Vascular artefacts in fMRI of early visual cortex: The effects of resolution and field strength

Large draining veins residing on the cortical surface are recognised as a major problem in fMRI measurements, leading to the displacement, distortion, and reduction in spatial localisation of signals. This is detrimental to the application of fMRI in advanced human brain imaging, such as in retinotopic mapping, where the BOLD signal becomes obscured by the artefacts from nearby draining veins (venous artefacts). There is consensus that at an increased magnetic field strength, the sensitivity to the contributions from these draining veins reduces, which promises the ability to capture measurements at greater sensitivity and specificity. With the advent of fMRI hardware and technologies, there is a great interest in understanding cortical layer-specific neuronal response that had been previously obscured due to the domination of signal change caused by venous artefacts. This forms the basis of support for fMRI at ultra-high magnetic field strength, with the conventional wisdom that the reduced sensitivity to macrovasculature (including draining veins) that comes with higher magnetic field strength can increase the sensitivity to underlying responses that closely reflect neuronal activation. However, this is debatable. Instead, there are instances where human neuronal response profiles displayed a pattern that seemed indicative of synaptic activities even without using ultra-high magnetic field strength. Recent trends in moving to ultra-high magnetic field strengths, especially for depth-dependent fMRI, beget the questions – is ultra-high magnetic field strength really necessary, and can it resolve the artefacts from draining veins? To elucidate these questions, this thesis aims to test the venous artefact and its impact on underlying signals across spatial resolutions and magnetic field strengths, focusing on the quality of the retinotopic organisation of the early visual cortex. The first experimental study was conducted to test the venous artefact and its impact on fMRI signals across the grey matter using high-resolution (isotropic resolution of 1 mm) fMRI images collected at 3 T. Using two surface reconstruction packages, the findings established that venous artefact occurs at the cortical surface and spreads within the grey matter. In this study, the ability of high-resolution fMRI at 3 T to conduct depth-dependent analyses was demonstrated. The second experimental study delves into the role of spatial resolution in the depth-dependent analysis of venous artefacts and their impact. The 1 mm 3 T fMRI images were spatially smoothed to simulate two additional sets of lower-effective resolution images. Here, the results found consistency in the venous artefact but a reduction in the venous effects. This suggests that at lower spatial resolutions, the venous artefact exists, but its impact on underlying signals is concealed. The third experiment incorporates two sets of 7 T fMRI images, with spatial resolutions of 1.6 mm and 0.8 mm, to test the venous artefacts at ultra-high magnetic field strength. The results showed evidence that venous artefacts remained prominent at 7 T. This study was extended into a comparative study by including the 3 T fMRI images used in the first study. Here, the generalisability of the venous artefact was established at 3 T and 7 T, as well as across various spatial resolutions. Finally, the fourth experiment explored a non- BOLD contrast, postulated to be less sensitive to contributions from the draining veins. In this study, VASO-fMRI was conducted with a spatial resolution of 1.1 mm and at 7 T to test the venous artefact and its impact. A reduction in the venous artefact and its impact was demonstrated. However, VASO images were found insufficient to inform the retinotopic organisation of the early visual cortex due to higher noise and lower signals, but they can be beneficial when used in conjunction with BOLD images. In summary, this thesis established the competence of high-resolution fMRI at 3 T for depth-dependent analysis. This suggests that the artefacts arising from draining veins can be avoided by avoiding surfaces or locations that are in proximity to these veins. Furthermore, this thesis sheds light on the generalisability of the venous artefact across magnetic field strengths and spatial resolutions. Finally, the results from the VASO-fMRI study demonstrated how VASO retinotopic mapping could benefit BOLD retinotopic mapping, especially when the BOLD response is highly polluted with macrovasculature

Comparative Chronic Valve and Venous Effects of Lumenless versus Stylet‐Delivered Pacing Leads in Patients with and Without Congenital Heart

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115920/1/pace12728.pd

What went wrong? The flawed concept of cerebrospinal venous insufficiency

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis (MS), coining the term of chronic cerebrospinal venous insufficiency ('CCSVI'). The diagnosis of 'CCSVI' is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS. Many investigators tried to replicate Zamboni's results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the 'CCSVI' concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat 'CCSVI' in the care of MS patients, outside of the setting of scientific research

Disambiguating the role of blood flow and global signal with partial information decomposition

