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Brain Imaging Techniques (Neuroimaging)

Brain imaging (neuroimaging) was invented in the 1880s by Angelo Mosso, who devised a technique referenced as the “human circulation balance.”  This technique was able to assess how blood was redistributed throughout the brain as an individual experienced emotion and/or engaged in intellectual tasks.  It wasn’t until the early 1900s that a newer, improved brain imaging technique called “pneumoencephalography” gained scientific attention.

The technique of pneumoencephalography involved the drainage of cerebrospinal fluid surrounding the brain and replacing it with oxygen.  Replacement of cerebrospinal fluid with oxygen allowed neurosurgeons and researchers to attain a clearer resolution of the brain with an x-ray.  Despite pneumonencephalography’s improvement over the “human circulation balance” technique, there were significant risks and safety concerns associated with the technique.

In 1972, a newer form of neuroimaging called the CT (computed tomography) scan emerged, followed by the 1977 development of the MRI (magnetic resonance imaging).  Following both CT and MRI scans, other brain scanning techniques involving the usage of radioactive tracers such as the SPECT and PET scan were developed.  These days the most popular form of neuroimaging technology is the fMRI (functional magnetic resonance imaging) which was introduced in the 1990s as an enhancement of the MRI.

Brain Imaging / Scanning Techniques (Neuroimaging)

Below is a compilation of brain imaging (neuroimaging) or brain scanning techniques that have been utilized throughout history along with a brief description of how they work, the associated advantages, and disadvantages associated with each development.  While the fMRI currently remains the most popular brain scanning technology, various other techniques such as: CT, PET, and SPECT are still commonly used for various purposes.  In addition, many of the brain imaging technologies are used simultaneously as “combined” scans.

“Human Circulation Balance”

Angelo Mosso is credited with the first neuroimaging technology developed to better understand what occurs within the brain.  Mosso was a neuroscientist from Italy and created the “human circulation balance” technique that allowed him to non-invasively measure blood redistribution throughout the brain during emotional or intellectual tasks.  Due to the fact that this technique was devised in the 1880s, it was relatively primitive technology.

  • How it works: Measures blood redistribution throughout the brain during emotional or intellectual tasks.
  • Advantages: First neuroimaging technique throughout history.
  • Disadvantages: Limited in its measures, subject to inaccuracies.

Note: Mosso was the first to document important variables in neuroimaging including: signal-to-noise, experimental paradigm choices, and a multitude of physiological factors.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23687118


Following the inception of the non-invasive “human circulation balance,” a newer technique called ventriculography was developed in 1918 by Walter Dandy, a neurosurgeon from the United States.  This technique incorporated the usage of a trephine, an instrument that was used to drill tiny holes into a person’s skull, followed by filtered air being pumped through the lateral ventricles of the brain.  The idea was that this would allow for clearer imaging of the brain’s structure on an x-ray.

Eventually the technique would evolve into “pneumoencephalography” (PEG).  The most prominent difference between PEG and cerebral ventriculography is that cerebrospinal fluid was drained via the lumbar (PEG), rather than drilling holes in the brain with a trephine (ventriculography).  The drainage of the cerebrospinal fluid allowed for enhanced structural resolution of the brain on an x-ray.

  • How it works: A person is placed under anesthesia, and cerebrospinal fluid is drained via the lumbar. Filtered air then replaces the cerebrospinal fluid, allowing for the brain to show up more clearly on an x-ray.
  • Advantages: Allowed professionals to attain a superior resolution of brain structure on an x-ray scan as a result of the filtered air and lack of cerebrospinal fluid. This helped surgeons localize brain regions, assess structure for surgeries, and make certain diagnoses.
  • Disadvantages: Associated with health risks such as infections, intracranial pressure changes, and/or blood loss. It was considered a painful technique and often produced significant side effects such as vomiting and migraines.

Note:  The technique of PEG remained a popular neuroimaging method until the 1970s.

Cerebral Angiography

This is a form of an angiography that provides imagery of the blood vessels within and surrounding the brain.  It was developed in 1927 by Egas Moniz, a Portuguese physician and involved insertion of a catheter within a larger artery, which would link up to the carotid artery.  A contrast agent would be introduced (via injection) and dispersed throughout the brain.

This allowed a radiograph reading (electromagnetic radiation) to collect information regarding blood vessels.  Researchers could determine whether blood vessels within the brain and surrounding the brain were “normal” (healthy) or “abnormal” (unhealthy).  This technique has now been replaced by superior neuroimaging technology, but remained highly useful until the 1970s.

