Optical Coherence Tomography Provides an Active Window on the Brain

Optical Coherence Tomography (OCT) is a powerful new tool for monitoring both degenerative and malignant activities occurring deep within the brain -- by looking into the eyes. The OCT scanner uses two light beams (diodes or pulse lasers) to generate a 3d image of the depth of the retinas. This information tells medical specialists many different things about what is happening inside the skull.

One beam of light is fired at the tissue and another at a reference mirror. When the reflected beams have travelled an identical distance, interference will make their combined beam brighter than if the distances are different. So by reflecting one beam off of different layers of tissue, and moving the reference mirror until the combined reflected beam is brightest, the technique can measure the depths of each section of tissue and build up a detailed image of its structure. It has proved particularly useful in ophthalmology because the semi-transparent nature of retinal tissue makes it possible for OCT to penetrate to greater depths - up to several millimetres. When applied to the OND it can give information about both the shape and thickness of retinal nerve fibres, allowing even subtle changes to be tracked.

Such changes can be used to monitor the progression of diseases non-invasively and relatively cheaply. Unlike MRI, which is expensive and can require patients to remain still for an hour or more, OCT is increasingly available in clinics and can be carried out in a few minutes. "It's extremely inexpensive compared to other tests," says Valenti.

One possibility is to use OCT to monitor the effectiveness of treatments for neurodegenerative diseases, says Danesh-Meyer: "These drugs can have a lot of side effects, so if they are not having a benefit then you won't want to continue with them." _NS

The progress of brain tumours, multiple sclerosis, Alzheimer's, Parkinson's, and other brain diseases can be tracked over time using this non-invasive technique.

As the technology improves and allows for faster, less uncomfortable scans, it is likely that a routine baseline scan will be done on all adolescents as part of their permanent medical records. Should any new symptoms warrant it, later OCT scans can be compared with the baseline study to look for signs of brain pathology.

Longer lives mean more chances for new pathology. Pathology in the brain has been historically very hard and expensive to track over time. Newer technologies such as the OCT should allow medical scientists and practitioners to determine which persons need treatment, and which treatments provide the best result. The time saved by such new procedures should translate into a more functional lifespan.

Proteomic Mass Spectrometry--Advanced Tools for Bio-Research

The average cell is flooded with an ever-changing population of proteins. To understand what a cell is doing, it helps to be able to take a "snapshot" of all the proteins, examining them carefully for signs of dangerous mutations.

Brian Druker of the Oregon Health and Science University in Portland and Roberto Polakiewicz, chief scientific officer of Cell Signaling Technology in Danvers, MA, have extended the role of proteomic mass spectrometry in order to detect cell signalling protein mutations that may lead to cancer.

"There are potentially hundreds of mutations in a given patient," says Jeffrey Tyner, a postdoc in Druker's lab. Only some of those mutations actually contribute to the cancer -- and evaluating all of them is time-consuming.

In essence, DNA sequencing reveals only what the cell could do. Protein mass spectrometry, in contrast, provides a clearer picture of what the cell is doing. That's why Cell Signaling Technology believes its approach is more efficient. "Proteomic [mass spectrometry] gives you the true readout of what's going on in the cell," says Mark Cobbold, a clinician scientist at the University of Birmingham, U.K.

Druker's mass spectrometry study focused on acute myeloid leukemia, the most common form of the disease. And, while three common gene mutations are often to blame for it, in 30 to 50 percent of cases, the cause is unknown, says Tyner.

Druker hopes to duplicate his success in previous work on another form of leukemia, which led to the first successful molecularly targeted cancer drug, Gleevec (Imatinib). Approved for clinical use in 2001, the drug works by specifically binding to an abnormal tyrosine kinase protein and inhibiting it. The drug has worked wonders for some patients. "Druker is taking molecular medicine forward. Now he's looking for other [leukemia targets] using a proteomics approach," Cobbold says.

Looking at a cell's actual molecular activity using mass spectrometry lets Druker avoid much of the guesswork in searching for cancer mechanisms. Instead of years, it took his lab just weeks to uncover a mutation in a gene for a kinase called JAK3 that causes the signaling molecule to be abnormally active. They found the mutation in a cell line, then verified the result in patients.

In proteomic mass spectrometry the researchers first break up cancer cells, purify their proteins, and cut them up. They then further purify stretches of protein characteristic of active tyrosine kinases. This mixture is put into the mass spectrometry machine, which sequences the proteins. With this information, researchers know which proteins are abnormally active and why -- because of a mutation, for example -- and can search for a drug that acts against them.

Tyner hopes their work can be translated into clinical tests for determining the molecular cause of a patient's tumor. Protein mass spectrometry profiles of cells from a tumor biopsy could identify which protein is running amok and what drug would work best on it. "It's very attractive, the idea of looking at signaling in tumors and from that uncovering [genetic] profiles," says Cobbold.

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Proteomics research is expanding almost exponentially, as its importance is sinking in. The Wikipedia link above provides several links to proteomics resources. Here is an animation that illustrates the use of mass spectrometry in protein sequencing. Here is a blog that specializes in mass spectrometry, and deals with proteomics occasionally.

This type of technology will become commonplace in the modern anti-aging clinical laboratory. Clients will be scheduled routinely for analysis of cell-signalling networks, both to formulate initial treatments, and to monitor ongoing treatment results. It is likely that many clients will learn initially about their cancers, or other serious diseases, from their anti-aging screening.

Because medical insurance companies are not likely to pay for these procedures for decades yet, early comprehensive anti-aging diagnosis and treatment will be quite expensive.