MRI – Scientists Talk Funny

Do MRI scans damage your genes?

MRI is a powerful, non-invasive diagnostic tool widely used to investigate anatomical structures and functions in the body.

Though generally considered to be safe, several studies in the last decade have reported an increase in DNA damage, or genotoxicity, due to cardiac MRI scans. Other research doesn’t support these findings — raising the controversial question of whether an MRI’s electromagnetic fields pose a health threat.

A multi-institutional research team explored this issue by reviewing the literature published between 2007 and 2016. Specifically, the group considered three questions during their review:

Do MRIs really cause genotoxicity?
What are the potential adverse health effects of exposure to MRI electromagnetic fields?
What impact does this have on patient health?

As outlined in a commentary appearing in Radiation Research, the evidence correlating MRIs with genotoxicity “is, at best, mixed.” After emphasizing the limitations of existing studies, which typically included at most 20 participants and lacked sufficient quality control measures, the authors summarized:

“We conclude that while a few studies raise the possibility that MRI exams can damage a patient’s DNA, they are not sufficient to establish such effects, let alone any health risk to patients. … We consider that genotoxic effects of MRI are highly unlikely.”

A previous 2015 review paper published in Mutation Research called for comprehensive, international, multi-centered collaborative studies to address this issue, using a common and widely used MRI exposure protocol with a large number of patients.

The authors of the new review note that such studies would be very expensive and would require hundreds of thousands of participants, which may not be warranted.

“If you want to do something next, do a very well-designed, large study of the types that have already been done, but with better statistics and better controls,” said John Moulder, PhD, a professor emeritus at the Medical College of Wisconsin, in a recent news story. “And make sure that this punitive genotoxicity is even real before beginning more expensive follow-up studies.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

MRI use flushes gadolinium into San Francisco Bay

The levels of gadolinium in the San Francisco Bay have been steadily increasing over the past two decades, according to a study recently published in Environmental Science & Technology. Gadolinium is a rare-earth metal and the potential long-term effects of its exposure have not been studied in detail.

Russell Flegal, PhD, and his research team at UC Santa Cruz collected and analyzed water samples throughout the San Francisco Bay from 1993 to 2013, as part of the San Francisco Bay Regional Monitoring Program.

They found the gadolinium levels to be much higher in the southern end of the Bay, which is home to about 5 million people and densely populated with medical and industrial facilities, than in the central and northern regions. They also observed a sevenfold rise in gadolinium concentration in the South Bay over that time period.

The study attributes the rising level of gadolinium contamination largely to the growing number of magnetic resonance imaging (MRI) scans performed with a gadolinium contrast agent. A gadolinium contrast agent is used for about 30 percent of MRI scans to improve the clarity of the images. It is injected into the patient then excreted out of the body in urine within 24 hours.

Lewis Shin, MD, assistant professor of radiology and a MRI radiologist, explained to me the importance of using intravenous gadolinium contrast agents:

“Gadolinium contrast agents allow us to detect abnormalities that would otherwise be hidden from view and to improve our characterization of the abnormalities that we do find. Gadolinium is not always used; for example, if a physician is just concerned about identifying a herniated disk in the spine, an MRI without contrast agent is sufficient.

However, gadolinium is routinely administered to detect and characterize lesions if there is a clinical concern of cancer. Also, if a patient was previously treated for cancer, gadolinium administration is often extremely helpful to detect early recurrences. In summary, MRI with a gadolinium contrast agent greatly improves our ability to make an accurate diagnosis not only for cancer but for many other disease processes as well.”

According to UCSC researchers, gadolinium is not removed by standard wastewater treatment technologies, so it is discharged by wastewater treatment plants into surface waters that reach the Bay.

Shin expressed some surprise when he learned about this study:

“The majority of radiologists probably don’t even think about gadolinium once it’s excreted out of a patient’s body. Of course it’s concerning that there is a rise in gadolinium levels in the environment, but the next questions are how is this impacting the environment and whether there is a safe level or not? Since most of the gadolinium contrast agents used for MRI studies are excreted through the urine within 12 to 24 hours, one strategy to reduce environmental release of gadolinium could be to collect patients’ urine for a brief period of time for proper disposal or even recycling of the gadolinium itself.”

