Neuroscience

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Posts tagged brain tissue

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MagLab MRI machine provides in-depth analysis of strokes New research conducted at the Florida State University-based National High Magnetic Field Laboratory has revealed a new, innovative way to classify the severity of a stroke, aid in diagnosis and evaluate potential treatments. “Stroke affects millions of adults and children worldwide,” said Sam Grant, MagLab researcher and associate professor of chemical and biomedical engineering at the FAMU-FSU College of Engineering. “This research offers a new technique for the chemical analysis of metabolites during stroke and a means of evaluating dynamic changes in cell processes and size in living tissue.” The research is detailed in two papers, “Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields,” in Nature Communications and “Metabolic T1 dynamics and longitudinal relaxation enhancement in vivo at ultrahigh magnetic fields on ischemia” in the Journal of Cerebral Blood Flow and Metabolism. The new technique is a way of narrowly applying energy to the metabolites of a specimen exposed to a very high magnetic field. Metabolites are the biological compounds used in the chemical process of breaking down food or other chemicals into energy and producing new materials. By selectively “exciting” these metabolites and analyzing their distribution and confinement in brain tissue, the research team can investigate the metabolic microenvironment and tell whether cells were shrinking or expanding, a critical tool to understanding the severity of stroke, Grant said. That information could help medical professionals better treat patients. “Strokes cause an interruption of blood and oxygen to flow to the brain,” explained Jens Rosenberg, another MagLab researcher and one of Grant’s co-authors. “Through this research, we can see how neurons and other neural cells respond to the disruption of blood flow after stroke and use that information to better understand the full impacts of stroke.”    The MagLab’s flagship 900 MHz Ultra Widebore NMR magnet system was a critical component to the research. Utilizing this powerful magnet, the research team, which included scientists from the Champaulimod Center in Portugal and the Weizmann Institute of Science in Israel, were able to acquire localized chemical signatures of metabolites from 125-microliter volumes within the brain with high sensitivity and fidelity in six seconds. Typical MRIs at hospitals or doctor’s offices measure around 1.5 – 3 tesla (the unit of magnetic field strength), while the 900 MHz measures a whopping 21.1 tesla, providing at least seven times the sensitivity. “This very high field coupled with the RF pulse sequence design by our collaborators and homebuilt RF probes offer a unique non-invasive way of evaluating stroke evolution and potential treatments,” Rosenberg said. The team also sees exciting possibilities to use this technique to further investigate debilitating diseases. “By evaluating spectral regions previously undetectable, we hope to fingerprint certain diseases, like ischemic stroke, so that we can identify new characteristics that are specific to pathological conditions at the metabolic level in vivo,” Grant said. “There is a lot of work to be done to identify these dynamic changes and decide when and how our treatments can be most effective.” Further research on metabolites using this technique could also be used for analysis of neurological disorders such as dementia, schizophrenia, Lou Gehrig’s, Parkinson’s, Alzheimer’s and Huntington’s diseases. (Image credit)

MagLab MRI machine provides in-depth analysis of strokes

New research conducted at the Florida State University-based National High Magnetic Field Laboratory has revealed a new, innovative way to classify the severity of a stroke, aid in diagnosis and evaluate potential treatments.

“Stroke affects millions of adults and children worldwide,” said Sam Grant, MagLab researcher and associate professor of chemical and biomedical engineering at the FAMU-FSU College of Engineering. “This research offers a new technique for the chemical analysis of metabolites during stroke and a means of evaluating dynamic changes in cell processes and size in living tissue.”

The research is detailed in two papers, “Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields,” in Nature Communications and “Metabolic T1 dynamics and longitudinal relaxation enhancement in vivo at ultrahigh magnetic fields on ischemia” in the Journal of Cerebral Blood Flow and Metabolism.

The new technique is a way of narrowly applying energy to the metabolites of a specimen exposed to a very high magnetic field. Metabolites are the biological compounds used in the chemical process of breaking down food or other chemicals into energy and producing new materials.

By selectively “exciting” these metabolites and analyzing their distribution and confinement in brain tissue, the research team can investigate the metabolic microenvironment and tell whether cells were shrinking or expanding, a critical tool to understanding the severity of stroke, Grant said.

That information could help medical professionals better treat patients.

“Strokes cause an interruption of blood and oxygen to flow to the brain,” explained Jens Rosenberg, another MagLab researcher and one of Grant’s co-authors. “Through this research, we can see how neurons and other neural cells respond to the disruption of blood flow after stroke and use that information to better understand the full impacts of stroke.”   

The MagLab’s flagship 900 MHz Ultra Widebore NMR magnet system was a critical component to the research. Utilizing this powerful magnet, the research team, which included scientists from the Champaulimod Center in Portugal and the Weizmann Institute of Science in Israel, were able to acquire localized chemical signatures of metabolites from 125-microliter volumes within the brain with high sensitivity and fidelity in six seconds.

Typical MRIs at hospitals or doctor’s offices measure around 1.5 – 3 tesla (the unit of magnetic field strength), while the 900 MHz measures a whopping 21.1 tesla, providing at least seven times the sensitivity.

“This very high field coupled with the RF pulse sequence design by our collaborators and homebuilt RF probes offer a unique non-invasive way of evaluating stroke evolution and potential treatments,” Rosenberg said.

The team also sees exciting possibilities to use this technique to further investigate debilitating diseases.

“By evaluating spectral regions previously undetectable, we hope to fingerprint certain diseases, like ischemic stroke, so that we can identify new characteristics that are specific to pathological conditions at the metabolic level in vivo,” Grant said. “There is a lot of work to be done to identify these dynamic changes and decide when and how our treatments can be most effective.”

Further research on metabolites using this technique could also be used for analysis of neurological disorders such as dementia, schizophrenia, Lou Gehrig’s, Parkinson’s, Alzheimer’s and Huntington’s diseases.

(Image credit)

Filed under stroke metabolites MRS brain tissue neurological disorders neuroscience science

