Hemodynamics
Research Papers
Wall shear stress and pressure patterns in aortic stenosis patients with and without aortic dilation captured by high-performance image-based computational fluid dynamics
Spatial patterns of elevated wall shear stress and pressure due to blood flow past aortic stenosis (AS) are studied using GPU-accelerated patient-specific computational fluid dynamics. Three cases of moderate to severe AS, one with a dilated ascending aorta and two within the normal range (root diameter less than 4cm) are simulated for physiological waveforms obtained from echocardiography. The computational framework is built based on sharp-interface Immersed Boundary Method, where aortic geometries segmented from CT angiograms are integrated into a high-order incompressible Navier-Stokes solver. The key question addressed here is, given the presence of turbulence due to AS which increases wall shear stress (WSS) levels, why some AS patients undergo much less aortic dilation. Recent case studies of AS have linked the existence of an elevated WSS hotspot (due to impingement of AS on the aortic wall) to the dilation process. Herein we further investigate the WSS distribution for cases with and without dilation to understand the possible hemodynamics which may impact the dilation process. We show that the spatial distribution of elevated WSS is significantly more focused for the case with dilation than those without dilation. We further show that this focal area accommodates a persistent pocket of high pressure, which may have contributed to the dilation process through an increased wall-normal forcing. The cases without dilation, on the contrary, showed a rather oscillatory pressure behaviour, with no persistent pressure "buildup" effect. We further argue that a more proximal branching of the aortic arch could explain the lack of a focal area of elevated WSS and pressure, because it interferes with the impingement process due to fluid suction effects. These phenomena are further illustrated using an idealized aortic geometry. We finally show that a restored inflow eliminates the focal area of elevated WSS and pressure zone from the ascending aorta.
View Full Paper →BOLD hemodynamic response function changes significantly with healthy aging
Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18-30 years of age) and 173 older participants (54-74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB's Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.
View Full Paper →Dominance of layer-specific microvessel dilation in contrast-enhanced high-resolution fMRI: Comparison between hemodynamic spread and vascular architecture with CLARITY
Contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI response peaks are specific to the layer of evoked synaptic activity (Poplawsky et al., 2015), but the spatial resolution limit of CBVw fMRI is unknown. In this study, we measured the laminar spread of the CBVw fMRI evoked response in the external plexiform layer (EPL, 265 ± 65 μm anatomical thickness, mean ± SD, n = 30 locations from 5 rats) of the rat olfactory bulb during electrical stimulation of the lateral olfactory tract and examined its potential vascular source. First, we obtained the evoked CBVw fMRI responses with a 55 × 55 μm2 in-plane resolution and a 500-μm thickness at 9.4 T, and found that the fMRI signal peaked predominantly in the inner half of EPL (136 ± 54 μm anatomical thickness). The mean full-width at half-maximum of these fMRI peaks was 347 ± 102 μm and the functional spread was approximately 100 or 200 μm when the effects of the laminar thicknesses of EPL or inner EPL were removed, respectively. Second, we visualized the vascular architecture of EPL from a different rat using a Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel (CLARITY)-based tissue preparation method and confocal microscopy. Microvascular segments with an outer diameter of <11 μm accounted for 64.3% of the total vascular volume within EPL and had a mean segment length of 55 ± 40 μm (n = 472). Additionally, vessels that crossed the EPL border had a mean segment length outside of EPL equal to 73 ± 61 μm (n = 28), which is comparable to half of the functional spread (50-100 μm). Therefore, we conclude that dilation of these microvessels, including capillaries, likely dominate the CBVw fMRI response and that the biological limit of the fMRI spatial resolution is approximately the average length of 1-2 microvessel segments, which may be sufficient for examining sublaminar circuits.
View Full Paper →Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review
Advances in imaging technologies have allowed for the analysis of functional magnetic resonance imaging data in real-time (rtfMRI), leading to the development of neurofeedback (nf) training. This rtfMRI-nf training utilizes functional magnetic resonance imaging (fMRI) tomographic localization capacity to allow a person to see and regulate the localized hemodynamic signal from his or her own brain. In this review, we summarize the results of several studies that have developed and applied neurofeedback training to healthy and depressed individuals with the amygdala as the neurofeedback target and the goal to increase the hemodynamic response during positive autobiographical memory recall. We review these studies and highlight some of the challenges and advances in developing an rtfMRI-nf paradigm for broader use in psychiatric populations. The work described focuses on our line of research aiming to develop the rtfMRI-nf into an intervention, and includes a discussion of the selection of a region of interest for feedback, selecting a control condition, behavioral and cognitive effects of training, and predicting which participants are most likely to respond well to training. While the results of these studies are encouraging and suggest the clinical potential of amygdala rtfMRI-nf in alleviating symptoms of major depressive disorder, larger studies are warranted to confirm its efficacy.
View Full Paper →Self-regulation strategy, feedback timing and hemodynamic properties modulate learning in a simulated fMRI neurofeedback environment
Direct manipulation of brain activity can be used to investigate causal brain-behavior relationships. Current noninvasive neural stimulation techniques are too coarse to manipulate behaviors that correlate with fine-grained spatial patterns recorded by fMRI. However, these activity patterns can be manipulated by having people learn to self-regulate their own recorded neural activity. This technique, known as fMRI neurofeedback, faces challenges as many participants are unable to self-regulate. The causes of this non-responder effect are not well understood due to the cost and complexity of such investigation in the MRI scanner. Here, we investigated the temporal dynamics of the hemodynamic response measured by fMRI as a potential cause of the non-responder effect. Learning to self-regulate the hemodynamic response involves a difficult temporal credit-assignment problem because this signal is both delayed and blurred over time. Two factors critical to this problem are the prescribed self-regulation strategy (cognitive or automatic) and feedback timing (continuous or intermittent). Here, we sought to evaluate how these factors interact with the temporal dynamics of fMRI without using the MRI scanner. We first examined the role of cognitive strategies by having participants learn to regulate a simulated neurofeedback signal using a unidimensional strategy: pressing one of two buttons to rotate a visual grating that stimulates a model of visual cortex. Under these conditions, continuous feedback led to faster regulation compared to intermittent feedback. Yet, since many neurofeedback studies prescribe implicit self-regulation strategies, we created a computational model of automatic reward-based learning to examine whether this result held true for automatic processing. When feedback was delayed and blurred based on the hemodynamics of fMRI, this model learned more reliably from intermittent feedback compared to continuous feedback. These results suggest that different self-regulation mechanisms prefer different feedback timings, and that these factors can be effectively explored and optimized via simulation prior to deployment in the MRI scanner.
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