January 2014

Reporter’s Notebook: RSNA 2013
Radiology Today
Vol. 15 No. 1 P. 16

Editor’s note: This article is based on materials distributed for the press conferences at RSNA 2013 in Chicago.

Tomosynthesis Boosts Cancer Detection, Reduces Recall
Using digital breast tomosynthesis (DBT) led to reduced recall rates and an increase in cancer detection in a large breast cancer screening program, according to a study presented at RSNA 2013.

Digital mammography is the gold standard for breast cancer screening but yields false-positive findings associated with a higher recall rate for additional imaging or biopsy. However, unlike conventional 2D mammography, DBT allows for 3D reconstruction of the breast tissue, which then can be viewed as sequential slices through the breast.

Because DBT technology is relatively new, it typically is used as a supplemental screening tool. But since October 2011, every patient screened for breast cancer at the Hospital of the University of Pennsylvania in Philadelphia has been screened using DBT, according to Emily F. Conant, MD, chief of breast imaging and the study's lead author. “We have used DBT on all of our breast screening patients,” she said. “Every patient has had it—we have not selected patients because of their risk or breast density or if they were willing to pay extra. We did not charge extra and were able to provide all of our women with this new technology.”

For the study, Conant and colleagues compared imaging results from 15,633 women who underwent DBT at the Hospital of the University of Pennsylvania beginning in 2011 with those of 10,753 patients imaged with digital mammography the prior year. Six radiologists trained in DBT interpretation reviewed the images.

The researchers found that, compared with digital mammography, the average recall rate using DBT decreased from 10.4% to 8.78%, and the cancer detection rate increased from 3.51 to 5.24 (per 1,000 patients). The overall positive predictive value increased from 4.1% to 6% with DBT.

“Our study showed that we reduced our callback rate and increased our cancer detection rate,” Conant said. “The degree to which these rates were affected varied by radiologist. But importantly, the ratio of callback to cancer detection rate improved significantly for our radiologists.”

Conant noted that tomosynthesis is an evolving platform, and researchers already are seeing a significant improvement in important screening outcomes.

“It's the most exciting improvement to mammography that I have seen in my career, even more important than the conversion from film-screen mammography to digital mammography,” she said. “The coming years will be very exciting, as we see further improvements in this technology.”


Screening Interval Affects Lymph Node Involvement
Patients who underwent more frequent screening mammography had a significantly lower rate of lymph node positivity compared with women who went for longer intervals between screening mammography exams in a study of screening mammography-detected breast cancers. Results of the study were presented at RSNA 2013.

In its earliest stages, breast cancer is confined to the breast and can be treated by surgically removing the cancer cells. As the disease progresses, breast cancer cells may spread to the lymph nodes and then to other areas of the body.

“On its pathway to other places in the body, the first place breast cancer typically drains into before metastasizing is the lymph nodes,” said Lilian Wang, MD, an assistant professor of radiology at Northwestern University Feinberg School of Medicine in Chicago. “When breast cancer has spread into the lymph nodes, the patient is often treated both locally and systemically, with either hormone therapy, chemotherapy, trastuzumab, or some combination of these therapies.”

Historically, health care organizations such as RSNA and the American Cancer Society have recommended annual screening with mammography for women beginning at age 40. However, in 2009, the US Preventive Services Task Force (USPSTF) announced a controversial new recommendation for biennial screening for women between the ages of 50 and 74. “Our study looks at what would happen if the revised guidelines issued by USPSTF were followed by women,” Wang said.

The retrospective study, conducted at Northwestern Memorial Hospital, included 332 women with breast cancer identified by screening mammography between 2007 and 2010. The women were divided into one of three groups based on the length of time between their screening mammography exams: less than 1.5 years, 1.5 to three years, and more than three years. There were 207, 73, and 52 patients in each category, respectively.

Controlling for age, breast density, high-risk status, and a family history of breast cancer, the researchers determined that women in the less than 1.5 years interval group had the lowest lymph node positivity rate at 8.7%. The rate of lymph node involvement was significantly higher in the 1.5- to three-year and over three-year interval groups at 20.5% and 15.4%, respectively.

