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David W. Holdsworth

Bio: David W. Holdsworth is an academic researcher from University of Western Ontario. The author has contributed to research in topics: Imaging phantom & Image resolution. The author has an hindex of 54, co-authored 313 publications receiving 9522 citations. Previous affiliations of David W. Holdsworth include London Health Sciences Centre & University of Toronto.


Papers
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Journal Article
TL;DR: Anatomic realism of lumen geometry and flow pulsatility is essential for elucidating the patient-specific nature of aneurysm hemodynamics and may be used to provide key hemodynamic information for prospective studies of anuerysm growth and rupture or to predict the response of an individual aneurYSm to therapeutic options.
Abstract: BACKGROUND AND PURPOSE: Blood flow dynamics are thought to play an important role in the pathogenesis and treatment of intracranial aneurysms; however, hemodynamic quantities of interest are difficult to measure in vivo. This study shows that computational fluid dynamics (CFD) combined with computed rotational angiography can provide such hemodynamic information in a patient-specific and prospective manner. METHODS: A 58-year-old woman presented with partial right IIIrd cranial nerve palsy due to a giant carotid-posterior communicating artery aneurysm that was subsequently coiled. Computed rotational angiography provided high resolution volumetric image data from which the lumen geometry was extracted. This and a representative flow rate waveform were provided as boundary conditions for finite element CFD simulation of the 3D pulsatile velocity field. RESULTS: CFD analysis revealed high speed flow entering the aneurysm at the proximal and distal ends of the neck, promoting the formation of both persistent and transient vortices within the aneurysm sac. This produced dynamic patterns of elevated and oscillatory wall shear stresses distal to the neck and along the sidewalls of the aneurysm. These hemodynamic features were consistent with patterns of contrast agent wash-in during cine angiography and with the configuration of coil compaction observed at 6-month follow-up. CONCLUSION: Anatomic realism of lumen geometry and flow pulsatility is essential for elucidating the patient-specific nature of aneurysm hemodynamics. Such image-based CFD analysis may be used to provide key hemodynamic information for prospective studies of aneurysm growth and rupture or to predict the response of an individual aneurysm to therapeutic options.

436 citations

Journal ArticleDOI
TL;DR: Micro-CT has the potential to replace serial histology as the reference standard in many in vitro studies, and provides a practical approach to obtain quantitative information during some longitudinal investigations in vivo.

343 citations

Journal ArticleDOI
TL;DR: It is proposed that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.
Abstract: Knowledge of human blood-flow waveforms is required for in vitro investigations and numerical modelling. Parameters of interest include: velocity and flow waveform shapes, inter- and intra-subject variability and frequency content. We characterized the blood-velocity waveforms in the left and right common carotid arteries (CCAs) of 17 normal volunteers (24 to 34 years), analysing 3560 cardiac cycles in total. Instantaneous peak-velocity (Vpeak) measurements were obtained using pulsed-Doppler ultrasound with simultaneous collection of ECG data. An archetypal Vpeak waveform was created using velocity and timing parameters at waveform feature points. We report the following timing (post-R-wave) and peak-velocity parameters: cardiac interbeat interval (T(RR)) = 0.917 s (intra-subject standard deviation = +/- 0.045 s); cycle-averaged peak-velocity (V(CYC)) = 38.8 cm s(-1) (+/-1.5 cm s(-1)); maximum systolic Vpeak = 108.2 cm s(-1) (+/-3.8 cm s(-1)) at 0.152 s (+/-0.008 s); dicrotic notch Vpeak = 19.4 cm s(-1) (+/-2.9 cm s(-1)) at 0.398 s (+/-0.007 s). Frequency components below 12 Hz constituted 95% of the amplitude spectrum. Flow waveforms were computed from Vpeak by analytical solution of Womersley flow conditions (derived mean flow = 6.0 ml s(-1)). We propose that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.

324 citations

Journal ArticleDOI
TL;DR: Retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms from the two internal carotid arteries and two vertebral arteries of 17 young, normal volunteers, suggesting that the representative waveform shapes presented here may be used to characterize normal ICA and VA flow rate dynamics.
Abstract: Knowledge of normal cerebrovascular volumetric flow rate (VFR) dynamics is of interest for establishing baselines, and for providing input data to cerebrovascular model studies. Retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms from the two internal carotid arteries (ICA) and two vertebral arteries (VA) of 17 young, normal volunteers (16M:1F) at rest in a supine posture. After normalizing each waveform to its respective cycle-averaged VFR, the timing and amplitude of feature points from the individual waveforms were averaged together to produce archetypal ICA and VA waveform shapes. Despite significant inter-individual differences in cycle-averaged VFR within the ICA compared to VA (275+/-52 versus 91+/-18 mL min-1), the respective waveform shapes were qualitatively similar overall. The VA waveform shape did, however, exhibit significantly higher amplitudes (e.g., peak:average VFR of 1.78+/-0.30 versus 1.66+/-0.16; p<0.05) and significantly higher variability both between and within subjects. A significant correlation was observed between peak and cycle-averaged VFR, suggesting that the representative waveform shapes presented here-when scaled by an individual's cycle-averaged VFR-may be used to characterize normal ICA and VA flow rate dynamics. This capability may be of particular utility for studies where cerebrovascular flow dynamics are required, but only average flow rates are available.

310 citations

Journal ArticleDOI
TL;DR: It is shown that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion, in in vivo micro-computed tomography and digital subtraction angiography.
Abstract: Small-animal imaging has a critical role in phenotyping, drug discovery and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo x-ray based small-animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.

256 citations


Cited by
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[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

Journal ArticleDOI
TL;DR: Benefit of carotid endarterectomy was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms, and decisions about treatment for patients in this category must take into account recognized risk factors.
Abstract: Background Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. Methods Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were availa...

3,206 citations

Book
24 Feb 2012
TL;DR: This book is a tutorial written by researchers and developers behind the FEniCS Project and explores an advanced, expressive approach to the development of mathematical software.
Abstract: This book is a tutorial written by researchers and developers behind the FEniCS Project and explores an advanced, expressive approach to the development of mathematical software. The presentation spans mathematical background, software design and the use of FEniCS in applications. Theoretical aspects are complemented with computer code which is available as free/open source software. The book begins with a special introductory tutorial for beginners. Followingare chapters in Part I addressing fundamental aspects of the approach to automating the creation of finite element solvers. Chapters in Part II address the design and implementation of the FEnicS software. Chapters in Part III present the application of FEniCS to a wide range of applications, including fluid flow, solid mechanics, electromagnetics and geophysics.

2,372 citations

Journal ArticleDOI
TL;DR: This article cites 228 articles, 79 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article sign up in the box at the Collections Topic.
Abstract: References http://genesdev.cshlp.org/content/17/5/545.full.html#related-urls Article cited in: http://genesdev.cshlp.org/content/17/5/545.full.html#ref-list-1 This article cites 228 articles, 79 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article sign up in the box at the Collections Topic (33 articles) Molecular Physiology and Metabolism • (98 articles) Cancer and Disease Models • Articles on similar topics can be found in the following collections

2,282 citations