A Theory of Everything in Venn Diagram Form

An exceptionally clever visualization of a grand unifying theory (not mine :-). Eat that, Lie Group E₈! (In case there was any doubt, I'm a nerd.)

Wellcome to the Circulation

Thanks to our friend and self-styled quasi-media activist Roberta Buiani, currently transplanted to Cambridge, for sending this link to "William Harvey and the circulation of blood", a great 1978 film from the Wellcome Collection. (Note early on the comments about Galen being so revered for centuries that no one dared question his presumptions about the circulation. Guess it didn't hurt that Harvey had tenure and the ear of the king :-)

Enjoy it while you can, because the closing of the Wellcome Trust Centre for the History of Medicine earlier this year may be an unwelcome (sorry :-) harbinger of things to come in the Dark Age Ahead...

Paper published in J Biomech Eng

Image-based CFD tends to rely on lots of explicit and implicit assumptions, and there are also various overt and hidden sources of uncertainty. As part of our ongoing attempts to understand the impact of these, in 2006 we published a study asking, and we thought answering, whether for "Inlet Conditions for Image-Based CFD Models of the Carotid Bifurcation: Is it Reasonable to Assume Fully Developed Flow". Then, in 2009 a paper came out saying that "Choice of In Vivo Versus Idealized Velocity Boundary Conditions Influences Physiologically Relevant Flow Patterns in a Subject-Specific Simulation of Flow in the Human Carotid Bifurcation".

Well, we thought, that's bad news, not only because it seemed to contradict our work, but because it's tough to acquire and impose subject-specific velocity conditions, at least in comparison to acquiring or assuming flow rates and imposing fully-developed (idealized) velocity conditions. Admittedly, one of the drawbacks of our study was that we perturbed the fully-developed inlet conditions by imposing ideally curved and helical inlet sections. And we since had learned that common carotid artery (CCA) inlet segments are rarely so ideally curved, and their velocity profiles can be quite complex. So we decided to revisit the question, but now with the advantage of the high quality carotid MRI scans available through our collaborations on the VALIDATE study.

Specifically, in "Effect of Common Carotid Artery Inlet Length on Normal Carotid Bifurcation Hemodynamics", we started with carotid bifurcations (a dozen of 'em, more than either of the earlier studies -- we wanted to leave no doubt :-) having their actual CCA segments almost down to their aortic arch origins. As shown in the figure above, these were progressively truncated, and CFD simulations carried out on the whole lot (60 simulations in total!) using fully-developed inlet conditions. In the end we found that three diameters of CCA inlet length are required before it is reasonable to impose fully-developed flow, at least for the purposes of quantifying common measures of "disturbed flow" within the uncertainty of the image-based CFD pipeline itself.

So why the difference of opinion? Both earlier studies had looked at different hemodynamic quantities for sure, but we believe the big difference was in their inlet lengths: we estimated that the CCA in the 2009 paper was closer to one diameter in length, whereas those in our 2006 paper were (lucky for us) closer to three diameters. This doesn't mean that one paper is more right or wrong than the other. It just means that one needs to consider the (formerly) hidden variable of CCA length before deciding whether it's reasonable or not to impose fully-developed flow.

Best thesis cover

Some on our side of the pond may not be aware that some across the pond have an elegant way of packaging their PhD theses as readable booklets. Invariably they have explanatory, but often earnest, cover figures that gamely illustrate the work within.

Now, I'm not a big fan of Futurama (more inclined to The Simpsons or, showing my age, The Flintstones), but I must admit to a bout of LMAO when I opened up a package containing this thesis generously sent to me by Carole Leguy.

Kudos to Carole (and Ana Soares, also credited) for their delightful (and eerily accurate :-) rendering of the vagaries of hemodynamical measurement; and to Carole's supervisors for allowing her scratch the patina of academic seriousness.

Congratulations to Amir Manbachi

My bad for being a couple of months late is posting this: Congratulations to Amir Manbachi on the successful defense of his Master's thesis, "Characterization of common carotid artery geometry and its impact on velocity profile shape". Amir is now doing a PhD on the topic of ultrasound-guided therapy, and is also patiently waiting for me to get my act together so we can submit a paper on his Master's work!