“Our study shows that screening mammography performed at an interval of less than 1.5 years reduces the rate of lymph node positivity, thereby improving patient prognosis,” Wang said. “We should be following the guidelines of the American Cancer Society and other organizations, recommending that women undergo annual screening mammography beginning at age 40.”


Cardiac MRI Study: Energy Drinks Alter Heart Function
Healthy adults who consumed energy drinks high in caffeine and taurine had significantly increased heart contraction rates one hour later, according to a study presented at RSNA 2013.

“Until now, we haven't known exactly what effect these energy drinks have on the function of the heart,” said radiology resident Jonas Dörner, MD, of the cardiovascular imaging section at the University of Bonn, Germany, which is led by the study's principal investigator, Daniel K. Thomas, MD. “There are concerns about the products' potential adverse side effects on heart function, especially in adolescents and young adults, but there is little or no regulation of energy drink sales.”

A 2013 report from the Substance Abuse and Mental Health Services Administration stated that in the United States from 2007 to 2011, the number of emergency department visits related to energy drink consumption nearly doubled, increasing from 10,068 to 20,783. Most of the cases were identified among patients aged 18 to 25, followed by those aged 26 to 39.

“Usually, energy drinks contain taurine and caffeine as their main pharmacological ingredients,” Dörner said. “The amount of caffeine is up to three times higher than in other caffeinated beverages like coffee or cola. There are many side effects known to be associated with a high intake of caffeine, including rapid heart rate, palpitations, rise in blood pressure and, in the most severe cases, seizures or sudden death.”

For the study, which is ongoing, Dörner and colleagues used cardiac MRI to measure the effect of energy drink consumption on heart function in 18 healthy volunteers, including 15 men and three women with a mean age of 27.5 years. Each of the volunteers underwent cardiac MRI before and one hour after consuming an energy drink containing 400 mg of taurine and 32 mg of caffeine.

Compared with the baseline images, results of cardiac MRI performed one hour after the study participants consumed the energy drink revealed significantly increased peak strain and peak systolic strain rates (measurements of contractility) in the left ventricle of the heart, which receives oxygenated blood from the lungs and pumps it to the aorta, which distributes it throughout the rest of the body.

“We don't know exactly how or if this greater contractility of the heart impacts daily activities or athletic performance,” Dörner said. “We need additional studies to understand this mechanism and to determine how long the effect of the energy drink lasts.”

The researchers found no significant differences in heart rate, blood pressure, or the amount of blood ejected from the left ventricle of the heart between the volunteers' baseline and second MRI exams.

“We've shown that energy drink consumption has a short-term impact on cardiac contractility,” Dörner said. “Further studies are needed to evaluate the impact of long-term energy drink consumption and the effect of such drinks on individuals with heart disease.”

Dörner said that while long-term risks to the heart from drinking energy drinks remain unknown, he advises that children and people with known cardiac arrhythmias should avoid energy drinks because changes in contractility could trigger arrhythmias. He also cautions that additional study is needed to address risks posed by the consumption of energy drinks in combination with alcohol.


Imaging Shows Long-Term Impact of Veterans’ Blast-Induced Brain Injuries
Using a special type of MRI, researchers have found that soldiers who suffered mild traumatic brain injury (MTBI) induced by blast exposure exhibit long-term brain differences, according to a study presented at RSNA 2013.

Recent wars have resulted in veterans with an exposure rate of approximately 20% to blast-induced MTBI, or trauma resulting from mortar fire and improvised explosive devices. Diagnosis can be challenging, especially in mild cases.

“Mild traumatic brain injury is difficult to identify using standard CT or MRI,” said study coauthor P. Tyler Roskos, PhD, a neuropsychologist and assistant research professor at the Saint Louis University School of Medicine. “Other methods may have added sensitivity.”

