Posts tagged PET
Articles and news from the latest research reports.
Fluorescent compounds allow clinicians to visualize Alzheimer’s disease as it progresses
What if doctors could visualize all of the processes that take place in the brain during the development and progression of Alzheimer’s disease? Such a window would provide a powerful aid for diagnosing the condition, monitoring the effectiveness of treatments, and testing new preventive and therapeutic agents. Now, researchers reporting in the September 18 issue of the Cell Press journal Neuron have developed a new class of imaging agents that enables them to visualize tau protein aggregates, a pathological hallmark of Alzheimer’s disease and related neurodegenerative disorders, directly in the brains of living patients.
In the brains of patients with Alzheimer’s disease, tau proteins aggregate together and become tangled, while fragments of another protein, called amyloid beta, accumulate into deposits or plaques. Tau tangles are not only considered an important marker of neurodegeneration in Alzheimer’s disease but are also a hallmark of non-Alzheimer’s neurodegenerative disorders, tauopathies that do not involve amyloid beta plaques. While imaging technologies have been developed to observe the spread of amyloid beta plaques in patients’ brains, tau tangles were previously not easily monitored in the living patient.
In this latest research in mice and humans, investigators developed fluorescent compounds that bind to tau (called PBBs) and used them in positron emission tomography (PET) tests to correlate the spread of tau tangles in the brain with moderate Alzheimer’s disease progression. “PET images of tau accumulation are highly complementary to images of senile amyloid beta plaques and provide robust information on brain regions developing or at risk for tau-induced neuronal death,” says senior author Dr. Makoto Higuchi, of the National Institute of Radiological Sciences in Japan. “This is of critical significance, as tau lesions are known to be more intimately associated with neuronal loss than senile plaques.”
The advance may also be helpful for diagnosing, monitoring, and treating other neurological conditions because tau tangles are not limited to Alzheimer’s disease but also play a role in various types of dementias and movement disorders.
Combination of Two Imaging Techniques Allows New Insights into Brain Function
The ability to measure brain functions non-invasively is important both
for clinical diagnoses and research in Neurology and Psychology. Two main imaging techniques are used: positron emission tomography (PET), which reveals metabolic processes in the brain; and activity of different brain regions is measured on the basis of the cells’ oxygen consumption by magnetic resonance imaging (MRI). A direct comparison of PET and MRI measurements was previously difficult because each had to be performed in a separate machine.
Researchers from the Werner Siemens Imaging Center at the University of Tübingen under the direction of Professor Bernd J. Pichler in collaboration with the Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, and the Tübingen Max Planck Institute for Intelligent Systems have now successfully combined both methods. The researchers are able to explore functional processes in the brain in detail and can better assess what course of action to take. These results were achieved by the use of a PET insert enabling complementary, simultaneous PET/MRI scans. It was developed and built at the University of Tübingen.
The researchers could identify in certain regions a mismatch between glucose metabolism related brain activation measured with PET and oxygenation related signals, measured with MRI. Furthermore information about functional connectivity in the brain could be derived from MRI and from dynamic PET data. These results help to further decipher the nature of brain function, and are ultimately useful for basic research as well as clinical practice. The study, by lead author Dr. Hans Wehrl of Professor Bernd J. Pichler’s research team is soon to be published in the journal “Nature Medicine”.
In PET imaging the distribution of a weakly radioactive substance is shown in cross sections of the body, enabling doctors to see many different metabolic and physiological functions at work. Functional MRI (fMRI) allows researchers to depict changes in blood oxygenation that are associated with brain function. This measurement of functional active brain regions is also important for the planning of brain surgeries, where particular care must be taken in certain areas. The ability to collect different kinds of data from different scans simultaneously represents a major step forward in the fields using these technologies.
(Source: alphagalileo.org)
In a National Institutes of Health (NIH) funded clinical trial, researchers at Emory have discovered that specific patterns of brain activity may indicate whether a depressed patient will or will not respond to treatment with medication or psychotherapy. The study was published June 12, 2013, in JAMA Psychiatry Online First.
The choice of medication versus psychotherapy is often based on the preference of the patient or clinician, rather than objective factors. On average, only 35-40 percent of patients get well with whatever treatment they start with.
