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Imaging, Neuroscience, Research, Videos

Exploring the science of decision making

Exploring the science of decision making

Every day we make decisions that affect our work, personal relationships and health. With stakes this high, it’s no wonder many of us dread decision-making and wish we knew how to make better choices.

The first step towards making better decisions is to understand how the process works. This animation from Worldview Stanford’s upcoming course, The Science of Decision Making, shows the regions of the brain that are activated as we evaluate information.

Enrollment is now open for this interdisciplinary course, which explores and applies the nitty-gritty science of making a choice. If you’re unable to participate in the class, but you’d like to learn more about how to make better decisions, you can visit the Worldview Stanford blog for a sample of animations, videos and content from this course and their other offerings (.pdf).

Previously: Exploring the intelligence-gathering and decision-making processes of infantsIs there a connection between consuming mass media and making healthy choices?Genetics may influence financial risk-takingStanford neurobiologist Bill Newsome: Seeking gains for the brain and How does the brain plan movement? Stanford grad students explain in a video

Cancer, Imaging, In the News, Research, Technology

Stanford instructor called out for his innovative – and beautiful – imaging work

Stanford instructor called out for his innovative - and beautiful - imaging work

breast cancer cells

I’ll skip the name word play – it’s just too obvious – but I won’t skip Michael Angelo’s work. Angelo, MD, a pathology instructor at Stanford, developed a new imaging technique that labels antibodies with metallic elements, then uses an ion beam to scan the tissue, revealing up to 100 proteins at once in a single cancer cell.

This technique, called multiplexed ion beam imaging, or MIBI, captured the attention of the National Institutes of Health, which featured Angelo in its NIH Director’s Blog this week. The images are lovely to look at, but also quite useful to learn more about tissue types.

Here’s Angelo describing the image above:

Angelo used MIBI to analyze a human breast tumor sample for nine proteins simultaneously—each protein stained with an antibody tagged with a metal reporter. Six of the nine proteins are illustrated here. The subpopulation of cells that are positive for three proteins often used to guide breast cancer treatment (estrogen receptor a, progesterone receptor, Ki-67) have yellow nuclei, while aqua marks the nuclei of another group of cells that’s positive for only two of the proteins (estrogen receptor a, progesterone receptor). In the membrane and cytoplasmic regions of the cell, red indicates actin, blue indicates vimentin, which is a protein associated with highly aggressive tumors, and the green is E-cadherin, which is expressed at lower levels in rapidly growing tumors than in less aggressive ones.

Taken together, such “multi-dimensional” information on the types and amounts of proteins in a patient’s tumor sample may give oncologists a clearer idea of how quickly that tumor is growing and which types of treatments may work best for that particular patient.  It also shows dramatically how much heterogeneity is present in a group of breast cancer cells that would have appeared identical by less sophisticated methods.

Angelo was given a NIH Director’s Early Independence Award last fall, and he’s ramping up his investigations of breast cancer.

Imaging, Mental Health, Neuroscience, NIH, Research, Stanford News

Study: Major psychiatric disorders share common deficits in brain’s executive-function network

Study: Major psychiatric disorders share common deficits in brain's executive-function network

marble brainPsychiatric disorders, traditionally distinguished from one another based on symptoms, may in reality not be as discrete as we think.

In a huge meta-analysis just published in JAMA Psychiatry, Stanford neuroscientist and psychiatrist Amit Etkin, MD, PhD, and his colleagues pooled the results from 193 different studies. This allowed them to compare brain images from 7,381 patients diagnosed with any of six conditions – schizophrenia, bipolar disorder, major depression, addiction, obsessive-compulsive disorder, and a cluster of anxiety syndromes – to one another, as well as to brain images from 8,511 healthy patients.

Compared with healthy brains, patients in all six psychiatric categories showed a loss of gray matter in each of three separate brain structures. These three areas, along with others, tend to fire in synchrony and are known to participate in the brain’s so-called “executive-function network,” which is associated with high-level functions including planning, decision-making, task-switching, concentrating in the face of distractions, and damping counterproductive impulses.

The findings call into question a longstanding tendency to distinguish psychiatric disorders chiefly by their symptoms

(“Gray matter” refers to information-processing nerve-cell concentrations in the brain, as opposed to the “white matter” tracts that, like connecting cables, shuttle information from one part of the brain to another.)

As Etkin told me when I interviewed him for the news release we issued on this study, “these three structures can be viewed as the alarm system for the brain.” More from our release:

“They work together, signaling to other brain regions when reality deviates from expectations – that something important and unpredicted has happened, or something important has failed to happen.” That signaling guides future behavior in directions more likely to obtain desired results.