One of those methods is diffusion tensor imaging (DTI), an MRI technique used to identify microstructural injury to white matter, the part of the brain that consists mostly of signal-carrying axons. Damage-associated changes in water movement along the axons are comparable in certain respects with what might happen with a garden hose, according to coauthor Thomas M. Malone, BA, a research associate at Saint Louis University School of Medicine. “As water passes through the hose from the faucet to the sprinkler, it goes in the same direction, but if you were to puncture the hose with a rake, the water would shoot out the sides,” he said.

In the study, researchers compared DTI-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with MTBI with those of 10 healthy controls. FA measures the uniformity of water diffusion throughout the brain, and low FA tends to indicate areas of axonal injury. The average time elapsed between the blast-induced injury and DTI among the patients was 51.3 months. “The time since injury is a novel component to our study,” Roskos said. “Most other blast-related MTBI studies examine patients in the acute phase of injury.”

Comparison of FA values showed significant differences between the two groups, and there were significant correlations between FA values and attention, delayed memory, and psychomotor test scores. Since the victims were, on average, more than four years removed from their injuries, the results suggest the presence of a long-term impact of blast injury on the brain. “This long-term impact on the brain may account for ongoing cognitive and behavioral symptoms in some veterans with a history of blast-related MTBI,” Roskos said.

The results also indicate that DTI is sensitive to group differences in blast-related MTBI even in the postacute phase. “DTI shows promise in enhanced sensitivity for detecting MTBI compared to MRI/CT, even in the chronic phase,” Roskos said. “Identification of changes in specific brain regions may help in diagnosis and treatment of MTBI among veterans.”

Roskos explained that this research is aimed at finding better ways for clinicians to differentiate between MTBI and posttraumatic stress disorder (PTSD) in veterans in order to improve treatment.

“It makes a difference because PTSD is psychological in nature, and MTBI is neurological,” he said. “Many veterans in the health care system are dealing with MTBI, PTSD, or both. Our emphasis today is to find the best treatments and measure the patient's progress. Imaging has the potential to do that.”


MRgFUS Offers Noninvasive Treatment for Breast Cancer
Focused ultrasound under MR guidance may offer a safe and effective noninvasive treatment for breast cancer, according to research presented at RSNA 2013.

MR-guided focused ultrasound (MRgFUS) ablation requires no incision or puncture to perform. Instead, it uses the acoustic energy from high-intensity focused ultrasound to heat and ablate diseased tissue. Continuous MRI is used to locate the lesions and monitor the temperature change during the process. The primary potential advantages of MRgFUS over other breast cancer treatments are is that it is a noninvasive, outpatient procedure offering a quick recovery time, and precise measurement of temperature changes during the procedure.

“In the treatment stage, we are able to precisely visualize where the energy is having an effect and to measure exactly the rise in temperature,” said Alessandro Napoli, MD, PhD, an assistant professor of radiology at Sapienza University of Rome. “Temperature monitoring is particularly important, since too low of a temperature is ineffective and too high of a temperature may be dangerous.”

Napoli and colleagues assessed the safety and efficacy of MRgFUS in 12 patients with invasive ductal breast cancer before surgical removal of the cancer and biopsy of the lymph nodes. They used 3T MRI to confirm the presence and treatable location of cancerous lesions. The patients then underwent single-session MRgFUS treatment. Researchers evaluated treatment efficacy through postsurgery pathology.

None of the patients experienced significant complications during or immediately after the procedure. In 10 of the 12 patients, MRI showed no enhancement in the treatment area after the procedure. Postsurgery histological evaluation confirmed the absence of residual disease in the treatment area in those 10 patients.

“This procedure allows for safe ablation of breast cancer,” Napoli said. “At pathology, no significant viable tumor was found in the specimens from these 10 patients.”

In the other two cases, treatment failed because of transducer malfunction, and the pathologist observed residual tumor in the samples.

According to Napoli, MRI guidance is crucial for correct identification of lesions, treatment planning, and real-time control during the procedure. Specifically, monitoring with MRI allows for efficiently depositing energy into the region of treatment at the correct range of between approximately 140˚ and 158˚F. “This is carried out by a special sequence that is called MR thermometry,” he said. “Only MRI presently has the ability to determine in real time fine temperature quantification.”