Paper published in J Biomech Eng

In 2008 we demonstrated a significant correlation between certain geometric variables and the amount of disturbed flow at the carotid bifurcation. Now working with Qi Zhang and Mort Friedman -- yes, that Mort Friedman, the father of the geometric risk hypothesis -- we extended and improved these correlations in "Use of factor analysis to characterize arterial geometry and predict hemodynamic risk: application to the human carotid bifurcation." To me the strength of factor analysis is not just its ability to rationally combine variables to create factors that improve correlations, but also the ability to identify why certain variables (in the present case, bifurcation angle) are not correlated with disturbed flow. Less directly, the debates we had about why certain geometric factors are better correlated with disturbed flow helped inspire us to identify better geometric variables (to be presented at SPIE Medical Imaging 2011), which can only lead to better factors, etc. And in case you didn't notice the subtle use of bold text, yes there is an issue of terminology that I'm still trying to get used to!

Paper published in Ultrasound Med Biol

In 2005 we showed how Doppler ultrasound spectra could be synthesized in real-time from CFD data, provided that simplistic assumptions were made about the sample volume (SV) power distribution and intrinsic spectral broadening (ISB). In the first paper arising from Luis Aguilar's doctoral thesis work, "On the Synthesis of Sample Volumes for Real-Time Spectral Doppler Ultrasound Simulation", we show how acoustic monopoles can be used to overcome the SV assumption. For Luis' next trick, he will show how this approach can also be used to overcome the ISB assumption, and probably much, much more...

Too many papers, too little time...

Doing a literature search this morning, I stumbled across "The reliability of high resolution MRI in the measurement of early stage carotid wall thickening" by Boussel et al. What struck me immediately was their Figure 2 (left), which nicely shows that MRI tends to overestimate normal wall thickness compared to ultrasound intima-media thickness (IMT) measurements, something the authors said was "potentially due to the inclusion of the adventitia by MRI".

As it turns out, I had downloaded a copy into my Papers database on January 5, 2008. Why is this relevant? Because, in Febrauary 2008 we submitted a paper entitled "On the overestimation of early wall thickening at the carotid bulb by black blood MRI...". Looking at their figure now (and probably then), I noticed how similar it looked to our predictions. So now, almost two years later, I plotted their data (hand digitized using a great shareware program, getdata) over the data from Figure 8 of our paper. As shown to the right, the trends are indeed remarkably consistent.

There are some discrepancies, of course. Boussel et al.'s data were acquired with 0.6-mm pixels, but would seem to fall between our predictions of 0.3 - 0.5 mm pixels. This may be because their images were segmented manually, whereas our predictions were based on automated edge-detection. (Thanks to Bill Kerwin from the University of Seattle for later explaining to me why the latter probably overestimates the problem relative to the former.)

It would have been nice to have included this comparison in our paper, for it bolsters our conclusion that the spatial resolution of MRI, rather than the adventitia, is the culprit. Oh well, better later than never! But, and per the title of this post, there are just too many papers out there to be able to read and remember them all. My Papers database has 3446 PDF files as of today, most of them probably relevant to my research, but the vast majority probably inhaled and forgotten like a fast food dinner, rather than savoured and remembered like a gourmet meal. A weak metaphor perhaps, but maybe science could do with a "slow food" movement...

Shit my dad says about radiology

For those of you disconnected from mainstream media, Shit My Dad Says -- I refuse to sanitize the title -- documents the pearls of wisdom passed down from a father to his son over the years. Being Twitter-free and Facebook-phobic, I only heard about this a few weeks ago from my daughter, who is a devoted follower, and then a few days ago I received the recently-published book, unsolicited, from my father as a birthday present. (Hmm, I wonder what this says about me as a father and as a son, Dr. Freud?)

What does this have to do with Biomedical Simulation? Well, a few minutes on Google and then PubMed reveals that the father, introduced in the book as having worked "in nuclear medicine at the University of California-San Diego", is indeed a former academic radiologist at UCSD, specializing in nuclear and adolescent(!) medicine, with quite a few papers in journals that I read. (OK, it's a stretch, but allow me this tenuous brush with greatness.)

All this to say: if you don't believe there's wit and wisdom behind the media hype, check out Samuel E. Halpern's editorial "Of Models and Men" from 1977. They don't write 'em like that anymore!

