Applications - Breast Imaging

Breast cancer is a principal concern in women's health. Currently, one woman in eight will develop breast cancer at some time during her life. Clinical experience has shown that early detection is key to reduced morbidity and long term survival. Presently, x-ray mammography is the gold standard used for routine screening and monitoring the response to therapy. Many women find the experience of a mammogram, with its need for breast compression, distinctively unpleasant. In addition, the reliance of x-ray findings on anatomical features that are present only in the more developed tumors presents a notable challenge for early detection. Still other limitations of the technique include is its limited use in younger women having radio-dense breasts and the reliance on use of ionizing radiation.

Breast Cancer 

Tumor neo-angiogenesis

A hallmark in the development of a cancerous tumor is its ability to trigger the formation of new blood vessels to provide nutrients necessary for its growth. This proces s - known as neo-angiogenesis - does not follow the normal angiogenic mechanisms found in healthy tissue, and results in the development of a vascular network that is largely devoid of the normal control mechanisms and has vessels that exhibit aberrant morphology and impaired perfusion. Frequently this produces disturbances in intercellular fluid balances that can add to diffusion barriers caused by the distorted vascular architecture. A consequence of this is that tumors are thought to function on the brink of hypoxemia. Clinically this is known to interfere with the delivery of chemotherapeutic agents and response to radiotherapy. It is our view that the tumor environment, with its impaired perfusion, increased blood volume resulting from increased vessel density and enhanced levels of deoxyhemoglobin, is ideally matched to the expected sensitivity of NIRx systems to identify discriminatory features linked to tumor angiogenesis and other factors associated with tumor growth. Notably the expression of these features can be expected to vary in accordance with different forms of functional provocations. For instance, it is logical to expect that the existence of an impaired vascular network will be more susceptible to induced hypoxemia than will be the surrounding tissue. Similarly, maneuvers that produce changes in the bulk perfusion of the breast can likewise be expected to reveal local disturbances in flow associated with the developing tumor. Still other types of functional disturbances might be observable as a consequence of an aberrant vascular network. One example is the idea that developing tumors might cause regional disturbances in the normal control mechanisms that modulate blood flow to tissue. Clearly the implication is that there is a host of vascular dynamic behaviors that can be exploited to act as a contrast feature to detect neo-angiogenetic vascular disturbances. These include vascular dynamics at rest as well as responses to a variety of possible external stimuli (e.g., breathing challenges, temperature changes, etc.). Shown here are a few exemplary results that support this idea obtained using the DYNOT  232 imager on subjects diagnosed with breast cancer.

The image in panel A was produced from a subject asked to undergo a prolonged breath hold (60 sec) in an effort to induce hypoxemia. The image shows a high contrast feature positioned in the anterior region of the breast near the nipple whose size and location coincides well with comparative findings from ultrasound.

In panel B we show a result obtained wherein blood flow to the breast was affected by deep regulated breathing. The expected finding here is that, in healthy tissue, changes in blood flow caused by deep breathing will be uniformly synchronized throughout the breast. A map of time delays in the response of the venous vasculature to the induced respiratory rhythm (phase map at the respiratory frequency) can reveal this. In the healthy breast we see that the response is largely uniform. In the tumor-bearing breast, we see a large phase contrast feature spanning from the lower medial to the upper lateral quadrant indicating the occurrence of a time delay in venous return in response deep breathing. Significantly, this feature agrees well with the presence of a large tumor revealed by x-ray having a similar location.

In panel C we have explored yet another well-known feature of vascular physiology - the modulation of the natural vascular rhythms. This phenomenology occurs in response to complex interactions involving both local tissue and central control mechanisms (e.g., neural modulation of the microvasculature) that serve to redirect blood flow on a local level. This behavior is readily observable from a time-frequency analysis of images obtained from the breast of a subject at rest. In the example shown we present a contrast map that reveals the presence of a diffuse region having altered modulation. Comparison of this map to the corresponding map obtained using ultrasound indicates that the region of tissue exhibiting an altered response extends well beyond the boarder of the tumor. This finding raises the intriguing possibility of early tumor detection (perhaps sizes well below that seen by x-ray) based on the response of the surrounding tissue to the growing tumor.

Significantly, the examples cited represent distinctly different contrast mechanisms. Common to all is the fact that the observed features are associated with functional disturbances. It is our view that many more such features can be defined and that these will serve to discriminate the presence of cancereous tumors and differentiate them from other pathologies. It deserves emphasis that in all cases shown, results were obtained without breast compression, need for injectable contrast agents or use of ionizing radiation. On a fundamental level, we believe that our technology is intrinsically better suited for early detection of tumors than other techniques because there is a better match between features of tumor biology and the type of sensing methods used to explore these.

Value / Advantages

• Intrinsically greater sensitivity to early detection of tumors.
• No compression required, increased patient comfort.
• No injection required.
• Added information gathered from simultaneous bilateral scans.
• No interference from dense breasts or implants.
• High patient throughput.
• No ionization radiation; hence, more frequent screening without corresponding health concerns.