Diffuse optical tomography (DOT) and diffuse optical spectroscopy (DOS) are non-invasive techniques that use near-infrared (NIR) light to measure the optical properties of tissue. Fibre optics are used to illuminate tissue, while sensitive detectors pick up the transmitted and scattered photons. Reconstruction software can then use the photon distribution to produce images (DOT) or quantitative maps (DOS) of haemoglobin concentration, oxygen saturation, water and lipid concentration, and scattering particle size – all of which are well known as predictors of disease.

Optical interrogation of these parameters hasn't been studied extensively in tumours as yet. However, tumours have significantly different vasculature to that of healthy tissue, which means that DOT and DOS should be able to differentiate them from benign lumps. "Near-infrared could serve the role of providing more information about the things that light up on an MR scan and potentially reduce the number of MR-guided biopsies," Brian Pogue, a professor of engineering at Dartmouth College (Hanover, NH), told medicalphysicsweb.

Complicated cases

Pogue's team has been working on a breast-imaging system that combines MRI with DOS. With the help of Philips Medical Research in the US, the scientists have developed a frequency-domain NIR spectroscopy (NIRS) system that can be built into the breast coil of an MR scanner. "It's a series of fibre optics that touch the breast and allow us to do NIRS detector transmission measurements," he explained. "It's like a CT scanner in some ways, but with fibre optics instead of X-rays."

MRI scans are commonly used to examine women in whom mammograms reveal an abnormality, who are at high-risk of developing breast cancer or who have complicated breasts due to implants or previous surgery. Even after an MRI examination, most of these women will have to undergo a biopsy. However, Pogue thinks that the use of DOS can improve this situation. "For complicated cases where you see multiple things light up that look like tumours, having a second checking system to determine the biophysical characteristics would be useful," he said.

His team is currently in the midst of a clinical trial that will examine 60 women over three years. So far the researchers have imaged five women, one of whom was a false negative (i.e. the MR scan indicated a tumour when in fact there was none). In this case the combined system passed with flying colours: "The NIR signature showed that it didn't have the characteristics of a tumour," explained Pogue.

Under pressure

It would be even more advantageous if optical imaging could be used to help to spot cancers at the initial screening stage (i.e. a diffuse optical system that works alongside conventional X-ray mammography). A team at Massachusetts General Hospital (MGH; Boston, MA) has been developing such a combined system for several years. However, according to team member Qianqian Fang, the compression applied to the breast during mammography makes interpretation of the optical data much trickier.

"We've hypothesized that the pressure redistributes the blood and causes a low total haemoglobin region in the centre of the breast," he told medicalphysicsweb. "The important question is whether that pressure redistribution will have an impact on lesion detection." A successful combined X-ray/DOT mammography system would allow doctors to differentiate tumours from benign lumps with much more confidence at an early stage.

The MGH approach consists of a DOT system, with source and detector probes designed to attach to the compression paddles of a tomosynthesis mammography unit. This means that the researchers can acquire optical images of the breast immediately before or after the X-ray scan, with the breast in exactly the same position as during the mammogram. The optical and X-ray images can then be strictly co-registered, allowing for direct comparison.

During the last year the MGH team has been trying out the system on real patients. It is now analysing the data. Measurements of the bulk optical properties of breast tissue agreed well with published values, but the reconstructed haemoglobin maps showed odd patterns. After eliminating all of the alternatives, the researchers concluded that these are due to blood redistribution as a result of the compression applied to the breasts during imaging. On the basis of the current data, though, it's not possible to tell how this affects the system's ability to spot tumours.

"If you're assuming that tumours have a higher vascular density then there are more vessels and more blood," Fang explained. "When you apply pressure, will the blood squeeze more from the tumour or more from the background?" In the first scenario, the contrast would decrease; in the second, it would get better. "The answer to this is very important for evaluating whether our system has real clinical value," he added.

The MGH team is now in the midst of investigating how pressure affects tissue dynamics, in the hope of finding biomarkers that will reliably distinguish tumours from healthy tissue and further increase the utility of the system.

Predicting radiation response

Diffuse optical techniques could also have a positive impact on breast-cancer therapy. At the moment it is standard practice after lumpectomy to irradiate the whole breast. The problem with this brute-force approach is that it damages a large area of healthy tissue, which may not be necessary for many women. Catherine Klifa and Catherine Park of the radiology and radiation oncology departments at the University of California at San Francisco (UCSF) believe that information obtained using DOS could predict how individual breasts will respond to radiation and allow doctors to plan the treatment accordingly.

"Many patients could benefit from a different or shorter treatment, but it is hard to class patients as good responders versus less good responders," Klifa told medicalphysicsweb. "There are currently no quantitative tools that are available to clinicians to evaluate the effects of radiation on breast tissue non-invasively." Her team thinks that a combined MRI/DOS system can fill this gap. What's more, results from a recent feasibility study appear to back up that assertion.

Using a DOS device built by Bruce Tromberg and colleagues at the University of California Irvine (UCI), together with an MRI scanner, Klifa and Park's team obtained quantitative structural and functional information about the tissue at several locations in the breast. Eight cancer patients were scanned with both modalities before surgery, and at the beginning and end of the subsequent radiotherapy course. "By combining both MRI and DOS data, we expect to quantify small changes due to radiation therapy and potentially better understand the mechanisms of radiation effects on breast tissue," said Klifa.

The data obtained suggest that the combined system can spot tissue changes caused by irradiation. Larger studies are now needed to understand these changes, but Klifa is optimistic about the potential of optical imaging in this area: "We can envision the use of MRI and DOS – or potentially DOS alone, which would obviously be faster, easier and cheaper – to help separate potential good responders from less good responders, who could then benefit from a different treatment management."

And the bottom line? "DOS is still for research use only," Klifa concluded. "[However], many teams are attempting to use it on a more general scale in order to help clinicians in cancer management. It is possible that DOS could become a lot more used due to its portability, flexibility and non-invasiveness." And, of course, a modest price tag should also help.

• Additional research for this article is based on papers presented at SPIE's Biomedical Optics Symposiumin San Jose, CA, in January. See also Optical mammography: the ideal adjunct? and Special report: breast imaging on medicalphysicsweb.