Posts tagged cerebral blood flow
Articles and news from the latest research reports.
A New Window of Opportunity to Prevent Cardiovascular and Cerebrovascular Diseases
Future prevention and treatment strategies for vascular diseases may lie in the evaluation of early brain imaging tests long before heart attacks or strokes occur, according to a systematic review conducted by a team of cardiologists, neuroscientists, and psychiatrists from Icahn School of Medicine at Mount Sinai and published in the October issue of JACC Cardiovascular Imaging.
For the review, Mount Sinai researchers examined all relevant brain imaging studies conducted over the last 33 years. They looked at studies that used every available brain imaging modality in patients with vascular disease risk factors but no symptoms that would lead to a diagnosis of diseased blood vessels (vascular disease) in the heart or brain, or periphery (e.g. arms and legs).
The review demonstrates that patients with high blood pressure, diabetes, obesity, high cholesterol, smoking, or metabolic syndrome, but no symptoms, still had visible signs on their neuroimaging scans of structural and functional brain changes long before the development of any events related to vascular diseases of the heart (heart attack) or brain (stroke).
"This is the first time we have been able to disentangle the brain effects of vascular disease risk factors from the brain effects of cardiovascular and cerebrovascular disease and/or events after they develop," says the article’s lead author, Joseph I. Friedman, MD, Associate Professor in the Departments of Psychiatry and Neuroscience at Icahn School of Medicine at Mount Sinai. "Moreover, subtle cognitive impairment is an important clinical manifestation of these vascular disease risk factor-related brain imaging changes in these otherwise healthy persons."
Dr. Friedman added that, because diminished cognitive capacity adversely impacts a person’s ability to benefit from treatment for these medical conditions, early identification of these brain changes may “present a new window of opportunity” for doctors to intervene early and improve prevention of advancement from vascular disease risk factors to established cardiovascular and cerebrovascular diseases. His team is currently testing these hypotheses in ongoing studies at Mount Sinai.
"Patients need to start today to control their vascular risk factors, otherwise their brains may forever harbor physical changes leading to devastating heart and vascular conditions impacting their future overall health and even cognitive decline causing diseases like dementia or when it exists it can accelerate Alzheimer’s," says study author, Valentin Fuster, MD, PhD, Director of Mount Sinai Heart, Physician-in-Chief of The Mount Sinai Hospital, and Chief of the Division of Cardiology at Icahn School of Medicine at Mount Sinai. "Our publication raises the possibility that these early brain changes are major warning signs of what the future may hold for these asymptomatic patients. These high risk patients, along with their doctors, hold the power to modify their daily vascular risk factors to help halt the future course of the manifestation of their potentially looming cardiovascular diseases."
"We hope our publication serves as a primer for cardiologists and other doctors interpreting the early neuroimaging data of their patients who may be high risk for vascular disease," says senior article author Jagat Narula, MD, PhD, Director of Cardiovascular Imaging, Professor of Medicine and Philip J. and Harriet L. Goodhart Chair in Cardiology at Icahn School of Medicine at Mount Sinai. "These subtle brain changes are clues to us physicians that our patients need to start to lower their vascular risk factors always and way before symptoms or a cardiac or brain event happens. This simple step to lower vascular risk factors can have huge impacts on global prevention efforts of cardiovascular diseases."
Researchers identified the following impact of key vascular risk factors on the structural and functional brain health of asymptomatic patients:
- Hypertension is associated with globally appreciable brain volume reductions,
connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions. - Diabetes is associated with connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions.
- Obesity is associated with brain volume reductions, reduced brain blood flow and metabolism.
- High total cholesterol and LDL cholesterol are associated with brain volume reductions, and connecting brain fiber abnormalities. In addition, high triglycerides is associated with reduced brain blood flow, and high total cholesterol is associated with reduced brain metabolism.
- Smoking is associated with brain volume reductions, and alterations of the normal pattern of blood flow. In addition, it causes reduced MAO B (Monoamine Oxidase B) which metabolizes dopamine, the neurotransmitter chemical that controls the brain’s reward and pleasure zones.