All hail Lewis Fry Richardson (1881-1953)

First time I came across his name was indirectly, as an undergrad, learning about something called "Richardson extrapolation", a method for inferring the convergence of a numerical analysis. Then, much (much) later, as I was rethinking turbulence in blood, I came across Richardson as one of the pioneers of modern turbulent flow theory, and as the author of this unsurpassedly clever and concise description of turbulence:

Big whorls have little whorls
that feed on their velocity,
And little whorls have lesser whorls
and so on to viscosity.

Shortly thereafter -- OK, so I didn't pay close attention to my reading of Gleick's "Chaos" many years back -- I learned about Richardson's anticipation of fractals via his musings on the measurement of coastlines, something that arose out of his interest in divining the mathematical rules underlying human conflict; and of his anticipation of chaos theory through his pioneering work in weather prediction. By virtue of what some might call his mania for the latter, he arguably founded modern numerical analysis and finite difference methods.

If that weren't enough, thanks to my reading of Abigail Swillens' fine PhD thesis, I learned that Richardson filed the first patent for underwater echo-ranging (apparently inspired by the sinking of the Titanic), a precursor to sonar and, by extension, medical ultrasound.

In short, virtually everything I do in my research can be traced back, with far fewer than six degrees of separation, to Lewis Fry Richardson. For more about Richardson's life and works, there's the at-your-fingertips Wikipedia of course, but also a nice 1998 review in the Annual Reviews of Fluid Mechanics.

Paper published in J Biomech Eng

Not long ago we reported differences in the characteristic shape of older vs. young adult carotid flow rate waveforms, which got us wondering whether and how such age-related differences might affect predictions of disturbed flow. In "Carotid bifurcation hemodynamics in older adults: effect of measured versus assumed flow waveform", we went a step further by testing the impact of not only waveform shape, but also mean flow rates, using the actual subject-specific measured flow condition as a gold standard. As it turned out, errors in mean flow had a greater impact on nominal metrics of disturbed flow, particularly oscillatory shear index (OSI); however, these effects were on the order of those due other assumptions we typically make regarding, say, blood rheology or inlet velocity profiles. Take-home message: don't sweat the waveform shape, but if you can measure the mean flow rates, go for it!

Back from Conference-land

Finally back from a marathon of conferences and other academic (and s ome non-academic) activities. Top left, Dolores and I in the group photo for the 1st International Conference on Medical Imaging and Philosophy, in Ulm, Germany. Next, to the right, I am in Ghent University academic drag, apparently nerding out with Abigail Swillens after her successful PhD public defense. Next, to the left, I'm playing Where's Waldo in the group photo from the IV International Symposium on Modelling of Physiological Flows. Finally, to the right are Dolores and I paying our respects to Mendeleev in his hometown of St. Petersburg (not Florida :-)

Not pictured (yet) is me at the ASME Summer Bioengineering Conference, in Naples (Florida) and, simultaneously, Dolores at the 6th European Meeting of the Society for Literature, Science and the Arts, in Riga, Latvia.

Citations in talks

Here at the ASME Summer Bioengineering Conference, I was struck by how unhelpful some of the talks can be when referring to published works. This, by the way, is not a knock against SBC (a conference near and dear to my heart and one for which I will be Program Chair in 2012), but something that's bugged me for years at many conferences and seminars. It's just that the happy convergence of staying indoors to avoid the sweltering heat and now having a blog inspired me to finally write about this pet peeve of mine. (OK, I admit that I sympathized with the author of Eats, Shoots & Leaves, so read on -- or not -- in that context. :-)

Particularly, it is frustrating to see a citation to, say, "Zhang et al., 2008" on a slide. Try doing a PubMed or Google Scholar search on this. OK, maybe it makes sense in the context of the slide's bullet point, but when you -- well I, anyway -- are scribbling notes and trying to pay attention to the talk and trying not to spill the coffee cup that you've sneaked into the session, it's hard to remember to write down a few choice keywords from the slide to remind you what the reference is about.

Of course this shorthand derives from the fact that "Zhang et al., 2008" is how one would cite it in a journal article, but there you can find a handy reference list at the back for the details. In a talk, that don't make no sense. Instead, for years I have found the following to be a compact but still-informative construct: "Zhang+, Ann Biomed Eng 2008". The plus sign saves the precious 5-7 characters of "et al", "et al." or (shudder) "et. al.". The journal name is absolutely essential for honing the search result from potentially thousands of hits to just a few. The year hones the search further, and also alerts you right away to whether this is a classic work or recent finding.