The studies of psychiatric patients that Etkin’s team employed all used a technique that yields high-resolution images of the brain’s component structures but can say nothing about how or when these structures work or interact with one another. However, that kind of imaging data was available for the healthy subjects. And, on analysis, those healthy peoples’ performance on classic tests of executive-function (such as  asking the test-taker to note the color of the word “blue,” displayed in a color other than blue, after seeing it briefly flashed on a screen) correlated strongly with the volume of gray matter in the three suspect brain areas, supporting the idea that the anatomical loss in psychiatric patients was physiologically meaningful.

The findings call into question a longstanding tendency to distinguish psychiatric disorders chiefly by their symptoms rather than their underlying brain pathology – and, by implication, suggest that disparate conditions may be amenable to some common remedy.

As National Institute of Mental Health Director Thomas Insel, MD, told me in an interview about the study, the Stanford investigators “have stepped back from the trees to look at the forest and see a pattern in that forest that wasn’t apparent when you just look at the trees.”

Previously: Hope for the globby thing inside our skulls, Brain study offers intriguing clues toward new therapies for psychiatric disorders and Study shows abnormalities in brains of anxiety-disorder patients
Photo by Philippe Put

Applied Biotechnology, Bioengineering, Biomed Bites, Cancer, Imaging, Technology, Videos

Beam me up! Detecting disease with non-invasive technology

Beam me up! Detecting disease with non-invasive technology

Here’s this week’s Biomed Bites, a feature appearing each Thursday that introduces readers to Stanford’s most innovative biomedical researchers.

Star Trek fans rejoice! Stanford radiologist Sam Gambhir, MD, PhD, hopes that someday he’ll be able to scan patients using a handheld device — similar to the one used by Bones in the popular sci-fi series — to check their health.

“Our long-term goals are to be able to figure out what’s going on in each and every one of you cells anywhere in your body by essentially scanning you,” Gambhir said in the video above. “We’ve been working on this area for well over three decades.”

This is useful because it will help doctors diagnose diseases such as cancer months or even years before the symptoms become apparent, Gambhir said.

And these advances aren’t light-years away. “Many of the things we’re doing have already started to move into the hospital setting and are being tested in patients. Many others will come in the years to follow,” he said.

Gambhir is chair of the Department of Radiology. He also directs the Molecular Imaging Program and the Canary Center for Cancer Early Detection.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Stanford partnering with Google [x] and Duke to better understand the human body, Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later and Developing a new molecular imaging system and technique for early disease detection

Imaging, Neuroscience, Research, Science, Stanford News

New insights into how the brain stays bright

New insights into how the brain stays bright

Neon brainAxel Brunger, PhD, professor and chair of Stanford’s Department of Molecular and Cellular Physioogy , and a team composed of several Stanford colleagues and UCSF scientists including Yifan Cheng, PhD, have moved neuroscience a step forward with a close-up inspection of a brain-wide nano-recycling operation.

A healthy adult brain accounts for about 2 percent of a healthy person’s weight, and it consumes about 20 percent of all the energy that person’s body uses. That’s a lot of sugar getting burned up in your head, and here’s why: Incessant chit-chat throughout the brain’s staggeringly complex circuitry. A single nerve cell (of the brain’s estimated 100 billion) may communicate directly with as many as a million others, with the median in the vicinity of 10,000.

To transmit signals to one another, nerve cells release specialized chemicals called neurotransmitters into small gaps called synapses that separate one nerve cell in a circuit from the next. The firing patterns of our synapses underwrite our consciousness, emotions and behavior. The simple act of tasting a doughnut requires millions of simultaneous and precise synaptic firing events throughout the brain and, in turn, precisely coordinated timing of neurotransmitter release.

You’d better believe these chemicals don’t just ooze out of nerve cells at random. Prior to their release, they’re sequestered within membrane-bound packets, or vesicles, inside the cells. Every time a nerve cell transmits a signal to the next one – which can be more than 100 times a second – hundreds of tiny chemical-packed vesicles approach the edge of the first nerve cell and fuse with its outer membrane, like a small bubble merging with a larger one surrounding it. At just the right time, numerous vesicles’ stored contents spill out into the synapse, to be quickly taken up by receptors dotting the nearby edge of the nerve cell on the synapse’s far side, where, like little electronic ones and zeroes in a computer circuit, they may either trigger or impede the firing of an impulse along that next nerve cell.

