Chondroitin Sulfate/Glucosasmine Supplements: Effective for Osteoarthritis?

Chondroitin Sulfate/Glucosasmine Supplements: Effective for Osteoarthritis?

I’ve both heard and read from several places that clinical studies show no real significant improvement using these two supplements.

However, the anecdotal evidence is quite shocking, and I still think it is surprising even after having read advocacy for supplements two years ago.

My blog is starting to sound a bit too clinical than truly reflective of my own research. I’ll try posting a few other “quick” posts like these to better reflect my research interests.

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Why OA characterization is still key

Why OA characterization is still key: “… there is a need of a method to segregate patients with different OA subtypes in order to pair them with an optimal mode of action. This may help redeem the OA clinical trial area…”:

See the abstract/full text paper

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Writing Manuscripts/Papers

I’m amazed at how much work, diligence, and time writing papers can take. Professors, scientists, and fellow grad students who have done so have my utmost respect.

Trying wholeheartedly to get my first ever attempt at a first-author manuscript submitted, pending more edits and pieces of advice from my peers and supervisors. Fingers crossed!

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Compressed Sensing Overview

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: NIBIB Plenary Session on Innovations in Imaging: How Compressed Sensing will Change the World of MR

Title: Compressed Sensing Overview

Presenter: David Donoho

Date Presented: Monday May 7, 2012

Dr. David Donoho is a statistics professor at Stanford University. I think it is always interesting to listen to professors specializing in majors not necessarily common in MR research. Donoho was a great speaker, and I clearly remember his introduction about how his hotel location was strangely relevant to his talk – Donoho’s hotel is next to a casino, a place he considers a prime example of randomness.

Although compressed sensing (CS) has been “in vogue” since 2005, it has enjoyed a much earlier history.

I wrote nearly a year ago but forgot to “press” it.

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MRI: from Science to Society

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: Lauterbur Lecture

Title: MRI: from Science to Society

Presenter: Vivian S. Lee, M.D., Ph.D., M.B.A.

Date Presented: Monday May 7, 2012

Vivian S. Lee was the ISMRM president for both the Executive Committee and the Board of Trustees. She has served numerous other positions with ISMRM and is the CEO of University of Utah Health Care. She has also served as the Senior Vice President for Health Sciences at the University of Utah and Dean of the University’s School of Medicine. She gave a talk at ISMRM’s opening plenary session early Monday morning discussing MRI’s past, current and future impact on society in relation to past, current and future scientific progress. This was a general talk that I feel all people in the MR industry need to consider in securing a brighter future for MRI in creating a more positive impact on society.

I was helping a dear UW-Madison colleague, Fang Liu, to prepare his final version of his Powerpoint presentation for his talk on MSK relaxometry, so I missed part of Lee’s talk, although I really wish I didn’t! However, I did catch a significant part of Lee’s talk and I feel it still made a significant impact on my perception of MR research.

One question we as MR researchers should consider is if we are focusing on the right issues. Lee pulled up a list of the top causes of morbidity (disclaiming beforehand that this is only one possible approach and not necessarily the best in answering this question) and noted that MR research does cover a fair majority of these causes. However, when comparing 1. the top-ranked medical issues in terms of cost, and 2. the volume of abstracts from ISMRM identified for each category, it is clear that MR researchers place a disproportionate amount of attention toward mental disorders and not enough in arthritis, lung, or cardiovascular disorders. In fact, a correlation measure between the most costly medical issues and the number of abstracts in each category shows very nearly zero correlation (R2 = 0.006)!

