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Imaging

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.

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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

Aging, Imaging, Ophthalmology, Patient Care, Research, Stanford News

New way to predict advance of age-related macular degeneration

New way to predict advance of age-related macular degeneration

eyeballAge-related macular degeneration, in which the macula – the key area of the retina responsible for vision – begins to degenerate, is the leading cause of blindness and central vision loss among adults older than 65. Some 10-15 million Americans suffer from the disease.

If those numbers don’t scare you, try these: “It affects 14%-24% of the U.S. population aged 65-74 years and 35 -40% of people aged 74 years or more have the disease.” Yow!

Most cases of AMD don’t lead to blindness. But if the disorder progresses to an advanced stage where abnormal blood vessels accumulate underneath the macula and leak blood and fluid, irreversible damage to the macula can quickly ensue if treatment doesn’t arrive right on time.

Timing that treatment just right is a real issue. As I wrote in my recent release about a promising development in this field:

[U]ntil now, there has been no effective way to tell which individuals with AMD are likely to progress to the wet stage. Current treatments are costly and invasive – they typically involve injections of medicines directly into the eyeball – making the notion of treating people with early or intermediate stages of AMD a non-starter. Doctors and patients have to hope the next office visit will be early enough to catch wet AMD at its onset, before it takes too great a toll.

Here’s the good news: A team led by Stanford radiologist and biomedical informatician Daniel Rubin, MD, has found a new way to forecast which patients with age-related macular degeneration are likely to progress to the most debilitating form of the disease – and when.

The advance, chronicled in a study in Investigative Ophthalmology & Visual Science, is a formula – derived from extensive computer analysis of thousands of retinal scans of hundreds of patients’ eyes – that recommends, on a personalized basis,  when to schedule an individual patient’s next office visit in order to optimize the prospect of catching AMD progression before it causes blindness.

The formula predicts, with high accuracy, whether and when a patient with mild or intermediate AMD will progress to the dangerous advanced stage. And it does so simply by crunching imaging data that is already commonly collected in eye doctors’ offices anyway.

“Our technique involves no new procedures in the doctor’s office – patients get the same care they’ve been getting anyway,” Rubin told me. His team just tacked on a sophisticated, computerized image-processing step.

Previously: Treating common forms of blindness using tissue generated with ink-jet printing technology, To maintain good eyesight, make healthy vision a priority and Stanford researchers develop web-based tool to streamline interpretation of medical images
Image courtesy of Daniel Rubin

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

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

patchbrainHow can you treat a disease when you don’t know what causes it? Such a mystery disease is chronic fatigue syndrome, which not so long ago was written off by many physicians as a psychiatric phenomenon because they just couldn’t figure out what else might be behind it. No one was even able to identify an anatomical or physiological “signature” of the disorder that could distinguish it from any number of medical lookalikes.

“If you don’t understand the disease, you’re throwing darts blindfolded,” Stanford neuroradiologist Mike Zeineh, MD, PhD, told me about a week ago. Zeineh is working to rip that blindfold from CFS researchers’ eyes.

From a release I wrote about some breaking CFS research by Zeineh and his colleagues:

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

A study just published in Radiology may help to resolve those ambiguities. Comparing brain images of 15 CFS patients with those from 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing similar symptoms, Zeineh and his colleagues found distinct differences between the brains of patients with CFS and those of healthy people.

The 15 patients were chosen from a group of 200 people with CFS whom Stanford infectious-disease expert Jose Montoya, MD, has been following for several years in an effort to identify the syndrome’s underlying mechanisms and speed the search for treatments. (Montoya is a co-author of the new study.)

In particular, the CFS patients’ brains had less overall white matter (cable-like brain infrastructure devoted to carrying signals rather than processing information), aberrant structure in a portion of a white-matter tract called the right arcuate fasciculus, and thickened gray matter (that’s the data-crunching apparatus of the brain) in the two places where the right arcuate fasciculus originates and terminates.

Exactly what all this means is not clear yet, but it’s unlikely to be spurious. Montoya is excited about the discovery. “In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” he told me.

No, not a cure yet. But a well-aimed ray of light that can guide long-befuddled CFS dart-throwers in their quest to score a bullseye.

Previously: Unbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Unraveling the mystery of chronic-fatigue syndrome
Photo by Kai Schreiber

Cancer, Events, Genetics, Imaging, Stanford News, Surgery, Women's Health

Don't hide from breast cancer – facing it early is key

Don't hide from breast cancer - facing it early is key

cat_hiding-pgMy cat suffers from acute anxiety. Although she and I have lived together for more than 12 years, and the worst thing I’ve ever done to her was cut her nails, she’s terrified of me. (She’s also very smart – she runs from the sound of my car, but not my husband’s). During trips to vet, Bibs hides her eyes in the crook of my elbow.

It’s a strategy that’s only minimally effective. After all, what I can’t see, or don’t recognize, can still hurt me.

Take breast cancer. It terrifies most women. And if you don’t look for it, you won’t find it. But if you do look, and find it early, you might save your life and your breast, says Amanda Wheeler, MD, a Stanford breast surgeon. She joined other Stanford breast cancer experts at a recent public program sponsored by the Stanford Women’s Cancer Center called “The Latest Advancements in Screening and Treatment for Breast Cancer.”

“One of our biggest challenge is women are scared of breast cancer, but[we have to get] the word out that we have such great advances, we’ve just got to catch it early,” Wheeler said.

She pointed to a tiny dot on a screen. At that size, Wheeler said, breast cancer is almost 100 percent curable. She performs a small lumpectomy. If it’s a little bigger, she can still probably save the nipple.

And if the entire breast must be removed, surgeons like Rahim Nazerali, MD, come in. Nazarali explained the importance of choosing a reconstruction surgeon carefully: The doctor should be accredited by the American Society of Plastic Surgeons and have experience with microsurgery, preferably on the breast. There are different ways to remold a breast and doctors can use either a synthetic implant or a patient’s own tissue, from their abdomen, hips or thighs, Nazerali explained.

All of Wheeler and Nazerali’s artistry depends on expert imaging performed by specialists like Jafi Lipson, MD, whose message at the event was simple and encouraging.

Thanks to many new developments, mammography isn’t the only way to detect nascent breast cancers, Lipson said. Her team can employ 3-D mammography, or tomosynthesis, to reveal a layered look at a breast. And genetic screening, particularly for those with a history of breast cancer in the family, can provide the earliest warning signal of all, the breast cancer team said.

Women no longer need to hide their eyes from the risk, the experts emphasized. Women should take a peek – there’s help coping with what they may find.

Previously: Screening could slash number of breast cancer cases, The squeeze: Compression during mammography important for accurate breast cancer detection, Despite genetic advances, detection still key in breast cancer, NIH Director highlights Stanford research on breast cancer surgery choices, Breast cancer awareness: Beneath the pink packaging and Using 3-D technology to screen for breast cancer
Photo by Notigatos

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