This is the slide series as presented to my MEG class of Feb 2016. 1 A general approach. DefiniAons combining words biology and magneAsm. You oEen see there words improperly combined. 2 Looking into BiomagneAsm, a bit closer. A minor and a major way that biomagneAsm is produced. 3 Minor way: To see magneAc parAcles in the lung, first (A) you magneAze the lung area with a strong bar magnet, then (B) there is a resulAng magneAc field around the torso, which can easily be measured. This field can be quite strong, depending on the amount of magneAc material in the lung. The idea here is to show one way to deal with contaminaAng magneAc material. 4 Major way: A very general picture of biomagneAsm produced by currents. In this example, the volume conductor is a wet biological blob of any kind. For example a piece of brain, or the muscle in your arm. There is a generator of electric current in the blob, where the current is shown as light lines with arrows. These currents sum up to produce a magneAc field around the blob – the heavy line. Not shown here are the surface potenAals (volts) over the blob. 5 Same idea as previous slide, but now the volume conductor is specifically the brain. The generator in now the red arrow, and the currents are now the yellow lines. The magneAc field is now shown as heavy green lines. Outside the head are shown both the MEG pick-­‐up coil, and EEG electrodes (not shown in previous slide). 6 Some basic words and terms we will be using. 7 Various forces we will talk about. 8 Specifically, the magneAc force. DefiniAon of a magneAc field. Small le_ers refer to a physics phenomenon of no interest to MEG, but Included here only for completeness. 9 Just for the fun of it, for those of you who have a taste of real physics equaAons, here is the accurate definiAon of a magneAc force. 10 The famous and useful right-­‐hand rule, which comes out of the previous physics equaAon. Refers to source currents and the magneAc fields they produce. 11 Strength level of weak magneAc fields, in the study of bio-­‐
magneAsm. Two important points to note: See next slide. 12 Each of these needs much discussion. We begin next with the first point, the SQUID. 13 A one-­‐channel SQUID system, showing only the basic elements. 14 These three kinds of pickup coils are used in nearly all MEG systems around the world. At the MarAnos Center we use a combinaAon of the first and third types. 15 Here is a schemaAc of those two types, first used in Cohen’s MIT lab in 1975. Circles were used in those “old days”, instead of of the rectangles of today. 16 This is what the same arrangement looks like, in our Elekta system. The blue view at right shows the spacing of “the squares” over the head. More of the same, a few slides later. 17 One big development during the 1980’s was the move from single-­‐
channel to mulA-­‐channel systems. Here is a 37-­‐channel MEG at about the Ame of 1985. 18 Here is one type of contemporary whole-­‐head system, made by 4-­‐D of California, now out-­‐of-­‐business. But many of their systems are sAll being used. These days, there is only one really acAve manufacturer of whole-­‐head systems: Owned by Elekta of Sweden, where the MEGs are made by Neuromag of Finland. 19 Here is the Elekta system, which is what we have at MarAnos Center. There are three sensors at each of 102 locaAons (small squares) over the head. The three sensors are two crossed planar gradiometers, as shown previously. 20 Actually, this is exactly what our pickup coils look like. About 1.5 inch, on a side. Somewhat different than the original circles. 21 This is how the channels are numbered in our Elekta MEG system. There are three related numbers at each locaAon, two gradiometers and one magnetometer. 22 Here we show actual data. These are the raw traces of magnet-­‐
ometer channels only, due to auditory evoked response, averaged over 286 sweeps. Gradiometer traces are omi_ed here. Each trace is Bz versus Ame, where the total Ame is about 1 sec. The white verAcal line is a marker at the first big auditory signal, oEen called N100, which occurs at 97.3 msec for this subject. Next, we will see the Bz map over the head, at this parAcular Ame. 23 Here is the instantaneous map that we menAoned in the last slide, the well-­‐known N100 due to auditory evoked to the right ear, averaged. This form of map is the basic MEG map that we need, to look for the sources of MEG. The specific pa_ern seen here is called the dipole pa_ern, character-­‐