Just my $0.02 on the matter. Now considering an expedition to the beach so I can, as the late, great George Carlin used to say, neutralize the blue.

Yiemeng Hoi awarded postdoctoral fellowship

Congratulations to BSL postdoc Yiemeng Hoi, who has been awarded a two-year Research Fellowship from the Heart & Stroke Foundation of Canada.

Bibliometric indicators

Many of us have a love/hate relationship with bibliometric indicators, those numbers imposed on, and by, us to quantify the unquantifiable. The latest issue of Radiology provides a nice overview of these, giving some historical perspective and summarizing the pros and cons. (The previous issue of Radiology also provides what appears to be the first in a series of tips and tricks on the use of Powerpoint, something else with which many of us have a love/hate relationship...)

Update: And speaking of love/hate relationships, The New York Times has a funny/frightening article about the US military obsession with Powerpoint.

Centre for Innovation in Information Visualization and Data-Driven Design (CIV-DDD)

Congratulations to York University and the Ontario College of Art and Design (OCAD) for establishing the CIV-DDD with the help of a $11.5-million investment from the Ontario Research Fund and industrial and academic partners. A (very) small part of this is the BSL's commitment of manpower to help develop and understand ways of making sense out of the huge biological, biomechanical, and clinical datasets that are flooding labs like ours (not that we're complaining :-)

Amir Manbachi wins Lorne Phenix Award

Congratulations to BSL Master's student Amir Manbachi, for receiving this year's Lorne Phenix Award from UofT's Cardiovascular Sciences Collaborative Program (CSCP). Most of the students participating in the CSCP have their thesis projects on cardiovascular physiology or biology, and so it was a pleasant surprise that Amir's work on common carotid artery geometry and flow characterization stood out (in a good way).

Tesla Talk at UCL, March 9th

On Tuesday, March 9th, Dolores Steinman will be giving a Tesla Talk, entitled "Investigating the body: Current medical visual culture", at University College London.

Position paper published in Ann Biomed Eng

In March 2008 the illuminati of the biofluids community -- I know, I'm just begging for the BSL blog to be flagged as a conspiracy theory site -- got together for the Fifth Sixth Fifth Bio-Fluids Symposium and Workshop at Caltech. Much fun was had by all and, as a reward, the session organizers were conscripted to summarize their respective areas in a series of position papers, much as we did five years ago after the 2003 Symposium. These are just starting to show up online now, and will be published soon in a special issue of the Annals of Biomedical Engineering.

I have to say I had a great experience co-authoring, with Charley Taylor, our position paper, "Image-based modeling of blood flow and vessel wall dynamics: Applications, methods and future directions". Those of you who know Charley and I might be able to tell who wrote what sections, but reading the paper again -- it was submitted back in April 2009 -- it still feels seamless, and we're both really proud of it. After summarizing the impressive developments of various applications and methods over the past five years, the paper presents a pseudo-SWOT analysis to highlight the promise, but especially the potential pitfalls, as image-based modelling moves into its second decade.

Paper published in Physiol Meas

Model studies of large artery flow often employ flow waveforms measured from normal, young adults, such as Holdsworth et al.'s widely-used common carotid artery waveform. As the title of our new paper makes clear, in "Characterization of volumetric flow rate waveforms at the carotid bifurcations of older adults" we provide a more age-appropriate set of waveforms for model studies of older adults, as part of our work on the VALIDATE study of factors in vascular aging. In addition to lots of descriptive statistics (thanks to a sample size of nearly 100), we note some interesting trends with age and, thanks to the comments of one reviewer, sex (not gender, which apparently means something else altogether).

Welcome to Alex Martinez

The BSL welcomes Alejandro (Alex) Martinez, from UofT's MIE undergraduate program, who will be starting Master's degree research this month. Alex's thesis project will focus on the further development (and, eventually, deployment) of an open-source MRI simulation environment that Luca Antiga and I have been working on (and off) for a few years.

A personal history of diversity

Just came across the BMES Inaugural Diversity Lecture by Sheldon Weinbaum, in which he gives a broad and personal history of efforts to promote diversity. I've always been impressed by the originality of his scientific ideas, and the passion with which he pursues, presents and defends them. So it should have come as no surprise -- but did anyway -- that he has been on the front lines of the culture wars for nearly half a century(!).