Diffusion and Intravoxel Incoherent Motion MR Imaging–based Virtual Elastography: A Hypothesis-generating Study in the Liver Radiology 2017; 285:609–619 Denis Le Bihan, MD, PhD • Shintaro Ichikawa, MD, PhD • Utaroh Motosugi, MD, PhD Herbert Y. Kressel, MD Hi. This is Herb Kressel and know by going to high b values or higher sensitivity to welcome to the November Radiology podcast. Today we diffusion; we are more sensitive to the interaction of the have a very special conversation with Professor Denny water of molecules with a tissue component such as cell Le Bihan who is the founding director of Neurospin a membranes or fibers. So diffusion is not free like in a high-field MRI research institute in Paris. Dr. Le Bihan is glass what we call Gaussian diffusion. In tissues, diffusion also a visiting professor in the Department of Radiology is hindered by obstacles, so this is called non-Gaussian at Kyoto University and the Kyoto Prefectural Hospital. diffusion. So the sADC is just a translation, so instead of Welcome Dr. Le Bihan. measuring the ADC with zero and 1,000, to increase the weight of non-Gaussian diffusion we shifted for instance Denis Le Bihan, MD, PhD Welcome and thank you so from 200 to 1500. So by this very simple move, but shift- much for inviting me with this very important task for ing the ADC we get more weight to the interaction of me and I’m thrilled to explain our findings. water molecules with a tissue component. H.Y.K. Oh good. The paper that Dr. Le Bihan and col- H.Y.K. Okay. Do you have a figure to show us this? leagues have authored is entitled “Diffusion and Intravox- el Incoherent Motion (IVM) MRI-based Virtual Elastog- D.L.B. I think so and I show you for instance on the top raphy: A Hypothesis-generating Study in the Liver.” Now of the figure in the CSF if we look at the water diffusing Denny I don’t get it. How can diffusion tell you about in CSF it’s free. That’s what we call Gaussian diffusion. tissue elastography? But in all tissues, let’s say a tumor or in the liver with no fibrosis whatsoever, the distribution of the displacement D.L.B. Well that is part of the concept we are trying to of the molecules is shorter, is smaller. That’s what we call introduce. Elastography is a way to measure elasticity of hindered diffusion. So now if we go under this diagram, tissues to get diagnosis based on tumors are harder than we show that because of this non-Gaussian diffusion, the background soft tissues, but elasticity of tissues is deeply attenuation of the signal is curved. So the slope has low rooted in the microstructure of tissues, so the density of b values between 0 and 1000. It’s bigger than the slope in cells, of fibers, and so on. But on the other hand, diffu- red let’s say between 200 and 1500. sion MRI is highly sensitive to the tissue microstructure, but it is a completely different physical mechanism so the H.Y.K. I see idea I had very provocative idea was that well diffusion and elastography should have the same rules. Is it pos- D.L.B. But that’s what we want to see. To characterize sible that we can get elasticity of tissues from diffusion tissues better we want to shift from the standard ADC to measurements or diffusion measurements from elasticity the sADC for sensitive or shifted ADC. So the calculation measurements? That was my idea. is exactly the same. Two b values, but just the b values are different. H.Y.K. Okay, so you use something called the tissue ADC as a potential biomarker for tissue elastography in H.Y.K. Okay so now we have this shifted ADC so the the liver in this paper. Many people are familiar with next question is how might one go from deriving the ADC but not with the shifted ADC concept. What is it? shifted ADC to actually using it as a marker of liver fibro- How might you determine it and how does it relate to sis for example? this type of measurement? D.L.B. Well the idea that if there is a relationship be- D.L.B. Yeah so I introduced ADC the apparent diffu- tween diffusion and elastography, I mean or specifically sion coefficient in my paper from 1986 in Radiology, a elasticity which is measured in kilopascals we should look long time ago. ADC has been a very good success and at which biomarker works best. And the sADC by con- it is used everywhere. The problem with the ADC, ADC struction, by principle, is a highly successful candidate. at that time was measured with low b values, now we In fact in our article we compare different ADCs and this ADC 200/1500 was the best. So we have no model, no H.Y.K. Yes. physical model, to link today the tissue microstructure to the tissue elasticity. I don’t think we can get any model. D.L.B. So they have a strong experience. The idea It’s too complicated. was to compare directly measurements of real standard MREs with potential virtual MRE from diffusion. So the H.Y.K. Okay. liver was the obvious target because this is where MRE is done most of the time. D.L.B. And we don’t have a model also to link the sADC to the tissue components. So we have to work as (inau- H.Y.K. Okay. And so what did you find? What were the dible) way, is there a relationship between the sADC and results? the tissue elasticity. So the idea is very simple we scan a few patients, we measure the sADC in the liver and we D.L.B. Well the first result on the first set of patients measure the elasticity of the tissue using standard MRE. is that we found this striking linear relationship between And we looked, is there a correlation between the two. sADC and elasticity. Then we expanded that to more patients and so reversing the equation so we can obtain H.Y.K. So you were looking for a correlation between new of the elasticity of the tissue from sADC and we the sADC values that you derived and the measured MRE compared it with the new value obtained from MRE. As magnetic resonance elastography values as derived con- you can see on the same figure on the right now, the cor- ventionally. relation is unbelievable. So the virtual shear stiffness we obtained from diffusion SADC, is almost the same as the D.L.B. (inaudible) relationship. one we obtained with real, standard MRE. H.Y.K. Do you have a figure to tell us about this? H.Y.K. Interesting. D.L.B. Yeah so if we look at the next figure, where we D.L.B. So basically you can replace the measurements plotted the sADC versus the tissue elasticity, what we see obtained with a mechanical device without any measure- is that we have a straight line. It’s a linear relationship. ment of mechanical vibration, just from the measure- When I started this concept, I was almost certain there ment of the sADC. would be a relationship from what I said, but not that it would be a linear relationship. Myself I was completely H.Y.K. Good now maybe you could tell us a little more surprised by the results. So there is a linear relationship about the output. So how do the diffusion based elasto- which means that we can translate the sADC measure- grams compare to the standard MRE elastograms and I ment into elasticity of the tissue in kilopascal. think you have the figure if I remember from the article that actually shows the appearance of them and maybe H.Y.K. Okay. you could talk about that a little bit. D.L.B. (inaudible) D.L.B. Right, so on this figure there are two cases. One which is a F3 fibrosis and the one is a 4. So first what we H.Y.K. So tell me let’s get on to the details of the study have to say quantitatively if we measure elasticity with that we published now. I know we’ve been going through standard MRE we get about the same numbers as if we some of the methodology, but what was the rationale use the sADC. That’s a very big result. for the study that you published here? What were you trying to find? The relationship that you’re talking about H.Y.K. Yeah. is of tissue elasticity to diffusion is general. How did you choose the liver as the area to interrogate and what did D.L.B. But now there is more. With standard MRE usu- you do? ally you have only one slice. Technically it’s possible to do more, but most of the time only one slice is acquired. D.L.B. Yeah so that’s very, very easy to respond. If fact Also, the spatial resolution of the MR, real MR elasto- potentially any organ can be used or checked and in- gram, is limited because we have to take into account the vestigated with diffusion MRI as elasticity measure. But wave lengths of the propagating shear waves. Because of the first step was to validate the concept. And today MR that we cannot get small results.