  • How it works: A catheter is inserted within the femoral artery (or any large artery) and maneuvered through the circulatory system into the carotid artery. Next, a contrast agent is injected and radiographs are collected as the contrast agent moves throughout the arterial system of the brain.  An expert can then determine whether there are any abnormalities of blood vessels within the brain (or in surrounding areas).
  • Advantages: Allows medical professionals to assess blood vessels with neuroimaging. Allowed for immediate administration of treatment based on findings.  It also helped experts determine whether a person was fully “brain dead” based on the blood vessel information.  Has been refined and is still used by neurosurgeons.
  • Disadvantages: Risks were associated with the “contrast agents,” many of which were toxic and/or carried significant adverse long-term effects. Others experienced injury to the brain as a result of these contrast agents.

CT (Computerized Tomography)

Computerized (Axial) Tomography was invented in 1972 by Godfrey Hounsfield (of EMI Laboratories) and Allan Cormack.  Both were given the Nobel Peace Prize for their invention of the CT scan, a major contribution to science and medicine.  The CT scan (also known as X-ray computed tomography) uses computer generated combinations of x-ray images taken from multiple angles.

When images are taken from multiple angles, they allow for production of tomographic (cross-sectional) images of specific areas of a scanned object.  These cross-sectional images allow medical professionals to observe the insides of a bodily part (e.g. the brain) in a non-invasive manner.

  • How it works: Many x-rays are taken from many angles surrounding the brain. These angles are then processed by a computer to generate cross-sectional imagery of the brain.  Digital geometry processing is then used to create a 3D image of the inside of the brain from the many 2D x-ray scans that have been collected.
  • Advantages: Provides 3D imagery of the brain in a non-invasive manner. Allows for more accurate diagnoses of medical conditions and improved resolution. Can be used for all parts of the body and can scan one specific region at a time.
  • Disadvantages: May increase cancer risk (as a result of radiation), cause kidney problems, and often involves injection of intravenous agents. The intravenous injection of exogenous agents can trigger unwanted side effects, adverse long-term effects, and potential allergic reactions.

SPECT (Single Positron Emission Computed Tomography)

SPECT is a form of nuclear tomographic imaging that uses rotating gamma cameras to provide 2D or 3D depictions of certain regions within the brain.  This technology uses radioisotopes that emit gamma rays in conjunction with a gamma camera that collects data.  The gamma camera transmits the data to a computer, that projects a 2D or 3D image of active brain regions based on the radioisotope activity within the brain.

  • How it works: Individuals undergoing a SPECT scan are fist injected with a radioactive tracer.  This tracer is quickly transported to the brain and allows the gamma camera to determine cerebral blood flow.  The information is then presented on a computer for professional assessment and interpretation in the form of a 2D or 3D image.
  • Advantages: Provides a “snapshot” in time of cerebral blood flow from the precise injection time of the radioactive tracer. This allows professionals to understand brain activity during complex neurological conditions such as seizures. It also allows for analysis of biological activity in highly-specific regions of the brain.  The SPECT scan remains lower cost than PET scans and is capable of using tracers with long half-lives.
  • Disadvantages: Relatively poor resolution.

PET (Positron Emission Technology)

The first PET scanner was created in 1973 by the trio of Michel Ter-Pogossian, Edward J. Hoffman, and Michael Phelps.  PET scans measure “emissions” produced by radioactive tracers that are injected into a person’s blood stream.  Collected data is then processed by a computer and used to generate colorful 2D or 3D images of the radioactive tracers based on their metabolic activity within the brain.

PET scans are extremely useful in that they provide neurologists with measures of metabolic activity within the brain.  This allows neurologists to determine whether an individual has incurred various forms of brain damage, neurodegeneration, or a stroke.  Many consider PET scans extremely useful for rapidly detecting cases of dementia, which are more difficult to diagnose with MRI scans.