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Modeling shockwaves through the brain Since the start of the military conflicts in Iraq and Afghanistan, more than 300,000 soldiers have returned to the United States with traumatic brain injury (TBI) caused by exposure to bomb blasts — and in particular, exposure to improvised explosive devices, or IEDs. Symptoms of traumatic brain injury can range from the mild, such as lingering headaches and nausea, to more severe impairments in memory and cognition. Since 2007, the U.S. Department of Defense has recognized the critical importance and complexity of this problem, and has made significant investments in traumatic brain injury research. Nevertheless, there remain many gaps in scientists’ understanding of the effects of blasts on the human brain; most new knowledge has come from experiments with animals. Now MIT researchers have developed a scaling law that predicts a human’s risk of brain injury, based on previous studies of blasts’ effects on animal brains. The method may help the military develop more protective helmets, as well as aid clinicians in diagnosing traumatic brain injury — often referred to as the “invisible wounds” of battle. “We’re really focusing on mild traumatic brain injury, where we know the least, but the problem is the largest,” says Raul Radovitzky, a professor of aeronautics and astronautics and associate director of the MIT Institute for Soldier Nanotechnologies (ISN). “It often remains undetected. And there’s wide consensus that this is clearly a big issue.” While previous scaling laws predicted that humans’ brains would be more resilient to blasts than animals’, Radovitzky’s team found the opposite: that in fact, humans are much more vulnerable, as they have thinner skulls to protect much larger brains. A group of ISN researchers led by Aurélie Jean, a postdoc in Radovitzky’s group, developed simulations of human, pig, and rat heads, and exposed each to blasts of different intensities. Their simulations predicted the effects of the blasts’ shockwaves as they propagated through the skulls and brains of each species. Based on the resulting differences in intracranial pressure, the team developed an equation, or scaling law, to estimate the risk of brain injury for each species. “The great thing about doing this on the computer is that it allows you to reduce and possibly eventually eliminate animal experiments,” Radovitzky says. The MIT team and co-author James Q. Zheng, chief scientist at the U.S. Army’s soldier protection and individual equipment program, detail their results this week in the Proceedings of the National Academy of Sciences. Air (through the) head A blast wave is the shockwave, or wall of compressed air, that rushes outward from the epicenter of an explosion. Aside from the physical fallout of shrapnel and other chemical elements, the blast wave alone can cause severe injuries to the lungs and brain. In the brain, a shockwave can slam through soft tissue, with potentially devastating effects. In 2010, Radovitzky’s group, working in concert with the Defense and Veterans Brain Injury Center, a part of the U.S. military health system, developed a highly sophisticated, image-based computational model of the human head that illustrates the ways in which pressurized air moves through its soft tissues. With this model, the researchers showed how the energy from a blast wave can easily reach the brain through openings such as the eyes and sinuses — and also how covering the face with a mask can prevent such injuries. Since then, the team has developed similar models for pigs and rats, capturing the mechanical response of brain tissue to shockwaves. In their current work, the researchers calculated the vulnerability of each species to brain injury by establishing a mathematical relationship between properties of the skull, brain, and surrounding flesh, and the propagation of incoming shockwaves. The group considered each brain structure’s volume, density, and celerity — how fast stress waves propagate through a tissue. They then simulated the brain’s response to blasts of different intensities. “What the simulation allows you to do is take what happens outside, which is the same across species, and look at how strong was the effect of the blast inside the brain,” Jean says. In general, they found that an animal’s skull and other fleshy structures act as a shield, blunting the effects of a blast wave: The thicker these structures are, the less vulnerable an animal is to injury. Compared with the more prominent skulls of rats and pigs, a human’s thinner skull increases the risk for traumatic brain injury. Shifting the problem This finding runs counter to previous theories, which held that an animal’s vulnerability to blasts depends on its overall mass, but which ignored the role of protective physical structures. According to these theories, humans, being more massive than pigs or rats, would be better protected against blast waves. Radovitzky says this reasoning stems from studies of “blast lung” — blast-induced injuries such as tearing, hemorrhaging, and swelling of the lungs, where it was found that mass matters: The larger an animal is, the more resilient it may be to lung damage. Informed by such studies, the military has since developed bulletproof vests that have dramatically decreased the number of blast-induced lung injuries in recent years. “There have essentially been no reported cases of blast lung in the last 10 years in Iraq or Afghanistan,” Radovitzky notes. “Now we’ve shifted that problem to traumatic brain injury.” In collaboration with Army colleagues, Radovitzky and his group are performing basic research to help the Army develop helmets that better protect soldiers. To this end, the team is extending the simulation approach they used for blast to other types of threats. His group is also collaborating with audiologists at Massachusetts General Hospital, where victims of the Boston Marathon bombing are being treated for ruptured eardrums. “They have an exact map of where each victim was, relative to the blast,” Radovitzky says. “In principle, we could simulate the event, find out the level of exposure of each of those victims, put it in our scaling law, and we could estimate their risk of developing a traumatic brain injury that may not be detected in an MRI.”  Joe Rosen, a professor of surgery at Dartmouth Medical School, sees the group’s scaling law as a promising window into identifying a long-sought mechanism for blast-induced traumatic brain injury.  “Eighty percent of the injuries coming off the battlefield are blast-induced, and mild TBIs may not have any evidence of injury, but they end up the rest of their lives impaired,” says Rosen, who was not involved in the research. “Maybe we can realize they’re getting doses of these blasts, and that a cumulative dose is what causes [TBI], and before that point, we can pull them off the field. I think this work will be important, because it puts a stake in the ground so we can start making some progress.”

Modeling shockwaves through the brain

Since the start of the military conflicts in Iraq and Afghanistan, more than 300,000 soldiers have returned to the United States with traumatic brain injury (TBI) caused by exposure to bomb blasts — and in particular, exposure to improvised explosive devices, or IEDs. Symptoms of traumatic brain injury can range from the mild, such as lingering headaches and nausea, to more severe impairments in memory and cognition.

Since 2007, the U.S. Department of Defense has recognized the critical importance and complexity of this problem, and has made significant investments in traumatic brain injury research. Nevertheless, there remain many gaps in scientists’ understanding of the effects of blasts on the human brain; most new knowledge has come from experiments with animals.

Now MIT researchers have developed a scaling law that predicts a human’s risk of brain injury, based on previous studies of blasts’ effects on animal brains. The method may help the military develop more protective helmets, as well as aid clinicians in diagnosing traumatic brain injury — often referred to as the “invisible wounds” of battle.

“We’re really focusing on mild traumatic brain injury, where we know the least, but the problem is the largest,” says Raul Radovitzky, a professor of aeronautics and astronautics and associate director of the MIT Institute for Soldier Nanotechnologies (ISN). “It often remains undetected. And there’s wide consensus that this is clearly a big issue.”

While previous scaling laws predicted that humans’ brains would be more resilient to blasts than animals’, Radovitzky’s team found the opposite: that in fact, humans are much more vulnerable, as they have thinner skulls to protect much larger brains.

A group of ISN researchers led by Aurélie Jean, a postdoc in Radovitzky’s group, developed simulations of human, pig, and rat heads, and exposed each to blasts of different intensities. Their simulations predicted the effects of the blasts’ shockwaves as they propagated through the skulls and brains of each species. Based on the resulting differences in intracranial pressure, the team developed an equation, or scaling law, to estimate the risk of brain injury for each species.

“The great thing about doing this on the computer is that it allows you to reduce and possibly eventually eliminate animal experiments,” Radovitzky says.

The MIT team and co-author James Q. Zheng, chief scientist at the U.S. Army’s soldier protection and individual equipment program, detail their results this week in the Proceedings of the National Academy of Sciences.

Air (through the) head

A blast wave is the shockwave, or wall of compressed air, that rushes outward from the epicenter of an explosion. Aside from the physical fallout of shrapnel and other chemical elements, the blast wave alone can cause severe injuries to the lungs and brain. In the brain, a shockwave can slam through soft tissue, with potentially devastating effects.

In 2010, Radovitzky’s group, working in concert with the Defense and Veterans Brain Injury Center, a part of the U.S. military health system, developed a highly sophisticated, image-based computational model of the human head that illustrates the ways in which pressurized air moves through its soft tissues. With this model, the researchers showed how the energy from a blast wave can easily reach the brain through openings such as the eyes and sinuses — and also how covering the face with a mask can prevent such injuries. Since then, the team has developed similar models for pigs and rats, capturing the mechanical response of brain tissue to shockwaves.

In their current work, the researchers calculated the vulnerability of each species to brain injury by establishing a mathematical relationship between properties of the skull, brain, and surrounding flesh, and the propagation of incoming shockwaves. The group considered each brain structure’s volume, density, and celerity — how fast stress waves propagate through a tissue. They then simulated the brain’s response to blasts of different intensities.

“What the simulation allows you to do is take what happens outside, which is the same across species, and look at how strong was the effect of the blast inside the brain,” Jean says.

In general, they found that an animal’s skull and other fleshy structures act as a shield, blunting the effects of a blast wave: The thicker these structures are, the less vulnerable an animal is to injury. Compared with the more prominent skulls of rats and pigs, a human’s thinner skull increases the risk for traumatic brain injury.

Shifting the problem

This finding runs counter to previous theories, which held that an animal’s vulnerability to blasts depends on its overall mass, but which ignored the role of protective physical structures. According to these theories, humans, being more massive than pigs or rats, would be better protected against blast waves.

Radovitzky says this reasoning stems from studies of “blast lung” — blast-induced injuries such as tearing, hemorrhaging, and swelling of the lungs, where it was found that mass matters: The larger an animal is, the more resilient it may be to lung damage. Informed by such studies, the military has since developed bulletproof vests that have dramatically decreased the number of blast-induced lung injuries in recent years.

“There have essentially been no reported cases of blast lung in the last 10 years in Iraq or Afghanistan,” Radovitzky notes. “Now we’ve shifted that problem to traumatic brain injury.”

In collaboration with Army colleagues, Radovitzky and his group are performing basic research to help the Army develop helmets that better protect soldiers. To this end, the team is extending the simulation approach they used for blast to other types of threats.

His group is also collaborating with audiologists at Massachusetts General Hospital, where victims of the Boston Marathon bombing are being treated for ruptured eardrums.

