Medical Imaging 101 pt 4: PET
Yikes, it’s been a long time since I added to my #CHMedicalImagingSeries. Today I’ll be talking about Positron Emission Tomography (PET). If you missed the first part, I gave an overview of the major imaging modalities and why I’m doing this (see Medical Imaging 101 pt 1). PET is the first imaging modality in the series that requires an exogenous agent, i.e., there is no background signal. That can be a good thing. If your agent is targeted, you would have the best contrast, i.e., you only see the targeted tissue/organ. PET is predominantly used in neurology and oncology.
Physics for raw data acquisition
PET scanners look a lot like a CT scanner. Recall CT scanners have a rotating gantry with an x-ray source and a detector (see Medical Imaging 101 pt 2: CT). PET scanners have a ring detector. Individual detectors are placed side-by-side to form a ring. The detectors are crystals, specifically scintillation crystals. Scintillation is the phenomenon where light is emitted when the scintillator (liquid or crystal) absorbs radiation. For example Siemens uses lutetium oxyorthosilicate (LSO) in their detector. Bismuth germanate (BGO) can also be used and there are many others. Different crystals have different efficiencies and sensitivities for different energy windows. The next step is a photo-multiplier tube (PMT). The PMT is used to get the light from the crystal to an electronic detector. A more compact and modern alternative is an avalanche photodiode (APD). APDs are important as there is a move to combine PET and MRI in the same scanner and APDs can work in a magnetic field unlike the PMTs. Most of the major clinical MRI manufacturers have a combined, clinical PET-MRI scanners. They are not that common (yet) because they are super expensive.
So how do the detectors and radionuclide work together? The radionuclide for PET has to undergo beta decay, i.e., emit a positron. The positron travels through the tissue until it slows down enough to interact with an electron whereby they annihilate each other. A pair of gamma rays are given off and this is an important aspect of the 3D nature of PET. Recall the detectors are in a ring. The pair of gamma rays are detected on different parts of the ring and geometry is used to find the source of the positron.
Contrast
Because there is no background gamma rays from within your body, the contrast is completely from the injected/ingested radiotracer. The majority of PET images use F-18 labeled fluorodeoxyglucose, which is an analog of glucose. FDG gets trapped in highly metabolically active cells because it’s taken in like glucose but can’t be processed like glucose. Therefore, PET is good at detecting tumors as they are relatively more metabolically active, relative to say muscle. There’s an example image below (last image) with FDG at the bottom. The figure shows 3 mouse images with 3 different F-18 labeled tracers. FDG, as mentioned already, is for metabolism. FLT (3′-deoxy-3′-fluorothymidine) is used to image proliferation potential. Like FDG, FLT is good at detecting rapidly multiplying cells. The top row is a radiotracer that images thymidine kinase (tk) expression, which is related to the therapy they were using. The top row shows that the treated tumor on the right is expressing tk while the tumor on the left is not.
How is the 3D image made: Sinogram
Sinograms are analogous to the projection data I discussed in the CT post. The collision pairs form a line of response (LOR). You generate a sinogram by plotting the angular orientation of the LOR vs. the displacement of the LOR from the center of the detector ring. As you can guess from the name, you end up with parts of sine waves. In the YouTube video below, you can see the reverse process, i.e., the Shepp Logan phantom is transformed into a sinogram. (it’s a classic digital phantom, in imaging parlance, phantoms are devices (real or digital) that are meant to mimic an object of interest for testing)
Radon Transform Of The Shepp Logan Phantom
In the sinogram figure (third below), you can see the results of plotting 4 LORs. In C and D, you can see a complex sinogram of the brain image in D. The sinograms can be used with filtered back projection as explained in the CT post, to create a 3D image.
Strengths
PET is much more sensitive than MRI or CT, i.e., it can detect much lower concentrations of the contrast agent. It has relatively higher resolution than SPECT, which I will talk about in the next part of the series. In theory it can detect in the nanomolar range, whereas MRI is more in the micromolar range (for exogenous contrast agents). Because of the high sensitivity, PET is a good candidate for labeling drugs for distribution (pharmacokinetics) studies. With MRI for example, you would have to use iron or gadolinium chelates which are larger than a PET isotope and require large quantities due to the lower sensitivity relative to PET.
Weakness
The use of radiation carries with it a whole host of issues. Obviously there are health and regulatory issues. Another weakness for F-18 in particular is it’s relatively short half-life, which is about 110 minutes. So in less than 2 hours, half of the activity will be gone. That means repeated injections are necessary for longitudinal studies. PET isotopes are made in a particle accelerator called a cyclotron. For isotopes with really short half-lives, the PET scanner has to be very close to the cyclotron. PET has lower spatial resolution compared to MRI and CT.
Something unique: annihilation
As mentioned already, PET detection involves the annihilation of a positron and electron. The LOR depends on the speed of the detectors. Because the emitted photons are not exactly 180 degrees apart, the speed of the detector can influence the data which has an effect on the image reconstruction.