  • How it works: Metabolically active chemicals with radioactive properties called “radiotracers” are injected into a person’s bloodstream. As the radiotracers accumulate in the brain, gamma rays emitted by the radiotracers are detected with a gamma camera system.  Snapshots of the radiotracer concentrations taken by the gamma camera are transmitted to a computer, which generates 2D and/or 3D images.  This provides medical professionals with information about the brain’s metabolic activity, allowing them to make diagnoses.
  • Advantages: Portrays blood flow, oxygen, and glucose metabolism. Metabolic activity can be used to understand neural functionality, structural abnormalities, and biochemical changes (e.g. neurotransmission).  PET scans can be used to diagnose an array of neurological disorders and conditions (e.g. tumors, strokes, dementia).  Moreover, PET scans can depict metabolic activity during specific tasks. This type of scan is considered to have relatively low radiation.
  • Disadvantages: High operating costs make them expensive for consumers. Radioactive tracers may provoke allergic reactions and lead to adverse long-term effects. There is a risk for significant radiation exposure when combined with CT scans.

MRI (Magnetic Resonance Imaging)

The MRI was invented in 1977 by professor Raymond Damadian and was first used to scan an entire human body.  It is currently the most widely-used form of neuroimaging technology.  Magnetic resonance imaging scans are commonly used in hospitals to determine specific activity within the brain, as well as many other tissues and organs throughout the body.

fMRI: A newer method of MRI scanning called “fMRI” (functional magnetic resonance imaging) involves studying blood flow to various areas of the brain to determine function.  With the fMRI introduced in the 1990s, scientists have been able to track blood oxygen levels and determine the specific regions of the brain are active during certain tasks.  The development of the fMRI has lead to preclinical therapeutic techniques such as “decoded neurofeedback” for treating psychiatric conditions.

  • How it works: An MRI machine is comprised of 2 powerful, large magnets. The human body consists of mostly water molecules, containing hydrogen and oxygen atoms.  Protons within the center of these atoms are sensitive to the magnetic fields generated by the magnets and are aligned in an orderly manner upon exposure to the magnets.  Intermittent bursts of radio waves  then force the protons out of alignment, allowing transmission of the changes to receivers.  These receivers send details to a computer that generates imaging based on millions of protons.
  • Advantages: Revolution in brain scanning and mapping. Used for diagnoses, assistance in medical procedures, and as part of neuroscientific research. MRIs are widely available and non-invasive.  They do not use ionizing (harmful) radiation, making them superior to CT scans. Refinements have been made to improve existing MRI technology and continued future improvements are expected to continue in accordance with Moore’s law.
  • Disadvantages: Can promote bouts of claustrophobia for certain individuals due to the fact that the scan is conducted in extremely tight spaces. May also cause hearing loss due to the loudness of the noise generated over an extended period of time.

MRS: Another technique called “magnetic resonance spectroscopy” is a non-invasive way to determine metabolism within the brain.  MRS can be conducted as part of an MRI scan on most instruments and has been approved by the FDA.  It uses different software than an MRI that alters the collected signals, generating a graph of chemicals within the brain.  Due to the fact that this is a newer technique, it is unknown as to whether it is useful and/or accurate for diagnostic purposes.

Other types of brain scanning technology…

There are remain other types of neuroimaging (brain scanning) techniques that are less commonly discussed and/or utilized.  Many of these techniques collect highly-specific measures of brain activity and are commonly used by neuroscientists for research.

Magnetoencephalogram (MEG)

This is a neuroimaging technique that was devised in 1968 by David Cohen, a physicist from the University of Illinois.  It is capable of generating a map of brain activity via recording of magnetic fields generated by endogenous electrical currents within the brain.  The maps are recorded with sensitive instruments called magnetometers.

The most common magnetometers used for magnetoencephalography are called “SQUID” – an acronym for “superconducting quantum interference devices.”   Other forms of magnetometers called SERFs (spin exchange relaxation-free) are being tested for newer machines.  MEG machines were refined significantly in the 1980s, incorporating more than 300 sensors to cover the scalp; this increased speed and efficiency.

  • How it works: Magnetoencephalography uses superconducting sensors (SQUID) that are submerged in a liquid helium cooling unit within a magnetically shielded room. The SQUID sensors are positioned within a few centimeters of the brain, and are able to amplify the subtle magnetic fields generated by tens-of-thousands of neurons.  Information is then sent to a computer, which allows researchers to pinpoint neural activity to the nearest millisecond.
  • Advantages: Non-invasive technique that records brain activity. Can determine the region in the brain responsible for generating brain activity.  Measurements can be conducted and pinpointed to the nearest millisecond. Helpful for neuroscientific research, specifically processes of cognitive function and perception.  MEG may aid in assessment of abnormalities within specific regions and parts of the brain and is more accurate than an fMRI for assessing temporal and spatial information.  While undergoing an MEG scan, the head can be moved and the equipment makes no noise.
  • Disadvantages: There aren’t any significant disadvantages associated with MEG technology.