"To be ill with depression any longer than necessary can be perilous," says Helen Mayberg,md principal investigator for the study and professor of psychiatry, neurology and radiology at Emory University School of Medicine. "This is a serious illness and the prolonged suffering resulting from an ineffective treatment can have serious medical, personal and social consequences. Our goal is not just to get patients well, but to get them well as fast as possible, using the treatment that is best for each individual."
Mayberg’s positron emission tomography (PET) studies over the years have given clues about what may be going on in the brain when people are depressed, and how different treatments affect brain activity.
These studies have also suggested that scan patterns prior to treatment might provide important clues as to which treatment to choose. In this study, the investigators used PET scans to measure brain glucose metabolism, an important index of brain functioning to test this hypothesis.
Participants in the trial were randomly assigned to receive a 12-week course of either the SSRI medication escitalopram or cognitive behavior therapy (CBT) after first undergoing a pretreatment PET scan.
The team found that activity in one particular region of the brain, the anterior insula, could discriminate patients who recovered from those who were non-responders to the treatment assigned. Specifically, patients with low activity in the insula showed remission with CBT, but poor response to medication; patients with high activity in the insula did well with medication, and poorly with CBT.
"These data suggest that if you treat based on a patient’s brain type, you increase the chance of getting them into remission," says Mayberg.
Mayberg is quick to add that this approach needs to be replicated before it would be appropriate for routine treatment selection decisions for individual depressed patients. It is, however, a first step to better define different types of depression that can be used to select a specific treatment for a patient.
A treatment stratification approach is done routinely in the management of other medical conditions such as infections, cancer, and heart disease, notes Mayberg. “The study reported here provides important first results towards the development of brain-based treatment algorithms that match a patient to the treatment with the highest likelihood of success, while also avoiding those treatments that will be ineffective.”
High Sugar Intake Linked to Low Dopamine Release in Insulin Resistant Patients
PET study led by Stony Brook Professor indicates that overeating and weight gain contributing to onset of diabetes could be related to a deficit in reward circuits in the brain
Using positron emission tomography (PET) imaging of the brain, researchers have identified a sweet spot that operates in a disorderly way when simple sugars are introduced to people with insulin resistance, a precursor to type 2 diabetes. For those who have the metabolic syndrome, a sugar drink resulted in a lower-than-normal release of the chemical dopamine in a major pleasure center of the brain. This chemical response may be indicative of a deficient reward system, which could potentially be setting the stage for insulin resistance. This research could revolutionize the medical community’s understanding of how food-reward signaling contributes to obesity, according to a study presented at the Society of Nuclear Medicine and Molecular Imaging’s 2013 Annual Meeting.
"Insulin resistance is a significant contributor to obesity and diabetes," said Gene-Jack Wang, MD, lead author of the study and Professor of Radiology at Stony Brook University and researcher at the U.S. Department of Energy’s Brookhaven National Laboratory in Upton, N.Y. "A better understanding of the cerebral mechanisms underlying abnormal eating behaviors with insulin resistance would help in the development of interventions to counteract the deterioration caused by overeating and subsequent obesity. We suggest that insulin resistance and its association with less dopamine release in a central brain reward region might promote overeating to compensate for this deficit."
An estimated one-third of Americans are obese, according to the U.S. Centers for Disease Control and Prevention. The American Diabetes Association estimates that about 26 million Americans are living with diabetes and another 79 million are thought to be prediabetic, including those with insulin resistance.
The tendency to overeat may be caused by a complex biochemical relationship, as evidenced by preliminary research with rodents. Dr. Wang’s research marks the first clinical study of its kind with human subjects.
"Animal studies indicated that increased insulin resistance precedes the lack of control associated with pathological overeating," said Wang. "They also showed that sugar ingestion releases dopamine in brain regions associated with reward. However, the central mechanism that contributes to insulin resistance, pathological eating and weight gain is unknown."
He continued, “In this study we were able to confirm an abnormal dopamine response to glucose ingestion in the nucleus accumbens, where much of the brain’s reward circuitry is located. This may be the link we have been looking for between insulin resistance and obesity. To test this, we gave a glucose drink to an insulin-sensitive control group and an insulin-resistant group of individuals and we compared the release of dopamine in the brain reward center using PET.”