Example:
Because all of my PET images are part of unfinished and therefore unpublished projects, I’m using this example from the Wiki page. It’s a PET image of a female patient using FDG. The display is called a maximum intensity projection (MIP) which basically sums all of the signal in each direction (view) to help with the 3D visualization. The very dark red object at the bottom is FDG accumulating in her bladder. You can also notice high metabolic activity in her brain, which is normal. The kidneys show up brighter than the background, not so much due to cancer or high metabolic activity but due to the kidneys removing the FDG from her blood. Hence the accumulation in the bladder. Also note that FDG is small enough and not targeted such that there is background signal, albeit not a lot. It’s quite clear that she has cancer in her liver. Her history tells us that it is a metastasis from a colorectal tumor.
Here are two examples of PET/MRI.
More on Functional vs. Anatomic Images
Sister post to the Visible Human project
Stay tuned for the next part: SPECT. I’ll compare SPECT and PET as they have many similarities. Don’t forget, it’s #ScienceEveryday, except when it’s #ScineceSunday
Medical Imaging 101 pt 1
Medical Imaging 101 pt 2: CT
Medical Imaging 101 pt 3: MRI
References and image sources
Abi Berger
BMJ. 2003 June 28; 326(7404): 1449
MGH F-18 FLT
Female PET image:
Sinogram from J. Nuc Med 2002
How stuff works. (good animation of the annihilation event)
Information about F-18 FLT.
http://en.wikipedia.org/wiki/Positron_emission_tomography
Chad Haney Thank you for this in-depth introduction of medical imaging. Very cool!!
You are welcome Shang Heng Wei
I just had to read this while half asleep, now I’m wide awake and reading about the production and use of medical isotopes. Thanks for helping me lose sleep in the quest for knowledge Chad Haney
Very informative! Great post Chad Haney 🙂
Great read, thanks Chad! 🙂
+chad haney i join your school .. do more like this
Thank you for sharing, I’ve learnt something new today already and it is not even 9am.
What Pinto Xavier said. 🙂
Just brilliant, agent detection at lower concentrations would be very useful, though the weaknesses seem quite limiting. I must read more about PET. Fascinating indeed!
it’s post like these that I find are keepers ……….
good work Chad Haney
LOL Thex Dar
Thanks everyone. It takes a lot of time to do these posts. It’s like the rabbit hole in Alice in Wonderland. One link leads to another, one picture leads to another.
Great work, thank you. Is there a site on which we can go and ask for a second opinion, using the CD with the images done during a scan? Can a PET scan interactions and results be affected by a CT scan programmed and done just with an hour before the PET scan?( The radioactive substance that is supposed to decay, for the PET scan – after which you have to drink liquids for 2 hours and then you are in the machine for other 2 hours – was injected at just one hour after the CT scan done with X-ray)
Gabriela Anghel sorry it took me a while to get to your question. I don’t think there is a site where you can get a second opinion using a CD with images from your scan. You can bring the CD or DVD to another physician to get a second opinion without having to get more images taken.
I’m not sure I understand the second part of your question but I think you are trying to ask if a delay after getting the contrast agent will have an effect. It will, the question is, is it a significant or meaningful effect. There are a lot of variables at play here and I’m not a physician. I’m an engineer. I don’t want to interfere with any diagnosis.
Most clinical PET scanners have CT built in. Typically you get a CT scan and then a PET scan, without leaving the scanner. Depending on what part of the body, the scan was focused on, it may not be a significant problem to do the CT scan 1 hr before the PET scan.
Again, I’m 100% clear on what you are asking. You might want to send me a private message. I can try to help without you posting too much private information here.
Gabriela Anghel No-well there wasn’t last year, but I’ve been actually thinking of creating a platform to do so. Another idea is to get #patientslikeme (a startup in Boston), to integrate film /medical media into their system. I’ve meant to email them RE this for a year or two now. I always urge people to sign a release form for film medical records and get a copy of every scan for a number of purposes.
FYI : PatientsLikeMe is a patient network that improves lives and a real-time research platform that advances medicine. Through our network, people connect with others who have the same disease or condition and track and share their own experiences. In the process, they generate data about the real-world nature of disease that helps companies and organizations develop more effective products, services and care.
Chad Haney Nice^2.
Thanks Marie Antoinette LeDonne I’d be interested in learning more about PatientsLikeMe. My one fear, based on what I’ve seen on G+, is that people often offer anecdotal based suggestions that are really woo (placebo).
Chad Haney Oh. So I don’t work for them or anything. In fact, I live in SF now. I have merely noticed that there is a great need for something like this. Try http://www.patientslikeme.com/ to learn more 😉 I hashtagged patientslikeme to give them a *hint. 😉 If you’re in Boston anytime soon, I recommend walking in their doors and requesting a field trip!
Thanks Marie Antoinette LeDonne I’ll check it out. Who knows, maybe it will become a future post.