Secondly, MR research may be placed under scrutiny by the medical industry for the lack of MR studies utilizing evidence-based medicine. When looking at various medical journals, the median sample size for each study was at least 261 (for articles from medical journals looking at imaging), but the median sample size for studies reported in imaging journals is 32. Imaging journals mostly cover pilot and cohort studies, and not evidence-based medical research. Lee then discussed how, in light of the now limited-than-ever financial situations for the medical industry, clinicians and medical societies are reaching a consensus of recommendations against (or at least, not in favor) of MR imaging for medical strategies. Imaging as a whole, in fact, has received little acclaim in the new financial paradigm for hospitals around the world (minus a few exceptions – Australia was noted). It is obvious that MR is under increased scrutiny from the medical industry and society, and Lee feels that this is likely due to the lack of evidence-based medicine research. In Lee’s words, evidence-based medicine research leads to evidence-based funding.

Furthermore, Lee asked if MR research is adding value to society over other technologies. In other words, are MR researchers in any way demonstrating how MRI is a superior modality for a particular application in any respect over other methods, such as echocardiograms? Lee found a lack of comparative effectiveness research, and noted that it is this lack of CER that we simply don’t know the answer to this question.

Lee believes that creating imaging consortiums may be a potential way for MR researchers to address these key questions. She noted one such consortium, called MESA, short for Multiethnic Study of Atherosclerosis.

In light of the changing medical paradigm, these questions are imperative to securing the future of MR research.

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Clinical Assessment: Cartilage Repair (Clinical Issues/Surgical Options and Limitations)

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: Clinical Intensive Course – Musculoskeletal MRI: Imaging Following Surgical Repair

Title: Clinical Assessment: Cartilage Repair (Clinical Issues/Surgical Options & Limitations)

Presenter: Constance Chu, MD

Date Presented: Sunday May 6, 2012

Asides from being highly revered in the MSK radiology and ISMRM community, Constance Chu is the director of the Cartilage Restoration Center at the University of Pittsburgh. While being clinical in nature, this talk helped to highlight some key aspects that I should consider in the long-term to do meaningful research for MSK clinicians and radiologists.

Chu started her talk with a general overview of the constituent breakdown of cartilage – i.e. cartilage consists of water, collagen, proteoglycan, and a small amount of cells. She remarked (rather cleverly) that articular cartilage appears rather “bland” – that said, articular cartilage serves very special functions for the body and no synthetic materials can sustainably replace articular cartilage.

After her introduction, Chu differentiated between partial thickness and full thickness defects. These were short slides, but I could not catch everything – my understanding is that partial thickness defects do not heal, and full thickness defects are not the same as osteochondral defects. Any comments to offer more insight on this would be very helpful!

One clinical concern about these defects is that doctors tend to overestimate the size of these defects. Chu displayed a picture of specimens with cartilage defects alongside US coins, demonstrating that while doctors sometimes refer to a cartilage defect as being the “size of a quarter”, this is a gross overestimate of the real cartilage defect size. Decision-making for cartilage treatments should consider lesion size, patient size, bone involvement, and other such factors.

The rest (admittedly comprising the bulk) of the talk focused on case studies in pre- and post- surgery differences as seen through imaging. Some of these studies were ex-vivo animal models, while some as I recall also included the analysis of the progression of human treatments.

One thing I did catch was that stem-cell based OA repair methods need to consider variable healing potential depending on donor sex and age, as reported by Payne et. al. 2011.

This is one talk that I feel I could not adequately cover due to my lack of clinical knowledge, and so I would like to emphasize how appreciative I would be of any helpful comments sharing any important implications of this talk! 🙂

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MT Properties of Tissue

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: Educational Course – MR Properties of Tissue

Title: MT Properties of Tissue

Presenter: Peter van Zijl

Date Presented: Saturday May 5, 2012

Peter van Zijl is the founding director of the Kirby Research Center at the Kennedy Krieger Institute, associated with John Hopkins University. He gave a (very) informative talk on Saturday about the history and science of magnetization transfer (MT). His talk was absolutely amazing (I think it was definitely one of the top 3 presentations I have yet seen at this year’s conference), although there are good reasons I may be biased toward this position, given my personal association with qMT and MSK research.

