The 10-20 System

In Chapter 7 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the 10-20 system of electrodes on the scalp used to record the electroencephalogram.

Much can be learned about the brain by measuring the electric potential on the scalp surface. Such data are called the electroencephalogram (EEG)… Typically, the EEG is measured from 21 electrodes attached to the scalp according to the 10-20 system (Fig. 7.34).

Fig. 7.34. The standard 10-20 system of electrodes to record the EEG.

Why is this placement of electrodes called the “10-20” system? Consider the path starting at the nasion (between the eyes, just above the bridge of the nose), passing over the top of the head, and ending at the inion (a small protuberance at the lower back of the skull). This path is shown as the vertical dashed line in the top view of the head in Fig. 7.34. Five electrodes (O_z, P_z, C_z, F_z, and F_pz) are placed 10, 20, 20, 20, 20, and 10% of the distance along the path. All those 10s and 20s give rise to the name “10-20 system.” The electrodes O_z and F_pz aren’t part of the 10-20 system, so they’re not shown in Fig. 7.34, but their positions are used to properly place the other electrodes.

Now, consider the path starting just behind the left ear (auricle, A₁, sometimes known as the mastoid), passing over the top of the head through C_z, and ending just behind the right ear (A₂); the horizontal dashed line in Fig. 7.34. Five electrodes (T₃, C₃, C_z, C₄, and T₄) are placed 10, 20, 20, 20, 20, and 10% of the distance along the path.

Next, examine the dashed circle in Fig. 7.34, which represents a circumference of the head through O_z, T₃, F_pz, and T₄. Ten electrodes (O₁, T₅, T₃, F₇, F_p1, F_p2, F₈, T₄, T₆, and O₂) are equally spaced along this circumference, each 10% of the way around the circle.

Finally, consider a great circle path passing from F_p1 through C₃ to O₁. The electrode F₃ is halfway between F_p1 and C₃. Similar reasoning gets you the positions of P₃, F₄ and P₄.

How do these electrodes get their funny names? The first letter indicates the region of the brain: F for frontal (front), T for temporal (side, named for your temples), P for parietal (center-back), O for occipital (lower back), Fp for pre-frontal, and C for central. A subscript z means along the midline. Even numbers are used for the right of the head, and odd numbers for the left.

The 10-20 system was proposed by a committee of the International Federation of Clinical Neurophysiology, in order to standardize EEG recordings among different laboratories. 

Measurement of the 10-20 system of electrodes (part 1).
https://www.youtube.com/watch?v=ciGgCoPpPFY

Measurement of the 10-20 system of electrodes (part 2).

https://www.youtube.com/watch?v=Qd4kIvPOQM8

MRI Safety

Will Morton, a staff writer for AuntMinnie.com, published an article about safety issues during magnetic resonance imaging. It begins

As the push toward stronger and faster MRI scanners continues, so does concern over magnet safety, according to Filiz Yetisir, who discussed the potential effects MRI has on patients at the recent International Society for Magnetic Resonance in Medicine virtual meeting (ISMRM 2021).

Main Magnet

An MRI device creates a magnetic field having a strength of several tesla. Any magnetic objects near the device can be sucked into the main field, becoming dangerous projectiles. For instance, in 2001 a six-year-old was killed by an oxygen cylinder. Yetisir warns: “Remember, the magnet’s always on.”

Gradient Coils

The gradient coils used during imaging produce magnetic fields much weaker than the dc main field, but they are turned on and off throughout the imaging pulse sequence. This causes two safety concerns. 1) The changing magnetic field induces eddy currents in the patient, which can stimulate nerves—an effect similar to transcranial magnetic simulation. 2) The switching of current in the gradient coils creates mechanical vibrations, leading to noise so loud that ear plugs may be needed to prevent hearing loss.

Radiofrequency Fields

A radiofrequency magnetic field—which rotates the spins into the plane perpendicular to the main magnet—is an essential part of any MRI pulse sequence. This field can induce eddy currents that heat the tissue. Generally the field isn’t strong enough to cause significant heating, but if a person has metal implants or tattoos, the heating may be increased locally. Any implanted medical device, such as a pacemaker, can interact with all three types of magnetic fields.

Gadolinium

One issue Morton’s article doesn’t discuss is the toxicity of contrast agents such as gadolinium used in some MRI studies.

AuntMinnie.com is one of those websites that’s valuable for readers of Intermediate Physics for Medicine and Biology.

Screenshot of AuntMinnie.com

AuntMinnie.com provides the first comprehensive community internet site for radiologists and related professionals in the medical imaging industry.

We provide a forum for radiologists, business managers, technologists, members of organized medicine, and industry to meet, transact, research, and collaborate on topics within the field of radiology with the ease and speed that only the internet can provide.

AuntMinnie features the latest news and information about medical imaging. Staff members include executives, editors, and software engineers with years of experience in the radiology industry.

