TAG: "Imaging"

New test makes Parkinson’s-like disorder detectable in young adults


Brain abnormalities may begin to develop two decades before symptoms might occur.

UC Davis MIND Institute

The very earliest signs of a debilitating neurodegenerative disorder, in which physical symptoms are not apparent until the fifth decade of life, are detectable in individuals as young as 30 years old using a new, sophisticated type of neuroimaging, researchers at UC Davis, the University of Illinois and UCLA have found.

People with the condition — fragile X-associated tremor/ataxia syndrome (FXTAS) — experience tremors, poor balance, cognitive impairments and Parkinsonism. The genetic condition results from a mutation in the fragile X mental retardation gene (FMR1). FXTAS develops in about 40 percent of male and 15 percent of female carriers of the mutated FMR1 gene.

“Our findings suggest that the brain abnormalities of FXTAS may begin to develop about two decades before symptoms might occur,” said Tony J. Simon, study senior author and professor, Department of Psychiatry and Behavioral Sciences.

“Altered Structural Brain Connectome in Young Adult Fragile X Premutation Carriers,” is published in Human Brain Mapping.

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The next step in MRI


New imaging technique shows the wrist in motion.

Radiologist Robert Boutin was part of the UC Davis team that developed a technique for capturing MRIs of the moving wrist.

The wrist is one of the body’s most intricate structures, and impairments in any part of its system of bones and joints — which make all hand movement possible — can drastically affect daily life. For Cathy Wilson, it affects her livelihood as well.

Wilson is an Educational Sign Language interpreter, an instructor of American Sign Language and the parent of a deaf daughter. A wrist injury from an auto accident left her with painful electric shock sensations and an audible clicking noise each time she twisted her wrist.

“The clicking is a complete distraction for my students and causes me irritation and fatigue after a full day of communicating with my hands,” she said. “It also limits my abilities to communicate with my daughter.”

The search for answers led the Red Bluff resident to UC Davis orthopaedic surgeon Robert Szabo, an expert at repairing hand and wrist injuries. During a clinical exam, he ruled out all but two wrist parts, “but treatment plans can be very different depending on the specific site of the problem,” Szabo said.

He recommended a study of Wilson’s wrist using “Active MRI,” a new type of imaging developed at UC Davis that creates live-action video of the wrist in motion. The results showed two subluxations: one snapping tendon and a near joint dislocation.

“Both problems could be clearly recorded and visualized using the new technique,” said Szabo.

Active MRI was developed by radiologist Robert Boutin and medical physicists Abhijit Chaudhari and Michael Buonocore in conjunction with Szabo, who saw the need to improve imaging of joints and bones for accurate diagnosis and to guide surgery.

A typical MRI exam obtains sets of images in three-to-five minute time blocks. Any movement during that time blurs the images.

“Routine MRI provides exquisite details, but only if the body is completely motionless in one particular position,” said Boutin. “But bodies are made to move.”

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Gulf War illness not in veterans’ heads, but in their mitochondria


UC San Diego findings could help lead to new treatments for affected individuals.

Beatrice Golomb, UC San Diego

Researchers at the UC San Diego School of Medicine have demonstrated for the first time that veterans of the 1990-91 Persian Gulf War who suffer from “Gulf War illness” have impaired function of mitochondria – the energy powerhouses of cells.

The findings, published in today’s (March 27) issue of PLOS ONE, could help lead to new treatments benefiting affected individuals – and to new ways of protecting servicepersons (and civilians) from similar problems in the future, said principal investigator Beatrice A. Golomb M.D., Ph.D., professor of medicine.

Golomb, with associate Hayley Koslik and Gavin Hamilton, Ph.D., a research scientist and magnetic resonance physicist, used the imaging technology to compare Gulf War veterans with diagnosed Gulf War illness to healthy controls. Cases were matched by age, sex and ethnicity.

The technique used – 31-phosphorus magnetic resonance spectroscopy or 31P-MRS – reveals amounts of phosphorus-containing compounds in cells. Such compounds are important for cell energy production, in particular phosphocreatine or PCr, which declines in muscle cells during exercise. PCr recovery takes longer when mitochondrial function is impaired, and delayed recovery is recognized as a robust marker of mitochondrial dysfunction.

