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Creating Improved Maps of Tumor Locations for Enhanced Cancer Eradication

Sandeep Hunjan
Department of Radiation Oncology
Stanford University School of Medicine
June 2002

The continuing "catch-22" for radiation treatment of tumors is that in order to kill tumors with radiation, the therapeutic radiation beams must travel through, and damage, normal healthy tissue in order to reach the target. Current radiotherapy methods can deliver high radiation doses accurately to desired locations. However, the images being used to guide the radiation beams are normally only pictures of anatomical structures, which don't always accurately highlight the tumor's location. Obviously, accurate maps of tumor locations are required before blasting potentially lethal beams of radiation through normal, healthy regions in an attempt to reach and destroy tumors.

Unfortunately, tumors are remarkably similar to the normal surrounding tissues so they often do not light up in regular medical images. But, there is one consistent difference between tumors and normal tissues, which is that tumor cells multiply at an abnormally fast rate. This means that they require more building blocks for construction of new cells.
In my research, I create maps that show the distribution of an essential building block of all cells, choline, which is detectable using a method called Magnetic Resonance Spectroscopy, or MRS. Choline is actually used in the construction of cells walls, among other things. Higher levels of choline in this map indicate regions where cells are being constructed (or synthesized) at a higher rate. I then incorporate these more accurate roadmaps, which pinpoint regions of increased cell synthesis, into the whole radiotherapy treatment process so that areas of aggressive tumors with the highest rate of reproduction are more clearly distinguished from normal tissues. Using clearer roadmaps in this manner should result in the highest dose being delivered to aggressive tumors with elevated growth rates, while normal tissue will get decreased doses, resulting in fewer side effects.

A continuing challenge for researchers and doctors who study and treat cancer is how to kill the cancer cells yet spare the surrounding, normal tissue. Intensity Modulated Radiation Therapy (IMRT) is a promising new advanced technique that holds the potential to tip the odds in favor of destroying the cancer while reducing damage to healthy cells. The method allows very accurate delivery of high radiation doses to tumors, while "sparing" normal tissues, meaning that normal tissues are not harmed. However, cancer can still come back if a few active tumor cells remain after therapy is complete. In order to reduce the chances of this happening, an imaging method is needed that can create a roadmap to highlight the most dangerous regions of the tumor, which are most active and hence need to be targeted with the highest radiation dose. Current medical imaging methods cannot always do this because most tumors are similar to the normal surrounding tissues and only visible when they are large enough to deform normal structures. However, radiotherapy treatment planning has no choice but to use these images for lack of a better map.

Magnetic Resonance Spectroscopy (MRS) is a non-invasive test, which can measure metabolites, or chemicals, in the body by using powerful magnets instead of harmful radiation. One of the metabolites detectable by MRS is choline, which is needed by the tumor to make more cells and hence grow. An additional major advantage of MRS is that it can simply be added onto the MR Imaging (MRI) scan which a patient will already be having since MRI machines require no further equipment upgrades to acquire MRS scans. This could decrease return visits and prevent unnecessary anxiety if a suspicious looking region turns out to be normal according to the MRS. This research proposes to use the MRS technique to create an imaging method that can be used to produce maps showing the distribution of the most active, hence dangerous, areas of tumors, which need to be targeted with the highest radiation dose during radiation therapy. I am currently able to make MRS maps with 1 cm resolution of the choline distribution and am working on methods of increasing the resolution, and hence the accuracy, of the MRS maps. The next step will be to incorporate these images into the radiotherapy treatment planning procedure to guide radiotherapy.

The success of this project could significantly refine the promising IMRT technique further leading to lower overall radiation dose to the patient. This would result in less side effects, but higher dose to the aggressively growing areas of the tumor. This would also result in a lesser chance of tumor recurrence after treatment.