Photoacoustic imaging of melanoma in vivo.

Photoacoustic tomography is the basis behind a new imaging technology being developed in hopes of providing more flexible and cost effective devices for physicians. The technique takes advantage of ultrasonic emissions produced when a non-ionizing laser pulse is directed towards a tissue. The emissions, resulting from transient thermoelastic expansion of the target tissue due to absorption of the laser energy, are detected and analyzed with various algorithms to construct an image (2D or 3D) of the targeted area. This differs from the reliance on the doppler shift produced by the reflected laser beam in the SPTT.

Images of vasculature like the one seen on the right can be produced by using photoacoustic tomography without the injection of contrast as differences between the molecular composition of the target can be used instead. In the example to the right, the difference between oxygenated and deoxygenated blood is an effective natural contrast. Photoacoustic tomography also presents other benefits over traditional imaging techniques as explained by The Economist:

CT scans also involve potentially harmful ionising radiation. And MRI and CT scans are very expensive, using machines that cost millions of dollars and require dedicated staff to operate them. Photoacoustic tomography, by contrast, could eventually be performed using portable hand-held devices, similar to those used for ultrasound scanning. This would allow doctors to diagnose and monitor patients in clinics, and reduce the need to refer them to consultants.

The adaptability of this nascent technology is also impressive as researchers are already looking at using it to detect specific ailments such as brain lesions and cancer. In the case of cancer, the ability to accurately image vasculature could allow doctors to monitor patients for the development of new blood vessels (angiogenesis) a hallmark of cancer development.

While there are some issues to work out with this new technique, such as the lack of imaging depth (ultrasound signal emitted is reduced the deeper the tissue lies) and ultrasound distortion from varying tissue types within the human body (e.g. bone vs muscle), photoacoustic imaging is a very promising new technology.

(Source)

There’s an imaging technique that’s been emerging over the last ten or so years called imaging mass spectrometry, which can tell you where a whole bunch of different molecules are in tissue all in one go! Basically, you take a slice of the tissue you want to image, apply a chemical resin to it (which is called a “matrix”), and then you shine a fairly strong laser at the tissue. This causes a physical reaction in which the resin absorbs the laser, ionizes, and causes molecules from the tissue to get ejected into the air. The mass spectrometer then sucks those ejected molecules into its cavernous depths and weighs them, breaks them apart, and then weighs their fragments to try to identify what the molecules are. For proteins, this identification process is actually quite easily done.

What you end up with is a really remarkable picture, a 2D map of where a range of different molecules are in the slice of tissue. You can look at the distribution of molecules of different specific weights across the entire slice. By stacking images of adjacent slices, you can then reconstruct an approximate 3D map of where molecules are in a tissue, like a brain or a tumor. Pretty neat!

A section of a mouse brain imaged for molecules of various weight (from Stoeckli et al. (2001) Nature Medicine 7, 493–496.)

Up until now, there have been two main ways to see macromolecules like proteins and RNA in biological tissue. First, you can look at where a specific macromolecule is by sticking a fluorescent dye to it and looking for that “tag.” It’s a great technique, but it’s also pretty laborious and limited in scope, because you can only examine at most three or four things at a time or the colors will start overlapping together a little too much to reliably distinguish what you’re looking at. In addition, you have to know what molecules you’re interested in first in order to tag them.

Second, you can look at cells as a whole using high energy techniques like transmission electron microscopy (TEM), which uses beams of electrons to “X-ray” cells. Since electrons have a very short wavelength, that means that they can be blocked and scattered even by very small structures, including groups of proteins, which means that a TEM image can look at a lot of things with an insanely high amount of detail. Unfortunately, electron microscopy won’t really tell you what you’re looking at, though there are a few techniques (like sticking gold beads to stuff you’re interested in) that try to get around that. Nonetheless, it doesn’t tell you much besides the overall “visual” picture.

Imaging mass spectrometry gets over a lot of these hurdles of traditional microscopy by directly associating molecular weights with specific coordinates in a tissue sample. And because the mass spectrum measures a wide range of weights, a computer algorithm can potentially tease out patterns that might not have occurred to a researcher or doctor looking for a few things at a time. The amount of information that can be obtained from a simple mass spectrum image is tremendous. With newer, cheaper super-accuracy mass spectrometers coming out, such as the orbitrap, this technology is growing in popularity outside of specialized physics labs, and it promises to revolutionize the way a lot of science and medicine is done. In the clinic, for example, a ton more information could come out of a biopsy all at once using this technology, from identifying cancer markers to positively identifying infectious agents and inflammation. I look forward to what’s coming in the future!

But, rather than bore you with those trivial details, why not just show you.

Before the Web: Read (Science 15 August 2008: Vol. 321. no. 5891, pp. 970 – 974) and its tiny paper figures and hope that you can visualize what’s going on.

After the Web: Read the paper online, Read a blog post on said paper (from science blog Mystery Rays from Outer Space). Watch this video of neutrophils (a type of white blood cell responsible for attacking infection, tagged Green) infiltrating a mouse ear that has just been injected with beads (tagged Blue) and Leishmania major (a bacteria, tagged Red).

4-dimensional image series from the ear pinna of a LYS-eGFP mouse in which blue fluorescent beads and L. major had been deposited adjacent to one another in the skin of the same ear. eGFP-expressing cells are shown in green, L. major-RFP is shown in red, and beads are shown in blue. Playback speed is 1200x. Scale bar, 200?m

Comment on blog post and ask blog author question about how neutrophils are attracted to the beads. Get a response. Make my own blog post about the discovery. Reflect on the impact of the Web on science.