Affected Gulf War veterans displayed significantly delayed PCr recovery after an exercise challenge. In fact, said Golomb, there was almost no overlap in the recovery times of Gulf War illness veterans compared to controls: All but one control participant had a recovery time-constant clustered under 31 seconds. In contrast, all but one Gulf Illness veteran had a recovery time-constant exceeding 35 seconds, with times ranging as high as 70 seconds.

There were 14 participants in the study: seven Gulf War illness cases and seven matching controls. Golomb notes that the use of 1:1 matching markedly improves statistical “power,” allowing a smaller sample size. The separation between the two groups was “visibly striking, and the large average difference was statistically significant,” she said.

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UC faculty drive efforts to improve CT safety


Special journal issue is part of ongoing effort to reduce CT risks.

John Boone, UC Davis

UC Davis clinicians and physicists have recommended new strategies to make computed tomography (CT) safer, including adoption of a new metric for dose measurement, ways to manage exposure protocols that differ by CT brand and specific approaches to reduce exposure during needle biopsies. The recommendations are detailed in papers published in the March issue of the Journal of the American College of Radiology (JACR).

In response to concerns about the radiation dose in CT, JACR devoted the entire issue to CT safety. The federal government estimates that more than 80 million CT scans are performed in the United States each year. UC Davis specialists contributed three studies to the special issue.

CT is a powerful diagnostic technology that images organs and other internal structures. These scans can both detect life-threatening conditions and rule them out, giving clinicians precise information to develop a care plan. But there are risks. Ionizing radiation can damage cells and has been found to be a weak carcinogen. The challenge for radiologists and medical physicists is to find the optimal dosage for each CT exam.

“The higher the dose, the better the images,” said John Boone, vice chair of research in the Department of Radiology. “But you also want the lowest possible doses. So you need to find that balance between acceptable image quality and acceptable dosage.”

In the paper “Dose is Not Always What it Seems…,” Anthony Seibert, professor of radiology, and colleagues discuss the need to improve dose calculations. They point to an actual case, in which a pediatric patient, who had scans before and after surgery, appeared to receive an overdose on the second CT. Further investigation showed that the problem was a misleading metric – the volume CT dose index (CTDIvol), a standard measure of radiation output in CT. Manufacturers use phantoms along with instruments that measure radiation to assess CTDIvol. However, different companies use phantoms of different sizes. In addition, many dose estimates are based on adult sizes, making pediatric estimates more difficult.

“In this case, the difference was the way the manufacturers handled the metrics,” said Seibert. “A large phantom tends to underestimate dose, while a small phantom tends to overestimate it. When we compensated for the different-sized phantoms, it turned out the patient received almost the same dose in both scans.”

To help prevent future problems, the team recommended a new metric, size-specific dose estimate (SSDE), which provides a better way to measure patient doses and can also help compare scanners from different companies. It also addresses the dire need to more accurately estimate dose from CT across a range of patient sizes, from newborn to NFL linebacker.

“I think SSDE is one step closer to a dose metric that will be more accurate in depicting the actual risk to patients,” said Seibert.

This is not the only area where differences between scanners can obscure dosage. In another paper, “Methods for CT Automatic Exposure…,” Boone, Seibert and colleagues addressed the challenges of optimizing different machines.

Physicists and radiologists must set up automatic exposure protocols, which vary doses based on tissue thickness. However, since manufacturers use different methods to control doses, transferring these settings between machines can be difficult and time-consuming.

“It takes a lot of effort to optimize any given scanner,” said Boone. “Going through the procedures for every possible exam could take two years.”

To ease the way, the UC Davis team developed equations to translate settings among three machines, two made by GE and one by Siemens. The proposed approach provides a more efficient way to manage CT protocols between different CT scanners.

A third paper, “Radiation Dose Optimization for CT-Guided Interventional Procedures…,” outlines how practitioners can lower radiation doses while performing interventional procedures under CT guidance. CT is often used to guide these procedures, ensuring the needle is precisely located.

Ramit Lamba, director of CT, outlines a number of methods to reduce radiation doses for both patients and doctors performing the procedures. He recommends using ultrasound, instead of CT, to guide some biopsies. He also recommends reducing scan lengths, lowering the tube current using dose-efficient scanning modes and limiting the number of guidance scans.

The special JACR issue is one piece of an ongoing effort to reduce CT risks. As part of the University of California Dose Optimization and Standardization Endeavor (UC DOSE), all five UC medical centers are collaborating to improve CT protocols and education.