“They have an exact map of where each victim was, relative to the blast,” Radovitzky says. “In principle, we could simulate the event, find out the level of exposure of each of those victims, put it in our scaling law, and we could estimate their risk of developing a traumatic brain injury that may not be detected in an MRI.” 

Joe Rosen, a professor of surgery at Dartmouth Medical School, sees the group’s scaling law as a promising window into identifying a long-sought mechanism for blast-induced traumatic brain injury. 

“Eighty percent of the injuries coming off the battlefield are blast-induced, and mild TBIs may not have any evidence of injury, but they end up the rest of their lives impaired,” says Rosen, who was not involved in the research. “Maybe we can realize they’re getting doses of these blasts, and that a cumulative dose is what causes [TBI], and before that point, we can pull them off the field. I think this work will be important, because it puts a stake in the ground so we can start making some progress.”

Filed under brain injury TBI brain tissue neuroscience science

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Scientists track the rise and fall of brain volume throughout life We can witness our bodies mature, then gradually grow wrinkled and weaker with age, but it is only recently that scientists have been able to track a similar progression in the nerve bundles of our brains. That tissue increases in volume until around age 40, then slowly shrinks. By the end of our lives the tissue is about the volume of a 7-year-old. So finds a team of Stanford scientists who used a new magnetic resonance imaging technique to show, for the first time, how human brain tissue changes throughout life. Knowing what’s normal at different ages, doctors can now image a patient’s brain, compare it to this standard curve and be able to tell if a person is out of the normal range, much like the way a growth chart can help identify kids who have fallen below their growth curve. The researchers have already used the technique to identify previously overlooked changes in the brain of people with multiple sclerosis. "This allows us to look at people who have come into the clinic, compare them to the norm and potentially diagnose or monitor abnormalities due to different diseases or changes due to medications," said Jason Yeatman, a graduate student in psychology and first author on a paper published today in Nature Communications. Aviv Mezer, a research associate, was senior author on the paper. Both collaborated with Brian Wandell, a professor of psychology, and his team. For decades scientists have been able to image the brain using magnetic resonance imaging (MRI) and detect tumors, brain activity or abnormalities in people with some diseases, but those measurements were all subjective. A scientist measuring some aspect of the brain in one lab couldn’t directly compare findings with someone in another lab. And because no two scans could be compared, there was no way to look at a patient’s image and know whether it fell outside the normal range. Limitation overcome "A big problem in MRI is variation between instruments," Mezer said. Last year Mezer and Wandell led an interdisciplinary team to develop a technique that can be used to compare MRI scans quantitatively between labs, described in Nature Medicine. “Now with that method we found a way to measure the underlying tissue and not the instrumental bias. So that means that we can measure 100 subjects here and Jason can measure another 100 in Seattle (where he is now a postdoctoral fellow) and we can put them all in a database for the community.” The technique the team had developed measures the amount of white matter tissue in the brain. That amount of white matter comes primarily from an insulating covering called myelin that allows nerves to fire most efficiently and is a hallmark of brain maturation, though the white matter can also be composed of other types of cells in the brain. White matter plays a critical role in brain development and decline, and several diseases including schizophrenia and autism are associated with white matter abnormalities. Despite its importance in normal development and disease, no metric existed for determining whether any person’s white matter fell within a normal range, particularly if the people were imaged on different machines. Mezer and Yeatman decided to use the newly developed quantitative technique to develop a normal curve for white matter levels throughout life. They imaged 24 regions within the brains of 102 people ages 7 to 85, and from that established a set of curves showing the increase and then eventual decrease in white matter in each of the 24 regions throughout life. What they found is that the normal curve for brain composition is rainbow-shaped. It starts and ends with roughly the same amount of white matter and peaks between ages 30 and 50. But each of the 24 regions changes a different amount. Some parts of the brain, like those that control movement, are long, flat arcs, staying relatively stable throughout life. Others, like the areas involved in thinking and learning, are steep arches, maturing dramatically and then falling off quickly. (The group did point out that their samples started at age 7 and a lot of brain development had already occurred.) Continued collaboration "Regions of the brain supporting high-level cognitive functions develop longer and have more degradation," Yeatman said. "Understanding how that relates to cognition will be really important and interesting." Yeatman is now a postdoctoral scholar at the University of Washington, and Mezer is now an assistant professor at the Hebrew University of Jerusalem. They plan to continue collaborating with each other and with other members of the Wandell lab, looking at how brain composition correlates with learning and how it could be used to diagnose diseases, learning disabilities or mental health issues. The group has already shown that they can identify people with multiple sclerosis (MS) as falling outside the normal curve. People with MS develop what are known as lesions – regions in the brain or spinal cord where myelin is missing. In this paper, the team showed that they could identify people with MS as being off the normal curve throughout regions of the brain, including places where there are no visible lesions. This could provide an alternate method of monitoring and diagnosing MS, they say. Wandell has had a particular interest in studying the changes that happen in the brain as a child learns to read. Until now, if a family brought a child into the clinic with learning disabilities, Wandell and other scientists had no way to diagnose whether the child’s brain was developing normally, or to determine the relationship between learning delays and white matter abnormalities. "Now that we know what the normal distribution is, when a single person comes in you can ask how their child compares to the normal distribution. That’s where this is headed," said Wandell, who is also the Isaac and Madeline Stein Family professor and a Stanford Bio-X affiliate. Wandell runs the Center for Cognitive and Neurobiological Imaging (CNI), where Mezer and the team developed the MRI technique to quantify white matter, and where the scans for this study were conducted. The ability to share data among scientists is an issue Wandell has championed at the CNI and has been promoting in his work helping the Stanford Neurosciences Institute plan the computing strategy for their new facility. “Sharing of data and computational methods is critical for scientific progress,” Wandell said. In line with that goal, the new standard curve for white matter is something scientists around the world can use and contribute data to.

Scientists track the rise and fall of brain volume throughout life

We can witness our bodies mature, then gradually grow wrinkled and weaker with age, but it is only recently that scientists have been able to track a similar progression in the nerve bundles of our brains. That tissue increases in volume until around age 40, then slowly shrinks. By the end of our lives the tissue is about the volume of a 7-year-old.

So finds a team of Stanford scientists who used a new magnetic resonance imaging technique to show, for the first time, how human brain tissue changes throughout life. Knowing what’s normal at different ages, doctors can now image a patient’s brain, compare it to this standard curve and be able to tell if a person is out of the normal range, much like the way a growth chart can help identify kids who have fallen below their growth curve. The researchers have already used the technique to identify previously overlooked changes in the brain of people with multiple sclerosis.

"This allows us to look at people who have come into the clinic, compare them to the norm and potentially diagnose or monitor abnormalities due to different diseases or changes due to medications," said Jason Yeatman, a graduate student in psychology and first author on a paper published today in Nature Communications. Aviv Mezer, a research associate, was senior author on the paper. Both collaborated with Brian Wandell, a professor of psychology, and his team.

For decades scientists have been able to image the brain using magnetic resonance imaging (MRI) and detect tumors, brain activity or abnormalities in people with some diseases, but those measurements were all subjective. A scientist measuring some aspect of the brain in one lab couldn’t directly compare findings with someone in another lab. And because no two scans could be compared, there was no way to look at a patient’s image and know whether it fell outside the normal range.

Limitation overcome

"A big problem in MRI is variation between instruments," Mezer said. Last year Mezer and Wandell led an interdisciplinary team to develop a technique that can be used to compare MRI scans quantitatively between labs, described in Nature Medicine. “Now with that method we found a way to measure the underlying tissue and not the instrumental bias. So that means that we can measure 100 subjects here and Jason can measure another 100 in Seattle (where he is now a postdoctoral fellow) and we can put them all in a database for the community.”

The technique the team had developed measures the amount of white matter tissue in the brain. That amount of white matter comes primarily from an insulating covering called myelin that allows nerves to fire most efficiently and is a hallmark of brain maturation, though the white matter can also be composed of other types of cells in the brain.

White matter plays a critical role in brain development and decline, and several diseases including schizophrenia and autism are associated with white matter abnormalities. Despite its importance in normal development and disease, no metric existed for determining whether any person’s white matter fell within a normal range, particularly if the people were imaged on different machines.