Global signal (GS) is an ubiquitous construct in resting state functional magnetic resonance imaging (rs-fMRI), associated to nuisance, but containing by definition most of the neuronal signal. Global signal regression (GSR) effectively removes the impact of physiological noise and other artifacts, but at the same time it alters correlational patterns in unpredicted ways. Performing GSR taking into account the underlying physiology (mainly the blood arrival time) has been proven to be beneficial. From these observations we aimed to: 1) characterize the effect of GSR on network-level functional connectivity in a large dataset; 2) assess the complementary role of global signal and vessels; and 3) use the framework of partial information decomposition to further look into the joint dynamics of the global signal and vessels, and their respective influence on the dynamics of cortical areas. We observe that GSR affects intrinsic connectivity networks in the connectome in a non-uniform way. Furthermore, by estimating the predictive information of blood flow and the global signal using partial information decomposition, we observe that both signals are present in different amounts across intrinsic connectivity networks. Simulations showed that differences in blood arrival time can largely explain this phenomenon, while using hemodynamic and calcium mouse recordings we were able to confirm the presence of vascular effects, as calcium recordings lack hemodynamic information. With these results we confirm network-specific effects of GSR and the importance of taking blood flow into account for improving de-noising methods. Additionally, and beyond the mere issue of data denoising, we quantify the diverse and complementary effect of global and vessel BOLD signals on the dynamics of cortical areas

Effects of phase regression on high-resolution functional MRI of the primary visual cortex

High-resolution functional MRI studies have become a powerful tool to non-invasively probe the sub-millimeter functional organization of the human cortex. Advances in MR hardware, imaging techniques and sophisticated post-processing methods have allowed high resolution fMRI to be used in both the clinical and academic neurosciences. However, consensus within the community regarding the use of gradient echo (GE) or spin echo (SE) based acquisition remains largely divided. On one hand, GE provides a high temporal signal-to-noise ratio (tSNR) technique sensitive to both the macro- and micro-vascular signal while SE based methods are more specific to microvasculature but suffer from lower tSNR and specific absorption rate limitations, especially at high field and with short repetition times. Fortunately, the phase of the GE-EPI signal is sensitive to vessel size and this provides a potential avenue to reduce the macrovascular weighting of the signal (phase regression, Menon 2002). In order to determine the efficacy of this technique at high-resolution, phase regression was applied to GE-EPI timeseries and compared to SE-EPI to determine if GE-EPI\u27s specificity to the microvascular compartment improved. To do this, functional data was collected from seven subjects on a neuro-optimized 7 T system at 800 μm isotropic resolution with both GE-EPI and SE-EPI while observing an 8 Hz contrast reversing checkerboard. Phase data from the GE-EPI was used to create a microvasculature-weighted time series (GE-EPI-PR). Anatomical imaging (MP2RAGE) was also collected to allow for surface segmentation so that the functional results could be projected onto a surface. A multi-echo gradient echo sequence was collected and used to identify venous vasculature. The GE-EPI-PR surface activation maps showed a high qualitative similarity with SE-EPI and also produced laminar activity profiles similar to SE-EPI. When the GE-EPI and GE-EPI-PR distributions were compared to SE-EPI it was shown that GE-EPI-PR had similar distribution characteristics to SE-EPI (p \u3c 0.05) across the top 60% of cortex. Furthermore, it was shown that GE-EPI-PR has a higher contrast-to-noise ratio (0.5 ± 0.2, mean ± std. dev. across layers) than SE-EPI (0.27 ± 0.07) demonstrating the technique has higher sensitivity than SE-EPI. Taken together this evidence suggests phase regression is a useful method in low SNR studies such as high-resolution fMRI

The effect of vascular changes on the photoplethysmographic signal at different hand elevations

In order to further understand the contribution of venous and arterial effects to the photoplethysmographic (PPG) signal, recordings were made from twenty healthy volunteer subjects during an exercise in which the right hand was raised and lowered with reference to heart level. Red (R) and infrared (IR) PPG signals were obtained from the right index finger using a custom-made PPG processing system. Laser Doppler flowmetry (LDF) signals were also recorded from an adjacent fingertip. The signals were compared with simultaneous PPG signals obtained from the left index finger. On lowering the hand to 50 cm below heart level, both ac and dc PPG amplitudes from the finger decreased (e.g. 18.70% and 63.15% decrease in infrared dc and ac signals respectively). The decrease in dc amplitude most likely corresponded to increased venous volume, while the decrease in ac PPG amplitude was due to regulatory adjustments on the arterial side in response to venous distension. Conversely, ac and dc PPG amplitudes increased on raising the arm above heart level. Morphological changes in the ac PPG signal are thought to be due to vascular resistance changes, predominately venous, as the hand position is changed

Advances in image acquisition and filtering for MRI neuroimaging at 7 tesla

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths. First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion of the MRI experiment for use with multi-channel RF coils. It is demonstrated that in 2D MRI experiments, shimming on a slice-by slice basis allows utilization of an extra degree of freedom available from the slice dimension, resulting in significant gains in image homogeneity and reduced RF power requirements. After acceptable images are available, we move to address complications of high field imaging that manifest in the fMRI time series. In the second paper, the increased physiological noise present in BOLD time series at high field is addressed with a unique data-driven noise regressor scheme based upon information in the phase component of the MRI signal. It is demonstrated that this method identifies and removes a significant portion of physiological signals, and performs as good or better than other popular data driven methods that use only the magnitude signal information. Lastly, the BOLD phase signal is again leveraged to address the confounding role of veins in resting state BOLD fMRI experiments. The phase regressor technique (previously developed by Dr. Menon) is modified and applied to resting state fMRI to remove macro vascular contributions in the datasets, leading to changes in spatial extent and connectivity of common resting state networks on single subjects and at the group level

Comparison between local and regional anesthesia in arteriovenous fistula creation.