“We’re trying to educate radiologists and medical physicists because the practice of CT is not consistent,” said Boone. “If someone is using higher doses to get results they could obtain with less radiation, we need to help them find the safer alternative.”

Other researchers included Rebecca Smith-Bindman of UC San Francisco; Sarah E. McKenney, formerly of UC Davis; and Sandra L Wootton-Gorges of UC Davis.

UC DOSE is funded through a pilot grant from the University of California Office of the President.

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MRI-guided laser treatment for brain cancer a first in state


Technology helps treat malignant tumor deep inside a patient’s brain.

Neurosurgeon Clark Chen treats recurrent brain cancer with MRI-guided laser technology at UC San Diego Health System.

Using a novel magnetic resonance imaging (MRI)-guided laser technology, neurosurgeons at UC San Diego Health System have successfully treated a malignant tumor deep inside a patient’s brain. This is the first time that this FDA-approved laser-based treatment has been performed in California.

“The patient’s brain tumor was located in the thalamus. Normally, to access a tumor in this region, the surgeon would have to remove considerable healthy brain tissue, thus subjecting the patient to significant neurologic injury,” said neurosurgeon Clark C. Chen, M.D., Ph.D., vice chairman of research, UC San Diego Division of Neurosurgery.  “This MRI-guided laser technology helps neurosurgeons preserve healthy brain tissues while allowing treatment of tumors that would otherwise be inoperable.”

Chen and his team used a technique called laser interstitial thermal therapy. The procedure is performed inside an MRI machine while the patient is under general anesthesia.  A dime-size hole is created in the patient’s skull to access the tumor. A laser probe is then inserted into the tumor under real-time MRI monitoring and computer guidance. When the tumor is reached, the laser beam is activated, heating and destroying tumor cells.

“It is well-known that MRI can be used to generate detailed images of the brain. What is less known is that MRI can also be used to measure the internal temperature of the brain,” said Chen. “With this application, I can view the tumor in real time as it is being destroyed while customizing the effects of the laser to the tumor without injuries to the surrounding normal brain. This incredible visualization allows neurosurgeons to preserve billions of neuronal connections that are essential for normal brain function.”

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New MRI technique creates ‘movie’ of wrist in motion


“Active MRI” could be useful in assessing wrist problems.

If a picture is worth 1,000 words then a movie is worth far more, especially when it comes to diagnosing wrist problems.

UC Davis radiologists, medical physicists and orthopaedic surgeons have found a way to create “movies” of the wrist in motion using a series of brief magnetic resonance imaging scans. Called “Active MRI,” the technique could be useful in diagnosing subtle changes in physiology that indicate the onset of conditions such as wrist instability.

The outcome of the team’s first test of the new technique is published online today (Dec. 31) in the journal PLoS ONE.

“These fast images are like a live-action movie,” said Robert Boutin, professor of radiology at UC Davis and lead author of the study. “The movie can be slowed, stopped or even reversed as needed. Now patients can reproduce the motion that’s bothering them while they’re inside the scanner, and physicians can assess how the wrist is actually working. After all, some patients only have pain or other symptoms with movement.”

Wrist instability, explained senior author Abhijit Chaudhari, occurs when carpal bones become misaligned and affect joint function, often as a result of trauma that injures the ligaments between wrist bones. It causes abnormal mobility and chronic pain that can lead to osteoarthritis, a major socioeconomic burden to patients and health care systems. Good outcomes in managing the condition are more likely with early diagnosis, when less-invasive treatments are possible.

Methods such as dynamic computed tomography and fluoroscopy can image the moving wrist, but these approaches involve radiation and do not show soft tissue such as ligaments — a major part of the wrist’s intricate architecture — as well as MRI scans.

“MRI scans provide detailed anatomical information of wrist structures without using ionizing radiation, but they cannot help diagnose problems with bone or tendon position that are best seen when the wrist is moving,” said Chaudhari, assistant professor of radiology at UC Davis. “Active-MRI provides a detailed and ‘real time’ view of the kinesiology of the wrist in action using a widely available and safe technology.”

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Kids whose bond with mother was disrupted early in life show changes in brain


UCLA researchers examine impact on amygdala.

Nim Tottenham, UCLA

Nim Tottenham, UCLA

Children who experience profound neglect have been found to be more prone to a behavior known as “indiscriminate friendliness,” characterized by an inappropriate willingness to approach adults, including strangers.

