BaSO4, X-ray Contrast

Many of you have probably seen the post by Mindy Weisberger showing the awesome CT images of various animal’s vasculature. The main point of that article is the development of a contrast agent for x-ray computed tomography (CT).

Since I haven’t had time to post to my Medical Imaging Collection, I figured I’d take the opportunity to clear up a few things about the technology and stop neglecting my medical imaging collection.

There are two main classes of x-ray contrast agents. Iodine based agents and barium sulfate (BaSO4) based agents. Iodinated agents are typically given intravenously (IV) and sometimes orally. BaSO4 agents are only given orally for live patients/animals. Iodonated agents are soluble in water and often look like water (not very viscous). BaSO4 agents look like thick milk of magnesia (very viscous). There are many reasons why BaSo4 cannot be given IV (viscosity, osmolarity, etc.). BaSO4 agents are routinely used in about 5 million x-ray procedures in the USA. Its use can be traced back to 1910. Iodinated agents are used in around 20 million procedures (Chem. Rev 1999, 99, 2353-2377).

The agent in the article is called BriteVu, developed by Scarlet Imaging. It’s a BaSO4 based agent with minerals and silica added. I plan on purchasing some to see what makes it superior to plain BaSO4 or even if it is superior. So the first thing to correct in the article is that this isn’t noninvasive in the sense that it can’t be used in vivo. It’s noninvasive but it’s terminal. I think most people assume when you say noninvasive that you also imply survival.

The second misleading issues is that clinical scanners can image fast enough for iodine based agents to work. This is only applicable for animal work where there is only one or two scanners that are as fast as clinical CT scanners. So what does speed have to do with iodinated agents? Unlike BaSO4 agents, they diffuse out of the vasculature very rapidly and are cleared from the body rapidly (relatively speaking). A preclinical scanner does not have a slip-ring like a clinical scanner and therefore is much slower. By the time the x-ray source and detector have traveled around the animal, the agent is already diffusing out. The math used to reconstruct the images would break down because you have an important feature (the vasculature) changing over the time course of the image. See the links below for more information about slip-rings. This is unlike motion artifacts (e.g. breathing) that can be corrected for.

In two of the images below of a mouse, Kiessling et al show that an iodinated agent can be use in vivo with a live mouse. Their prototype slip-ring preclinical scanner is probably over $1million. Nevertheless, it is possible to image fast enough to use iodine in vivo in an animal. You will see that they image the mouse with an iodinated agent, iomeprol 400, on the right side and BaSO4 on the left side for comparison. Keep in mind, the left side image is only possible as a terminal experiment. The other mouse figure shows a 3D rendering to demonstrate how you can visualize the vasculature of a tumor on a mouse. The other five images are from Scarlet Imaging.

Mindy’s post:

https://plus.google.com/+MindyWeisberger/posts/NhBBaniLqmP

More information about CT and slip-rings.

Medical Imaging 101 pt 2: CT

http://goo.gl/IHaFw

Fast CT from GE Healthcare

https://goo.gl/AV6Z59

Image sources:

Scarlet Imaging

https://www.scarletimaging.com/

Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis

Kiessling et al Nature Medicine 10, 1133 – 1138 (2004)

7 September 2004; | doi:10.1038/nm1101

http://www.nature.com/nm/journal/v10/n10/abs/nm1101.html

Duke University has an experimental microCT that can be used to image mouse hearts, which beat up to 600 bpm.

http://www.civm.duhs.duke.edu/4DmicroSpectCT2013/