Each instance of bubble-like fusion – and this happens not only in neurotransmitter release but in hormone secretion and other processes throughout the body – is carefully managed by a complex of interconnecting proteins, collectively known as the SNARE complex. The molecular equivalent of a clamp, the SNARE complex guides the vesicle ever nearer to the nerve-cell’s surface and then, at just the right moment, squishes it up against the cell’s outer membrane. The vesicle bursts, spilling its contents into the synapse.

Myriad repetitions of this process typify the average day in the life of the average nerve cell. This requires not only a ton of energy (which I guess is where the doughnut comes in) but ultra-efficient recycling. The entire SNARE complex must be constantly disassembled, then reassembled. In a new study in Nature, Brunger and his associates snagged a set of near-atomic-scale snapshots of the SNARE complex as well as the molecular machinery that recycles its components, allowing them to make sophisticated guesses about how the whole thing works. (See the Howard Hughes Medical Institute’s news release on the study here.)

This has been a long time coming. In fact, Brunger’s lab first determined the molecular structure of the SNARE complex, via X-ray crystallography, in 1998. The careful decades-long process of tracking down the SNARE complex’s components and their interactions won Stanford neuroscientist Tom Sudhof, MD, the 2013 Nobel Prize in Medicine. But despite its immense importance, you probably haven’t heard much about it. Studies of molecular structures are in general opaque to lay readers, complicated systems such as the SNARE complex all the more so. The popular press pays attention to the awarding of the Nobel, but seldom to the long, towering staircase of incremental discoveries that was climbed to earn it.

Previously: Revealed: The likely role of Parkinson’s protein in the healthy brain, Step by step, Sudhof stalked the devil in the details, snagged a Nobel and But is it news? How the Nobel prize transformed “noteworthy” into “newsworthy”
Photo by Carolyn Speranza

Big data, Cancer, Health Disparities, Imaging, Public Health, Women's Health

A new way of reaching women who need mammograms

A new way of reaching women who need mammograms

black Woman_receives_mammogramI’ve taken cancer screenings for granted since I’m one of those fortunate enough to have health insurance, and it didn’t occur to me that many uninsured women were going without regular mammograms to screen for breast cancer. A story today on Kaiser Health News mentions this fact and highlights a partnership that Chicago public-health officials have forged with a company named Civis. The private company includes staffers that helped with the Obama campaign’s get-out-the-vote efforts, and then moved on to help find people eligible to enroll for health insurance through the Affordable Health Care Act. The company used its expertise to identify women who were in the right age group (over 40) and were uninsured in Chicago’s South Side area; those women then were then sent fliers about free screenings available to them.

The article describes some other cities using similar “big data” efforts for public-health purposes:

This project represents a distinctive step in public health outreach, said Jonathan Weiner, professor and director of the Johns Hopkins Center for Population Health IT in Baltimore. But Chicago is not the only city investigating how population data can be used in health programs, he added, citing New York City, Baltimore and San Diego as other examples.

“It’s a growing trend that some of the techniques first developed for commercial applications are now spinning off for health applications,” he said. So far, he said, “these techniques have not been as widely applied for social good and public health,” but that appears to be changing.

The early signs say that the new effort in Chicago, which started earlier this year, is working. One hospital saw a big jump in the number of free mammograms, from 10 a month to 31, though the full impact may not be understood for a few months. It’s not “a silver bullet” as one expert cited in the story notes, but it’s a much more precise tool than most public-health outreach programs have had access to until now.

Previously: Screening could slash number of breast cancer casesDespite genetic advances, detection still key in breast cancerStudy questions effects of breast cancer screenings on survival rates and New mammogram guidelines echo ones developed by physicians group
Photo by National Cancer Institute

Imaging, Neuroscience, Patient Care, Pediatrics, Research

Stanford-led study suggests changes to brain scanning guidelines for preemies

Stanford-led study suggests changes to brain scanning guidelines for preemies

preemieOne big challenge of having a premature baby: the uncertainty. With good medical care, a great many preemies do very well, but some face long-term disabilities, medical complications and developmental delays, and others, sadly, die in infancy. Unfortunately, doctors can’t always tell how a baby will fare in the long term.

A new study, led by a Stanford team and conducted at 16 sites around the country, is part of the ongoing effort to change that. The researchers examined what type and timing of brain scans give doctors the greatest ability to predict preemies’ neurodevelopmental outcomes in toddlerhood. The research, published online today in Pediatrics, found that for babies born more than 12 weeks early who survive to near their original due dates, brain scans performed near their due date are better predictors than scans done near birth.

