The analysis of small deposits of calcium in breast tissue can help differentiate cancerous and benign tumors, but it is sometimes not easy to make such a diagnosis. Now a team of researchers in the US believes a new method that uses a special type of spectroscopy to locate calcium deposits during a biopsy, could greatly improve the accuracy of diagnosis.
The team, from Massachusetts Institute of Technology (MIT) and Case Western Reserve University (CWRU), writes about the work that led them to this conclusion in a paper published online in Proceedings of the National Academy of Sciences on 24 December.
Microcalcifications, or small deposits of calcium, form when calcium from the bloodstream deposits onto degraded proteins and fats left behind by injured and dying cells.
They can be a telltale sign of breast cancer, but most tumors that contain them are benign.
Microcalcifications are most often seen in breast tumors, but they can also occur, albeit rarely, in other types of cancer, says co-senior author Maryann Fitzmaurice, senior research associate and adjunct associate professor of pathology and oncology at CWRU, in a statement.
Calcification also plays a major role in atherosclerosis, or hardening of the arteries.
When microcalcifications show on a mammogram, doctors do a follow-up biopsy of the suspect tissue to test for cancer.
Figures show that in around 1 in 10 cases with such microcalcifications, the tumor is cancerous, so the follow-up biopsy is critical.
During the procedure, the radiologist takes X-rays from three different angles to locate the tiny calcium deposits, then inserts a needle into the tissue and removes up to 10 tissue samples.
A pathologist then tests these samples to see if they contain microcalcifications.
But in 15 to 25% of cases, it is not easy to locate and take a tissue sample accurately, resulting in an inconclusive diagnosis. This means the patient has to have more X-rays and undergo more invasive surgery to retrieve further samples.
But, as Fitzmaurice explains, this second attempt is rarely successful:
“If they don’t get them on the first pass, they usually don’t get them at all.”
“It can become a very long and arduous procedure for the patient, with a lot of extra X-ray exposure, and in the end they still don’t get what they’re after, in one out of five patients,” she adds.
Spectroscopy is a way of determining the composition of a material by studying how it absorbs or scatters radiation such as light. It is often used in physical and analytical chemistry, and there are many applications now in medicine too.
One of the challenges in applying the technique to medicine is cost and speed: often the equipment is very expensive and slow to deliver results in “real time”.
For the past several years, the MIT and CWRU team has been working on overcoming this challenge to help the radiologist determine, in a matter of seconds, if the tissue contains microcalcifications or not.
At first they tried a method based on Raman spectroscopy, which uses light to measure energy shifts in molecular vibrations, revealing precise molecular structures. The advantage of this method is that it is very accurate at identifying microcalcifications. But the disadvantage is the equipment is expensive and the analysis takes a long time.
In this latest study, the researchers describe how they turned to another method, called “diffuse reflectance spectroscopy”, and found it gave results just as accurately as Raman spectroscopy, but much faster and at less cost.
Co-lead author Narahara Chari Dingari, a postdoc at MIT, says:
“With our new method, we could obtain similar results with less time and less expense.”
Diffuse reflectance spectroscopy collects and analyzes light after it has interacted with the sample. This gives a unique “spectrographic signature”.
In their PNAS paper, the authors describe how they examined 203 tissue samples within minutes of their removal from 23 patients.
Each sample could be one of three types, each with its own spectrographic signature. It could be healthy, it could contain lesions with no microcalcifications, or it could contain lesions with microcalcifications.
By analyzing these patterns, the team produced a computer algorithm that showed a success rate of 97% in identifying tissue with microcalcifications.
Jaqueline Soares, another lead author and MIT postdoc, suggests the changes in the way the different tissues absorb light are probably due to altered levels of specific proteins (elastin, desmosine and isodesmosine) that are often cross-linked with calcium deposits in diseased tissue.
James Tunnell is an associate professor of biomedical engineering at the University of Texas and was not involved in the study. He describes the study as a “good first step” toward a system that could have a big impact on breast cancer diagnosis.
“This technology can be integrated into the system that is already used to take biopsies. It’s a very simple technology that can get the same amount of accuracy as more complicated systems.”
The team envisages their technique being used by radiologists to provide enhanced “real time” guidance to current biopsy procedures.
Because it provides the analysis results within seconds, the new technique could help the radiologist to move the needle to another spot before taking any samples.
The researchers are planning to carry out a new study to test the approach in “real time”: as biposies are being carried out in patients.
Funds from the National Institutes of Health, the National Institute of Biomedical Imaging and Bioengineering and the National Cancer Institute helped finance the study.
Written by Catharine Paddock PhD