AuntMinnie.com reminds me of the Physicsworld medical physics website. Physicsworld is associated with the Institute of Physics, the main physics professional society in the United Kingdom. AuntMinnie is run by a consulting firm, the Science and Medicine Group of Arlington, Virginia. Both websites provide useful information about innovations and news in medical physics. 

Screenshot of MRISafety.com

For more information about MRI safety, see MRIsafety.com. For more information about the physics underlying these safety issues, see Chapter 18 of IPMB.

Photodynamic Therapy

In Chapter 14 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss photodynamic therapy.

Photodynamic therapy (PDT) uses a drug called a photosensitizer that is activated by light (Zhu and Finlay 2008; Wilson and Patterson 2008). PDT can treat accessible solid tumors such as basal cell carcinoma, a type of skin cancer (see Sect. 14.10.4). An example of PDT is the surface application of 5-aminolevulinic acid, which is absorbed by the tumor cells and is transformed metabolically into the photosensitizer protoporphyrin IX. When this molecule interacts with light in the 600–800-nm range (red and near infrared), often delivered with a diode laser, it converts molecular oxygen into a highly reactive singlet state that causes necrosis, apoptosis (programmed cell death), or damage to the vasculature that can make the tumor ischemic. Some internal tumors can be treated using light carried by optical fibers introduced through an endoscope.

The photosensitizer molecule interacts with near infrared light to damage tissue, kill cells, and harm blood vessels. A photon of infrared light doesn’t have much energy, and I’m surprised it can trigger all this destruction. What’s the structure of this molecule that causes so much carnage?

Let’s start with 5-aminolevulinic acid, which is an endogenous nonproteinogenic amino acid. By “endogenous” I mean it occurs naturally in the body. It’s part of the biochemical pathway that leads to the production of heme in animals, and chlorophyll in plants. By “amino acid” I mean it has an amine group (-NH₂) on one end and a carboxylic acid group (-COOH) on the other end. The amino acids that make up proteins have a single carbon atom connecting the amine to the carboxylic acid, like in glycine. 5-aminolevulinic acid, on the other hand, has several carbons linking the two groups. By “nonproteinogenic” I mean that this amino acid is not one that is encoded by our genome, and therefore it never occurs in proteins. Below is a drawing of the structure of 5-aminolevulinic acid.

The chemical structure of 5-aminolevulinic acid. From Wikipedia.

Protoporphyrin IX is a complicated molecule that appears in those same pathways leading to heme and chlorophyll. It contains four pyrrole subunits, each of which is a five-membered ring composed of four carbon atoms and one nitrogen atom. It is nearly planar, and has its four nitrogen atoms facing a central hole. I show its structure below. 

The chemical structure of protoporphyrin IX. From Wikipedia.

In heme, an iron atom occupies the central hole, and is where oxygen binds in the protein hemoglobin found in red blood cells. In chlorophyll, a magnesium atom sits in the central hole.

Most molecules (for instance, water, carbon dioxide, methane, ammonia, urea, and glucose) don’t react when exposed to visible or infrared light, but protoporphyrin IX does. It’s closely related to chlorophyll, which is a key molecule in photosynthesis. When sunlight interacts with chlorophyll, it triggers a series of chemical reactions that leads to the production of carbohydrates from water and carbon dioxide.

I guess I’m not so surprised after all that protoporphyrin IX can wreak so much havoc when exposed to light.

Electroporation

In Chapter 9 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I mention electroporation.

Electrical burns, cardiac pacing, and nerve and muscle stimulation are produced by electric or rapidly changing magnetic fields. Even stronger electric fields increase membrane permeability. This is believed to be due to the transient formation of pores (electroporation). Pores can be formed, for example, by microsecond-length pulses with a field strength in the membrane of about 10⁸ V m⁻¹ (Weaver 2000).

Weaver (2000)
IEEE Trans Plasma Sci,
28: 24–33.

The citation is to an article by James Weaver

Weaver, J. C. (2000) “Electroporation of Cells and Tissues,” IEEE Transactions on Plasma Science, Volume 28, Pages 24–33.

The abstract to the paper is given below.

Electrical pulses that cause the transmembrane voltage of fluid lipid bilayer membranes to reach at least U_m ≈ 0.2 V, usually 0.5–1 V, are hypothesized to create primary membrane “pores” with a minimum radius of ~1 nm. Transport of small ions such as Na⁺ and Cl⁻ through a dynamic pore population discharges the membrane even while an external pulse tends to increase U_m, leading to dramatic electrical behavior. Molecular transport through primary pores and pores enlarged by secondary processes provides the basis for transporting molecules into and out of biological cells. Cell electroporation in vitro is used mainly for transfection by DNA introduction, but many other interventions are possible, including microbial killing. Ex vivo electroporation provides manipulation of cells that are reintroduced into the body to provide therapy. In vivo electroporation of tissues enhances molecular transport through tissues and into their constituative cells. Tissue electroporation, by longer, large pulses, is involved in electrocution injury. Tissue electroporation by shorter, smaller pulses is under investigation for biomedical engineering applications of medical therapy aimed at cancer treatment, gene therapy, and transdermal drug delivery. The latter involves a complex barrier containing both high electrical resistance, multilamellar lipid bilayer membranes and a tough, electrically invisible protein matrix.

