 Good day everyone, today I am going to discuss about an important topic which is not much explored in the routine textbooks and which is given more in detail in the dedicated physics textbooks and journal articles. But yet it is confusing and important to know for the residents because I see many residents who have a common myth who think that it is a gadolinium that appears bright or white on MRA scans and I want to clarify this myth because unlike barium and iodinated contrast medium CT, they themselves appear bright on the scans but with gadolinium it is a different scenario. It is not the gadolinium itself that appears white but the neighboring water molecules which are influenced by the gadolinium. We will discuss how this happens and before that a little briefly I will be explaining about the type of ligands to which the gadolinium is attached and what is gadolinium. Gadolinium is a rare metal that belongs to the lanthanide series on the periodic table. So if you see the periodic table there are so many elements which are arranged in rows and columns and in that the lanthanide series is one of those columns in which gadolinium is included. Gadolinium has got the highest number of unpaid electrons, seven unpaid electrons in its full absorption. The key word here is unpaid because of this unpaid electrons the magnetic movement effect is very high. It exists as a paramagnetic metal at room temperatures and when it is bound with the ligand. Even in ionic form it still retains its seven unpaid electrons and it has got a very high magnetic movement as we discussed because electron magnetic dipole movement is very very high when compared to the protons magnetic movement. Till now we are more concerned with proton magnetic movement in MRI but we should know that the electrons magnetic dipole movement is very much high approximately 650 times greater than that of the protons magnetic movement. What is the ligand? What is this ligand we are discussing? Pure gadolinium if you inject is highly toxic. One of the reasons being it has got the same diameter the atomic diameter is same almost similar to that of the calcium ion. Calcium ion is we know that it is the vital component of the human physiological processes mechanism that takes place. Calcium is used in is utilized in the cell membranes in muscle contractility and so many other sites. This gadolinium having the same diameter as that of the calcium it kind of cheats the cells and it computes with calcium and it replaces where the calcium is supposed to be. So it is this is called competitive inhibition and the charge is also higher than that of the calcium. This also has got a factor in the cells selecting the gadolinium instead of calcium. So when gadolinium goes and sits in the place where calcium is supposed to be it inhibits the physiological and biochemical processes. So that is how gadolinium cheats the cells because its diameter is almost similar to that of calcium and also it has got a higher charge. So cell thinks higher charge prefers higher charges. So what do we do to make it non-toxic? We kill it with a ligand. A ligand is nothing but a molecule that is used to bind an atom. Here the various molecules the ligands we have are DTPA, DOTA, we will discuss about them. This ligand not only helates the gadolinium ion rendering it non-toxic but it also influences improves its excretion as well. So in Greek helos means claw. So you can see here how gadolinium is caught or wrapped by the ligand molecule and gadolinium is in the ion is in the center. Based on this chemical structure of ligand we have linear and macrocyclic. So linear I have typed the examples and macrocyclic I have mentioned the examples. So you can find them in your textbooks as well but what is the mechanism here? Linear molecules they wrap around the central ion of gadolinium. So I will show you the diagrammatic representation. See this is a linear DTPA ligand. When we introduce gadolinium into it see how this linear molecule wraps around the gadolinium. So you can take a simple analogy of a flight wrap. When in resting state it is open like an open mouth but when a fly rests inside it in the center it closes isn't it? So same is the mechanism here. This whole linear molecule kind of wraps around the gadolinium and casing it in the middle okay. So linear molecules wrap around the central ion. Areas macrocyclic they already have a fixed cage like structure okay. The chemical structure is like a fixed cage within which in the center the gadolinium ion resides okay. So compare it with a fixed bird cage and inside how a bird stays in the same kind of mechanism okay. Same kind of analogy. So gadolinium is in the center of a fixed cage. So according to the studies macrocyclic ligand variety are more stable compared to linear because it is difficult to extract the gadolinium ion from the macrocyclic ligand structure rather than a linear ligand structure and based on the ionicity also the contrast gadolinium contrast media can be categorized based on their ionicity that is the net charge. Here are some examples of ionic gadolinium contrast media non-ionic gadolinium contrast media. What do you mean by ionic contrast and non-ionic here? Here ionic molecules have a net negative charge after chelation that means after the chelation process is over still some net negative charge remains those are called as ionic gadolinium contrast media whereas non-ionic molecules they do not have any net charge the charge becomes zero okay after the chelation process is over and according to studies the ionic gadolinium contrast media are more stable compared to the non-ionic gadolinium contrast media. Now we come to the main part how gadolinium influences the water molecules to relax faster and and thus responsible for appearing bright on the MRI scans so you need to know the concept of molecular tumbling rate so till now we know that the protons hydrogen protons are the nuclei they wobble or precess when they are placed in the magnetic field isn't it so now we should know that it is not only the protons that precess or wobble but molecules as a whole also continuously move about they exhibit continuous tumbling movements so it may be a rotation movement or vibration or translation it's not due to the magnetic field they it's an inherent property of the molecule they are in continuous motion so we cannot see it without naked eye but the molecules are continuously moving about okay so these are the types of movements and they continuously collide with one another okay these movements are what are responsible for the fluctuating magnetic fields and stimulation for even relaxation we know that even relaxation is also called as spin lattice relaxation so spin lattice means the energy is transferred from the spins to their surroundings that is the lattice this energy transfer is most efficient when the tumbling rate that is the fluctuating magnetic field frequency coincides with the standard larmer frequency in which the magnetic field is being operated so that is why we know the packed molecules tumbling rate the movement of the packed molecules coincides with the standard larmer frequency that is why the t1 relaxation of packed is is high okay they relax very fast whereas the water molecules tumbling rate is very high