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Wednesday, June 25, 2014

Nuclear Imaging - PET scanning

PET scanning is a relatively old (late 1950s) technology.  What has brought this once obscure diagnostic tool to usefulness since the 1950s is powerful computers and improved detectors.  PET is an acronym for Positron Emission Tomography, which are probably all arcane terms for a non-tech geek.

A Positron is the antimatter version of an electron - it is an electron, but with a positive charge.  Only a handful of radioactive isotopes decay by emitting positrons, and only a few of these are short-lived enough to justify injecting into a patient. 

So we have described the first two terms:  Positron and Emission. 

Tomography means building a three dimensional image, for diagnostic purposes.  So there we have it:  Positron Emission Tomography.

An interesting thing about positrons; because they are antimatter, they don't last very long in a world that is made from normal matter.  When a positron is created as a result of a nuclear decay, it very rapidly collides with a normal electron.  The two particles are destroyed in a process called "mutual annihilation" and the destruction of their mass is converted (E = MC^2) to two gamma rays at energy levels of 511 KeV each.  The gamma rays normally leave the point of destruction at a path 180 degrees from each other.  This is useful to imaging, as will be seen later.

The positron-emitting isotopes chosen for imaging are Carbon-11 (half life 20 min), Nitrogen 13 (half life 10 min), Oxygen 15 (half life 2 min), Fluorine-18 (half life 110 min), and Rubidium-82 (half life 1.27 min).   A short half-life is desirable for reduced patient exposure.

Unfortunately, these nuclides cannot simply be injected into the patient and expect imaging results.  The positron emitter would simply diffuse throughout the body and the image would have no contrast.  Instead the positron emitter is attached to a bio-active molecule that the body requires for metabolism.  In this way the positron emitter accumulates in the body where it is desirable to generate an image.

The positron-emitter is therefore attached to a molecule that mimics blood sugar.  As cells metabolize this blood sugar (and aggressively growing cancer cells will use a great deal more sugar than normal cells), the positron-emitting nuclide will accumulate there, emitting positrons and generating mutual annihilation gamma rays.  This is how more gamma rays will be produced from tissue that is undergoing malignant growth than normal tissue.
 
After injection of the positron emitting tracer, the patient is placed inside a ring consisting of many, many gamma-ray detectors.  Based on how the pairs of gamma rays are detected, an image can be constructed of where the positron emitter has accumulated.  The pairing of the gamma rays helps to pinpoint exactly where the gamma rays originated.  This is the purpose of the Coincidence Processing Unit in the diagram below - to ensure only matched pairs of 180 degree apart gamma rays are used to build the image.

Below, a diagram of how a PET scanner works (courtesy Wikipedia):



Below, an image created by a PET scan, showing where the pairs of positrons and electrons are giving off their opposed gamma rays.


Because PET scanning requires the use of such short-lived radio-isotopes, using this diagnostic tool presents some logistical problems.  The positron-emitting nuclides are created in cyclotrons; large complex machines that hurl beams of relativistic electrons at target materials inside vacuum chambers.  Most of these very short-lived isotopes (except for the Fluorine 18, half life 110 minutes) would decay before they could be transported to a PET scanner.  For this reason, PET scanners are often located at universities where advanced nuclear and medical technologies exist side by side.

I find it fascinating how we have combined our understanding of nuclear decay, and the body's use of glucose for fuel to create an internal image that was undreamt of when the positron was first theoretically considered.  We had to wait for someone to invent a bio-active chemical that would act as a carrier for the positron emitter, high efficiency detectors with coincidence counting, and powerful computers that could take all that data and generate an image from it.  This confluence of diverse areas of science has led to an absolutely brilliant diagnostic tool!!!

Sunday, June 22, 2014

Nuclear Imaging - X rays

Nuclear imaging is the process of viewing the internals of a human body by using the body's own nuclear properties, injected or ingested radioisotopes, and/or by using external radiation sources.

The earliest known and most commonly used type of nuclear imaging is done by using X-rays.  Although X-rays are not exactly "nuclear", they are ionizing electromagnetic radiation, so I will discuss them.  X-rays are produced in vacuum tubes, although not just any vacuum tube will do the trick.

The earliest vacuum tubes, called Geissler Tubes, used gas at a mild vacuum, and were similar in nature to modern neon lights.  Different gases would yield various colors.  Handling the glass envelope would cause the tube to glow brightest at the point where it was being touched.

