Be More Specific… Or It May Not Be Causal?!!!

Well, if you are relaxed and heading nowhere in particular then I guess you probably won’t be too concerned with showing causality either. In our past few posts we have been discussing Bradford Hill’s criteria for determining causality (see Strength and Consistency for a refresher). If you are stressed out already, have a listen to “Come the morning” from an up and coming Canadian artist from Winnipeg, Manitoba – Sebastian Owl – before reading on.

Today we will talk about the third of the nine Hill criteria: Specificity

When considering the specificity of the association of interest, we wish to establish whether a single putative cause produces a specific effect. When specificity of an association is found, it provides additional support for a causal relationship.  But keep in mind that very often the effect under investigation may have more than one cause. So the absence of specificity in no way negates a causal relationship. This criterium of Hill’s is considered to be the least important and can often be over-ruled in the case of multi-causal relationships.

Next, post we will talk about the oh-so-important criterium: temporality.

If you are nowhere in particular then you are not being specific to your whereabouts – right? Anyway, why don’t you watch this great Film festival short by Mason Cardiff, Nowhere in particular, to decompress and…

… I’ll see you in the blogosphere.

Pascal Tyrrell

Consistent Associations May Be Causal Ones…?

Do you remember the Rain Man movie with Dustin Hoffman and Tom Cruise? Great movie that introduced Savant Syndrome to theater audiences all over the world. The savant syndrome is a rare condition in which persons with autistic disorder or other mental disabilities have extraordinary skills that stand in stark contrast to their overall handicap. There is a very interesting documentary on Kim Peeks who was the inspiration for the movie here. Anyway, last post we talked about strength – one of Bradford Hill’s criteria for causation (see here for a refresher). Today we will talk about consistency, a good qualifier for the often obsessive and ritualistic behaviors of autistic savant persons.

An association between two entities is consistent when results are replicated in multiple studies in different settings using different methods. So if a relationship is causal, we can expect to find it consistently in different studies and among different populations.  This implies that many studies need to be done before meaningful statements can be made about any causal relationship.

A great example of this is the long debated causal relationship between smoking cigarettes and lung cancer. It took hundreds, if not thousands of highly technical studies and many, many publications before a definitive conclusion could be made that cigarette smoking increases the risk of cancer and in a causal manner (see here for a statement from the CDC Surgeon General).  

So be consistent in your smoking cessation and you will consistently avoid the risk of lung cancer…

Next post we will tak about Bradford’s third criterium: specificity.

Relax listening to the very eighties styled theme music to Rain Man and…

… I’ll see you in the blogosphere.

Pascal Tyrrell

Causality and Who’s Running Up That Hill?

Yes, back to the eighties. They were my high school and undergrad years – so very memorable! This song – Running Up That Hill – by Kate Bush was her first great hit from that time.

So, why was she running up that hill you ask? Well, it was because she had finally come to realize the importance of establishing the minimal conditions needed to establish a causal relationship between two entities, of course! Somewhat like the story of Archimedes who leapt from his bath yelling “Eureka” in excitement having discovered a law of physics that would later become the building block to fluid mechanics (see Archimedes principle).

In 1965 (no, I was not born yet – but just!), Austin Bradford Hill a British medical statistician proposed minimal conditions needed to establish a causal relationship between two entities. These later became know as the Hill’s Criteria. Very often people get the relationship of association confused with that of causality. See my previous post Rebel Without a Cause for some insight on when an association can be considered as cause and effect.

Today we will talk about the first of the nine Hill criteria: Strength

– The strength of an association is defined as the size of a given association as measured by appropriate statistical tests.  The stronger the association, the more likely it is that the relation between the two entities of interest is cause and effect.  For example, the more highly correlated hypertension is with smoking, the stronger is the relation between the exposure, smoking, to the outcome, hypertension. Though we cannot be sure of the direction of the relationship (this will be achieved when we discuss Temporality) – as hypertension could hypothetically lead subjects to smoke – we can certainly decide that the strength of the association observed supports our argument of causation.

Look at that, we have completed the first criterium all ready! Next we will look at Consistency.

