard or impossible to obtain noninvasively, namely the arrival time of blood in each voxel, and the fraction of the variance in that voxel that’s accounted for by that moving signal, which is related to regional CBV (however there’s also a factor that’s due to blood oxygenation, so you have to interpret it carefully). You can use this information to understand the blood flow changes arising from vascular pathology, such as stroke or moyamoya disease, or to potentially see changes in blood flow due to a pharmacological intervention. In this case, the moving signal is not noise - it’s the signal of interest. So the various maps rapidtide produces can be used to describe hemodynamics.
However, if you are interested in local rather than global hemodynamics, due to, say, neuronal activation, then this moving signal is rather pernicious in-band noise. Global mean regression is often used to remove it, but this is not optimal - in fact it can generate spurious anticorrelations, which are not helpful. Rapidtide will regress out the moving signal, appropriately delayed in each voxel. This gives you better noise removal, and also avoids generating spurious correlations. For a detailed consideration of this, look here [Erdogan2016].
What is the difference between RIPTiDE and rapidtide?
RIPTiDe (Regressor Interpolation at Progressive Time Delays) is the name of the technique used for finding and removing time lagged physiological signals in fMRI data. In the original RIPTiDe papers, we generated a set of regressors over a range of different time shifts (starting from a regressor recorded outside of the brain), and then ran a GLM in FSL using the entire set of regressors. We realized that this 1) doesn’t give you the optimal delay value directly, which turns out to be a useful thing to know, and 2) burns degrees of freedom unnecessarily, since having one optimally delayed regressor in each voxel gets you pretty much the same degree of noise removal (this is assuming that in each voxel there is one and only one pool of delayed blood, which while not true, is true enough, since almost every voxel is dominated by a single pool of delayed blood), 3) is slow, since you’re doing way more calculation than you need to, and 4) doesn’t necessarily get you the best noise removal, since the systemic noise signal recorded outside the brain has its own characteristics and noise mechanisms that may make it diverge somewhat from what is actually getting into the brain (although on the plus side, it is inarguably non-neuronal, so you don’t have to have any arguments about slow neuronal waves).
In contrast rapidtide (lets say it means Rapid Time Delay) is the newer faster, self-contained python program that implements an updated version of the RIPTiDe algorithm) estimates delay in every voxel and recursively refines an estimate of the “true” systemic noise signal propagating through the brain by shifting and merging the voxel timecourses to undo this effect. This refinement procedure is shown in Figure 5 of Tong, 2019 (reference 6 in the Physiology section below). In recent years, I’ve personally become more interested in estimating blood flow in the brain than denoising resting state data, so a lot of the documentation talks about that, but the two procedures are tightly coupled, and as the final step, rapidtide does regress the optimally delayed refined estimate of the systemic noise signal out of the data. We have found that it works quite well for resting state noise removal while avoiding the major problems of global signal regression (which we refer to as “static global signal regression” as opposed to “dynamic global signal regression”, which is what rapidtide does). For a detailed exploration of this topic, see Erdogan, 2016 (also in the Physiology section below).
How does rapidtide work?
In order to perform this task, rapidtide does a number of things:
Obtain some initial estimate of the moving signal.
Preprocess this signal to emphasize the bloodborne component.
Analyze the signal to find and correct, if possible, non-ideal properties that may confound the estimation of time delays.
Preprocess the incoming dataset to determine which voxels are suitable for analysis, and to emphasize the bloodborne component.
Determine the time delay in each voxel by finding the time when the voxel timecourse has the maximum similarity to the moving signal.
Optionally use this time delay information to generate a better estimate of the moving signal.
Repeat steps 3-7 as needed.
Parametrize the similarity between the moving signal and each voxels’ timecourse, and save these metrics.
Optionally regress the voxelwise time delayed moving signal out of the original dataset.
Each of these steps has nuances which will be discussed below.
Tong, Y., Hocke, L.M., and Frederick, B.B., Low Frequency Systemic Hemodynamic “Noise” in Resting State BOLD fMRI: Characteristics, Causes, Implications, Mitigation Strategies, and Applications. Front Neurosci, 2019. 13: p. 787. | http://dx.doi.org/10.3389/fnins.2019.00787
Erdoğan S, Tong Y, Hocke L, Lindsey K, Frederick B. Correcting resting state fMRI-BOLD signals for blood arrival time enhances functional connectivity analysis. Front. Hum. Neurosci., 28 June 2016 | http://dx.doi.org/10.3389/fnhum.2016.00311