UCLA researchers are now reporting some of the first evidence from human studies suggesting that this behavior is rooted in brain adaptations associated with early-life experiences. The findings appear in the Dec. 1 issue of the peer-reviewed journal Biological Psychiatry.

The UCLA group used functional magnetic resonance imaging (fMRI) to demonstrate that youths who experienced early maternal deprivation — specifically, time in an institution such as an orphanage prior to being adopted — show similar responses to their adoptive mother and to strangers in a brain structure called the amygdala; for children never raised in an institutional setting, the amygdala is far more active in response to the adoptive mother.

This reduced amygdala discrimination in the brain correlated with parental reports of indiscriminate friendliness. The longer the child spent in an institution before being adopted, the greater the effects.

“The early relationship between children and their parents or primary caregivers has implications for their social interaction later in life, and we believe the amygdala is involved in this process,” said Aviva Olsavsky, a resident physician in psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and the study’s first author. “Our findings suggest that even for children who have formed attachments to their adoptive parents, this early period of deprivation has led to changes in the brain that were likely adaptations and that may persist over time.”

Indiscriminate friendliness is in some sense a misnomer. The behavior is not characterized by a deep friendliness but simply by a lack of reticence that most young children show toward strangers.

“This can be a very frightening behavior for parents,” said Nim Tottenham, an associate professor of psychology at UCLA and the study’s senior author. “The stranger anxiety or wariness that young children typically show is a sign that they understand their parents are very special people who are their source of security. That early emotional attachment serves as a bedrock for many of the developmental processes that follow.”

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Psychologists report new insights on human brain, consciousness


UCLA research is a step toward developing scientific definition of consciousness.

Martin Monti, UCLA

Martin Monti, UCLA

UCLA psychologists have used brain-imaging techniques to study what happens to the human brain when it slips into unconsciousness. Their research, published today (Oct. 17) in the online journal PLOS Computational Biology, is an initial step toward developing a scientific definition of consciousness.

“In terms of brain function, the difference between being conscious and unconscious is a bit like the difference between driving from Los Angeles to New York in a straight line versus having to cover the same route hopping on and off several buses that force you to take a ‘zig-zag’ route and stop in several places,” said lead study author Martin Monti, an assistant professor of psychology and neurosurgery at UCLA.

Monti and his colleagues used functional magnetic resonance imaging (fMRI) to study how the flow of information in the brains of 12 healthy volunteers changed as they lost consciousness under anesthesia with propofol. The participants ranged in age from 18 to 31 and were evenly divided between men and women.

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Early imaging, diagnosis of Alzheimer’s leads to better outcomes


Study comes as Medicare reviews reimbursement policies for PET scans in dementia cases.

Daniel Silverman, UCLA

Daniel Silverman, UCLA

UCLA researchers report for the first time that patients with early symptoms of Alzheimer’s disease who are diagnosed sooner than usual using a brain-imaging test receive medications earlier and have significantly better clinical outcomes over subsequent years.

The findings come from the Metabolic Cerebral Imaging in Incipient Dementia study, an ongoing national clinical trial sponsored by the Centers for Medicare and Medicaid Services (CMS). The interim data show that patients whose doctors gleaned information from a brain PET scan performed with the tracer FDG — which measures energy being used throughout regions of the brain — did better over two years of follow-up than those whose doctors were randomized to not have access to the scan information.

“During the subsequent two years after their PET scans, these patients had superior executive function, better memory abilities and greater preservation of overall cognitive function,” said Dr. Daniel Silverman, a professor of molecular and medical pharmacology at UCLA and the study’s principal investigator.

The research, Silverman said, provides “the first direct evidence that patients whose early Alzheimer’s disease is revealed by FDG–PET will do better than patients with the same condition but with their brain metabolism pattern remaining unknown to their doctors and themselves.”

The findings from the study are being presented Sept. 26 at the Medical Biotech Forum in China.

Medicare currently does not reimburse for PET scans for patients who show signs of persistent cognitive decline but do not yet have dementia, Silverman said. By the time Medicare covers an FDG–PET scan — for which they reimburse about $1,200 per patient — significant damage, some of it irreversible, has already been done to the brain tissue.

Medicare currently is re-examining reimbursement policies for PET scans obtained in dementia cases, specifically with respect to amyloid imaging (which includes Alzheimer’s imaging). A national coverage decision is expected Oct. 1, Silverman said.

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Smartphone ‘microscope’ can detect a single virus, nanoparticles


Device created by UCLA researchers weighs less than half a pound.