isAcally made by a simple localized source. It is from this map that we determine the locaAon and angle of the source, at that parAcular Ame. 24 Now we change the subject. Recall that when we looked at the spectrum of weak magneAc fields, we saw two big things to deal with: How the SQUID detector basically works, and how to deal with the huge magneAc background. We are now ready for the second thing: the magneAc background. 25 Measuring the heart, by Baule and McFee. This was the first valid measurement of magneAc fields produced by the human body, The measurement was made in an open field outside Syracuse, NY, without any magneAc shielding. The external unwanted magneAc field, for example produced by power lines, was parAally cancelled by using two large coil detectors, connected in opposiAon. The heart signal was indeed seen, barely, above the parAally-­‐cancelled noise. This introduces the gradiometer, as one way of reducing the background. 26 These two are more advanced gradiometers, now commonly used in the MEG. The axial gradiometer was used early, in about 1973, just aEer the first SQUID MEG measurement (with a magnetometer). The planar gradiometer soon followed. 27 Then came the magneAcally shielded room, called the MSR. The first was built by me at the U.of Illinois (downtown Chicago). I can’t resist here showing off my next room, at MIT in 1969, the first really good shielded room in biomagneAsm. The first biomag SQUID measurement was made in this MSR. Three mechanisms of shielding were used. Two were called “passive shielding”, and the third was called “acAve shielding”. This MSR is seen to be roughly spherical in shape, shown by physics to be an efficient shape, for shielding. 28 But first, before conAnuing, an old, stupid biomag joke. Sorry about that… 29 This is the first passive mechanism, used in every MSR in biomag, oEen called high-­‐mu shielding. There are ferro-­‐
magneAc sheets in the walls, called high-­‐mu sheets. The original external disturbing field (black arrows) induces poles in the walls (red) which make a new field opposing the original field, leaving a small residue (thin black arrow). Therefore the original background has been reduced. This mechanism is largely independent of background frequency. 30 Second passive mechanism, oEen called ac or eddy-­‐current shielding, used in most MSRs. There are aluminum sheets in the walls, joined together with special low-­‐resisAvity joints. A changing external disturbing field (big black arrow) induces a (red) current in the aluminum loop, which in turn generates an external changing field opposing the original field; this leaves a residue (small black arrow). The higher the frequency of the disturbing field, the be_er is the shielding. 31 Before considering further methods of reducing background, its best now to introduce the concept of “shielding factor” (SF), the quanAty describing how well the MSR is performing its job. By definiAon, the shielding factor is the raAo of background disturbance at the MEG system, without and with shielding. A big number means the shielding is good. Here is a measurement of this raAo for our MSR, as a funcAon of frequency of magneAc disturbance. The yellow points shows the behavior before the aluminum sheets are properly joined, and the blue points aEer gold-­‐plaAng the joints. The lower, flat part of the curve is due to the high-­‐mu sheets, while the rising curves are due to eddy currents. The SF due to just hi-­‐mu sheets is seen to be about 2,000 -­‐-­‐ this is good. 32 Some MSRs have an external, acAve shielding system, where the mechanism is shown here. The big black arrow is the external, verAcal (fluctuaAng) disturbing field. This makes a signal in the fluxgate magnetometer (small blue line segment). The fluxgate amplifies this signal, and sends the red bucking currents in wires around the outside of room. These currents generate a new magneAc field (straight red arrow) which opposes the original black arrow, and leaves a smaller residual field, not shown here. There are now some new rooms with an internal acAve system as well, where special SQUIDS in the MEG dewar are the detectors, and bucking currents are in wires on the inside walls. 33 These are pure soEware approaches, where the magnetometer signals are analyzed for uniform or first order fields (SSP) which are then subtracted out, or for sources outside the head generally (SSS), which are also subtracted out. Both these methods can be most powerful, but have some drawbacks, especially SSS. 34 That is, we must show that MEG gives some different informaAon than does the EEG, and that this extra informaAon is worth all the money ! 