Mezer and Yeatman decided to use the newly developed quantitative technique to develop a normal curve for white matter levels throughout life. They imaged 24 regions within the brains of 102 people ages 7 to 85, and from that established a set of curves showing the increase and then eventual decrease in white matter in each of the 24 regions throughout life.

What they found is that the normal curve for brain composition is rainbow-shaped. It starts and ends with roughly the same amount of white matter and peaks between ages 30 and 50. But each of the 24 regions changes a different amount. Some parts of the brain, like those that control movement, are long, flat arcs, staying relatively stable throughout life.

Others, like the areas involved in thinking and learning, are steep arches, maturing dramatically and then falling off quickly. (The group did point out that their samples started at age 7 and a lot of brain development had already occurred.)

Continued collaboration

"Regions of the brain supporting high-level cognitive functions develop longer and have more degradation," Yeatman said. "Understanding how that relates to cognition will be really important and interesting." Yeatman is now a postdoctoral scholar at the University of Washington, and Mezer is now an assistant professor at the Hebrew University of Jerusalem. They plan to continue collaborating with each other and with other members of the Wandell lab, looking at how brain composition correlates with learning and how it could be used to diagnose diseases, learning disabilities or mental health issues.

The group has already shown that they can identify people with multiple sclerosis (MS) as falling outside the normal curve. People with MS develop what are known as lesions – regions in the brain or spinal cord where myelin is missing. In this paper, the team showed that they could identify people with MS as being off the normal curve throughout regions of the brain, including places where there are no visible lesions. This could provide an alternate method of monitoring and diagnosing MS, they say.

Wandell has had a particular interest in studying the changes that happen in the brain as a child learns to read. Until now, if a family brought a child into the clinic with learning disabilities, Wandell and other scientists had no way to diagnose whether the child’s brain was developing normally, or to determine the relationship between learning delays and white matter abnormalities.

"Now that we know what the normal distribution is, when a single person comes in you can ask how their child compares to the normal distribution. That’s where this is headed," said Wandell, who is also the Isaac and Madeline Stein Family professor and a Stanford Bio-X affiliate. Wandell runs the Center for Cognitive and Neurobiological Imaging (CNI), where Mezer and the team developed the MRI technique to quantify white matter, and where the scans for this study were conducted.

The ability to share data among scientists is an issue Wandell has championed at the CNI and has been promoting in his work helping the Stanford Neurosciences Institute plan the computing strategy for their new facility. “Sharing of data and computational methods is critical for scientific progress,” Wandell said. In line with that goal, the new standard curve for white matter is something scientists around the world can use and contribute data to.

Filed under brain tissue brain volume MS white matter neuroimaging neuroscience science

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Bioengineers Create Functional 3D Brain-like Tissue

Bioengineers have created three-dimensional brain-like tissue that functions like and has structural features similar to tissue in the rat brain and that can be kept alive in the lab for more than two months.

As a first demonstration of its potential, researchers used the brain-like tissue to study chemical and electrical changes that occur immediately following traumatic brain injury and, in a separate experiment, changes that occur in response to a drug. The tissue could provide a superior model for studying normal brain function as well as injury and disease, and could assist in the development of new treatments for brain dysfunction.

The brain-like tissue was developed at the Tissue Engineering Resource Center at Tufts University, Boston, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) to establish innovative biomaterials and tissue engineering models. David Kaplan, Ph.D., Stern Family Professor of Engineering at Tufts University is director of the center and led the research efforts to develop the tissue.

Currently, scientists grow neurons in petri dishes to study their behavior in a controllable environment. Yet neurons grown in two dimensions are unable to replicate the complex structural organization of brain tissue, which consists of segregated regions of grey and white matter. In the brain, grey matter is comprised primarily of neuron cell bodies, while white matter is made up of bundles of axons, which are the projections neurons send out to connect with one another. Because brain injuries and diseases often affect these areas differently, models are needed that exhibit grey and white matter compartmentalization.

Recently, tissue engineers have attempted to grow neurons in 3D gel environments, where they can freely establish connections in all directions. Yet these gel-based tissue models don’t live long and fail to yield robust, tissue-level function. This is because the extracellular environment is a complex matrix in which local signals establish different neighborhoods that encourage distinct cell growth and/or development and function. Simply providing the space for neurons to grow in three dimensions is not sufficient.

Now, in the Aug. 11th early online edition of the journal Proceedings of the National Academy of Sciences, a group of bioengineers report that they have successfully created functional 3D brain-like tissue that exhibits grey-white matter compartmentalization and can survive in the lab for more than two months.

“This work is an exceptional feat,” said Rosemarie Hunziker, Ph.D., program director of Tissue Engineering at NIBIB. “It combines a deep understand of brain physiology with a large and growing suite of bioengineering tools to create an environment that is both necessary and sufficient to mimic brain function.”

The key to generating the brain-like tissue was the creation of a novel composite structure that consisted of two biomaterials with different physical properties: a spongy scaffold made out of silk protein and a softer, collagen-based gel. The scaffold served as a structure onto which neurons could anchor themselves, and the gel encouraged axons to grow through it.

To achieve grey-white matter compartmentalization, the researchers cut the spongy scaffold into a donut shape and populated it with rat neurons. They then filled the middle of the donut with the collagen-based gel, which subsequently permeated the scaffold. In just a few days, the neurons formed functional networks around the pores of the scaffold, and sent longer axon projections through the center gel to connect with neurons on the opposite side of the donut. The result was a distinct white matter region (containing mostly cellular projections, the axons) formed in the center of the donut that was separate from the surrounding grey matter (where the cell bodies were concentrated).

Over a period of several weeks, the researchers conducted experiments to determine the health and function of the neurons growing in their 3D brain-like tissue and to compare them with neurons grown in a collagen gel-only environment or in a 2D dish. The researchers found that the neurons in the 3D brain-like tissues had higher expression of genes involved in neuron growth and function. In addition, the neurons grown in the 3D brain-like tissue maintained stable metabolic activity for up to five weeks, while the health of neurons grown in the gel-only environment began to deteriorate within 24 hours. In regard to function, neurons in the 3D brain-like tissue exhibited electrical activity and responsiveness that mimic signals seen in the intact brain, including a typical electrophysiological response pattern to a neurotoxin.

Because the 3D brain-like tissue displays physical properties similar to rodent brain tissue, the researchers sought to determine whether they could use it to study traumatic brain injury. To simulate a traumatic brain injury, a weight was dropped onto the brain-like tissue from varying heights. The researchers then recorded changes in the neurons’ electrical and chemical activity, which proved similar to what is ordinarily observed in animal studies of traumatic brain injury.

Kaplan says the ability to study traumatic injury in a tissue model offers advantages over animal studies, in which measurements are delayed while the brain is being dissected and prepared for experiments. “With the system we have, you can essentially track the tissue response to traumatic brain injury in real time,” said Kaplan. “Most importantly, you can also start to track repair and what happens over longer periods of time.”

Kaplan emphasized the importance of the brain-like tissue’s longevity for studying other brain disorders. “The fact that we can maintain this tissue for months in the lab means we can start to look at neurological diseases in ways that you can’t otherwise because you need long timeframes to study some of the key brain diseases,” he said.

Hunziker added, “Good models enable solid hypotheses that can be thoroughly tested. The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction as well as offer a better way to study normal brain physiology.”

Kaplan and his team are looking into how they can make their tissue model more brain-like. In this recent report, the researchers demonstrated that they can modify their donut scaffold so that it consists of six concentric rings, each able to be populated with different types of neurons. Such an arrangement would mimic the six layers of the human brain cortex, in which different types of neurons exist.

As part of the funding agreement for the Tissue Engineering Resource Center, NIBIB requires that new technologies generated at the center be shared with the greater biomedical research community.

“We look forward to building collaborations with other labs that want to build on this tissue model,” said Kaplan.

