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MAPS of Cancer

Our goal was to produce an interactive visualization from a mathematical model that successfully predicts metastases from head and neck cancer. We met this goal early in the project. The visualization is available for the public to view. Our work appears to fill a need for more information about this deadly disease. The idea of this project was to make an easily interpretable visualization based on what we call "functional maps" of disease. A functional map is a graphic summary of medical data, where distances between parts of the body are determined by the probability of disease, not by anatomical distances. Functional maps often beat little resemblance to anatomical maps, but they can be used to predict the spread of disease. The idea of modeling the spread of disease in an abstract multidimensional space is difficult for many people. Our goal was to make the important predictions easy to see. NASA must face this problem frequently: how to help laypersons and professionals see important trends in abstract, complex data. We took advantage of concepts perfected in NASA's graphics libraries. As an analogy, consider a functional map of early America. Suppose we choose travel times, rather than miles, as our measures of inter-city distances. For Abraham Lincoln, travel times would have been the more meaningful measure of separation between cities. In such a map New Orleans would be close to Memphis because of the Mississippi River. St. Louis would be close to Portland because of the Oregon Trail. Oklahoma City would be far from Little Rock because of the Cheyenne. Such a map would look puzzling to those of us who have always seen physical maps, but the functional map would be more useful in predicting the probabilities of inter-site transit. Continuing the analogy, we could predict the spread of social diseases such as gambling along the rivers and cattle rustling along the trails. We could simply print the functional map of America, but it would be more interesting to show meaningful patterns of dispersal. We had previously published the functional map of the head and neck, but it was difficult to explain to either patients or surgeons because that view of our body did not resemble anatomy. This discrepancy between functional and physical maps is just a mathematical restatement of the well-known fact that some diseases, such as head and neck cancer, spread in complex patterns, not always to the next nearest site. We had discovered that a computer could re-arrange anatomy so that this particular disease spreads to the next nearest site. The functional map explains over 95% of the metastases in 1400 patients. In a sense, we had graphed what our body "looks like" to a tumor. The tumor readily travels between adjacent areas in the functional map. The functional map is a succinct visual display of trends that are not easily appreciated in tables of probabilities.

Gray, Lincoln↗

Measuring the metastatic potential of cancer cells

Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

Morrison, Dennis R.↗

The Use of Microgravity To Emulate Three-Dimensional Tissue Interactions in Colorectal Cancer Metastasis

The hypothesis of this ground-based project was that simulated microgravity may be used to recreate with high fidelity the in vivo environment in tissue culture. The objectives were to determine whether: (1) simulated microgravity induces differentiation within poorly differentiated human colon carcinoma cells that are similar to that observed in experimental metastases in vivo in nude mice; and (2) the use of simulated microgravity helps define the experimental metastatic potential of human colorectal carcinoma.

Jessup, J. Milburn↗

NASA SMART Probe: Breast Cancer Application

There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

Mah, Robert W.↗