35 Looking at MEG-­‐EEG differences can be quite complicated, and here is my way of organizing and simplifying these differences…. 36 Intrinsic difference: Our starAng point is this simple circuit: a ba_ery, some wire, and two resistors. The arrows in the wire show that an electrical current is flowing in the circuit. We are interested in the current generated by the ba_ery. There are, in a sense, two ways to measure that current: an EEG-­‐like measurement, and an MEG-­‐like measurement. We will compare them. 37 Here is an EEG-­‐like measurement. We measure the voltage V across the resistor R1 . The current we want is then i = V/R1 where our accuracy depends on how well we know R1 . In an actual EEG measurement, this means that the accuracy in measuring the source depends on how well we know the resisAviAes of the Assues of the head. 38 This is an MEG-­‐like measurement, where we measure the magneAc field B due to the current i. So we here get i more directly, bypassing R1 . In a sense, we have eliminated an important source of error. This is sort of an intrinsic difference between MEG and EEG. 39 As we switch over from a “wire head” to a more realisAc head, lets first jump to our old biological blob, as an intermediate step. Note that we are now heading into the next secAon, conductor-­‐produced differences. We have finished with intrinsic differences. But before shaping the head, we ask: What shall we use use for our MEG source? That is: what shall we use as an “internal generator”? 40 The source of nearly all MEG and EEG is the group of pyramidal cells in the cortex. Perhaps mostly in layers 4 and 5. NoAce they are all arranged verAcally. This direcAonal arrangement makes the EEG and MEG possible. Lets take a closer look. 41 The leE is a general distant view of the pyramidal cell. At the right is a closer view, with some of the dendrites stripped away. Note the synapses, the end of axons, joining onto the dendrites. The source of EEG and MEG are the post-­‐synapAc signals within the dendrites. There are oEen thousands of these synapAc juncAons in one pyramidal cell. 42 A closer view yet, where Mat has turned the cell sideways, for convenience. As a crude approximaAon, an instantaneous snapshot shows the summaAon of all excitatory signals to look like the shown dipole. It turns out that the inhibitory signals look like a smaller dipole, pointed in the opposite direcAon. Now from very far away, if the source area is small, all these excitatory and inhibitory dipoles look like a single dipole, so that is what we will use for a source, in our coming volume-­‐
conductor model. But If the source area of the cortex is large or spread out, we cannot approximate the source as a single dipole. 43 We have thus determined the simplest source which we will use, and now return to our volume conductor. We will make a computer model of the head, in which we will shape the head. Using this model, we will calculate the MEG-­‐EEG differences. That is, we will see what the computer tells us about these differences, with a single dipole as the source. 44 This is a standard model of the head, widely used for MEG-­‐EEG computer calculaAons. It is a 4-­‐layer spherical model, with outer radius at 9.0 cm, and we here see the top slice of the sphere. Now let us calculate both the MEG map and the EEG map over this head, and compare them. We here show the dipole as tangenAal to the skull, but we can vary the angle as we wish. It is here 2.7 cm down from the top. Note the x and y axes. We will note three differences between the MEG and EEG maps, for this model. 45 This point is perhaps the most important difference between MEG and EEG. 46 We here illustrate this point with a single-­‐layer sphere, for simplicity. The argument is easily extended to 4 layers. This is the first difference, that something is missing from the MEG map. If we would have used a radial dipole source, we would have seen that it cannot be seen on the MEG map, at all. There is no super-­‐simple explanaAon of this important phenomenon. We will here use the “toroid explanaAon”, sAll quite simple. 47 The current loops around a radial dipole can imagined to be the sum of an infinite number of toroids, of various sizes or radii. Since each toroid produces zero external magneAc field, the total of the infinite number sAll produces zero external magneAc field. There will indeed be a magneAc field in the salt-­‐water, but no field anywhere in the air. I call this the most important MEG-­‐EEG difference. 