In this study, a total of 19 participants-including 11 healthy controls and eight insulin-resistant subjects-consumed a glucose drink and, on a separate day, an artificially sweetened drink containing sucralose. After each drink, PET imaging with C-11 raclopride-which binds to dopamine receptors-was performed. Researchers mapped lit-up areas of the brain and then gauged striatal dopamine receptor availability (which is inversely related to the amount of natural dopamine present in the brain). These results were matched with an evaluation in which patients were asked to document their eating behavior to assess any abnormal patterns in their day-to-day lives. Results showed agreement in receptor availability between insulin-resistant and healthy controls after ingestion of sucralose. However, after patients drank the sugary glucose, those who were insulin-resistant and had signs of disorderly eating were found to have remarkably lower natural dopamine release in response to glucose ingestion when compared with the insulin-sensitive control subjects.
"This study could help develop interventions, i.e., medication and lifestyle modification, for early-stage insulin-resistant subjects to counteract the deterioration that leads to obesity and/or diabetes," said Wang. "The findings set a path for future clinical studies using molecular imaging methods to assess the link of peripheral hormones with brain neurotransmitter systems and their association with eating behaviors."
PET Finds Increased Cognitive Reserve Levels in Highly Educated Pre-Alzheimer’s Patients
Highly educated individuals with mild cognitive impairment that later progressed to Alzheimer’s disease cope better with the disease than individuals with a lower level of education in the same situation, according to research published in the June issue of The Journal of Nuclear Medicine. In the study “Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project,”neural reserve and neural compensation were both shown to play a role in determining cognitive reserve, as evidenced by positron emission tomography (PET).
Cognitive reserve refers to the hypothesized capacity of an adult brain to cope with brain damage in order to maintain a relatively preserved functional level. Understanding the brain adaptation mechanisms underlying this process remains a critical question, and researchers of this study sought to investigate the metabolic basis of cognitive reserve in individuals with higher (more than 12 years) and lower (less than 12 years) levels of education who had mild cognitive impairment that progressed to Alzheimer’s disease, also known as prodromal Alzheimer’s disease.
“This study provides new insight into the functional mechanisms that mediate the cognitive reserve phenomenon in the early stages of Alzheimer’s disease,” said Silvia Morbelli, MD, lead author of the study. “A crucial role of the dorso-lateral prefrontal cortex was highlighted by demonstrating that this region is involved in a wide fronto-temporal and limbic functional network in patients with Alzheimer’s disease and high education, but not in poorly educated Alzheimer’s disease patients.”
In the study, 64 patients with prodromal Alzheimer’s disease and 90 control subjects—coming from the brain PET project (chaired by Flavio Nobili, MD, in Genoa, Italy) of the European Alzheimer Disease Consortium—underwentbrain 18F-FDG PET scans. Individuals were divided into a subgroup with a low level of education (42 controls and 36 prodromal Alzheimer’s disease patients) and a highly educated subgroup (40 controls and 28 prodromal Alzheimer’s disease patients). Brain metabolism was compared between education-matched groups of patients and controls, and then between highly and poorly educated prodromal Alzheimer’s disease patients.
Higher metabolic activity was shown in the dorso-lateral prefrontal cortex for prodromal Alzheimer’s disease patients. More extended and significant correlations of metabolism within the right dorso-lateral prefrontal cortex and other brain regions were found with highly educated than less educated prodromal Alzheimer’s disease patients or even highly educated controls.
This result suggests that neural reserve and neural compensation are activated in highly educated prodromal Alzheimer’s disease patients. Researchers concluded that evaluation of the implication of metabolic connectivity in cognitive reserve further confirms that adding a comprehensive evaluation of resting 18F-FDG PET brain distribution to standard inspection may allow a more complete comprehension of Alzheimer’s disease pathophysiology and possibly may increase 18F-FDG PET diagnostic sensitivity.
“This work supports the notion that employing the brain in complex tasks and developing our own education may help in forming stronger ‘defenses’ against cognitive deterioration once Alzheimer knocks at our door,” noted Morbelli.“It’s possible that, in the future, a combined approach evaluating resting metabolic connectivity and cognitive performance can be used on an individual basis to better predict cognitive decline or response to disease-modifying therapy.”
