TAG: "Imaging"

Finding a better way to track emerging cell therapies using MRIs


Technique might speed development of relevant therapies.

Cellular therapeutics – using intact cells to treat and cure disease – is a hugely promising new approach in medicine, but it is hindered by the inability of doctors and scientists to effectively track the movements, destination and persistence of these cells in patients without resorting to invasive procedures, like tissue sampling.

In a paper published Sept. 17 in the online journal Magnetic Resonance in Medicine, researchers at the UC San Diego School of Medicine, University of Pittsburgh and elsewhere describe the first human tests of using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.

“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said first author Eric T. Ahrens, Ph.D., professor in the Department of Radiology at UC San Diego. “Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses and engraftment success.”

Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes. The former have proven difficult to differentiate in vivo; the latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.

“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Ahrens. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

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CT scan is no better than ultrasound to detect kidney stones


UCSF study leader recommends change in standard practice.

Rebecca Smith-Bindman, UC San Francisco

To diagnose painful kidney stones in hospital emergency rooms, CT scans are no better than less-often-used ultrasound exams, according to a clinical study conducted at 15 medical centers and published in the Sept. 18 issue of the New England Journal of Medicine.

Unlike ultrasound, CT exposes patients to significant amounts of radiation. Although CT scans are favored by emergency-room physicians for kidney stone diagnosis, ultrasound should be used as the first step, according to senior study author Rebecca Smith-Bindman, M.D., a professor in the departments of radiology; epidemiology and biostatistics; and obstetrics, gynecology and reproductive medicine at UC San Francisco.

“Ultrasound is the right place to start,” Smith-Bindman said. “Radiation exposure is avoided, without any increase in any category of adverse events, and with no increase in cost.” Patients in the study who were first examined with ultrasound sometimes received a follow-up CT exam at the physician’s discretion.

“Our results do not suggest that patients should undergo only ultrasound imaging, but rather that ultrasonography should be used as the initial diagnostic imaging test, with further imaging studies performed at the discretion of the physician on the basis of clinical judgment,” the study authors said.

Kidney stone rates are increasing, and in a 2010 National Health and Nutrition Examination Survey, one in 11 people reported having had at least one kidney stone. The use of CT to diagnose kidney stones has risen 10-fold in the last 15 years. CT exams generally are conducted by radiologists, while ultrasound exams may be conducted by emergency room physicians as well as radiologists.

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Related link:
Innovation Profile: Rebecca Smith-Bindman

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MRI is a ‘game-changer’ in diagnosing prostate cancer


UC San Diego Health System is first to use new tool in San Diego.

Oncologists at UC San Diego Moores Cancer Center are the first in San Diego to meld magnetic resonance imaging (MRI) technology with a traditional ultrasound prostate exam to create a three-dimensional map of the prostate that allows physicians to view growths that were previously undetectable.

An ultrasound machine provides an imperfect view of the prostate, resulting in an under-diagnosis of cancer, said J. Kellogg Parsons, M.D., M.H.S., the UC San Diego Health System urologic oncologist who, along with Christopher Kane, M.D., chair of the Department of Urology and Karim Kader, M.D., Ph.D., urologic oncologist, is pioneering the new technology at Moores Cancer Center.

“With an ultrasound exam, we are typically unable to see the most suspicious areas of the prostate so we end up sampling different parts of the prostate that statistically speaking are more likely to have cancer,” said Parsons, who is also an associate professor in the Department of Urology at UC San Diego School of Medicine. “The MRI is a game-changer. It allows us to target the biopsy needles exactly where we think the cancer is located. It’s more precise.”

Armondo Lopez, a patient at Moores Cancer Center, had been given a clean bill of health using the traditional ultrasound biopsy method, but when his prostate-specific antigen (PSA) levels, a protein that is often elevated in men with prostate cancer, started to rise he began to worry. Parsons recommended a MRI-guided prostate biopsy. The new technology led to the diagnosis of an aggressive prostate cancer located in an area normally not visible using the ultrasound machine alone. The tumor was still in its early stage and treatable, said Parsons.

An early diagnosis typically improves a patient’s prognosis. In the United States, prostate cancer is the second leading cause of cancer death in men with more than 29,000 estimated deaths expected this year. The average age at the time of diagnosis is about 66.