- Metabolic Syndrome is associated with a greater burden of silent brain infarcts (SBIs), visible only on MRI, which represents subclinical cerebrovascular disease. In addition, it is associated with connecting brain fiber abnormalities, and alterations in the normal pattern of synchronized brain activity between different regions.
(Source: mountsinai.org)
Device lets docs stay ‘tuned in’ to brain bloodflow
For Dr. John Murkin, the medical device business is all about “making a better mouse trap.”
The Schulich School of Medicine & Dentistry professor is part of a team of Western and Lawson Health Research Institute (LHRI) researchers studying a new technology that may change the way patients undergoing cardiac surgery are monitored and managed in the hospital.
The device, known as CerOx, non-invasively monitors cerebral blood flow and helps physicians and nurses assess brain perfusion in real time. Murkin, who has been involved in the machine’s development, said this information could be used to support critical treatment decisions made to protect the patient from potential complications.
“We use near-infrared light routinely in all hospitals to measure oxygen saturation in the brain. That’s been out for 30 years,” Murkin said. “This new device is not just measuring oxygen saturation; it’s also measuring blood flow to the brain, in real time, and non-invasively.
“If a patient has a brain injury, the more you know about the brain, the better you are at being tuned into their needs.”
In cardiac surgery, cerebral monitoring significantly reduces complications, including permanent stroke.
An anesthetist at London Health Sciences Centre and a researcher at LHRI, Murkin has studied cognitive and neurological outcomes in cardiac surgery for more than three decades. He said there has been an unmet clinical need for a noninvasive tool that provides accurate, real-time measurements of cerebral blood flow in these highly vulnerable patients.
Currently, 11 different studies have evaluated CerOx in different applications.
“We’ve seen the potential of the machine and we’re convinced it works,” he added. “If you don’t know what’s going on in the brain, you can’t help. But, when you start to monitor this, and you see changes in blood flow, in oxygen saturation and its because of the blood pressure or hemoglobin, or whatever it is, if you pick things up early enough, you can hopefully avoid any possible complications.
“If you can monitor in real time, you can act in real time.”
The device is expected to be used primarly by physicians in neuro-critical care areas.
“While the device can alert you to potential problems, the next part is what are you going to do about it? You still need to act,” he said. “We want to start looking at what are some of the therapeutic interventions we can use to improve outcomes.”
CerOx was developed by U.S.- and Israel-based Ornim Medical, of which Murkin is a member of their scientific advisory board.
This is Your Brain’s Blood Vessels on Drugs
A new method for measuring and imaging how quickly blood flows in the brain could help doctors and researchers better understand how drug abuse affects the brain, which may aid in improving brain-cancer surgery and tissue engineering, and lead to better treatment options for recovering drug addicts. The new method, developed by a team of researchers from Stony Brook University in New York, USA and the U.S. National Institutes of Health, was published today in The Optical Society’s (OSA) open-access journal Biomedical Optics Express.
The researchers demonstrated their technique by using a laser-based method of measuring how cocaine disrupts blood flow in the brains of mice. The resulting images are the first of their kind that directly and clearly document such effects, according to co-author Yingtian Pan, associate professor in the Department of Biomedical Engineering at Stony Brook University. “We show that quantitative flow imaging can provide a lot of useful physiological and functional information that we haven’t had access to before,” he says.
Drugs such as cocaine can cause aneurysm-like bleeding and strokes, but the exact details of what happens to the brain’s blood vessels have remained elusive—partly because current imaging tools are limited in what they can see, Pan says. But using their new and improved methods, the team was able to observe exactly how cocaine affects the tiny blood vessels in a mouse’s brain. The images reveal that after 30 days of chronic cocaine injection or even after just repeated acute injection of cocaine, there’s a dramatic drop in blood flow speed. The researchers were, for the first time, able to identify cocaine-induced microischemia, when blood flow is shut down—a precursor to a stroke.