The UCSC researchers assert that the current levels of gadolinium observed in San Francisco Bay are well below the peak concentrations that could pose harmful effects on the aquatic ecosystem. However, they recommend in their paper, “new public policies and the development of more effective treatment technologies may be necessary to control sources and minimize future contamination.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Can MRI Brain Scans Predict Dyslexia Early?

Kindergartener learning to read a book (Holtsman/flickr)

For many, the word dyslexia represents painful struggles with reading and speech that impact their self-confidence –- 20 percent of school-aged children and over 40 million adults in the U.S. are dyslexic. Dyslexics are often very intelligent and can learn successfully with appropriate teaching methods, but early diagnosis and intervention are critical.

UC San Francisco (UCSF) researchers in the Dyslexia Program aim to predict whether children will develop dyslexia before they show signs of reading and speech problems, so early intervention can improve their quality of life.

“Early identification and interventions are extremely important in children with dyslexia as well as most neurodevelopmental disorders,” said Fumiko Hoeft, UCSF associate professor and member of the UCSF Dyslexia Center, in a press release. “Accumulation of research data such as ours may one day help us to identify kids who might be at risk for dyslexia, rather than waiting for children to become poor readers and experience failure.”

In a recent longitudinal study, Hoeft’s research team studied 38 young children using structural MRI to track their brain development between kindergarten and third grade as they formally learned to read in school. The participating children were healthy, native-English speakers with varying preliteracy skills and family histories of reading difficulties. They had MRI brain scans at age 5 or 6 and again 3 years later. At both time points, they also completed a battery of standardized tests, including reading and cognitive assessments.

In particular, the researchers were interested in the children’s white matter development, which is critical for perceiving, thinking and learning. They found that volume changes in the left hemisphere white matter in the temporo-parietal region (just behind and above the left ear) was highly predictive of reading outcomes. This region is known to be important for language, reading and speech.

Using MRI brain scans to measure these developmental changes improved the prediction accuracy of reading difficulties by 60%, compared to traditional assessments alone.

“What was intriguing in this study was that brain development in regions important to reading predicted above and beyond all these (other) measures,” said Hoelt.

Despite this predictive relationship, MRI brain imaging is unlikely to be a widespread means of diagnosis because of cost and time constraints. Instead, the researchers hope their findings lead to further investigation of what may be influencing the brain during this critical period of reading development.

The UCSF Dyslexia Center is also investigating cheaper methods for early diagnosis of reading problems. For example, they are collaborating with research labs worldwide to construct growth charts for the reading brain network, similar to those one would find in a doctor’s office for height and weight.

Since screening for reading disorder risk is currently a resource-intensive process, UCSF is also developing a tablet-based mobile health application that could be used by schools or parents as a fast, easy and cheap screening tool.

UCSF researchers hope that understanding each child’s neurocognitive profile will help educators provide improved, personalized education and interventions.

This is a repost of my KQED Science blog.

Hope for Alzheimer’s Patients?

PET image of brain using PIB — Courtesy of Dr. Jagust Lab, UC Berkeley

My mother died of Alzheimer’s at the age of 69, so I can personally attest to the horror of this disease. I can think of few things worse than slowly watching your cognitive abilities decline, particularly if you are aware of the progressive deterioration as my mother was. So I’m keeping a close watch on the latest Alzheimer’s research, including the research of my colleague William Jagust who is a neuroscientist at UC Berkeley.

Dr. Jagust is participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which is large multicenter project supported by NIH, private pharmaceutical companies and nonprofit organizations. The primary goal of ADNI is to discover indicators (biomarkers) that can track disease progression and hopefully diagnose Alzheimer’s early on. Basically, they want to help speed up and streamline drug and clinical trials by developing biomarkers that track Alzheimer’s more reliably.

The initial ADNI five-year research project completed last fall. It studied cognition, function, brain structure and biomarkers for 800 subjects (200 elderly controls, 400 subjects with mild cognitive impairment, and 200 subjects with Alzheimer’s). The clinical data from the patients went into a large database, including MRI scans, PET scans, blood tests, neuropsychological tests, and genetic tests. The truly unique thing is that this database can be accessed by the public through a website. Basically the raw data (with patient personal information removed) is made available for everyone to use, in hopes that this will help scientists more rapidly understand and treat Alzheimer’s. This ADNI project just received the second phase of funding, so the studies will be expanded.