Electroporation occurs for transmembrane potentials of a few hundred millivolts, which is only a few times the normal resting potential. I find it amazing that normal resting cells can are so precariously close to electroporating spontaneously. 

One of the most interesting uses of electroporation is transfection: the process of introducing DNA into a cell using a method other than viral infection. This could be used in an experiment in which DNA for a particular gene is transfected into many host cells. If an electric shock is not too violent, the pores created during electroporation will close over several seconds, allowing the cell to then continue its normal function while containing a foreign strand of DNA.

During defibrillation of the heart, the shock can be strong enough to damage or kill cardiac cells. One mechanism for cell injury during electrocution is electroporation followed by entry of extracellular ions such as Ca⁺⁺ that can kill a cell. This raises the possibility of using electroporation to treat cancer by irreversibly killing tumor cells.

Electroporation-based technologies and treatments. https://www.youtube.com/watch?v=u8IeoTg_wTE

Albumin

The structure of albumin. Created by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute, on Wikipedia.

A physicist working in medicine or biology needs to know some biochemistry. Not much, but enough to understand the structure and function of the most important biological molecules. For instance, one type of molecule that plays a key role in biology is protein. In the first section of Chapter 1 in Intermediate Physics for Medicine and Biology, Russ Hobbie and I write

Proteins are large, complex macromolecules that are vitally important for life. For example, hemoglobin is the protein in red blood cells that binds to and carries oxygen. Hemoglobin is roughly spherical, about 6 nm in diameter.

While hemoglobin is one of the most well-known and important proteins, in this post I’d like to introduce proteins using a different example: albumin. To be precise, human serum albumin. It’s nearly the same size and weight as hemoglobin, and both are found in the blood; hemoglobin in the red blood cells, and albumin in the plasma. Both are globular proteins, meaning they have a roughly spherical shape and are somewhat water soluble. Also, they are both transport proteins: hemoglobin transports oxygen, and albumin transports a variety of molecules including fatty acids and thyroid hormones.

Albumin is mentioned in Chapter 5 of IPMB because it’s the most abundant protein in blood serum, and therefore is important in determining the osmotic pressure of blood. It appears in a terrifying story told in Homework Problem 7 of Chapter 5, dealing with a hospital pharmacy that improperly dilutes a 25% solution of albumin with pure water instead of saline, causing a patient to go into renal failure. It’s also discussed in Chapter 17 of IPMB, where aggregated albumin microspheres are tagged with technetium-99m and used for nuclear medicine imaging.

All proteins are strings, or polymers, of amino acids. There are 21 amino acids commonly found in proteins. Each one has a different side chain. An amino acid is often denoted by a one-letter code. For example, G is glycine, R is arginine, and H is histidine. 

The amino acids. Created by Dancojocari on Wikopedia.

The primary structure of a protein is simply a list of its amino acids in order. Below is the primary structure of albumin.

MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEK

Amino acid polymers often fold into secondary structures. The most common is the alpha helix, held together by hydrogen bonds between hydrogen and nitrogen atoms in nearby amino acids. 

The tertiary structure refers to how the entire amino acid string folds up into its final shape. At the top of this post is a picture of the tertiary structure of albumin. You can see many red alpha helices. 

A mutation is when one or more of the amino acids is replaced by an incorrect one. For instance, in familial dysalbuminemic hyperthyroxinemia, one arginine amino acid is replaced by histidine, which affects how albumin interacts with the thyroid hormones.

Albumin is made in your liver, and a serum albumin blood test can assess liver function. Section 5.4.2 of IPMB discusses some illnesses caused by incorrect osmotic pressure of the blood, which are often associated with abnormal albumin concentrations.

5.4.2 Nephrotic Syndrome, Liver Disease, and Ascites

Patients can develop an abnormally low amount of protein in the blood serum, hypoproteinemia, which reduces the osmotic pressure of the blood. This can happen, for example, in nephrotic syndrome. The nephrons (the basic functioning units in the kidney) become permeable to protein, which is then lost in the urine. The lowering of the osmotic pressure in the blood means that the [driving pressure] rises. Therefore, there is a net movement of water into the interstitial fluid. Edema can result from hypoproteinemia from other causes, such as liver disease and malnutrition.

A patient with liver disease may suffer a collection of fluid in the abdomen. The veins of the abdomen flow through the liver before returning to the heart. This allows nutrients absorbed from the gut to be processed immediately and efficiently by the liver. Liver disease may not only decrease the plasma protein concentration, but the vessels going through the liver may become blocked, thereby raising the capillary pressure throughout the abdomen and especially in the liver. A migration of fluid out of the capillaries results. The surface of the liver “weeps” fluid into the abdomen. The excess abdominal fluid is called ascites.

Albumin is such a common, everyday protein that bovine serum albumin, from cows, is often used in laboratory experiments when a generic protein is required.