Note: There are “CSAMs” (chip-scale atomic magnetometers) being utilized.

Electroencephalogram (EEG)

Electroencephalography is a non-invasive method devised to record neuroelectrical impulses (brain waves) within the brain across the scalp.  It was first utilized in 1875 to measure electrical activity within the brains of animals such as rabbits.  Hans Berger, a German physiologist and psychiatrist is credited with inventing the electroencephalogram (EEG), a device which he used to record the first human brain waves in 1924.

Since the inception of the electroencephalogram, the machine has been used for a variety of diagnostic purposes such as to determine whether an individual has epilepsy.  Further, the device is commonly used to help individuals consciously manipulate their brain wave activity in the form of EEG neurofeedback.  EEG neurofeedback has been used to improve neural efficiency, brain functionality, and for the normalization of neuroelectrical abnormalities.

  • How it works: Electrodes are placed on the scalp and the EEG machine records fluctuations in voltage associated with changes in electrical current. These recordings are derived from a multitude of sites on the scalp, and are classified by frequency.  The higher the frequency, the lower the amplitude of the brain wave and the quicker the cycling (Hz) per second of the wave.  The lower the frequency, the higher the amplitude of the brain wave and slower the cycling (Hz) per second of the wave.
  • Advantages: Collects real-time data of the brain’s electrical activity in various regions to the nearest millisecond. Can be used to assess neuroelectrical abnormalities within the brain at a low cost.  May be used as an adjunct diagnostic tool for neurological conditions and is especially helpful for diagnosing epilepsy.  It is non-invasive, painless, and can be combined with other forms of brain scanning such as fMRI or PET.  Is also a helpful research tool in the field of neuroscience where it provides high resolution without exposure to radiation or magnetic fields.
  • Disadvantages: Limited to collecting electrical activity unless combined with another scan. Doesn’t measure activity below the cortex and cannot pinpoint neural activation of regions within the brain nor determine neurotransmission.  It sometimes takes awhile for an individual to connect to an EEG machine with electrodes and various pastes to keep them in place.

fNIRS (Functional Near-Infrared Spectroscopy)

This is a form of neuroimaging that collects data using near-infrared spectroscopy (NIRS).  It is non-invasive in that near-infrared light (within the range of 700 nm to 900 nm) is capable of assessing brain tissue based on light absorption, scattering properties, oxyhemoglobin and deoxyhemoglobin levels, and scattering of neurons.  This allows practitioners to determine brain activation and functionality based on the behavior of neurons.

The technique was discovered in the late 1970s, and near-infrared spectroscopy machines were developed in the mid-1980s.  Scientists recognize four modalities of fNIRS including: continuous wave (CW), frequency domain (FD), time resolved (TR), and spatially-resolved spectroscopy (SRS).  Continuous wave (CW) is the most common format due to simplicity, low cost, and accuracy for detecting changes in hemoglobin concentrations.

  • How it works: Near-infrared spectroscopy is used (non-invasively) to measure brain activity based on absorption (of the light), the way the light scatters, oxygenation, and cellular activity. Specifically light is emitted at different wavelengths (one above 810 nm, the other below), and differences between an “emitter” and “detector” provide feedback of hemoglobin concentrations. This information is then recorded and transmitted to a computer software, which is then subject to professional interpretation and analysis.
  • Advantages: Capable of monitoring changes in oxygenation via the usage of specific wavelengths of light. May be as effective as an fMRI for assessing cognitive tasks.  It is relatively low cost and portable.
  • Disadvantages: Cannot determine cortical activity exceeding 4 centimeters due to limited power of light emission.

The technique referred to as Diffuse Optical Imaging (DOI) or Diffuse Optical Tomography (DOT) also incorporate the usage of near-infrared spectroscopy.  This method is able to generate 3D imaging of a tissue by assessing differences in scattering of near-infrared light wavelengths.   Neuroscientists typically consider Diffuse Optical Imaging to be a form of functional near-infrared spectroscopy.

A type of near-infrared neurofeedback known as hemoencephalography (HEG) uses a similar concept of measuring cortical blood-flow based on differences in infrared-light.  This allows individuals to determine whether they have shifted sufficient blood to important executive regions of the brain such as the prefrontal cortex.  In addition, fNIRS has been integrated as a control mechanism for brain-computer interfaces.