(Source: interactive.snm.org)
Taste of beer, without effect from alcohol, triggers dopamine release in the brain
The taste of beer, without any effect from alcohol itself, can trigger dopamine release in the brain, which is associated with drinking and other drugs of abuse, according to Indiana University School of Medicine researchers.
Using positron emission tomography (PET), the researchers tested 49 men with two scans, one in which they tasted beer, and the second in which they tasted Gatorade, looking for evidence of increased levels of dopamine, a brain neurotransmitter long associated with alcohol and other drugs of abuse. The scans showed significantly more dopamine activity following the taste of beer than the sports drink. Moreover, the effect was significantly greater among participants with a family history of alcoholism.
Results of the study were published online Monday by the journal Neuropsychopharmacology.
"We believe this is the first experiment in humans to show that the taste of an alcoholic drink alone, without any intoxicating effect from the alcohol, can elicit this dopamine activity in the brain’s reward centers," said David A. Kareken, Ph.D., professor of neurology at the IU School of Medicine and the deputy director of the Indiana Alcohol Research Center.
The stronger effect in participants with close alcoholic relatives suggests that the release of dopamine in response to such alcohol-related cues may be an inherited risk factor for alcoholism, said Dr. Kareken.
Research for several decades has linked dopamine to the consumption of various drugs of abuse, although researchers have differing interpretations of the neurotransmitter’s role. Sensory cues that are closely associated with drug intoxication (ranging from tastes and smells to the sight of a tavern) have long been known to spark cravings and induce treatment relapse in recovering alcoholics. Many neuroscientists believe that dopamine plays a critical role in such cravings.
The study participants received a very small amount of their preferred beer — 15 milliliters — over a 15-minute time period, enabling them to taste the beer without resulting in any detectable blood alcohol level or intoxicating effect.
Using a PET scanning compound that targets dopamine receptors in the brain, the researchers were able to assess changes in dopamine levels occurring after the participants tasted the liquids.
In addition to the PET scan results, participants reported an increased beer craving after tasting beer, without similar responses after tasting the sports drink — even though many thought the Gatorade actually tasted better, said Brandon G. Oberlin, Ph.D., post-doctoral fellow and first author of the paper.
(Image: iStockphoto)
Researchers Identify Physiological Evidence of ‘Chemo Brain’
Chemotherapy can induce changes in the brain that may affect concentration and memory, according to a study presented at the annual meeting of the Radiological Society of North America (RSNA). Using positron emission tomography combined with computed tomography (PET/CT), researchers were able to detect physiological evidence of chemo brain, a common side effect in patients undergoing chemotherapy for cancer treatment.
"The chemo brain phenomenon is described as ‘mental fog’ and ‘loss of coping skills’ by patients who receive chemotherapy," said Rachel A. Lagos, D.O., diagnostic radiology resident at the West Virginia University School of Medicine and West Virginia University Hospitals in Morgantown, W.V. "Because this is such a common patient complaint, healthcare providers have generically referred to its occurrence as ‘chemo brain’ for more than two decades."
While the complaint may be common, the cause of chemo brain phenomenon has been difficult to pinpoint. Some prior studies using magnetic resonance imaging (MRI) have found small changes in brain volume after chemotherapy, but no definitive link has been found.
Instead of studying chemotherapy’s effect on the brain’s appearance, Dr. Lagos and colleagues set out to identify its effect on brain function. By using PET/CT, they were able to assess changes to the brain’s metabolism after chemotherapy.
"When we looked at the results, we were surprised at how obvious the changes were," Dr. Lagos said. "Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET/CT brain imaging."
PET/CT results demonstrated statistically significant decreases in regional brain metabolism that were closely associated with symptoms of chemo brain phenomenon.
"The study shows that there are specific areas of the brain that use less energy following chemotherapy," Dr. Lagos said. "These brain areas are the ones known to be responsible for planning and prioritizing."
Dr. Lagos believes that PET/CT could be used to help facilitate clinical diagnosis and allow for earlier intervention.