Professor Boone and radiologist discuss research, grant process
UC Davis biomedical engineering professor and Vice Chair of Radiology, John Boone, was recently awarded a $2.88 million grant for his research on using computed tomography (CT) in breast cancer screenings and diagnosis.
“Our real goal is to help our physician colleagues detect breast cancer earlier and increase the survivability of breast cancer,” Boone said. “We’re doing this research with the intention of ultimately helping humanity, which is really what most research in the medical world is about.”
Boone is also the president of the American Association of Physicists in Medicine. According to Boone, choosing to research breast cancer and CT was a natural combination of his strengths, as he has always had an interest for breast imaging and mammography.
“As an academic scientist, it’s important to follow research that has impact,” Boone said.
Breast cancer affects both men and women, though it is very uncommon in men. According to Boone, 12.5 percent of women will be diagnosed with breast cancer at some point in their life. The National Cancer Institute recommends that women over the age of 40 undergo annual screening in order to detect small tumors before they spread.
Annual screenings are typically conducted using mammography. If a mammogram reveals a suspicious lesion, the patient is taken for a diagnostic examination, which could involve an ultrasound or MRI scan. Boone aims to gain approval for CT as an alternative in both the screening and diagnostic stages.
“The problem with mammography is that you’re making a projection of a 2-D image from a 3-D object — the breast,” Boone said. “Every point means a path through the thickness of the breast, which is about five centimeters. So if a woman has dense breasts, some normal anatomy of the breast could get in the way of the lesion, reducing the probability of a radiologist detecting it.”
For the past 15 years, Boone’s lab has been working on making a 3-D image of the 3-D breast.
“The whole idea is to not have the issue where breast anatomy gets in the way of detection,” Boone said. “We’re actually slicing the breast image into tiny images using computers. That’s what CT does. That allows the radiologists to look at each slice one at a time, rather than at one dense five centimeter path.”
While mammography is relatively inexpensive, the issue of patient comfort arises.
“We conducted a survey on mammography compared to breast CT,” said Karen Lindfors, professor of Radiology and chief of Breast Imaging at UC Davis. “Patients preferred breast CT for comfort level because it doesn’t require breast compression.”
Some patients find mammography painful because the breast needs to be flattened in order to create the 2-D image. Breast flattening is not required for CT.
Mammography is a screening technology, but greater efforts are required if lesions are detected. Once a lesion is identified, diagnostic tests are required to determine whether the lesion is a tumor or not. At this level of examination, breast MRI is used, and is always accompanied by the injection of a contrast agent into a woman’s veins. This helps distinguish tumors.
The second part of Boone’s research aims to display CT as a more cost- and time-effective alternative to MRI.
“With CT, we’re also going to inject a different kind of contrast agent into the woman’s veins and image the breast with breast CT,” Boone said. “This can then be compared with MRI.”
The final stage in breast cancer diagnosis is a biopsy, in which a tissue sample is sent to pathologists who determine whether the tumor is cancerous.
“The hope is that we will be able to reduce number of biopsies of breasts with benign lesions and increase detection of those that are malignant,” Lindfors said. “We want to better differentiate non-malignant from malignant in the least invasive way.”
The Boone lab has been operating on grants of about $1 million per year for the past decade. After 15 years of research, the lab has reached the final clinical trials for CT in screening and diagnostics respectively.
“In the last five years, we’ve applied for maybe 30 grants, and got a few funded,” Boone said. “We’re in a relatively grim funding era with [the National Institute of Health], maybe eight out of 100 labs are chosen. It’s a pretty typical obstacle.”
According to AJ Cheline, Director of Marketing and Communications for the UC Davis Office of Research, a total of 67 projects at UC Davis have received awards from the NCI between 2012-2015. UC Davis receives an average of $20 million in funds from the NCI per year.
“As you can see, the average NCI award at UC Davis is about a million dollars,” Cheline said. “Between two to $10 million are very strong awards, so this award is definitely significant.”
The life sciences tend to receive the most awards, according to a survey published by the National Science Foundation. Stem cell, cancer, nutrition and pathological research tend to have the most impact and are fast growing paths, Cheline said.
“Reviewers pick apart your science, you edit the grant and resubmit,” Boone said. “It’s a matter of convincing smart people that your science is more important than other scientists’. But, 10 students have gotten PhD’s with this research, it’s been impactful, and we’ve published a lot. Now we’re just at the final clinical trials.”
Clinical trials have already been conducted on over 400 patients at UCD. Boone hopes to accrue 400 more patients in the next five years. Each patient will undergo two modalities of testing: screening and diagnostic. This means participants will get all four methods of testing, mammography, CT, MRI with contrast injection and CT with contrast injection.
“The women who participate in the trials will all be UC Davis patients with suspicious lesions,” Lindfors said. “CT will be compared to the other modalities to determine accuracy in information about malignancy as compared to non-malignancy.”
While all 400 women will have lesions, some will be benign and others will be malignant. Radiologists who are unfamiliar with the patients’ cases will examine the scans and rate on a scale of one to five how certain they are that the results show a tumor or not. After imaging trials are complete, all participants will be biopsied to determine whether or not the cells are cancerous.
“The results of these studies will tell us essentially how good CT is,” Boone said. “We’ll see how it compares against mammography in screening, and how contrast enhanced CT compares to MRI in the diagnostic environment.”
Boone hopes to see the integration of CT in breast imaging tests, first at the diagnostic level, then later as high risk screening tool and ultimately as a replacement for mammography.
While Boone’s team consists of biomedical engineering graduate students, in addition to medical physicists, radiologists and breast imaging experts, he encourages students to explore research.
“It’s a great joy to have the honor to be in this position,” Boone said. “It takes people who are smart, curious, creative and willing to work hard. The rewards of research are many. It isn’t for everybody, and it’s a tough business, but as undergraduates, especially scientists in training, explore this career path by participating as an undergrad in a research lab.”
According to Boone, research is an adventure of its own.
“Research, especially medical research, is a new frontier,” Boone said. “The Earth has been studied; there isn’t one place you can go that people haven’t been before. So the explorers of today really are researchers.”
Graphic by Jennifer Wu.