Lopez is thankful he will be able to celebrate his 58th wedding anniversary with his wife.

“Life is going on as normal,” said Lopez. “This is the wave of the future. I see this new technology as the way to save thousands of lives. I commend Dr. Parsons for taking the lead in San Diego in this area.”

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Mapping the infant brain


Findings may be key in identifying, treating earliest signs of neurodevelopmental disorders.

A recent study conducted by researchers at the UC San Diego School of Medicine and the University of Hawaii demonstrates a new approach to measuring early brain development of infants, resulting in more accurate whole brain growth charts and providing the first estimates for growth trajectories of subcortical areas during the first three months after birth. Assessing the size, asymmetry and rate of growth of different brain regions could be key in detecting and treating the earliest signs of neurodevelopmental disorders, such as autism or perinatal brain injury.

The study will be published in JAMA Neurology today (Aug. 11).

For the first time, researchers used magnetic resonance imaging (MRI) of the newborn brain to calculate the volume of multiple brain regions and to map out regional growth trajectories during the infant’s first 90 days of life. The study followed the brain growth of full term and premature babies with no neurological or major health issues.

“A better understanding of when and how neurodevelopmental disorders arise in the postnatal period may help assist in therapeutic development, while being able to quantify related changes in structure size would likely facilitate monitoring response to therapeutic intervention. Early intervention during a period of high neuroplasticity could mitigate the severity of the disorders in later years,” said Dominic Holland, Ph.D., first author of the study and researcher in the Department of Neurosciences at UC San Diego School of Medicine.

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New terahertz modulator could lead to more advanced medical, security imaging


Could be used to examine human tissue for signs for disease without damaging cells.

Electron microscope image showing the metasurface for a terahertz modulator developed by a group led by UCLA professor Mona Jarrahi.

A UCLA Henry Samueli School of Engineering and Applied Science research team has developed a breakthrough broadband modulator that could eventually lead to more advanced medical and security imaging systems.

Modulators manipulate the intensity of electromagnetic waves. For example, modulators in cell phones convert radio waves into digital signals that the devices can use and understand. In terahertz-based communication and imaging systems, they modify the intensity of terahertz waves.

Today’s technologies take advantage of many parts of the electromagnetic spectrum — notably light waves and radio waves — but they rarely operate in the terahertz band, which lies between infrared and microwave on the spectrum.

Led by Mona Jarrahi, UCLA associate professor of electrical engineering, the group developed a terahertz modulator that performs across a wide range of the terahertz band with very high efficiency and signal clarity. Among the device’s advantages are that it could easily be incorporated into existing integrated circuit manufacturing processes, can operate at room temperature and does not require an external light source to operate.

The terahertz band has been the subject of extensive research, in large part because of its potential for medical imaging and chemical sensing technologies. For example, terahertz waves could be used to examine human tissue for signs for disease without damaging cells or the other health risks posed by X-rays. They also could be used in security screenings to penetrate fabric or plastics that conceal weapons.

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Minor head injury not reason enough for CT scan in children


Study helps emergency physicians avoid CT scans that carry cancer risks for young patients.

Nathan Kuppermann, UC Davis

A nationwide study of more than 40,000 children evaluated in hospital emergency departments for head trauma found that if children had only loss of consciousness, and no other signs or symptoms related to the head trauma, they are very unlikely to have sustained serious brain injuries. Children who have only isolated loss of consciousness after head trauma do not routinely require computed tomography (CT) scans of the head, reported researchers from UC Davis Health System and Boston Children’s Hospital.

Although CT scans are the standard way to determine if a child has life-threatening bleeding in the brain that may necessitate surgical intervention, the radiation involved carries a small but quantifiable long-term risk of cancer. As such, the data indicates CT evaluation for children with head trauma should not be routinely used if they are at low risk for clinically significant traumatic brain injuries.

The findings were published today in the journal JAMA Pediatrics in an article titled “Isolated loss of consciousness in children with minor blunt head trauma.”

“Fear of missing a clinically significant head injury, and the wide availability of CT scanners, have been the main factors driving an increase in the use of CT imaging over the past two decades,” said Nathan Kuppermann, professor and chair of the UC Davis Department of Emergency Medicine, and principal investigator of the original study from which the data and current analysis of head injuries were derived. “Our findings can help doctors confidently make a decision to forego CT testing when their patients are unlikely to benefit from it, enabling physicians to first observe their patients for a period of time before deciding on CT use.”