Measuring blood flow is crucial for understanding how the brain is working, whether you’re a brain surgeon or a neuroscientist studying how drugs or disease influence brain physiology, metabolism and function, Pan said. Techniques like functional magnetic resonance imaging (fMRI) provide a good overall map of the flow of deoxygenated blood, but they don’t have a high enough resolution to study what happens inside tiny blood vessels called capillaries. Meanwhile, other methods like two-photon microscopy, which tracks the movement of red blood cells labeled with fluorescent dyes, have a small field of view that only measures few vessels at a time rather than blood flow in the cerebrovascular networks.
In the last few years, researchers including Pan and his colleagues have developed another method called optical coherence Doppler tomography (ODT). In this technique, laser light hits the moving blood cells and bounces back. By measuring the shift in the reflected light’s frequency—the same Doppler effect that causes the rise or fall of a siren’s pitch as it moves toward or away from you—researchers can determine how fast the blood is flowing.
It turns out that ODT offers a wide field of view at high resolution. “To my knowledge, this is a unique technology that can do both,” Pan said. And, it doesn’t require fluorescent dyes, which can trigger harmful side effects in human patients or leave unwanted artifacts—from interactions with a drug being tested, for example—when used for imaging animal brains.
Two problems with conventional ODT right now, however, are that it’s only sensitive to a limited range in blood-flow speeds and not sensitive enough to detect slow capillary flows, Pan explained. The researchers’ new method described in today’s Biomedical Optics Express paper incorporates a new processing method called phase summation that extends the range and allows for imaging capillary flows.
Another limitation of conventional ODT is that it doesn’t work when the blood vessel is perpendicular to the incoming laser beam. In an image, the part of the vessel that’s perpendicular to the line of sight wouldn’t be visible, instead appearing dark. But by tracking the blood vessel as it slopes up or down near this dark spot, the researchers developed a way to use that information to interpolate the missing data more accurately.
ODT can only see down to 1-1.5 millimeters below the surface, so the method is limited to smaller animals if researchers want to probe into deeper parts of the brain. But, Pan says, it would still be useful when the brain’s exposed in the operating room, to help surgeons operate on tumors, for example.
The new method is best suited to look at small blood vessels and networks, so it can be used to image the capillaries in the eye as well. Bioengineers can also use it to monitor the growth of new blood vessels when engineering tissue, Pan said. Additionally, information about blood flow in the brain could also be applied to developing new treatment options for recovering drug addicts.
Stuck in neutral: brain defect traps schizophrenics in twilight zone
People with schizophrenia struggle to turn goals into actions because brain structures governing desire and emotion are less active and fail to pass goal-directed messages to cortical regions affecting human decision-making, new research reveals.
Published in Biological Psychiatry, the finding by a University of Sydney research team is the first to illustrate the inability to initiate goal-directed behaviour common in people with schizophrenia.
The finding may explain why people with schizophrenia have difficulty achieving real-world goals such as making friends, completing education and finding employment.
"The apparent lack of motivation in schizophrenic patients isn’t because they lack goals or don’t enjoy rewards and pleasure," says the University of Sydney’s Dr Richard Morris, the study’s lead author.
"They enjoy as many experiences as other people, including food, movies and scenes of natural beauty.
"What appears to block them are specific brain deficits that prevent them from converting their desires and goals into choices and behaviour."
Using a control group research design, the researchers used a two-prong approach to reveal how and why schizophrenics fail to convert their preferences into congruent choices.
First, using a series of experiments involving choosing between different snack food rewards, experimenters revealed that:
- schizophrenic subjects had a liking for snack foods equivalent to healthy adults
- when researchers reduced the value of one of the snacks, both subjects and healthy adults subsequently preferred different snacks, as expected
- surprisingly, schizophrenic subjects had major difficulty choosing their preferred snack when provided with a choice between their preferred snack and the devalued snack.
Second, researchers used functional magnetic resonance imaging (fMRI) to measures brain activity while study subjects performed learning tasks involving snack foods.