Have a listen to “Strength Of A Women” by Shaggy to recover from today’s fun and…

… I’ll see you in the blogosphere.

Pascal Tyrrell

Kiersten Thomas – Summer 2015 ROP at UofT: Another great student experience… part deux!

Kiersten Thomas – ROP summer 2015

Hello, I’m one of Professor Pascal Tyrrell’s summer ROP students and a second year Immunology Specialist student at the University of Toronto. I have just completed my summer research project investigating the cost-effectiveness of using MRA to evaluate asymptomatic carotid artery stenosis. 

I learned a lot and had an amazing time conducting research with Dr. Eli Lechtman and my ROP partner Indranil Balki. Using TreeAge Pro to create and analyse decision trees, we demonstrated that the additional information gained from an MRA/IPH scan increases the effectiveness of MRA when imaging carotid artery stenosis. 

Our research suggests that the additional information of the presence of intraplaque hemorrhage (IPH) would lead to better patient care, reducing long-term stroke risks. This means that MRA/IPH can be cost-effective or even dominant when compared to the current imaging strategy that uses standard ultrasound as a first-line imaging modality, for evaluating all degrees of asymptomatic carotid artery stenosis. Take a look at my timeline to see some of the highlights of my summer!

Thank you Dr. Pascal for this wonderful summer. 

Kiersten Thomas

Indranil Balki – Summer 2015 ROP at UofT: Another great student experience!

Indranil Balki – ROP Summer 2015


I am one of Dr.Pascal’s 2nd year ROP students at the University of Toronto.  This summer, I had an amazing experience into the realm of research working with my partner Kiersten Thomas, mentor Dr. Eli Lechtman, and supervisor Prof. Pascal Tyrrell. This timeline-cum-infographic highlights some of the especially memorable moments of this journey.
Our main project was focused on constructing a computer simulation to model the effect of choosing either MRI or US as a first line imaging modality to diagnose and treat patients with Carotid Artery Disease. This project involved comprehensive literature search, discussions with experts (including the “Trip to Cambridge”), learning computer software and presentations!
Our team’s models’ main finding was that MRI can be both more effective and no more costly than US as a first line diagnosing tool in measuring carotid artery disease.

Thanks to Dr. Pascal for allowing me to share my experience on his blog and I hope you enjoy the read!
Indranil Balki

Another Reason Why a Brain Boo-Boo Is Bad.

Rostam Rashidkhani – YSP 2015

Rostam Rashidkhani is a grade 12 International Baccalaureate student at the Toronto French School and he was a Meds – Youth Summer Program student with me this summer.

Rostam is intrigued by the sciences and enjoys biology, chemistry, and physics in school. He has participated in a number of University of Toronto summer programs and is looking forward to University life!

This summer Rostam looked at what causes brain problems after traumatic brain injury and how best to detect these changes with MRI. Recent brain imaging studies, including those in former professional football players, indicate that persistent brain inflammation after a single moderate head injury or repeated milder traumatic brain injury may be very common, may contribute to cognitive problems. More importantly, the chronic brain inflammation related to traumatic brain injury may be treatable. Looking for chronic traumatic brain inflammation with followup MR may be a way to reduce cognitive impairment.

Well done, Rostam!

Enjoy the read and…

… see you in the blogosphere,

Pascal Tyrrell

Some R&R with UofT YSP and Elizabeth Lehner…

Elizabeth Lehner – YSP 2015

Maybe not all rest and relaxation but certainly radiology and rheumatology! Here is a great example of why collaboration between disciplines is so important in medicine. Elizabeth recently graduated from Iroquois Ridge High School and will be a new University of Toronto student this fall. See her post below. 

Great job Elizabeth!!!

Many people are familiar with the word arthritis. This is probably because one in six Canadians aged 15 years and older report having arthritis. Rheumatoid Arthritis is a specific form of arthritis that unfortunately can lead to severe disability and joint replacement. 