While the initial results are promising, Napoli cautions that more research will be needed before the approach can be adopted as a stand-alone treatment.


Breast Density Measurement May Predict Cancer Risk
Automated breast density measurement predicts breast cancer risk in younger women, and that risk may be related to the rate at which breast density changes in some women as they age, according to research presented at RSNA 2013.

 Breast density, as determined by mammography, already is known to be a strong and independent risk factor for breast cancer. The American Cancer Society (ACS) considers women with extremely dense breasts to be at a moderately increased risk of cancer and recommends they talk with their physicians about adding MRI screening to their yearly mammograms.

“Women under age 50 are most at risk from density-associated breast cancer, and breast cancer in younger women is frequently of a more aggressive type, with larger tumors and a higher risk of recurrence,” said the study's senior author, Nicholas Perry, MBBS, FRCS, FRCR, director at the London Breast Institute in the United Kingdom.

Perry and colleagues compared breast density and cancer risk between younger and older women and then analyzed how the risk relates to changes in breast density over time. The study group included 282 breast cancer cases and 317 healthy control participants who underwent full-field digital mammography, with breast density measured separately using an automated volumetric system.

“In general, we refer to breast density as being determined by mammographic appearance, and that has, by and large, in the past been done by visual estimation by the radiologist—in other words, subjective and qualitative,” Perry said. “The automated system we used in the study is an algorithm that can be automatically and easily applied to a digital mammogram, which allows an objective and therefore quantitative density measurement that is reproducible.”

Breast cancer patients showed higher mammographic density than healthy participants up to the age of 50. The healthy controls demonstrated a significant decline in density with age following a linear pattern, while there was considerably more variability in density regression among the breast cancer patients.

“The results are interesting because there would appear to be some form of different biological density mechanism for normal breasts compared to breasts with cancer, and this appears to be most obvious for younger women,” Perry said. “This is not likely to diminish the current ACS guidelines in any way, but it might add a new facet regarding the possibility of an early mammogram to establish an obvious risk factor, which may then lead to enhanced screening for those women with the densest breasts.”

For instance, some women might undergo a modified exposure exam at age 35 to establish breast density levels, Perry said. Those with denser breast tissue then could be followed more closely with mammography and additional imaging such as MRI or ultrasound for earlier cancer detection and treatment.

“It has been estimated that about 40% of life years lost to breast cancer are from women under 50 diagnosed outside of screening programs,” Perry said. “In my practice, which is largely composed of urban professional women, 40% of cancers year to year are diagnosed in women under 50 and 10% in women younger than 40.”


New Research Shows Promise for Possible HIV Cure
Researchers have used radioimmunotherapy (RIT) to destroy remaining HIV-infected cells in the blood samples of patients treated with antiretroviral therapy. The approach could provide a strategy for curing HIV infection, according to research presented at RSNA 2013.

Highly active antiretroviral therapy (HAART) has transformed the outlook for patients infected with HIV by suppressing the replication of the virus in the body. However, despite its success, scientists believe reservoirs of latently infected cells persist in the body, preventing the possibility of a permanent cure.

“In an HIV patient on HAART, drugs suppress viral replication, which means they keep the number of viral particles in a patient's bloodstream very low. However, HAART cannot kill the HIV-infected cells,” said the study's lead author, Ekaterina Dadachova, PhD, a professor of radiology, microbiology, and immunology at Albert Einstein College of Medicine in New York City. “Any strategy for curing HIV infection must include a method to eliminate viral-infected cells.”

In her study, Dadachova and a team of researchers administered RIT to blood samples from 15 HIV patients treated with HAART at the Einstein-Montefiore Center for AIDS Research.

RIT, which historically has been employed to treat cancer, uses monoclonal antibodies, or cloned cells that are recruited by the immune system to identify and neutralize antigens. The antibody, designed to recognize and bind to a specific cell antigen, is paired with a radioactive isotope. When injected into the patient's bloodstream, the laboratory-developed antibody travels to the target cell where the radiation is then delivered. “In RIT, the antibodies bind to the infected cells and kill them by radiation,” Dadachova said. “When HAART and RIT are used together, they kill the virus and the infected cells, respectively.”