48 Both these consequences are geographic, in a sense. 49 This is a the first consequence. WHERE the dipole is located determines how it is seen by the MEG and EEG. By the way, this is one way that the MEG and EEG are complementary. 50 This second consequence is just as important as the first. Actually, this is also a geographic thing, in a sense. 51 Here is an old published calculaAon, showing how the MEG signal falls off, compared with the the EEG, as a tangenAal dipole is placed deeper in a spherical head. Zero radius is at the outside of the sphere. Both MEG and EEG are normalized to be 100% at the outer surface. Thus, a deep tangenAal dipole is highly suppressed on the MEG, 52 As an aside, what happens in an actual head, not quite a perfect sphere? Lets think about geographic MEG-­‐EEG differences, and look at a numerical calculaAon done by Mat, using the MRI geography of a real head. In this calculaAon, the MEG doesn’t quite disappear when you think it should, but it does get quite small, so our geographic idea does hold up. The bluest MEG diagonal line is the bo_om of the sulcus. The next blue line, to its’ leE, is the top of the gyrus. 53 Now what happens to the second consequence in Mat’s precise digital calculaAon? It is seen that this consequence holds up well: The deep MEG signal gets very small, compared with the EEG. As with the ideal spherical head. 54 So this is the big conclusion of this first MEG-­‐EEG difference, not seeing the radial dipole. Lots of sources disappear from the MEG, or at least are much reduced. 55 Now we move to the second (and third) differences between MEG and EEG. We do this by calculaAng MEG and EEG maps over the head, for our tangenAal dipole. The two resulAng maps are shown on the upper spherical caps. These are seen to differ in a major way. They are at 90° to each other. The general shape, the same in MEG and EEG, is called the dipole pa_ern. We will next see the colored version of this pa_ern. This 90-­‐degree rotaAon is the second difference. 56 Here is an example of the usefulness of the 90-­‐degree difference. I believe these are Hari’s (Helsinki) data from the early 1980”s. On the EEG, the red areas are awkwardly over the ear, hence difficult to measure; in contrast, the MEG clearly shows both the red and blue of the dipole pa_ern. This 90-­‐degree rotaAon is another way MEG and EEG are comple-­‐
mentary (geography was the first). 57 At this point, we digress for a moment to pracAce. a li_le pa_ern recogniAon. We see here the pa_ern differences between MEG and EEG, when the dipole is tangenAal, radial, or Alted. An important point is that the EEG shows a Alted dipole, but the MEG cannot show this Alted pa_ern. 58 There is a third difference, and we will illustrated it by using this slide again. Remember that the MEG map is of the normal component of B, called Bn. It turns out, in the spherical model, that Bn is a result of the dipole only (called the impressed current); it does not see the orange-­‐colored volume currents. The equaAons in the computer tells us that fact, The MEG, in this ideal spherical case, sees only the deep original current. In contrast, the EEG is due to surface currents, which know about all the resisAviAes in the head, that they have passed through. The MEG thus sees the source “more clearly”. 59 In summary, this is a quickie soundbite, easily remembered ! 60 Note that our comparison is based on a dipole source. And the longer the latency, the less dipolar becomes the map. But there are sAll roughly dipolar maps as late as 540 msec, someAme… 61 One example from one of Eric Halgren’s publicaAons: An MEG map at 165 msec aEer visual sAmulus. The pa_ern is sAll quite dipolar, at this median latency. 62 Another example: Here is an auditory language semanAc event, where the MEG latency is 540 msec, quite far out. SAll a bit dipolar… 63 The general subject is here called “soluAon to the inverse problem”, beyond the scope of our simple-­‐physics course. The principles involved can get quite complicated… 64 But there are some simple cases, which do allow for seeing MEG-­‐EEG differences. 65 Here is one series of cases, approaching what is called a “magneAc dipole”. 66 I’m not sure how far the simultaneous idea will finally go, but the Baby MEG is “taking off”. 67 Prof. Okada’s system, at Children’s Hospital, Boston, with elaborate acAve shielding. 68 His helmet and dewar, inside his MSR. 69 His arrangement of brain magnetometers and background-­‐sensors. 70 His magnetometers as seen from the inside, without dewar. 71 72