This technique relies on the fact that cerebral blood flow and neuronal activity are coupled. When an area of the brain is in use, bloodflow to that region increases, thereby indicating neural activity. This neural activity can be presented graphically by colour-coding the strength of activation across the brain or in specific brain regions. The technique can localise neural activity to within millimetres.
Functional MRI results revealed the following:
- schizophrenic subjects had normal neural activity in the brain region responsible for decision-making (prefrontal cortex)
- among schizophrenic subjects, brain regions responsible, in part, for controlling actions and choice (the caudate) had far lower neural activity than in healthy subjects
- lower neural activity in the caudate regions was correlated with the difficulty that schizophrenic subjects’ had applying their food preferences to obtain future snack foods.
"Pathology in the caudate and associated brain regions may prevent schizophrenic subjects from properly evaluating their desires then transmitting that information to guide their behavior," says Dr Morris.
"This means that desires and goals are intact in people with schizophrenia, however they have difficulty choosing the right course of action to achieve those goals.
"This failure to integrate desire with action means people with schizophrenia are stuck in limbo, wanting a normal life but unable to take the necessary steps to achieve it."
Schizophrenia affects one per cent of people worldwide, including in Australia.
However so-called “poor motivation” in schizophrenia is a major economic concern because it is not treated by current medicines, and often means patients fail to finish their education or hold a full-time job.
(Source: sydney.edu.au)
Sex-specific changes in cerebral blood flow begin at puberty
Puberty is the defining process of adolescent development, beginning a cascade of changes throughout the body, including the brain. Penn Medicine researchers have discovered that cerebral blood flow (CBF) levels decreased similarly in males and females before puberty, but saw them diverge sharply in puberty, with levels increasing in females while decreasing further in males, which could give hints as to developing differences in behavior in men and women and sex-specific pre-dispositions to certain psychiatric disorders. Their findings are available in Proceedings of the National Academy of Science (PNAS).
"These findings help us understand normal neurodevelopment and could be a step towards creating normal ‘growth charts’ for brain development in kids. These results also show what every parent knows: boys and girls grow differently. This applies to the brain as well," says Theodore D. Satterthwaite, MD, MA, assistant professor in the Department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. "Hopefully, one day such growth charts might allow us to identify abnormal brain development much earlier before it leads to major mental illness."
Studies on structural brain development have shown that puberty is an important source of sex differences. Previous work has shown that CBF declines throughout childhood, but the effects of puberty on properties of brain physiology such as CBF, also known as cerebral perfusion, are not well known. “We know that adult women have higher blood flow than men, but it was not clear when that difference began, so we hypothesized that the gap between women and men would begin in adolescence and coincide with puberty,” Satterthwaite says.
The Penn team imaged the brains of 922 youth ages 8 through 22 using arterial spin labeled (ASL) MRI. The youth were all members of the Philadelphia Neurodevelopmental Cohort, a National Institute of Mental Health-funded collaboration between the University of Pennsylvania Brain Behavior Laboratory and the Center for Applied Genomics at the Children’s Hospital of Philadelphia.
They found support for their hypothesis.
Age related differences were observed in the amount and location of blood flow in males versus females, with blood flow declining at a similar rate before puberty and diverging markedly in mid-puberty. At around age 16, while male CBF values continue to decline with advanced age, females CBF values actually increased. This resulted in females having notably higher CBF than males by the end of adolescence. The difference between males and females was most notable in parts of the brain that are critical for social behaviors and emotion regulation such as the orbitofrontal cortex. The researchers speculate that such differences could be related to females’ well-established superior performance on social cognition tasks. Potentially, these effects could also be related to the higher risk in women for depression and anxiety disorders, and higher risk of flat affect and schizophrenia in men.
(Source: eurekalert.org)
Imaging Study Examines Effect of Fructose on Brain Regions That Regulate Appetite
In a study examining possible factors regarding the associations between fructose consumption and weight gain, brain magnetic resonance imaging of study participants indicated that ingestion of glucose but not fructose reduced cerebral blood flow and activity in brain regions that regulate appetite, and ingestion of glucose but not fructose produced increased ratings of satiety and fullness, according to a preliminary study published in the January 2 issue of JAMA.
“Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety,” according to background information in the article. “Thus, fructose possibly increases food-seeking behavior and increases food intake.” How brain regions associated with fructose- and glucose-mediated changes in animal feeding behaviors translates to humans is not completely understood.
Kathleen A. Page, M.D., of Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to examine neurophysiological factors that might underlie associations between fructose consumption and weight gain. The study included 20 healthy adult volunteers who underwent two magnetic resonance imaging sessions in conjunction with fructose or glucose drink ingestion. The primary outcome measure for the study was the relative changes in hypothalamic (a region of the brain) regional cerebral blood flow (CBF) after glucose or fructose ingestion.
The researchers found that there was a significantly greater reduction in hypothalamic CBF after glucose vs. fructose ingestion. “Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula, and striatum—brain regions that regulate appetite, motivation, and reward processing; glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety.”
“The disparate responses to fructose were associated with reduced systemic levels of the satiety-signaling hormone insulin and were not likely attributable to an inability of fructose to cross the blood-brain barrier into the hypothalamus or to a lack of hypothalamic expression of genes necessary for fructose metabolism.”
(Image: iStockphoto)
Brazilian Mediums Shed Light on Brain Activity During a Trance State
Researchers at Thomas Jefferson University and the University of Sao Paulo in Brazil analyzed the cerebral blood flow (CBF) of Brazilian mediums during the practice of psychography, described as a form of writing whereby a deceased person or spirit is believed to write through the medium’s hand. The new research revealed intriguing findings of decreased brain activity during the mediums’ dissociative state which generated complex written content. Their findings appear in the November 16th edition of the online journal PLOS ONE.
The 10 mediums—five less expert and five experienced—were injected with a radioactive tracer to capture their brain activity during normal writing and during the practice of psychography which involves the subject entering a trance-like state. The subjects were scanned using SPECT (single photon emission computed tomography) to highlight the areas of the brain that are active and inactive during the practice.
The researchers found that the experienced psychographers showed lower levels of activity in the left hippocampus (limbic system), right superior temporal gyrus, and the frontal lobe regions of the left anterior cingulate and right precentral gyrus during psychography compared to their normal (non-trance) writing. The frontal lobe areas are associated with reasoning, planning, generating language, movement, and problem solving, perhaps reflecting an absence of focus, self-awareness and consciousness during psychography, the researchers hypothesize.
Less expert psychographers showed just the opposite—increased levels of CBF in the same frontal areas during psychography compared to normal writing. The difference was significant compared to the experienced mediums. This finding may be related to their more purposeful attempt at performing the psychography. The absence of current mental disorders in the groups is in line with current evidence that dissociative experiences are common in the general population and not necessarily related to mental disorders, especially in religious/spiritual groups. Further research should address criteria for distinguishing between healthy and pathological dissociative expressions in the scope of mediumship.
Stony Brook Researchers Develop Neuroimaging Technique Capturing Cocaine’s Devastating Effect on Brain Blood Flow
Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal’s October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.
In “Cocaine-induced cortical microischemia in the rodent brain: clinical implications,” the researchers discovered that cocaine administered in doses equivalent to those normally taken by abusers caused constriction in blood vessels that inhibited CBF for varying lengths of time. Brain arteries, veins, and even capillaries, the smallest vessels, were affected by the doses. CBF was markedly decreased within just two-to-three minutes after drug administration. In some vessels, a decrease in CBF reached 70 percent. Recovery time for the vessels varied. Cocaine interrupted CBF in some arteriolar branches for more than 45 minutes. This effect became more pronounced after repeated cocaine administration.
“Our study revealed evidence of cocaine-induced cerebral microischemic changes in multiple experimental models, and we were able to clearly image the process and vasoactive effects at a microvascular level,” said study Principal Investigator Yingtian Pan, PhD, Professor, Department of Biomedical Engineering, Stony Brook University. “These clinical changes jeopardize oxygen delivery to cerebral tissue making it vulnerable to ischemia and neuronal death.”