For the study, Dadachova's team paired the monoclonal antibody (mAb2556) designed to target a protein expressed on the surface of HIV-infected cells with the radionuclide bismuth-213.

The researchers found that RIT could kill HIV-infected lymphocytes previously treated with HAART, reducing the HIV infection in the blood samples to undetectable levels. “The elimination of HIV-infected cells with RIT was profound and specific,” Dadachova said. “The radionuclide we used delivered radiation only to HIV-infected cells without damaging nearby cells.”

An important part of the study tested the radiolabeled antibody’s ability to reach HIV-infected cells in the brain and central nervous system. Using an in vitro human blood-brain barrier model, the researchers demonstrated that radiolabeled mAb2556 could cross the blood-brain barrier and kill HIV-infected cells without any overt damage to the barrier itself.

“Antiretroviral treatment only partially penetrates the blood-brain barrier, which means that even if a patient is free of HIV systemically, the virus is still able to rage on in the brain, causing cognitive disorders and mental decline,” Dadachova said. “Our study showed that RIT is able to kill HIV-infected cells both systemically and within the central nervous system.”

Dadachova said clinical trials in HIV patients are the next step in evaluating the treatment.


MRI Study: Low Brain Iron in ADHD Patients
MRI provides a noninvasive way to measure iron levels in the brains of people with ADHD, according to a study presented at RSNA. Researchers said the method could help physicians and parents make better-informed decisions about medication.

ADHD affects 5% of school-age children, according to the American Psychiatric Association. Psychostimulant medications such as Ritalin are among the medications commonly used to reduce ADHD symptoms. Psychostimulants affect levels of dopamine, a neurotransmitter in the brain associated with addiction.

“Studies show that psychostimulant drugs increase dopamine levels and help the kids that we suspect have lower dopamine levels,” said Vitria Adisetiyo, PhD, a postdoctoral research fellow at the Medical University of South Carolina in Charleston. “As brain iron is required for dopamine synthesis, assessment of iron levels with MRI may provide a noninvasive, indirect measure of dopamine.”

Adisetiyo and colleagues explored this possibility by measuring brain iron in 22 children and adolescents with ADHD and 27 healthy control children and adolescents using an MRI technique called magnetic field correlation (MFC) imaging. The technique is relatively new, having been introduced in 2006 by study coauthors and faculty members Joseph A. Helpern, PhD, and Jens H. Jensen, PhD. “MRI relaxation rates are the more conventional way to measure brain iron, but they are not very specific,” Adisetiyo said. “We added MFC because it offers more refined specificity.”

The results showed that the 12 ADHD patients who had never been on medication had significantly lower MFC than the 10 ADHD patients who had been on psychostimulant medication or the 27 typically developing children and adolescents in the control group. In contrast, no significant group differences were detected using relaxation rates or serum measures. The lower brain iron levels in the nonmedicated group appeared to normalize with psychostimulant medication.

MFC imaging's ability to noninvasively detect the low iron levels may help improve ADHD diagnosis and guide optimal treatment. Noninvasive methods particularly are important in a pediatric population, according to Adisetiyo. “This method enables us to exploit inherent biomarkers in the body and indirectly measure dopamine levels without needing any contrast agent,” she said.

If the results can be replicated in larger studies, then MFC may have a future role in determining which patients would benefit from psychostimulants, an important consideration because the medications can become addictive in some patients and lead to abuse of other psychostimulant drugs like cocaine. “It would be beneficial, when the psychiatrist is less confident of a diagnosis, if you could put a patient in a scanner for 15 minutes and confirm that brain iron is low,” Adisetiyo said. “And we could possibly identify kids with normal iron levels who could potentially become addicts.”

Along with replicating the results in a larger population of patients, the researchers hope to expand their studies to look at the relationship between cocaine addiction and brain iron.