Zijl first explained the different mechanisms that cause the MT effect. There are 2 main reasons, but when described in detail there are actually 6 different mechanisms for the MT effect:

1. Through space dipole-dipole coupling. This mechanism explains that two magnetic dipoles directly interact in what is called dipole-dipole coupling.

2. Chemical exchange.

1b. Relayed dipolar transfer spin diffusion

2b. Exchange-relayed dipolar transfer

2c. Dipole-dipole relayed exchange transfer

2d. Inter-molecular dipole transfer

He went through each mechanism relatively quickly, and so if any readers have any questions on this, let me know and I will see to contacting van Zijl or other scientists with comparable knowledge on the matter.

van Zijl went on to explain how the spins on one proton can transfer to another after RF saturation transfer. Basically, after transferring some spins to the neighboring proton, the two protons relax to an equilibrium state due to T1 relaxation. This RF saturation effect gave rise to the Nuclear Overhauser Enhancement (NOE) effect. While the effect is extremely complex in nature, it basically explains a changes in spin population when neighboring dipolar coupled spins are saturated.

In vivo MT provides a very complex imaging environment. In short, sequences need  to consider physiological conditions and account for multiple physical compartments with multiple spin sites.

van Zijl went on to explain the differences between continuous and pulsed saturation transfer for MT. He pointed out a very interesting sequence that used two on-resonance RF pulses to induce an MT saturation effect. What I understood from this sequence is that the pulses were sufficiently close enough together that the T1* effects of the bound vs free protons provided different signal intensities for each compartment. van Zijl then pointed out myelin and demyelination applications using magnetic transfer contrast (MTC) methods.

van Zijl argues that MT imaging is likely affected by mobile proteins and peptides because we clearly know water interacts with proteins along different groups, including amides, amines, and hydroxyl groups.

Chemical Exchange Saturation Transfer (CEST) exploits the MT effect to detect low concentrations of macromolecules. Using CEST, researchers were able to use animal models to see MTR differences between ischemic vs non-ischemic conditions, and cancerous vs non-cancerous conditions. It was also possible to measure glycogen and GAG (in the knee) content using CEST. van Zijl concluded with a plug for the OctoberCEST conference in Maryland, USA.

Here are a couple (unorganized) notes I found personally useful:

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Compartment Specificity in MR

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: Educational Course – MR Properties of Tissue

Title: Compartment Specificity in MR

Presenter: Itamar Ronen

Date Presented: Saturday May 5, 2012

Itamar Ronen is an associate professor from Leiden University Medical Center. I have not read any of his works before, although he seems to have held quite a few significant titles at previous institutions. I came to his talk about compartment specificity in MR because I wanted to obtain a better understanding of how the MR community utilizes MR components to resolve various tissue compartments in the body. Personally, I think this was a great talk to gain insight on this issue.

There are two criteria that researchers generally use to define an MR compartment. A compartment: 1. must contain an “MR visible” species (such as the 1H in H20, Na+, the phosphate group in ATP, NAA, or the 23F in PFC..) and 2. does not have to be impermeable to that species, but should allow enough residence (or was it residual?) time for distinct MR properties. Compartment specificity is important because it: 1. provides a basis for understanding disease (for instance, in axonal vs. myelin damage in multiple sclerosis, or to investigate what happens in ischemic stroke); 2. helps us understand physiology (e.g. neuronal activation and neurotransmitter release/reuptake); 3. elucidates microscopic features in gray and white matter; and 4. improves specificity of signal for methods such as tractography.

For MR compartmentalization, there are some well-known properties MR researchers look for: 1. Relaxation times T1, T2, etc.; 2. Diffusion properties, perfusion, and flow; 3. Magnetization transfer properties; and 4. Chemical shift (either naturally incurring or induced differences).