Over the past several weeks, I participated in the 2015 YSP research program with the Division of Teaching Laboratories within the Faculty of Medicine at the University of Toronto and had the opportunity to look more closely at Rheumatoid Arthritis and ways to better diagnose this debilitating disease.

Under the supervision of Prof. Pascal Tyrrell and the Department of Medical Imaging at U of T, I was introduced to various imaging modalities including MRI machines, CT scanners and ultrasound machines. The work by Dr. Tyrrell was of particular interest given his studies on inflammation and the use of the various imaging modalities.

As part of this program I also participated in specific lab tasks including dissections and micropipetting and was exposed to clinical work such as suturing and operating an ultrasound machine. In addition, the program provided me with the opportunity to participate in daily workshops led by two instructors from the Division of Teaching Laboratories, Jastaran Singh and Jabir Mohamed. These workshops provided important overviews on a variety of topics relating to research that were very interesting.

The things I learned in this program provided me with a much better understanding of various research and medical issues that I think will be of use to me as I begin my studies at the University of Toronto this fall.
I would very much like to thank Prof. Pascal Tyrrell, Jastaran Singh and Jabir Mohamed for allowing me to be exposed to the various projects and for answering the many questions that I had during the program. Thank you!

Elizabeth Lehner

MiWord of the Day Is… UBO?!!!

I must mean UFO or Unidentified Flying Object? You remember the movie Close Encounters of the Thrid Kind? Spielberg’s massive hit in 1977 following his release of the original Jaws. Back in those days UFO sightings were often in the news (or tabloids anyway) and this movie hit the sweet spot. It even helped launch the toy “Simon” which as it turns out was very similar to the multicolored, note-playing alien saucers featured in the movie – coincidence?

So, what the heck is UBO? Well, as it turns out the human body exhibits a variety of anatomical details in the ever so important Magnetic Resonance Imaging (MRI) scan that we have all learned to love (see our series on MRI and Carotid Stenosis). The majority of patients have similar anatomical features on imaging but some fall outside these normative patterns. When radiologists come across findings that are difficult  to interpret they will often refer to them as “Unidentified Bright Objects”. The challenge, of course, is that the radiologist needs to decide whether to label the anatomy in the image an “UBO” – essentially an image artifact – or “disease”.

This is where the rubber meets the road. Interpretation of MRI scans is work done by people, and, as with all jobs, the quality of performance varies. Therefore, the accuracy of the MRI exam is heavily dependent on the quality of the radiologists who interpret them. It is for this reason that the training a radiologist receives is crucial to his/her success. In addition, there is an important relationship that exists between the radiologist and the primary care physician as they have to balance indications of abnormality in MRI scans with the information provided by other techniques such as the clinical exam. A successful diagnosis relies on a good team effort. 

Go Team!

Now for the fun part (see the rules here), using UBO in a sentence by the end of the day:

Serious: Went for my MRI today. Told me that the UBO on imaging was just an artifact. Nothing to worry about. Phew!

Less serious: Hey Bob, did you hear on the news the report of another UBO hovering over farmer John’s field last night?  Or was that UFO? I always get those two mixed up…

Listen to UB [4] 0’s Red Red Wine to decompress and…

…I’ll see you in the blogosphere.

Pascal Tyrrell

An “Egg-cellent” Journey to Investigate Carotid Artery Stenosis in Cambridge, Ontario…

Last Wednesday, my ROP students Kiersten and Indranil, and UofT medical student Eli Lechtman had the opportunity to interview the legendary (see here) Dr. Kim Tysdale – a general practitioner in Cambridge, Ontario.

Why do you ask? Well each year 50,000 Canadians suffer from a stroke with 26% due to carotid artery disease. Carotid artery stenosis is the narrowing of the carotid arteries due to plaque buildup (see atherosclerosis). These plaques can then rupture and create blood clots that travel up to the brain. In turn, these blood clots then get stuck in the brain’s smaller blood vessels, causing a stroke. So plaque = bad and ruptured plaque = worse!