Whether the presence of a single factor suggestive of brain injury is reason enough to justify obtaining a CT scan has been a question Kuppermann and colleagues with the Pediatric Emergency Care Applied Research Network (PECARN) have been actively exploring through a series of studies over the past few years. The current study found that children who lost consciousness after head trauma, but then were awake and alert in the emergency department, and had none of the other five factors determined important by PECARN guidelines for identifying children at low risk for clinically significant brain injuries after head trauma (called the PECARN traumatic brain injury prediction rules), had a very low rate of clinically important brain injuries – only 0.5 percent, or 1 in 200 children.

If a child had isolated loss of consciousness without any other signs or symptoms of head trauma (i.e., including factors outside of the PECARN traumatic brain injury prediction rules), the incidence of an important brain injury dropped to only 0.2 percent, or 1 in 500 children. Furthermore, the duration of the loss of consciousness did not significantly affect risk.

“Children with clinically important brain injuries rarely have loss of consciousness alone, and almost always present other symptoms, such as vomiting or showing signs of neurological problems,” said Lois K. Lee, lead author of the current study and director of trauma research at Boston Children’s Hospital. “Being able to make treatment decisions backed by strong data helps doctors and parents feel better about deciding whether further testing is really needed.”

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Dr. Michael Buonocore, UC Davis professor of radiology, dies


Dedicated scientist was 59.

Michael Buonocore

Michael H. Buonocore, a professor in the UC Davis Department of Radiology for 27 years, died of cancer on June 21. He was 59.

“Dr. Buonocore was a brilliant scientist who preferred to stay out of the limelight, often performing his clinical physics evaluation of the MR scanners late in the evening,” said Raymond Dougherty, professor and chair of the Department of Radiology. “He dedicated himself to team science and collaborated with many faculty at UC Davis, nationally and internationally. His loss to our department as a scientist and esteemed colleague is enormous.”

Dr. Buonocore was born on Oct. 24, 1954, in Rochester, N.Y. He received his bachelor’s degree in chemistry and physics from Syracuse University in 1977. He then enrolled at Stanford University, where he received his master’s degree in electrical engineering in 1979, his Ph.D. in electrical engineering in 1982, and his medical degree in 1983.

From 1983-86, Dr. Buonocore served as chief scientist of Resonex, a magnetic resonance company, where one of his chief contributions was the invention of a widely used technique in modern magnetic resonance imaging (MRI) systems. He left Resonex in 1986 to work as a research scientist at the UC Berkeley Pure and Applied Mathematics Department.

In July 1987, Dr. Buonocore joined the UC Davis Department of Radiology and quickly developed clinical and research MRI opportunities for the UC Davis School of Medicine and UC Davis Medical Center. He developed many courses in advanced MRI for the biomedical engineering program at UC Davis, and was an advisor and mentor for many students.

Dr. Buonocore specialized in functional MRI and was a brain mapping expert. He implemented many novel and advanced MRI programs for the non-invasive measurement of physiological processes, working in consultation with fellow faculty members in the radiology department, as well as faculty in other departments, including psychiatry, neurology, cognitive neuroscience and anesthesiology.

His most successful projects included measurement and visualization of blood flow in the heart and major vessels; measurement of neural activation in the cerebral cortex during cognitive and sensorimotor tasks; measurement of kidney filtration parameters; and measurement of tissue perfusion in breast tumors.

Dr. Buonocore served as MRI technical director for the radiology department, and as technical director of the UC Davis Imaging Research center.

Dr. Buonocore is survived by his wife, Kim, and his son, Christopher.

In lieu of flowers, gifts may be made to the Dr. Michael Buonocore Memorial Fund by contacting Jennifer Marsteen of UC Davis Health System Health Sciences Development at (916) 734-9448. The fund will be used to advance research and teaching in magnetic resonance imaging in medicine at UC Davis, a cause to which Dr. Buonocore devoted much of his professional career.

Planning for a memorial service is under way.

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Using bubbles to reveal fertility problems


New ultrasound procedure can identify blockages in fallopian tubes.