Below, sketches of various Geissler Tubes, used mainly for amusement in the late 19th century.  All images courtesy of Wikipedia.



The Crookes Tube was another vacuum tube, but built with a different structure and improved vacuum.  This tube was a highly evacuated glass tube with a cathode, an anode, and a flight path for electrons (although this was not understood at the time).  The anode was set off to one side of the tube, and very high DC voltage was applied to the tube.

Below, a Crookes Tube.  Negative voltage is applied at left, making this the cathode (electron emitter).  Positive voltage is applied at bottom, making this the anode (electron collector).  A thin piece of metal in the shape of the Maltese Cross is suspended in the middle, in order to cast a shadow at the end of the tube.

Because this tube had very few gas molecules in it, and because the voltage was so high, a heated tungsten emitter was not necessary to cause current flow from the cathode to the anode.  So for this reason the Crookes Tube is called a "Cold Cathode" tube.

What occurs inside a Crookes Tube is the elecrons leave the emitter, pulled by the very high DC voltage between emitter and collector.  The traces of gas remaining in the tube are struck by these high-energy electrons, and are stripped of their electrons as well.  All the traces of gas inside the tube are ionized (thus the glow).  Electrons move from the emitter at such high speed that their momentum prevents them from going directly to the collector.  Instead they fly right past the collector, and either impact a piece of metal suspended inside the tube, or impact the glass tube wall.  In this respect, a Crookes Tube might be considered the forerunner of the Cathode Ray Tube (CRT) screen. 

Crookes Tubes were laboratory curiousities for about 20 years, because nobody understood what invisible rays were casting the shadow on the front end of the tube.  Clearly the metal object was blocking something from reaching the other end of the tube!  These rays were called "Cathode Rays", and eventually JJ Thompson proved that the "Cathode Rays" were negatively charged particles, which eventually received the name "electron".  Until that time, the atom was thought to be the smallest known piece of matter, and nobody understood that electricity was the flow of electrons.

Crookes tubes have another important aspect besides generating an electron shadow image.  They also produce X-rays.  X-rays were discovered and researched by Wilhelm Röntgen in 1895. Röntgen and many other scientists at the time were experimenting with Crookes Tubes.  While many scientists noticed that photographic plates fogged in the vicinity of Crookes Tubes, only Röntgen realized that penetrating radiation was being generated. By the way, Crookes Tubes are readily available on Ebay.

Below, the world's first Radiograph (X-ray picture) of the hand of Anna Bertha, Röntgen's wife.

At voltages over about 5000 volts, Crookes Tubes create X-rays in a process called "Bremsstrahlung".  Sorry, I have no idea how to pronounce that :).  What the word means is "Braking Radiation", which is not very difficult to understand.

At 5000 volts, the electron is moving at about 20% of lightspeed.  (It's easy to understand why it doesn't make the bend to directly reach the anode!!!)  At 20% of lightspeed, the electron smacks into the metal object or the glass envelope of the Crookes tube and comes to a stop.  What becomes of all that kinetic energy?  X-rays!

Here we get into the realm of special relativity; the 5000 (or more) volts between the emitter and collector have added speed to our elctrons.  This increase in speed also increases their mass, and this increase in mass can be calculated.  When the electon moving at 20% of light speed comes to rest, this mass it gained is immediately lost and converted (E=mc^2) to energy, in the form of X-rays.  The higher the voltage used between the emitter and collector, the more energetic the X-rays.

And so just as kinetic energy removed by slowing down a vehicler is converted to heat energy in the brakes, the kinetic energy of the electron is also converted.  And yes, a vehicle traveling at high velocity has slightly more mass than one at rest.  To be measureable, this mass increase would probably have to be taken at some fraction of light speed. :)

From Wiki:
The medical applications of X-rays created the first practical use for Crookes tubes, and workshops began manufacturing specialized Crookes tubes to generate X-rays, the first X-ray tubes. The anode was made of a heavy metal, usually platinum, which generated more X-rays, and was tilted at an angle to the cathode, so the X-rays would radiate through the side of the tube. The cathode had a concave spherical surface which focused the electrons into a small spot around 1 mm in diameter on the anode, in order to approximate a point source of X-rays, which gave the sharpest radiographs. These cold cathode type X-ray tubes were used until about 1920, when they were superseded by the hot cathode Coolidge X-ray tube.