Filed under brain tissue white matter gray matter brain function homeostasis neurons neuroscience science

158 notes

(Image caption: MRI scans showing brain damage in the stroke patients before treatment. Source: Stem Cells Translational Medicine.) Stem cells show promise for stroke in pilot study A stroke therapy using stem cells extracted from patients’ bone marrow has shown promising results in the first trial of its kind in humans. Five patients received the treatment in a pilot study conducted by doctors at Imperial College Healthcare NHS Trust and scientists at Imperial College London. The therapy was found to be safe, and all the patients showed improvements in clinical measures of disability. The findings are published in the journal Stem Cells Translational Medicine. It is the first UK human trial of a stem cell treatment for acute stroke to be published. The therapy uses a type of cell called CD34+ cells, a set of stem cells in the bone marrow that give rise to blood cells and blood vessel lining cells. Previous research has shown that treatment using these cells can significantly improve recovery from stroke in animals. Rather than developing into brain cells themselves, the cells are thought to release chemicals that trigger the growth of new brain tissue and new blood vessels in the area damaged by stroke. The patients were treated within seven days of a severe stroke, in contrast to several other stem cell trials, most of which have treated patients after six months or later. The Imperial researchers believe early treatment may improve the chances of a better recovery. A bone marrow sample was taken from each patient. The CD34+ cells were isolated from the sample and then infused into an artery that supplies the brain. No previous trial has selectively used CD34+ cells, so early after the stroke, until now. Although the trial was mainly designed to assess the safety and tolerability of the treatment, the patients all showed improvements in their condition in clinical tests over a six-month follow-up period. Four out of five patients had the most severe type of stroke: only four per cent of people who experience this kind of stroke are expected to be alive and independent six months later. In the trial, all four of these patients were alive and three were independent after six months. Dr Soma Banerjee, a lead author and Consultant in Stroke Medicine at Imperial College Healthcare NHS Trust, said: “This study showed that the treatment appears to be safe and that it’s feasible to treat patients early when they might be more likely to benefit. The improvements we saw in these patients are very encouraging, but it’s too early to draw definitive conclusions about the effectiveness of the therapy. We need to do more tests to work out the best dose and timescale for treatment before starting larger trials.” Over 150,000 people have a stroke in England every year. Survivors can be affected by a wide range of mental and physical symptoms, and many never recover their independence. Stem cell therapy is seen as an exciting new potential avenue of treatment for stroke, but its exact role is yet to be clearly defined. Dr Paul Bentley, also a lead author of the study, from the Department of Medicine at Imperial College London, said: “This is the first trial to isolate stem cells from human bone marrow and inject them directly into the damaged brain area using keyhole techniques. Our group are currently looking at new brain scanning techniques to monitor the effects of cells once they have been injected.” Professor Nagy Habib, Principal Investigator of the study, from the Department of Surgery and Cancer at Imperial College London, said: “These are early but exciting data worth pursuing. Scientific evidence from our lab further supports the clinical findings and our aim is to develop a drug, based on the factors secreted by stem cells, that could be stored in the hospital pharmacy so that it is administered to the patient immediately following the diagnosis of stroke in the emergency room. This may diminish the minimum time to therapy and therefore optimise outcome. Now the hard work starts to raise funds for this exciting research.”

(Image caption: MRI scans showing brain damage in the stroke patients before treatment. Source: Stem Cells Translational Medicine.)

Stem cells show promise for stroke in pilot study

A stroke therapy using stem cells extracted from patients’ bone marrow has shown promising results in the first trial of its kind in humans.

Five patients received the treatment in a pilot study conducted by doctors at Imperial College Healthcare NHS Trust and scientists at Imperial College London.

The therapy was found to be safe, and all the patients showed improvements in clinical measures of disability.

The findings are published in the journal Stem Cells Translational Medicine. It is the first UK human trial of a stem cell treatment for acute stroke to be published.

The therapy uses a type of cell called CD34+ cells, a set of stem cells in the bone marrow that give rise to blood cells and blood vessel lining cells. Previous research has shown that treatment using these cells can significantly improve recovery from stroke in animals. Rather than developing into brain cells themselves, the cells are thought to release chemicals that trigger the growth of new brain tissue and new blood vessels in the area damaged by stroke.

The patients were treated within seven days of a severe stroke, in contrast to several other stem cell trials, most of which have treated patients after six months or later. The Imperial researchers believe early treatment may improve the chances of a better recovery.

A bone marrow sample was taken from each patient. The CD34+ cells were isolated from the sample and then infused into an artery that supplies the brain. No previous trial has selectively used CD34+ cells, so early after the stroke, until now.

Although the trial was mainly designed to assess the safety and tolerability of the treatment, the patients all showed improvements in their condition in clinical tests over a six-month follow-up period.

Four out of five patients had the most severe type of stroke: only four per cent of people who experience this kind of stroke are expected to be alive and independent six months later. In the trial, all four of these patients were alive and three were independent after six months.

Dr Soma Banerjee, a lead author and Consultant in Stroke Medicine at Imperial College Healthcare NHS Trust, said: “This study showed that the treatment appears to be safe and that it’s feasible to treat patients early when they might be more likely to benefit. The improvements we saw in these patients are very encouraging, but it’s too early to draw definitive conclusions about the effectiveness of the therapy. We need to do more tests to work out the best dose and timescale for treatment before starting larger trials.”

Over 150,000 people have a stroke in England every year. Survivors can be affected by a wide range of mental and physical symptoms, and many never recover their independence.

Stem cell therapy is seen as an exciting new potential avenue of treatment for stroke, but its exact role is yet to be clearly defined.

Dr Paul Bentley, also a lead author of the study, from the Department of Medicine at Imperial College London, said: “This is the first trial to isolate stem cells from human bone marrow and inject them directly into the damaged brain area using keyhole techniques. Our group are currently looking at new brain scanning techniques to monitor the effects of cells once they have been injected.”

Professor Nagy Habib, Principal Investigator of the study, from the Department of Surgery and Cancer at Imperial College London, said: “These are early but exciting data worth pursuing. Scientific evidence from our lab further supports the clinical findings and our aim is to develop a drug, based on the factors secreted by stem cells, that could be stored in the hospital pharmacy so that it is administered to the patient immediately following the diagnosis of stroke in the emergency room. This may diminish the minimum time to therapy and therefore optimise outcome. Now the hard work starts to raise funds for this exciting research.”