PURPOSE: Assessment of the effectiveness of Brachial Plexus Block (BPB) via axillary approach compared to regional anesthesia for arteriovenous fistula surgery in patients affected by end-stage renal disease. METHODS: We compared forty patients randomly divided into two groups. Group A underwent BPB procedure with 15 mL ropivacaine 1% and 10 mL of saline (0.9% NaCl) via axillary approach. Group B received local anesthesia with lidocaine 2%. The forearm blood vessels were assessed by Doppler ultrasonography before and after the intervention. RESULTS: BPB performed on Group A was associated with a considerable venous dilation and a significant decrease (48.7%, P<.05) in pulsatility index (PI) measured by Doppler ultrasound. In Group B, PI and venous dilation remained unaltered in the postoperative phase. No complications such as thrombosis or occlusion were encountered among patients who underwent BPB. CONCLUSIONS: The axillary-approached BPB was more advantageous than local anesthesia. Its effectiveness was because of venous dilation and the decrease in the PI, consequent to the reduction in peripheral resistances and the increase in local blood flow, thus offering an ideal background for fistula creation and short-term patency

The role of protease-activated receptor-1 in the human vasculature

BACKGROUND Thrombin is a powerful cardiovascular agonist and a vital link between thrombosis and inflammation. In addition to its role in the coagulation cascade, it directly activates platelets, inflammatory cells, endothelium and vascular smooth muscle. Proteaseactivated receptor-1 (PAR-1) has been proposed as the principal thrombin receptor in man although its actions in vivo have not been defined. The aim of this thesis was to determine the direct vascular actions of PAR-1 agonism in the human venous and arterial circulations.OBJECTIVES The effects of PAR-1 activation on dorsal hand vein diameter were measured by the Aellig technique in healthy volunteers, compared with activation of the trypsin receptor PAR-2, and further assessed in the presence or absence of norepinephrine, the glycoprotein (GP)IIb/IIIa antagonist tirofiban, and endothelial denudation. In the arterial circulation, forearm blood flow was measured by venous occlusion plethysmography. Intra-arterial PAR-1 activating peptide was co-infused with tirofiban, and compared with PAR-2 activation and bradykinin infusion. Platelet-monocyte binding (a sensitive measure of platelet activation) and tissue plasminogen activator release (t-PA) were measured throughout. In subsequent studies, effects of inhibition of the endothelium-dependent vasodilators nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarisation factor (EDHF) on PAR-1 activation were assessed, as well as comparing the effects of PAR-1 activation in smokers and non-smokers.METHODS Activation of PAR-1 caused dose-dependent venoconstriction (P<0.001) that was unaffected by norepinephrine or tirofiban co-infusion and endothelial denudation. In forearm resistance vessels, arterial PAR-1 activation increased forearm blood flow (P<0.001), t-PA release (P<0.001) and platelet-monocyte binding (PO.OOOl). Activation of PAR-2 caused venous (P<0.001) and arterial (P<0.01) dilatation without t-PA release or platelet activation. Although blockade of prostacyclin production had no effect, PAR-1 induced arterial vasodilatation was attenuated by inhibition ofNO synthesis (PO.OOOl) and EDHF (PO.05), and abolished by their combination (PO.Ol). Smokers had impaired PAR-1 mediated vasodilatation and t-PA release.RESULTS We have, for the first time, demonstrated that PAR-1 agonism in vivo in man causes arterial dilatation, venoconstriction, platelet activation and t-PA release that is mediated through endothelium-dependent and independent pathways, and impaired in smokers. These unique and contrasting effects are of major physiological relevance to the regulation and resolution of intravascular thrombosis. These findings have implications for the development and therapeutic use of thrombin receptor antagonists and direct thrombin inhibitors

Outpatient Administration of Paclitaxel

Paclitaxel (Taxol®, Bristol-Meyers Squibb), anti neoplastic agent made from the bark of the Pacific yew tree, is undoubtedly one of the most exciting agents to be evaluated over the past decade. Paclitaxel has demonstrated significant promise against ovarian and metastatic breast cancer, and appears to be the most effective single agent to date for non-small-cell lung cancer in trials conducted by Eastern Cooperative Oncology Group (ECOG)