water molecules have got a very high tumbling rate which far exceeds the standard larmer frequency so they do not relax fast so that's why the t1 relaxation time is very high for water molecules that is the free bulk water molecules the same goes for solids because the solid molecules tumbling rate is less when compared to the larmer frequency and so they also do not relax as efficient as the packed molecules so the rate of relaxation depends on how well the tumbling rate matches with the larmer frequency for energy transfer so if you want to transfer energy so longitudinal relaxation means the energy has to be transferred from the spins to the surroundings this energy transfer is most efficient when this movement rate or frequency coincides with the larmer frequency so here so I have pictured an analogy as well all of you might be knowing this this is a brick game you we used to play in the pocket video games in the childhood or tetris you can see how each brick rotates or tumbles when it lands down isn't it so it's not in constant it usually rotates different it makes up different rotational shapes okay so in the same way when the molecule tumbles there is a fluctuating magnetic field around it this is the best example I'm going to show you so you observe how the water molecule water molecule has two hydrogen atoms and one oxygen atom okay this is the main magnetic field and you can see that the water molecule is in continuous motion and this continuous motion brings about changes in the magnetic field okay fluctuations in the magnetic field here you can see when the two hydrogen atoms are aligned with the magnetic field the local net magnetic field increases a bit and when they tumble perpendicular there is no net change in the magnetic field these do not influence the local magnetic field again when they rotate downwards there is a little subtraction the local magnetic field okay they do not they subtract from the main magnetic field so this is how the tumbling of the molecules influences the or fluctuates the local magnetic field and those protons which are situated in the neighboring the in the vicinity due to this fluctuation they also get influenced gadolinium actually enhances both p1 and t2 relaxation and the main mechanism behind it is proton electron dipole interaction it's not complicated the name is self-explanatory proton the the tissue that we are dealing with concept the water proton and electron okay because gadolinium has seven unfried electrons and dipole dipole is nothing but two poles any field that has two poles is called a dipole here north pole south pole pass to charge tail to charge their dipoles so they interact directly with one another that is what the word means here the phrase means proton electron dipole interactions and thereby the times are shortened you might wonder why t2 relaxation also occurs so that is a different mechanism that we are not going to discuss here it depends upon the concentration of the gadolinium in lower concentrations the t1 relaxation effect is dominates and in higher concentration the t2 relaxation effect dominates gadolinium molecule after it binds to the ligand has nine coordination sites they are nothing but think of coordination sites like a plugs okay attachment sites so gadolinium ion has nine coordination attachment sites out of these ligand by binds to eight sites okay you can count here one two three four five six seven eight so eight coordination sites are bound by the ligand and one site the ninth site is free for the attachment of the water molecule how the water molecule gets relaxed due to the presence of gadolinium ion there are three mechanisms that take place the relaxation may occur via inner sphere relaxation inner sphere means direct and close interaction with the gadolinium ion I will show you in a short while in the animation or it may be a second sphere relaxation by formation of hydrogen bonds or it may be outer sphere relaxation influence it as high water molecule diffuse nearby so this is the animation you observe how the gadolinium central ion and with the ligand it forms a molecule and this is the inner sphere the green one is the second sphere outer sphere and the surroundings will be our vicinity okay now each water molecule as I told you the ninth site is free for the attachment of the water molecule so it comes inside here it forms a it binds with the gadolinium it forms an interaction and it gets relaxed okay so the blue water molecules are those which are relaxed and the rest of the black water molecules are not relaxed okay so you can observe that after the relaxation is over it goes out into the neighboring bulk water and another molecule unrelexed water molecule takes its place and that gets relaxed okay the simplest analogy I can make up here is see suppose at the end of a stressful day you want to relax and you want to go to your music room okay so consider this as a room and gadolinium is where the music is playing work inside the room it's the speaker so what do you do you go inside the room sit there interact with the your stereo get relaxed and come out and suppose another person wants to get relaxed he can go inside interact with the music and go out now the music is loud enough that means it is very it is a powerful gadolinium I told you that powerful magnetic moment okay magnetic molecule so if the music is loud enough those people they need not go inside the room but those that are hearing staying near the walls of the room can also hear the music right so these are those people that are sticking their ears to the wall of the room and they are also getting relaxed by hearing that music okay that means the influence of the gadolinium is so powerful that's either it can go and interact in the inner sphere or it can interact via the second sphere as well at the wall of the molecule and if the music is loud loudest even those water molecules in the surrounding vicinity that means in the other rooms suppose someone is sitting in other room they can hear the music so loud they are especially playing heavy metal music they can hear the thump of that okay so if the music is too loud or if the power of the gadolinium mark is high even the neighboring diffusing molecules can also hear the music and they they also get relaxed okay so that is the best analogy which I can place here forever better understand so there are three mechanisms of relaxation in that sphere it goes inside and sits there then the second sphere near the walls they can also get relaxed and outer sphere the neighboring molecules as the diffuse nearby they also hear the music and get relaxed now in this way one molecule relax in going out the other molecule so if this type of exchange in one second 10 to the power of six hydrogen protons the gadolinium can relax 10 to the power of that means one million water molecules can get relaxed in this method in one second so you can imagine the fastness and the power of the gadolinium molecule so this process gets repeated 10 to the power of six times in a one second so this is a graph I'm showing you this is plain T1 relaxation without the gadolinium and post contrast you can see how rapid the relaxation takes place okay so the T1 relaxation time is very much shortened when you inject the gadolinium thank you