Filed under stem cells stroke CD34+ brain tissue medicine neuroscience science

169 notes

Study shows how brain tumor cells move and damage tissue, points to possible therapy Researchers at the University of Alabama at Birmingham have shed new light on how cells called gliomas migrate in the brain and cause devastating tumors. The findings, published June 19, 2014 in Nature Communications, show that gliomas — malignant glial cells — disrupt normal neural connections and hijack control of blood vessels. The study provides insight into the mechanisms of how glioma cells spread throughout the brain as a devastating form of brain cancer, and potentially offers a tantalizing opportunity for therapy. A hallmark of gliomas is that the cells can migrate away from a central tumor, invading healthy brain tissue. Even if a tumor mass is surgically removed, malignant cells that have migrated are left behind, and can grow into a new tumor. To grow, glioma cells need access to nutrients in the blood supply, and it is known that gliomas travel along blood vessels within the brain. Now, researchers in the lab of neuroscientist Harald Sontheimer, Ph.D., professor in the UAB Department of Neurobiology, have discovered that, as they move, gliomas dislodge astrocytic endfeet, which play a critical role in regulating blood flow in the brain. Astrocytes are star-shaped cells in the brain that surround blood vessels and connect to them through projections called endfeet, which extend from the astrocyte and latch onto the vessel wall. The surface of nearly every blood vessel in the brain is covered by endfeet, which regulate the smooth muscle cells on the walls of blood vessels. Through that connection, instructions can be given to the muscle cells to constrict the blood vessel and limit blood flow, or dilate the vessel and increase blood flow. Sontheimer, director of the UAB Center for Glial Biology in Medicine, says that, as a person performs different neurological functions, blood flow needs to be increased to the areas responsible for that function and correspondingly decreased in other areas to maintain balance. The arrival of a glioma cell changes all that. “Glioma cells traveling along blood vessels literally cut the connection of astrocytic endfeet with the vessels and push them out of the way,” said Sontheimer. “By disrupting this important neural connection, adverse cognitive effects could be expected. Additionally, our study showed that gliomas then take control of the blood vessels for their own ends. And those ends are primarily to obtain nutrients from blood so that they can continue to grow and spread.” Sontheimer’s team says the glioma cells tend to congregate at blood vessel junctions, almost as if camping alongside a stream where it joins a river. The ready supply of nutrients would allow the cell to grow into a larger tumor mass. By traveling on the outside of a blood vessel, glioma cells are able to access nutrients from the blood stream. As a side effect to that process, they damage the blood brain barrier. The barrier, a layer of endothelial cells, protects the brain by restricting passage of harmful substances from the blood stream into brain tissue. “We found that, when gliomas push away the astrocytic endfeet, damage occurs to the integrity of the endothelial cells that make up the blood brain barrier,” said Stefanie Robel, Ph.D., a postdoctoral researcher in Sontheimer’s lab and co-first author of the study. “The barrier becomes weakened, and begins to leak. A leak across the barrier can cause severe damage to brain tissue.” “That leakage appears to be a consequence of glioma cells’ migrating along the blood vessels in their search for nutrients,” said Stacey Watkins, an M.D./Ph.D. student in Sontheimer’s lab and co-first author. “When glioma cells contact the vessels, they have direct access to nutrients.” But amid the deleterious effects that Sontheimer’s team observed — shearing away the endfeet from their blood vessels, disrupting normal brain activity, hijacking control of blood vessels and causing leaks in the blood brain barrier — he says there may be a silver lining. The idea that gliomas cause the blood brain barrier to become porous and leak might open up a new avenue to kill the malignant cells as they migrate. Chemotherapy, usually delivered intravenously, is not considered an effective strategy for killing gliomas. Chemotherapeutic agents are very effective in killing cancer cells elsewhere in the body, but the predominant belief is that such drugs will not pass the blood brain barrier and thus will not reach their target. “Chemotherapy is typically not tried in cases of glioma until after other therapies such as surgery and radiation have been employed,” Sontheimer said. “Our findings, which suggest that gliomas actually weaken the blood brain barrier and cause leakage, might indicate that high-dose, intravenous chemotherapy used early on following a diagnosis of brain cancer would be beneficial.” The study, funded by the National Institutes of Health and the American Brain Tumor Association, was conducted on a clinically relevant mouse model of human malignant glioma. Sontheimer says logical next steps would be to further examine the cognitive impact of severing the astrocytic endfeet connection to blood vessels.

Study shows how brain tumor cells move and damage tissue, points to possible therapy

Researchers at the University of Alabama at Birmingham have shed new light on how cells called gliomas migrate in the brain and cause devastating tumors. The findings, published June 19, 2014 in Nature Communications, show that gliomas — malignant glial cells — disrupt normal neural connections and hijack control of blood vessels.

The study provides insight into the mechanisms of how glioma cells spread throughout the brain as a devastating form of brain cancer, and potentially offers a tantalizing opportunity for therapy.

A hallmark of gliomas is that the cells can migrate away from a central tumor, invading healthy brain tissue. Even if a tumor mass is surgically removed, malignant cells that have migrated are left behind, and can grow into a new tumor.

To grow, glioma cells need access to nutrients in the blood supply, and it is known that gliomas travel along blood vessels within the brain. Now, researchers in the lab of neuroscientist Harald Sontheimer, Ph.D., professor in the UAB Department of Neurobiology, have discovered that, as they move, gliomas dislodge astrocytic endfeet, which play a critical role in regulating blood flow in the brain.

Astrocytes are star-shaped cells in the brain that surround blood vessels and connect to them through projections called endfeet, which extend from the astrocyte and latch onto the vessel wall. The surface of nearly every blood vessel in the brain is covered by endfeet, which regulate the smooth muscle cells on the walls of blood vessels. Through that connection, instructions can be given to the muscle cells to constrict the blood vessel and limit blood flow, or dilate the vessel and increase blood flow.

Sontheimer, director of the UAB Center for Glial Biology in Medicine, says that, as a person performs different neurological functions, blood flow needs to be increased to the areas responsible for that function and correspondingly decreased in other areas to maintain balance.

The arrival of a glioma cell changes all that.

“Glioma cells traveling along blood vessels literally cut the connection of astrocytic endfeet with the vessels and push them out of the way,” said Sontheimer. “By disrupting this important neural connection, adverse cognitive effects could be expected. Additionally, our study showed that gliomas then take control of the blood vessels for their own ends. And those ends are primarily to obtain nutrients from blood so that they can continue to grow and spread.”

Sontheimer’s team says the glioma cells tend to congregate at blood vessel junctions, almost as if camping alongside a stream where it joins a river. The ready supply of nutrients would allow the cell to grow into a larger tumor mass.

By traveling on the outside of a blood vessel, glioma cells are able to access nutrients from the blood stream. As a side effect to that process, they damage the blood brain barrier. The barrier, a layer of endothelial cells, protects the brain by restricting passage of harmful substances from the blood stream into brain tissue.

“We found that, when gliomas push away the astrocytic endfeet, damage occurs to the integrity of the endothelial cells that make up the blood brain barrier,” said Stefanie Robel, Ph.D., a postdoctoral researcher in Sontheimer’s lab and co-first author of the study. “The barrier becomes weakened, and begins to leak. A leak across the barrier can cause severe damage to brain tissue.”

“That leakage appears to be a consequence of glioma cells’ migrating along the blood vessels in their search for nutrients,” said Stacey Watkins, an M.D./Ph.D. student in Sontheimer’s lab and co-first author. “When glioma cells contact the vessels, they have direct access to nutrients.”

But amid the deleterious effects that Sontheimer’s team observed — shearing away the endfeet from their blood vessels, disrupting normal brain activity, hijacking control of blood vessels and causing leaks in the blood brain barrier — he says there may be a silver lining. The idea that gliomas cause the blood brain barrier to become porous and leak might open up a new avenue to kill the malignant cells as they migrate.

Chemotherapy, usually delivered intravenously, is not considered an effective strategy for killing gliomas. Chemotherapeutic agents are very effective in killing cancer cells elsewhere in the body, but the predominant belief is that such drugs will not pass the blood brain barrier and thus will not reach their target.

“Chemotherapy is typically not tried in cases of glioma until after other therapies such as surgery and radiation have been employed,” Sontheimer said. “Our findings, which suggest that gliomas actually weaken the blood brain barrier and cause leakage, might indicate that high-dose, intravenous chemotherapy used early on following a diagnosis of brain cancer would be beneficial.”

The study, funded by the National Institutes of Health and the American Brain Tumor Association, was conducted on a clinically relevant mouse model of human malignant glioma.

Sontheimer says logical next steps would be to further examine the cognitive impact of severing the astrocytic endfeet connection to blood vessels.

Filed under glioma brain tumours glial cells brain tissue blood vessels neuroscience science