Below, a Crookes X-Ray Tube.  Note that the target anode is at an angle, to direct X-rays off to the right side of the tube.  The small object to the right of the cathode is to replenish gas in the tube as it ages.  Crookes tubes reguire a slight amount of gas to function.


Modern tubes use heated cathodes, which utilizes thermionic emission to generate electron flow.  They also have water-cooled anodes, to prevent the electron beam from warping or vaporizing portions of the anode. 



Below is an electrical diagram of a modern X-ray tube.  "Uh" is the circuit for heating the tungsten emitter (C).  "Ua" is the high voltage circuit used to create the electron beam that will generate the X-rays.  Win and Wout are water cooling for the anode (A).


Below, a modern X-ray tube.  Note the thinner section of glass where the X-rays leave the tube.  Looks a little scary to me...


The vast majority of X-ray radiography uses old-fashioned photographic techniques:  A cellulose plastic sheet which is coated with silver-halide emulsion is exposed to X-rays and developed by washing the exposed silver off the sheet.  In early days, a sheet of glass coated with emulsion was used.  Currently a plastic sheet with sensitive coating on both sides is used.  Coating both sides  increases the sensitivity of the film, thereby reducing the X-ray exposure required.



Modern X-ray radiography is replacing film with digital sensors.  The advantages of digital detectors are higher sensitivity (and so reduced exposure), immediate processing so that the shot (angle, contrast) can be re-imaged if necessary, chemical processing is eliminated, and digital enhancements can be used to improve the quality of the initial image.



Another X-ray imaging technique used early on was the Fluoroscope.  The patient would be placed between the X-ray source and a fluorescent screen.  The screen would glow like a TV, with the image of the inside of the patient.  This provided a physician with the exciting ability to see inside a patient in real-time!  The downside was heavy X-Ray exposure, both for the patient and the physician.



Below, a sketch of a doctor using a fluoroscope to remove a bullet from a WW1 soldier.  An unshielded Crookes X-ray tube is beneath the patient!


Amusingly, fluoroscopes were manufactured for use in shoe sales.  An X-ray source was built into a box which the customer stood on.  The salesman would then use the fluoroscope to check for fit.






Happily we now can use digital imaging techniques rather than requiring the use of fluorescent screen.  These are far more sensitive to X-rays than phosphorescent coatings on glass, and of course, require less exposure of the patient to ionizing radiation.



Below, a modern fluoroscope.  The machine has the ability to take snap-shots at adjustable intervals, eliminating the need for continuous X-ray exposure.

One of the techniques used in X-ray radiography (both in fluoroscope and X-ray film), is the use of liquids that are opaque to X-rays, called "contrast agents".  Barium Sulfate is an edible (?) cocktail containing the X-ray opaque element Barium.  When the Barium has been consumed and coated the lining of the patient's stomach and intestines, an X-ray image can be made.  This will clearly show the outline of the patient's gastro-intestinal tract, as the barium will absorb X-rays, blocking them from reaching the film/detector.
 

An X-ray of a normal stomach and lower intestine in a patient.  Note how the Barium Sulfate has made the internal organs more opaque to X-rays than even bone.

Likewise, contrast agents can be injected into the bloodstream, and an X-ray shot taken, in a process called Angiography.


Below, an X-ray image of a patient's veins near the rear base of the skull, taken with contrast agents injected into the bloodstream.
 



CT scans (Computer Tomography) is an impressive blend of the old technology of X-rays with the new technology of digital imaging.  By taking X-ray "slice" images at various angles, it is possible to use a computer to combine these images and build a three-dimensional image of the inside of the body.



The down-side to CT scanning is that many, many X-ray images must be taken to render a three dimensional image, and so exposure levels are quite high for this imaging technique.  I would need to have a very good reason to undergo a CT scan.



Next up:  PET scans.  And I am not talking about scanning dogs and cats!

Busy!

It has been a while since the previous blog post, and if anyone bothers to follow this goofy blog, I apologize.  Work has been pretty demanding of my time lately. 

The last time sheet I turned in had 120 hours on it, and the previous one had 140 hours on it.  Normal people only work 80 hours in a two week period.  The few days off I have had, I used the time to catch up on lawn care, trash disposal, a few home repairs, and on family time.

However the schedule looks a little better now, so I will try to get on, starting with the promised posts about nuclear medicine.