Most preemies already get at least one brain scan. That’s because national guidelines recommend that preemies’ doctors perform a cranial ultrasound seven to 14 days after birth to look for immediate problems such as bleeding into the brain. (Ultrasound is a good fit for the needs of fragile infants: Babies’ fontanelles provide “acoustic windows” to the brain, and ultrasound is non-invasive, uses no radiation, requires no sedation, and can be performed with a portable scanner brought to the bedside.) Some prior research has shown that these early scans can also give information about an infant’s risk of cognitive, motor and behavioral deficits or delays in childhood, but the predictive value of these early scans can be fairly low.

The new study examined both cranial ultrasound and MRI performed close to the baby’s due date, which is also when most preemies are ready to go home from the hospital. A lot changes in the brain during those first few weeks, perhaps explaining why later scans did a significantly better job of predicting which children would have persistent neurodevelopmental problems when the doctors checked in with them at 18 to 22 months of age.

“Neuroimaging may help us understand what a child’s outcome may look like, and ultimately help us focus our attention in terms of the type of follow-up and specific interventions that could best support a child after discharge from the hospital,” said Susan Hintz, MD, the study’s lead author and a neonatologist at Lucile Packard Children’s Hospital Stanford.

Continue Reading »

Imaging, Patient Care, Stanford News, Technology

Every foot has a story: Why communication is key in radiology

Every foot has a story: Why communication is key in radiology

11739904364_92e702bc65_zBack in the day, radiology departments were simpler. After obtaining an x-ray, the technologist would hand off the images to the radiologist. In the process, the radiologist might ask about the technologist’s family, how Aunt Lucy was faring or how that day’s commute had been. Maybe a senior technologist would walk by, glance at the pinned up images and offer the junior technologist some advice on how to improve the positioning of the patient. The primary care doctor and the junior radiologist might chat about the patient over their lunchtime tennis game.

Not to say it wasn’t busy — it was. But in a smaller, simpler environment, informal relationships were easier to maintain. Despite their informality, these relationships, and the communication that went with them, served as a powerful means to improve patient care, according to Stanford radiologist David Larson, MD.

Fast forward to today. At a busy, top-tier hospital, radiologists might not know their colleagues, much less the technologists or referring physicians. All images remain on computers — no need to pin anything up for public viewing, or to receive unsolicited comments, or advice.

The many technological improvements, as well as the scale and speed of modern radiology, have inadvertently thwarted communication, Larson and colleagues write in a paper recently published in the American Journal of Roentgenology. Here’s Larson:

In radiology, we’re in the business of information. Everything we do from the time that somebody even thinks of a question, to the time they ask for an imaging study, to when we then interpret the images, is really all about information.

So we need to be really good at moving that information efficiently and effectively, which means we need to be good at communicating… But in many ways, we’re thinking as if we still operate in a small, simple environment, even though we’re operating in a large, complex environment.

For example, Larson said, in addition to having the images, it’s also important for radiologists to know about a patient’s history. He said information that someone runs 20 miles a week, for example, makes a big difference when interpreting an image of a foot. “I have been in the situation where I looked at the study and was about to call it normal. Then I looked at the history, looked back at the study, and found the very subtle stress fracture,” Larson said. “A good history makes that possible.”

Larson pointed out that Stanford is continuously improving its own communication processes. For example, the hospital recently hired a reading room assistant, what Larson referred to as an “air traffic controller,” to direct queries and facilitate communication among physicians.

Previously: Despite genetic advances, detection still key in breast cancer, Using 3-D technology to screen for breast cancer and Better communication between caregivers reduces medical errors, study finds
Photo by Jill Carlson

Imaging, In the News, Neuroscience, Research, Stanford News

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

neural-pathways-221719_640The proof’s in the pudding, the old saying — which seems slightly seasonal — goes. So when a Stanford team compared images of brains affected by chronic fatigue syndrome, with those healthy brains, they found noticeable differences, including misshaped white matter, the cells that coordinate communication between brain regions. The news garnered immediate attention and has now been featured in a New York Times  piece:

The relationship between the symptoms experienced by patients and the findings is unclear. The two parts of the brain connected by the abnormally shaped white matter are believed to be important for language use, said Michael Zeineh, MD, a radiologist at Stanford and the lead author…

“This opens the door to more detailed investigations because now we have targets for future research,” he said.