194 notes

Optical brain scanner goes where other brain scanners can’t Scientists have advanced a brain-scanning technology that tracks what the brain is doing by shining dozens of tiny LED lights on the head. This new generation of neuroimaging compares favorably to other approaches but avoids the radiation exposure and bulky magnets the others require, according to new research at Washington University School of Medicine in St. Louis. The new optical approach to brain scanning is ideally suited for children and for patients with electronic implants, such as pacemakers, cochlear implants and deep brain stimulators (used to treat Parkinson’s disease). The magnetic fields in magnetic resonance imaging (MRI) often disrupt either the function or safety of implanted electrical devices, whereas there is no interference with the optical technique. The new technology is called diffuse optical tomography (DOT). While researchers have been developing it for more than 10 years, the method had been limited to small regions of the brain. The new DOT instrument covers two-thirds of the head and for the first time can image brain processes taking place in multiple regions and brain networks such as those involved in language processing and self-reflection (daydreaming). The results are now available online in Nature Photonics. “When the neuronal activity of a region in the brain increases, highly oxygenated blood flows to the parts of the brain doing more work, and we can detect that,” said senior author Joseph Culver, PhD, associate professor of radiology. “It’s roughly akin to spotting the rush of blood to someone’s cheeks when they blush.” The technique works by detecting light transmitted through the head and capturing the dynamic changes in the colors of the brain tissue.  Although DOT technology now is used in research settings, it has the potential to be helpful in many medical scenarios as a surrogate for functional MRI, the most commonly used imaging method for mapping human brain function. Functional MRI also tracks activity in the brain via changes in blood flow. In addition to greatly adding to our understanding of the human brain, fMRI is used to diagnose and monitor brain disease and therapy. Another commonly used method for mapping brain function is positron emission tomography (PET), which involves radiation exposure. Because DOT technology does not use radiation, multiple scans performed over time could be used to monitor the progress of patients treated for brain injuries, developmental disorders such as autism, neurodegenerative disorders such as Parkinson’s, and other diseases. Unlike fMRI and PET, DOT technology is designed to be portable, so it could be used at a patient’s beside or in the operating room. “With the new improvements in image quality, DOT is moving significantly closer to the resolution and positional accuracy of fMRI,” said first author Adam T. Eggebrecht, PhD, a postdoctoral research fellow. “That means DOT can be used as a stronger surrogate in situations where fMRI cannot be used.” The researchers have many ideas for applying DOT, including learning more about how deep brain stimulation helps Parkinson’s patients, imaging the brain during social interactions, and studying what happens to the brain during general anesthesia and when the heart is temporarily stopped during cardiac surgery. For the current study, the researchers validated the performance of DOT by comparing its results to fMRI scans. Data was collected using the same subjects, and the DOT and fMRI images were aligned. They looked for Broca’s area, a key area of the frontal lobe used for language and speech production. The overlap between the brain region identified as Broca’s area by DOT data and by fMRI scans was about 75 percent. In a second set of tests, researchers used DOT and fMRI to detect brain networks that are active when subjects are resting or daydreaming. Researchers’ interests in these networks have grown enormously over the past decade as the networks have been tied to many different aspects of brain health and sickness, such as schizophrenia, autism and Alzheimer’s disease. In these studies, the DOT data also showed remarkable similarity to fMRI — picking out the same cluster of three regions in both hemispheres. “With the improved image quality of the new DOT system, we are getting much closer to the accuracy of fMRI,” Culver said. “We’ve achieved a level of detail that, going forward, could make optical neuroimaging much more useful in research and the clinic.” While DOT doesn’t let scientists peer very deeply into the brain, researchers can get reliable data to a depth of about one centimeter of tissue. That centimeter contains some of the brain’s most important and interesting areas with many higher brain functions, such as memory, language and self-awareness represented. During DOT scans, the subject wears a cap composed of many light sources and sensors connected to cables. The full-scale DOT unit takes up an area slightly larger than an old-fashioned phone booth, but Culver and his colleagues have built versions of the scanner mounted on wheeled carts. They continue to work to make the technology more portable.

Optical brain scanner goes where other brain scanners can’t

Scientists have advanced a brain-scanning technology that tracks what the brain is doing by shining dozens of tiny LED lights on the head. This new generation of neuroimaging compares favorably to other approaches but avoids the radiation exposure and bulky magnets the others require, according to new research at Washington University School of Medicine in St. Louis.

The new optical approach to brain scanning is ideally suited for children and for patients with electronic implants, such as pacemakers, cochlear implants and deep brain stimulators (used to treat Parkinson’s disease). The magnetic fields in magnetic resonance imaging (MRI) often disrupt either the function or safety of implanted electrical devices, whereas there is no interference with the optical technique.

The new technology is called diffuse optical tomography (DOT). While researchers have been developing it for more than 10 years, the method had been limited to small regions of the brain. The new DOT instrument covers two-thirds of the head and for the first time can image brain processes taking place in multiple regions and brain networks such as those involved in language processing and self-reflection (daydreaming).

The results are now available online in Nature Photonics.

“When the neuronal activity of a region in the brain increases, highly oxygenated blood flows to the parts of the brain doing more work, and we can detect that,” said senior author Joseph Culver, PhD, associate professor of radiology. “It’s roughly akin to spotting the rush of blood to someone’s cheeks when they blush.”

The technique works by detecting light transmitted through the head and capturing the dynamic changes in the colors of the brain tissue. 

Although DOT technology now is used in research settings, it has the potential to be helpful in many medical scenarios as a surrogate for functional MRI, the most commonly used imaging method for mapping human brain function. Functional MRI also tracks activity in the brain via changes in blood flow. In addition to greatly adding to our understanding of the human brain, fMRI is used to diagnose and monitor brain disease and therapy.

Another commonly used method for mapping brain function is positron emission tomography (PET), which involves radiation exposure. Because DOT technology does not use radiation, multiple scans performed over time could be used to monitor the progress of patients treated for brain injuries, developmental disorders such as autism, neurodegenerative disorders such as Parkinson’s, and other diseases.

Unlike fMRI and PET, DOT technology is designed to be portable, so it could be used at a patient’s beside or in the operating room.

“With the new improvements in image quality, DOT is moving significantly closer to the resolution and positional accuracy of fMRI,” said first author Adam T. Eggebrecht, PhD, a postdoctoral research fellow. “That means DOT can be used as a stronger surrogate in situations where fMRI cannot be used.”

The researchers have many ideas for applying DOT, including learning more about how deep brain stimulation helps Parkinson’s patients, imaging the brain during social interactions, and studying what happens to the brain during general anesthesia and when the heart is temporarily stopped during cardiac surgery.

For the current study, the researchers validated the performance of DOT by comparing its results to fMRI scans. Data was collected using the same subjects, and the DOT and fMRI images were aligned. They looked for Broca’s area, a key area of the frontal lobe used for language and speech production. The overlap between the brain region identified as Broca’s area by DOT data and by fMRI scans was about 75 percent.

In a second set of tests, researchers used DOT and fMRI to detect brain networks that are active when subjects are resting or daydreaming. Researchers’ interests in these networks have grown enormously over the past decade as the networks have been tied to many different aspects of brain health and sickness, such as schizophrenia, autism and Alzheimer’s disease. In these studies, the DOT data also showed remarkable similarity to fMRI — picking out the same cluster of three regions in both hemispheres.

“With the improved image quality of the new DOT system, we are getting much closer to the accuracy of fMRI,” Culver said. “We’ve achieved a level of detail that, going forward, could make optical neuroimaging much more useful in research and the clinic.”

While DOT doesn’t let scientists peer very deeply into the brain, researchers can get reliable data to a depth of about one centimeter of tissue. That centimeter contains some of the brain’s most important and interesting areas with many higher brain functions, such as memory, language and self-awareness represented.

During DOT scans, the subject wears a cap composed of many light sources and sensors connected to cables. The full-scale DOT unit takes up an area slightly larger than an old-fashioned phone booth, but Culver and his colleagues have built versions of the scanner mounted on wheeled carts. They continue to work to make the technology more portable.

Filed under brain scans diffuse optical tomography neuroimaging brain tissue neuroscience science

142 notes

Study helps explain why MS is more common in women

A newly identified difference between the brains of women and men with multiple sclerosis (MS) may help explain why so many more women than men get the disease, researchers at Washington University School of Medicine in St. Louis report.

In recent years, the diagnosis of MS has increased more rapidly among women, who get the disorder nearly four times more than men. The reasons are unclear, but the new study is the first to associate a sex difference in the brain with MS.

image

(Image caption: An image of tissue from a female brain (left) affected by multiple sclerosis (MS) shows that the brain has much higher levels of a blood vessel receptor (shown in red) than a male brain affected by MS (right). The difference could help explain why so many more women get MS. Credit: Robyn Klein)

The findings appear May 8 in The Journal of Clinical Investigation.

Studying mice and people, the researchers found that females susceptible to MS produce higher levels of a blood vessel receptor protein, S1PR2, than males and that the protein is present at even higher levels in the brain areas that MS typically damages.

“It was a ‘Bingo!’ moment – our genetic studies led us right to this receptor,” said senior author Robyn Klein, MD, PhD. “When we looked at its function in mice, we found that it can determine whether immune cells cross blood vessels into the brain. These cells cause the inflammation that leads to MS.”

An investigational MS drug currently in clinical trials blocks other receptors in the same protein family but does not affect S1PR2. Klein recommended that researchers work to develop a drug that disables S1PR2.