What if we had a clue as to which plaque may rupture? Well, in turns out that the presence of intraplaque hemorrhage (IPH) can help us predict just that! IPH is bleeding within the plaques, which causes them to become more vulnerable (see vulnerable plaque). There is a 6 times greater risk of stroke in people with IPH! And…. a new medical imaging technique called MRIPH imaging allows for visualization of IPH. MRIPH is similar to traditional MRI but highlights the artery walls and looks at the arterial plaques. 

While in Cambridge, Kiersten, Indranil, and Eli presented Dr. Tysdale with an overview of medical imaging techniques for the assessment of carotid artery stenosis with an emphasis on the new MRIPH technique. Informing physicians like Dr. Tysdale which of his patients are more at risk of having vulnerable plaques (by providing information on IPH) could result in patients receiving more appropriate and timely treatment – thereby reducing the number of strokes! 

BTW, we had Dr Tysdale at “hello” (not sure what I am referring to? See here).

So what up with the eggs? Kiersten, Indranil, and Eli also had the chance to tour Dr. Tysdale’s beautiful country house and meet his lovely wife (and nurse!), Eva, who sent everyone home with fresh chicken eggs! Awesome.

Thank you Dr Tysdale for being such a great sport!

Here is their infographic of the trip (great job gang!). Enjoy!

Kiersten Thomas and Indranil Balki – ROP Summer 2015

Stay tuned for more ROP adventures!

Pascal Tyrrell

MiWord of the Day Is… Magnet!

Who hasn’t thought of having Magneto’s powers? No? Maybe you should watch this Magneto trailer for a refresher. 

Ok, now that we all want to be Magneto (secretly at least) what is it that is so appealing with having the power of magnetism? Bill Nye the Science Guy explains it very well in this clip. Have a gander.

In a nutshell, magnetism is a physical phenomena that consists of a field of energy created by “magnets” that attracts or repels other objects. Magnets come in two major flavors: permanent magnets made of materials (such as iron) and electromagnets – the strongest and most widely used in medical imaging. 

Interestingly, it is the sum of the magnetic fields of individual electrons that is responsible for all the fun (see quantum mechanics). In the case of electromagnetism the electric current in a wire produces a magnetic field in the same direction of the current. In the case of a permanent magnet it is the magnetic fields of the naturally occurring electrically charged particles of the atoms that make up the material (iron for example) that are responsible. However, for there to exist a force strong enough to attract or repel another object all of its magnetic ions must have their magnetic fields aligned and contributing to the net magnetization. This is how you can magnetize a needle when stroking it in a uniform directional way with a permanent magnet.

Magnetism is to MRI what radiation is to X-rays. The strength of magnets is measured in gauss and Tesla units. There are 10,000 gauss to a Tesla and the earth’s magnetic field is one half of a gauss. Today most clinical MRIs use superconducting magnets whose strength range up to 4 Tesla! Experimental MRIs can run up to 10 Tesla. Now that is more Magneto’s speed.

The powerful magnets allow for better spacial resolution allowing for better sensitivity of the image. However, all this magnetic strength comes at a cost: the production of chemical shift artifacts – ghosts of things that are not really there. This is why we have radiologists to make sense of it all.

OK. Now you are asking what the heck. Magneto in the X-Men movie was able to rip out the iron from a human so why doesn’t an MRI? Great question. Iron found in the human body is mostly found as ferritin (a type of iron oxide) and is NOT magnetic. The iron in hemoglobin is also NOT magnetic. Bummer. So how does Magneto do it? Well either the movie is not scientifically correct (now that would be a shocker) or possibly he could be drawing on magnetite (another iron oxide) that is magnetic and has been found in trace amounts in the blood and brain. It is so little though that it does not cause any concern for MRI. Oh well, so much for Magneto…

Now for the fun part (see the rules here), using magnet in a sentence by the end of the day:

Serious: Hey Bob, did you know that early MRI machines used permanent magnets?

Less serious: Went for my MRI today. Told them I was worried the MRI would rip all the iron out of my blood like in X-Men. They didn’t even know who Magneto was. Whaaaat?!!

OK, listen to Magnetic by Traphik to decompress and I’ll see you in the blogosphere…

Pascal Tyrrell