Sanjay Agarwal, UC San Diego

Many women struggling to become pregnant may suffer from some degree of tubal blockage. Traditionally, an X-ray hysterosalpingogram (HSG) that uses dye is the most common procedure to determine whether a blockage exists, but it can cause extreme discomfort to the patient. UC San Diego Health System’s doctors are the first fertility specialists in the county to use a new ultrasound technique to assess fallopian tubes by employing a mixture of saline and air bubbles that is less painful, avoids X-ray exposure and is more convenient to patients during an already vulnerable time.

Using the FemVue Sono HSG, the physician delivers the mixture of saline and air bubbles into the uterus through a small catheter, which then flows into the fallopian tubes. Under ultrasound, the air bubbles are highly visible as they travel through the tubes, allowing the physician to determine if a blockage exists.

“The traditional X-ray approach involves higher pressure and usually causes significant cramping as the dye is administered. The anticipated pain prevents some women from even attempting the test. Others cannot do the test because they are allergic to the dye. Assessing the tubes for a blockage is a key component of the diagnostic workup in fertile couples, and not doing so because of pain or allergy is a real concern,” said Sanjay Agarwal, M.D., director of fertility services in the Department of Reproductive Medicine at UC San Diego Health System. “The new approach is not only much more comfortable for patients, it also uses saline, so the issue of an allergy does not arise. We are also able to assess the cavity of the uterus at the same time – all without X-rays.”

Kristina, a mother who has been trying to conceive a second child for almost a year, agreed: “I was willing to do whatever it took to address the fertility issues we were facing, but after everything we had been through emotionally, it was a relief to undergo a procedure that wasn’t physically painful.”

The ultrasound is performed in the clinic, and at present, ideal candidates include those with a prior pregnancy and those at low risk for tubal disease.

“Like the traditional X-ray HSG, the new test should be performed after the period has ended but before ovulation. The fact that the patient can schedule this ultrasound-based test in the clinic and not in radiology prevents a delay in care and allows the patient’s physician to be more involved in the process,” said Agarwal, also director of the UC San Diego Center for Endometriosis Research and Treatment (CERT).

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UCSF Mission Bay hospitals to introduce patient-friendly scan suites


Design intended to help put patients at ease.

A model of a cable car-themed scan suite planned for the new UCSF Benioff Children's Hospital San Francisco.

Patients undergoing imaging at the new UCSF Medical Center at Mission Bay will be transported to the tranquility of Muir Woods, or take in the sights of San Francisco from a cable car or boat, thanks to images projected on the suites’ walls and ceiling. They can admire lush visuals, such as a sunset over Golden Gate Bridge, and listen to the sounds of nature or soothing music that they select themselves.

Younger patients at the new UCSF Benioff Children’s Hospital San Francisco may prefer a more active role. Instead of a stark room with a table and scanning equipment, they may opt for the driver’s seat of a trolley car, where they can trundle around the city, take in local landmarks and participate in hands-on activities working with a cast of animated critters. Or perhaps they prefer to captain a boat for a nautical expedition.

These suites will be available when UCSF Medical Center at Mission Bay opens on Feb. 1, 2015, for patients undergoing MRI or SPECT and CT, two imaging techniques that look inside the body and help doctors pinpoint any areas of disease. The procedures can take from 30 minutes to an hour and are used to diagnose a variety of conditions from tumors and congenital abnormalities, to skeletal trauma such as ACL injury.

Among cancer patients, scanning may be especially stressful because it determines the success or failure of treatment.

The design of the rooms was the result of collaboration between GE Healthcare and a UCSF team comprising faculty, staff, patients and their families participating in workshops and “visioning sessions” in which optimal features of the suites were identified and the feasibility of implementing them were discussed. Opinions were also sought from pediatric patients who viewed suite mock-ups.

Making the scan suites child-friendly was the primary focus, said John MacKenzie, M.D., chief of radiology at UCSF Benioff Children’s Hospital San Francisco, who provided a physician’s perspective and worked with the team from UCSF and GE Healthcare.

“Most children have never encountered an MRI machine before – it’s not something they see in a playground. Typically they enter an MRI room and hesitate when they’re told to hop on the table. But if instead they’re told, ‘Let’s go take a ride on the boat,’ they’re more likely to be intrigued than anxious,” said MacKenzie.

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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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