MS is highly unpredictable, flaring and fading at irregular intervals and producing a hodgepodge of symptoms that includes problems with mobility, vision, strength and balance. More than 2 million people worldwide have the condition.

In MS, inflammation caused by misdirected immune cells damages a protective coating that surrounds the branches of nerve cells in the brain and spinal column. This leads the branches to malfunction and sometimes causes them to wither away, disrupting nerve cell communication necessary for normal brain functions such as movement and coordination.

For the new research, Klein studied a mouse model of MS in which the females get the disease more often than the males. The scientists compared levels of gene activity in male and female brains. They also looked at gene activity in the regions of the female brain that MS damages and in other regions the disorder typically does not harm.

They identified 20 genes that were active at different levels in vulnerable female brain regions. Scientists don’t know what 16 of these genes do. Among the remaining genes, the increased activity of S1PR2 stood out because researchers knew from previous studies that the protein regulates how easy it is for cells and molecules to pass through the walls of blood vessels.

Additional experiments showed that S1PR2 opens up the blood-brain barrier, a structure in the brain’s blood vessels that tightly regulates the materials that cross into the brain and spinal fluid. This barrier normally blocks potentially harmful substances from entering the brain. Opening it up likely allows the inflammatory cells that cause MS to get into the central nervous system.

When the researchers tested brain tissue samples obtained from 20 patients after death, they found more S1PR2 in MS patients’ brains than in people without the disorder. Brain tissue from females also had higher levels of S1PR2 than male brain tissue. The highest levels of S1PR2 were found in the brains of two female patients whose symptoms flared and faded irregularly, a pattern scientists call relapsing and remitting MS.

Klein is collaborating with chemists to design a tracer that will allow scientists to monitor S1PR2 levels in the brains of people while they are living. She hopes this will lead to a fuller understanding of how S1PR2 contributes to MS.

“This is an exciting first step in resolving the mystery of why MS rates are dramatically higher in women and in finding better ways to reduce the incidence of this disorder and control symptoms,” said Klein, associate professor of medicine. Klein also is an associate professor of pathology and immunology and of neurobiology and anatomy.

(Source: news.wustl.edu)

Filed under MS sex differences S1PR2 immune cells blood-brain barrier brain tissue neuroscience science

96 notes

Study IDs new cause of brain bleeding immediately after stroke By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced brain damage. A complex and devastating neurological condition, stroke is the fourth-leading cause of death and primary reason for disability in the U.S. The blood-brain barrier is severely damaged in a stroke and lets blood-borne material into the brain, causing the permanent deficits in movement and cognition seen in stroke patients. Dritan Agalliu, assistant professor of developmental & cell biology at UC Irvine, and Axel Nimmerjahn of the Salk Institute for Biological Studies developed a novel transgenic mouse strain in which they use a fluorescent tag to see the tight, barrier-forming junctions between the cells that make up blood vessels in the central nervous system. This allows them to perceive dynamic changes in the barrier during and after strokes in living animals. While observing that barrier function is rapidly impaired after a stroke (within six hours), they unexpectedly found that this early barrier failure is not due to the breakdown of tight junctions between blood vessel cells, as had previously been suspected. In fact, junction deterioration did not occur until two days after the event. Instead, the scientists reported dramatic increases in carrier proteins called serum albumin flowing directly into brain tissue. These proteins travel through the cells composing blood vessels – endothelial cells – via a specialized transport system that normally operates only in non-brain vessels or immature vessels within the central nervous system. The researchers’ work indicates that this transport system underlies the initial failure of the barrier, permitting entry of blood material into the brain immediately after a stroke (within six hours). “These findings suggest new therapeutic directions aimed at regulating flow through endothelial cells in the barrier after a stroke occurs,” Agalliu said, “and any such therapies have the potential to reduce or prevent stroke-induced damage in the brain.” His team is currently using genetic techniques to block degradation of the tight junctions between endothelial cells in mice and examining the effect on stroke progression. Early post-stroke control of this specialized transport system identified by the Agalliu and Nimmerjahn labs may spur the discovery of imaging methods or biomarkers in humans to detect strokes as early as possible and thereby minimize damage.

Study IDs new cause of brain bleeding immediately after stroke

By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced brain damage.

A complex and devastating neurological condition, stroke is the fourth-leading cause of death and primary reason for disability in the U.S. The blood-brain barrier is severely damaged in a stroke and lets blood-borne material into the brain, causing the permanent deficits in movement and cognition seen in stroke patients.

Dritan Agalliu, assistant professor of developmental & cell biology at UC Irvine, and Axel Nimmerjahn of the Salk Institute for Biological Studies developed a novel transgenic mouse strain in which they use a fluorescent tag to see the tight, barrier-forming junctions between the cells that make up blood vessels in the central nervous system. This allows them to perceive dynamic changes in the barrier during and after strokes in living animals.

While observing that barrier function is rapidly impaired after a stroke (within six hours), they unexpectedly found that this early barrier failure is not due to the breakdown of tight junctions between blood vessel cells, as had previously been suspected. In fact, junction deterioration did not occur until two days after the event.

Instead, the scientists reported dramatic increases in carrier proteins called serum albumin flowing directly into brain tissue. These proteins travel through the cells composing blood vessels – endothelial cells – via a specialized transport system that normally operates only in non-brain vessels or immature vessels within the central nervous system. The researchers’ work indicates that this transport system underlies the initial failure of the barrier, permitting entry of blood material into the brain immediately after a stroke (within six hours).

“These findings suggest new therapeutic directions aimed at regulating flow through endothelial cells in the barrier after a stroke occurs,” Agalliu said, “and any such therapies have the potential to reduce or prevent stroke-induced damage in the brain.”

His team is currently using genetic techniques to block degradation of the tight junctions between endothelial cells in mice and examining the effect on stroke progression. Early post-stroke control of this specialized transport system identified by the Agalliu and Nimmerjahn labs may spur the discovery of imaging methods or biomarkers in humans to detect strokes as early as possible and thereby minimize damage.

Filed under stroke blood-brain barrier brain damage endothelial cells brain tissue neuroscience science

189 notes

Halting Immune Response Could Save Brain Cells After Stroke

A new study in animals shows that using a compound to block the body’s immune response greatly reduces disability after a stroke.

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The study by scientists from the University of Wisconsin School of Medicine and Public Health also showed that particular immune cells – CD4+ T-cells produce a mediator, called interleukin (IL)-21 that can cause further damage in stroke tissue.

Moreover, normal mice, ordinarily killed or disabled by an ischemic stroke, were given a shot of a compound that blocks the action of IL-21. Brain scans and brain sections showed that the treated mice suffered little or no stroke damage.   

“This is very exciting because we haven’t had a new drug for stroke in decades, and this suggests a target for such a drug,” says lead author Dr. Zsuzsanna Fabry, professor of pathology and laboratory medicine

Stroke is the fourth-leading killer in the world and an important cause of permanent disability. In an ischemic stroke, a clot blocks the flow of oxygen-rich blood to the brain. But Fabry explains that much of the damage to brain cells occurs after the clot is removed or dissolved by medicine. Blood rushes back into the brain tissue, bringing with it immune cells called T-cells, which flock to the source of an injury.

The study shows that after a stroke, the injured brain cells provoke the CD4+ T-cells to produce a substance, IL-21, that kills the neurons in the blood-deprived tissue of the brain. The study gave new insight how stroke induces neural injury.

Similar Findings in Humans

Fabry’s co-author Dr. Matyas Sandor, professor of pathology and laboratory medicine, says that the final part of the study looked at brain tissue from people who had died following ischemic strokes. It found that CD4+ T-cells and their protein, IL-21 are in high concentration in areas of the brain damaged by the stroke.

Sandor says the similarity suggests that the protein that blocks IL-21 could become a treatment for stroke, and would likely be administered at the same time as the current blood-clot dissolving drugs.

“We don’t have proof that it will work in humans,” he says, “but similar accumulation of IL-21 producing cells suggests that it might.”

The paper was published this week in the Journal of Experimental Medicine.

(Source: med.wisc.edu)

Filed under immune cells interleukin IL-21 stroke brain cells brain tissue medicine neuroscience science

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