Ronen then provided some interesting examples of these various MR properties and how they inform researchers about different compartments. One such example was diffusion. Ronen introduced diffusion in a Brownian motion context, showed a classical diffusion sequence from Stejskal-Tanner, explained ideal vs realistic conditions such as non-restricted displacement, and displayed ADC images explaining how both fast and slow water components arise from the intracellular space. He also mentioned T2 and DTS compartmentalization.

Here are a couple (unorganized) notes I found personally useful:

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Quantification of MT Effects and Quantitative MT Imaging

This post is part of a series of posts covering my various experiences at ISMRM 2012.

Presentation Type: Educational Course – MR Physics for Physicists

Title: Quantification of MT Effects and Quantitative MT Imaging

Presenter: J. Sled, PhD

Date Presented: Saturday May 5, 2012

Medical Biophysics Professor John Sled from the University of Toronto is one of the leading scientists I watch to give insights about qMT design. He gave a talk on Saturday covering a lot of ground on the literature on quantitative MT. I did not catch everything, but below is a summary of my attempt to follow along.

He started his talk describing the significance of  magnetization transfer (MT). One such explanation was that the T2 is too short in H nuclei associated with macromolecules, and so if we want to image these macromolecules using MR, we would have to resort to MT to indirectly image macromolecules. He explained further that MT is used in many neurological applications including multiple sclerosis (looking at white matter [WM]), dementia (looking at gray matter [GM]), traumatic brain injury, and normal development. There are a slew of non-neurological applications as well, including cartilage and angiography.

He then proceeded to explain a two-pool model, comprised of the “free pool” and the “restricted pool”. This is one way to classically explain the exchange between the “free” water protons with the “restricted” protons. Sled then showed a diagram of white matter at the microscopic level, pointing out the different compartments where water protons would interact with WM cells and how this gives rise to different T2s (I caught three T2 components: the extracellular component, the free T2 component inside myelin, and the restricted T2 component inside myelin).

Sled then explained various techniques that apply MT, starting with inversion recovery (IR), balanced steady state free procession (BSSFP), and off-resonance saturation MT techniques (including continuous wave MT and pulsed-wave MT).

One other important parameter Sled mentioned was the magnetic transfer ratio (MTR). He showed the audience different qMT maps of the brain and pointed out maps that showed WM/GM contrast.

In summarizing the strengths and weaknesses of qMT, Sled explained that qMT provides useful sensitive contrast, quantitative voxel-wise / regional analysis, additional parameters that could increase specificity over MT-weighting, and normalized the results because qualitative images are very dependent on scanner parameters (whereas qMT is more robust to these parameters). However, qMT takes time both in imaging and post-processing, and the modelling can be very complex.

Here are a couple (unorganized) notes I found personally useful:

  • The bound pool fraction F = PD_r / PD_f, where PD_r is the proton density of the restricted proton pool and the PD_f is the proton density of the free proton pool.
  • The exchange constant R has the relation R = k_f/F, where k_f is the forward exchange rate.
  • The literature sometimes differentiates k_f from k_b (forward vs. backward exchange rate), but many papers use just one exchange rate (k) to describe the exchange rate. The mathematical relation between k, k_f and k_b currently eludes me and I hope to look this up sometime this week.
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My ISMRM 2012 Coverage

As I stated before in an earlier post, the next posts over the next several days will detail any key findings at ISMRM 2012. I realize this can be personally overwhelming considering the amount of time and effort this takes relative to the amount of willpower I have, but I hope to try my best to keep this up to date and hopefully useful to me (and potentially others).

For each formal presentation, I intend on creating a separate post. Each post will include the title of the presentation, the section it was in, the presenter’s name, the date presented, and notes about the presentation. I have a handy legal pad which I am using to keep my notes on, and it is from this legal pad that I am transferring my notes here. The disclaimer here is that I am likely to make both major and minor errors due to issues in transcription or even fundamental understanding. That said, I invite all readers to view and comment on any corrections!

Here’s hoping to a great conference!

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