The Times also refers to another study, published in March, that found cerebral inflammation in patients who suffer from chronic fatigue syndrome, or, as it is also called, myalgic encephalomyelitis/ C.F.S. This is big news for a condition that’s often misdiagnosed — patients are sometimes forced to visit numerous doctors and battle insurance companies — all while fighting the debilitating symptoms — before securing a diagnosis.

The Times touches on the tricky politics of the disease as well:

Next month, a panel convened by the National Institutes of Health will hold a two-day workshop  charged with “advancing the research” on the illness of the disorder. The Institute of Medicine is conducting a separate, government-sponsored initiative to assess and evaluate the many sets of diagnostic criteria for M.E./C.F.S., with the results expected next year.

Advocacy groups have questioned the rationale for two separate efforts. They have also criticized the initiatives because in both cases many people with little or no expertise in M.E./C.F.S. will be voting on recommendations that could have a significant impact on the government’s future efforts.

Previously: Patients’ reaction to ME/CFS coverage in Stanford Medicine magazine, Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed and Unbroken: A chronic fatigue syndrome patient’s long road to recovery
Image by geralt

Chronic Disease, Imaging, Immunology, Neuroscience, Research, Stanford News

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

me-cfs-brain-zeineh

In the last few weeks, Stanford published two articles on chronic fatigue syndrome, a.k.a. myalgic encephalomyelitis, and the outpouring of positive feedback from ME/CFS patients has been tremendous. In my long-form Stanford Medicine story and video, I describe a young woman’s seven-year battle with the disease and the groundbreaking research being done by her physician, José Montoya, MD, and immunologist Mark Davis, PhD, to identify the biomarkers and root causes of ME/CFS. My colleague Bruce Goldman followed up with an elegantly written article describing the distinct differences between the brains of ME/CFS patients with those of healthy people, in a newly released study from this same research team.

While our primary job as medical science writers is to explain new research accurately, it’s a bonus to know that we captured the patient experience in a compassionate way, and that we have in some way eased their suffering with hope.

Here is a sampling of a few of these letters from around the world:

From British Columbia, Canada:
Thank you for an article that is very well done. I will be printing it for my MD and forwarding it to family and a few close friends because it captures this devastating illness so well. I will keep a copy for myself to remind me (on those dark days) that Dr. Montoya is in my corner.

From Sweden:
I would like to thank you for your very informative and interesting article! This kind of information of what research is going on at Stanford, etc., is very important for us patients with ME all over the world! There is a lot of disinformation coming out about this disease and I therefore very much appreciate your article and especially Dr. Montoya’s passionate engagement with this disease.

From Cali, Colombia:
Here in Cali, Colombia, the city of birth of Dr. Montoya, I feel very happy reading your excellent article, and learning the marvelous and difficult investigation performed by these brilliant scientists. I was moved to tears. Thank you.

From the San Francisco Bay Area:
I want to thank you very much for the powerful piece you wrote about ME/CFS. You tell the story in a very engaging way, which is so compelling. It’s not the usual doom/gloom/dark room story which my daughter and I have encountered frequently in what people write about ME/CFS. Family and friends with whom I have shared the article are appreciative of your writing so descriptively and articulately about all aspects of ME/CFS: the science, the inequity of research funding, the personal experience of a patient, the work of Drs. Montoya/Mark Davis/Holden Maecker.

From India:
Today I have gone through your article about Erin’s story. How she recovered from CFS had given me a ray of hope as I am also suffering from such an ailment for the last 6-8 years.

From Atlanta, Georgia:
I just read your beautifully written article on Immune System Disruption. First soccer caught my eye, then “swimming in the primordial soup of creative disruption” locked me in. I read every word … and I am going to spend the rest of the night in Atlanta copying [my internal medicine doctor] on the article.

From Australia:
Just wanted to thank you for your excellent article. It could really make a difference in raising awareness and I appreciate the quality of your writing. I have suffered from CFS/ME for many years in Australia and find the research project and your understanding very encouraging.

From the blogosphere:
I just wanted to thank you for taking the time to write such an in-depth, accurate article on our oft-ignored illness. Dr. Montoya is a hero within the ME/CFS community, but I didn’t know about the others at Stanford also working on ME/CFS — that gives me some hope for a better future! I plan to share your article on my ME/CFS blog and in several Facebook groups for ME/CFS that I belong to.

Previously: Some headway on chronic fatigue syndrome: Brain abnormalities pinpointedUnbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Stanford Medicine magazine traverses the immune system
Image, showing white matter differences between a ME/CFS patient sample an a healthy control, by Michael Zeineh/Stanford

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