OzcanNanoCamera

OzcanNanoCamera

Your smartphone now can see what the naked eye cannot: A single virus and bits of material less than one-thousandth of the width of a human hair.

Aydogan Ozcan, a professor of electrical engineering and bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, and his team have created a portable smartphone attachment that can be used to perform sophisticated field testing to detect viruses and bacteria without the need for bulky and expensive microscopes and lab equipment. The device weighs less than half a pound.

“This cellphone-based imaging platform could be used for specific and sensitive detection of sub-wavelength objects, including bacteria and viruses and therefore could enable the practice of nanotechnology and biomedical testing in field settings and even in remote and resource-limited environments,” Ozcan said. “These results also constitute the first time that single nanoparticles and viruses have been detected using a cellphone-based, field-portable imaging system.”

The new research, published on Sept. 9 in the American Chemical Society’s journal ACS Nano, comes on the heels of Ozcan’s other recent inventions, including a cellphone camera–enabled sensor for allergens in food products and a smart phone attachment that can conduct common kidney tests.

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‘Incidental findings’ rare but significant events in pediatric CT scans


Four percent of head-trauma scans have unexpected results that may need follow up.

The largest study of computed tomographic (CT) scans taken in emergency departments across the country for children with head injuries describes the prevalence of “incidental findings” —  results that were not expected from the injury — and categorizes them by urgency.

The article, titled “Incidental findings in children with blunt head trauma evaluated with cranial CT scans,” was published in the August issue of Pediatrics, and provides a context for doctors in emergency departments who encounter these situations.

“Incidental findings are a rare but significant event,” said Nathan Kuppermann, professor and chair of emergency medicine at the UC Davis Medical Center and principal investigator of the study. “It is important for doctors to look for abnormalities other than what they expect to find and to be prepared to interpret and communicate these findings to families.”

The study involved nearly 44,000 children seen for a head injury in 25 hospital emergency departments nationwide. Nearly 16,000 had CT scans to evaluate an injury, and about 4 percent of the scans revealed incidental findings ranging from enlarged tonsils to life-threatening cancers. Children with a known pre-existing brain abnormality were excluded from the analysis.

The researchers also stratified the incidental findings into three categories: those that needed immediate evaluation or treatment, those that needed appropriate timely outpatient follow up, and those that merited further investigation only if the problems were causing symptoms. Only 0.1 percent of the overall sample of CTs fell into the most serious category.

Due to the small percentage of patients with the most urgent incidental findings, the study authors do not recommend any changes to current CT scan guidelines. They believe emergency medicine physicians should continue to perform CT scans in children as is medically justified for their injury because a CT scan entails a small but known long-term risk of cancer from radiation exposure.

Genetic analysis, sophisticated imaging studies and other high-technology tests have made it possible to gain information that neither the doctor nor patient expects.  Knowing what to do with these findings, especially if they are likely to be inconsequential to a patient’s health, can be a dilemma for physicians. The authors believe physicians should weigh the patient’s right to know against financial costs and potential negative health effects from anxiety, additional testing and possibly even unnecessary treatment brought on by learning of the findings.

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Thyroid cancer biopsy guidelines should be simplified, researchers say


UCSF study calls for new standards to reduce unnecessary procedures.

Scanning thyroidA team led by UC San Francisco researchers has called for simplified guidelines on when to biopsy thyroid nodules for cancer, which they say would result in fewer unnecessary biopsies.

Their recommendation, based on a retrospective study published online this week in JAMA Internal Medicine, is to biopsy patients only when imaging reveals a thyroid nodule with microcalcifications – tiny flecks of calcium – or one that is more than two centimeters in diameter and completely solid. Any other findings represent too low a risk to require biopsy or continued surveillance for cancer, the scientists concluded.

More than 98 percent of detected nodules in the study were benign, not malignant cancers.

“Compared with other existing guidelines, many of which are complicated to apply, following these simple, evidence-based guidelines would substantially decrease the number of unnecessary thyroid biopsies in the United States,” said lead author Rebecca Smith-Bindman, M.D., a UCSF School of Medicine professor with the Department of Radiology and Biomedical Imaging and the Department of Epidemiology and Biostatistics. “Right now, we’re doing far too many thyroid biopsies in patients who are really at very low risk of having thyroid cancer,” she said.

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Innovation profile: Rebecca Smith-Bindman

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