Although the cause and progression of Alzheimer’s disease is not fully understood, current research indicates that the disease is associated with the formation of “amyloid plaques” and “neurofibrillary tangles” in the brain that damage nerve cells. What does this mean? Amyloid plaques are protein fragments that the body produces naturally. In a healthy brain, these protein fragments are broken down and eliminated. In a brain with Alzheimer’s, the fragments instead accumulate to form hard, insoluble plaques between nerve cells. This excess amyloid buildup occurs before clinical Alzheimer’s symptoms, so it may be used as a predictor of disease. Neurofibrillary tangles are insoluble twisted fibers found inside the brain’s cells. These tangles mainly consist of a protein called tau, which helps form microtubules that transport nutrients from one part of the nerve cell to another. In an Alzheimer’s brain, the tau protein is abnormal and the tangles collapse this important transport system.

Dr. Jagust and other researchers are studying this beta-amyloid buildup using medical imaging, including PET imaging with a new drug called [11C]Pittsburg Compound B. This new PET drug binds to beta-amyloid plaques and indicates their size and position. “With PET, we’re able to study the biochemistry of the brain, and with MRI we can study both the anatomy and structure of the brain,” Jagust said. “We can also study some of the function of the brain to see what parts of the brain are active during different cognitive tests. So when you put all this information together, you can get a very detailed picture of how the brain is functioning and how function and structure might change with age.” Last fall Jagust published an article on the relationships between biomarkers in aging and dementia. The group found that the confluence of three factors — beta-amyloid deposition, atrophy of the hippocampus (part of the brain that stores and sorts memories), and episodic memory loss — signals early stage of Alzheimer’s. Hopefully this new understanding will ultimately provide early and more accurate diagnosis.

I don’t have room here to summarize all the results from the Jagust lab, let alone all the other labs doing Alzheimer’s research. But I must say that I’m optimistic given the recent progress they have made in understanding the disease. There are also many clinical trials underway for new Alzheimer’s drugs, including ones that hope to stop cognitive deterioration instead of just reducing symptoms. I’m encouraged but I still tell my friends who are doing the research that they need to find a cure within the next 10 years, because I do not want to suffer through this frightening disease like my mother did.

PET Imaging — Not for Cats or Dogs

As a medical imaging researcher, I notice when medical imaging technologies are mentioned by popular news media or medical-themed television shows. Lately I’ve been seeing PET imaging mentioned more frequently, including on TV shows like House and Grey’s Anatomy. This probably just reflects the fact that dramatically increasing numbers of PET scans are being performed in real life in clinics and hospitals. So what is PET imaging? Funny that you ask, because I just happen to do research in this field.

In this context, PET stands for Positron Emission Tomography. During a PET scan, a trace amount of biologically-active, radioactive drug is injected into the patient’s vein. The drug localizes somewhere in the patient, depending on the metabolic properties of the selected drug. The drug then emits a positron (anti-particle of the electron), and the positron annihilates with an electron in the patient’s body. The resulting energy forms gamma ray pairs that pass through the patient and are detected by the PET scanner. These detected gamma ray signals are used to create a 3-D volumetric image or picture of the drug’s concentration in the body.

PET imaging technology is unique because it images a patient’s metabolism, whereas most other medical imaging techniques measure anatomical structure. For example, X-ray CT or MRI scans can be used to identify a tumor because they show the patient’s anatomy in detail. However, PET imaging can identify if the tumor is benign or cancerous, by measuring whether or not the tumor takes up the radioactive drug. In reality, you’d really like to know both though — detailed anatomical structure and metabolic function. Recent work has demonstrated the increased clinical diagnostic value of fusing imaging technologies based on function (e.g., PET, SPECT or functional MRI) with those based on structure (e.g., CT, MRI, or ultrasound). As a result, PET and CT scanners are now typically combined into a single gantry system, so that images can be taken from both devices sequentially during a single procedure.

Since PET measures metabolism instead of anatomical structure, it is mostly used to image organs whose size or shape does not indicate whether they are functioning properly, such as the brain or heart. It is also used to diagnose diseases that exhibit an abnormal metabolism, such as cancer.

Stay tuned this week when I discuss some Alzheimer’s research that utilizes PET imaging.

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