Scanning for Alzheimer's Disease

I recently had the opportunity observe a PET scan for Alzheimer's Disease.  This scan makes use of a recently FDA approved radioactive diagnostic agent, known as Amyvid (or Florbetapir F 18), to scan the brain for beta-amyloid plaques that are present in brains afflicted with Alzheimer's disease.  I thought that I would blog about this specific scan because it is relatively rare - although FDA approved Medicare does not cover the scan.

Beta-amyloid (Abeta) is the result of enzymes cutting amyloid precursor protein (APP.)  APP's function is not yet completely known, but it is known that APP freely passes through the fatty membrane of brain cells.  APP is typically cut into smaller segments that are designed to stay either inside or outside of brain cells.  There are many variations in the way that APP is cut, and one of the variations is Abeta.  A single Abeta molecule is relatively harmless and highly soluble, but Abeta is "sticky" and will stick to other Abeta molecules to form  oligomers.  Oligomers can exist in several different forms, however a misfolded one is believed to induce the misfolding of other oligomers.  Abeta in general is highly attracted to the synapses of brain cells, and once oligomers of Abeta progress into beta-amyloid plaque, the plaque is no longer soluble, will block synapses and eventually kill brain cells.

Amyvid was recently approved to aid in the diagnosis of Alzheimer's disease.  There are several tests that can indicate Alzheimer's disease, but none of them can fully diagnose Alzheimer's since Alzheimer's is best diagnosed postmortem.

The idea of a Florbetapir F 18 injection is that it will bind to only to beta-amyloid plaque and a PET scan can determine if the Florbetapir F 18 binded to the beta-amyloid plaque or not.  A positive scan will indicate that there are beta-amyloid plaque levels similar to those afflicted with Alzheimer's and Florbetapir F 18 binded to the beta-amyloid plaque, while a  negative scan will indicate that there is no or minimal levels of beta-amyloid plaque present in the brain and Florbetapir F 18 did not bind to the beta-amyloid plaque.

Amyvid has not been approved for the diagnosis of other cognitive disorders and alone does not diagnose Alzheimer's, although studies have shown Amyvid to have high sensitivity and specificity.

"Florbetapir gives patients with cognitive decline, their families and the physicians who treat them, more information about the amyloid plaques that may be found in their brain." - R. Edward Coleman, M.D., professor of radiology, Duke University Medical Center.

Nuclear ("Unclear") Medicine

Hi everyone!  I am currently in one of the most obscure fields of radiology known as nuclear medicine.  The goal of nuclear medicine is to treat and diagnose diseases based on cellular function and physiology, as opposed to waiting for changes in the physical features of tissue to diagnose conditions.  This is advantageous because potentially life threatening conditions can be identified in very early stages.

The main tools that nuclear medicine uses are radiopharmaceuticals.  Radiopharmaceuticals are formed from chemically bonding radionuclides (which are essentially radioactive materials) and pharmaceutical compounds.  Once formed, radiopharmaceudicals (which typically emit gamma radiation) target specific tissues in the body and then images of the target tissues are captured using a gamma camera in a form of diagnostic imaging known as scintigraphy.  A gamma camera can be thought of as a much more sophisticated pinhole camera, because the captured images are essentially pixelated by gamma of radiation.  The reason that gamma radiation is used instead of alpha or beta radiation is that gamma radiation has a much larger frequency and will penetrate through tissue much more easily, thus creating a better image.

Ventilation/Perfusion Scan

The above image is a ventilation/perfusion scan and is an example of why nuclear medicine is oftenly referred to as "unclear" medicine.  Every image in nuclear medicine looks this unclear, however it is at least obvious that these are lungs.  Despite how old fashioned this image looks, it can be used by a nuclear radiologist to check for a pulmonary embolism - a condition that can be fatal if untreated.

Bone Scintigraphy 

The above image is a bone scintigraphy/scan.  The scan has the same underlying idea as the other scans in nuclear medicine, except the pharmaceutical that is bonded to the radionuclide (typically technetium-99m) targets the bones.  This scan checks for bone abnormalities.  The idea is that the parts of the bones that are more active will have a higher amount of blood flow and absorb more of the radiopharmaceutical and show up as "dark spots" on the scan.  The dark spots can simply be from fractured bones trying to heal themselves, but they could also be from cancers on the bone.  For example, prostate cancer tends to spread to the spine and breast cancer tends to spread to the ribs.  I am no doctor, but this guy looks like he is in bad shape. An important detail to note here is that nuclear medicine does not diagnose what type of cancer a person has, but rather that there could be cancer.  For example, some people have naturally occurring symmetrical dark spots on bone scans that are not cancerous.

CT-PET Image

Another powerful tool available to nuclear radiologists is a PET-CT Scanner.  A lone CT or PET scan may be difficult to read and a doctor may overlook a small detail, but together a CT-PET scan is truly a guide to the human body.  The PET scan uses radioactive glucose to measure metabolic activity (the idea being that overactive and possibly cancerous cells will be metabolically over active) of tissues in the body, while the CT scan acts a map to determine where exactly a possibly cancerous tumor may be.  It is important to note that once again, nuclear medicine does not determine if a growth is truly cancerous, but rather that something could be cancerous.  For example, a PET scan simply measures metabolic activity through the use of radioactive glucose.  These tissues that are metabolically overactive will show up as brighter and as a "hot spot" on a PET scan, however something that is a "hot spot" on the PET-CT scan could be due to an injury or overactive lymph node as easily as it could be cancerous.  The ability to distinguish between "suspicious" and "non-suspicious" hot spots on PET-CT scans comes form both an expensive knowledge of physiology and experience - which is one reason why experienced attending Nuclear Radiologists make "the big bucks."   Last week, there was a patient that had a history of fungal infections and the attending nuclear radiologist was unable to determine if a nodule in the lungs was due to an infection or cancer.

The above images are PET-CT scans of the lungs, and both scans display a pulmonary nodule as a very bright hot spot.