Event-Related Optical Signal (EROS)

This is a brain imaging technique that uses infrared light via optical fibers to assess alterations in optical properties in specified regions of the brain.  This differs from Near-Infrared Spectroscopy (NIRS) in that it does not measure hemoglobin concentrations and doesn’t determine regional blood flow.  Instead, event-related optical signal (EROS) is able to assess scattering of neurons, ultimately generating an accurate portrayal of neuronal activity.

This method of brain scanning is able to identify brain activation in millimeter-sized regions within a short-duration (milliseconds).  The technique was conceived at the University of Illinois Urbana-Champaign.  It is considered an advancement in terms of cognitive neuroimaging.

  • How it works: Optical fibers generate infrared light and recordings are collected based on scattering of neurons.
  • Advantages: EROS is relatively inexpensive, non-invasive, and serves as a unique way to record brain activity.
  • Disadvantages: Unable to detect activity exceeding 4 centimeters beneath the cortex as a result of using near-infrared light.

Source: https://www.ncbi.nlm.nih.gov/pubmed/11477005

Voxel-Based Morphometry (VBM)

This is a neuroimaging technique that allows practitioners to assess anatomical alterations in the brain.  Voxel-based morphometry involves registering every brain to a template, which is able to then determine anatomical differences among a variety of brains.  Next, the images of brains are altered so that voxels serve as a composite of all brains collected.

After a variety of brains have been collected and a “composite” brain is generated, individual brains are compared to the composite.  Researchers are then able to determine significant individual anatomical differences based on their comparisons to the composite brain.

  • How it works: MRI (magnetic resonance imaging) scans are collected from a variety of brains. The scans are registered to a template and combined in as a “composite” or average brain via computerized software.  Next, specific differences are noted between individual fMRI data and the composite voxel-generated data.
  • Advantages: Can be used to compare your individual brain anatomy (structures and matter) to others. This allows professionals to determine whether there are any significant differences that may result in superior skills and/or poorer functionality. Allows researchers to distinguish healthy brains from unhealthy ones.
  • Disadvantages: Can be very sensitive to alignment of brain structures, tissue classification, cortical thickness, and various folding patterns – all of which may result in skewed data.

Diffusion MRI (dMRI)

This is a form of magnetic resonance imaging (MRI) that was developed in the 1980s.  It generates a map of neural tracts based on water molecule movement within the brain.  It’s basically like an MRI, except it specifically analyzes water diffusion.  Water within the brain moves around based on specific neural structures and neurons, making it easy to diagnose certain  neurological conditions (e.g. a stroke).

Diffusion MRI serves as a way to collect information on at both the cellular and microscopic level (microns).  This allows researchers to determine microscopic changes that wouldn’t be depicted on a scan of the brain in millimeters.  Depiction of microscopic changes from a diffusion MRI allows neurologists to determine whether a stroke occurred recently or months prior to the scan.

  • How it works: A form of MRI that involves assessing the movement of water molecules within the brain, portraying diffusion. The diffusion is depicted by a computer generated algorithm in 3D, allowing experts to determine subtle differences in the pathology of neurological conditions.  Tractographic reconstruction can then be used to assess various neural tracts within the brain.
  • Advantages: Helpful for research of neurological disorders, particularly strokes. Diffusion MRIs makes it easy to determine whether a stroke occurred yesterday compared to several months ago based on water diffusion.  They also make it easier to detect subtle differences between pathologies of neurological disorders.
  • Disadvantages: There aren’t any significant reported disadvantages associated with diffusion MRI techniques.

CUBIC (Clear Unobstructed Brain Imaging Cocktails)

In 2014, a new technique of whole-brain imaging called “CUBIC” was devised.  The term CUBIC is an acronym for “clear unobstructed brain imaging cocktails and computational analysis.”  Researchers using this technique collect samples of the brain, expose them to chemical concoctions (of aminoalcohols), ultimately breaking down lipids for increased resolution with single-photon excitation microscopy.

  • How it works: It involves taking brain samples and immersing them in chemical mixtures with aminoalcohols, which causes the tissues to appear clear and glassy. The aminoalcohols break down lipids that inhibit and scatter light.  Single-photon excitation microscopy is then used to gather imagery of proteins and neurons within the brain.
  • Advantages: Allows for quick, entire-brain imaging with single-photon excitation microscopy. Generates images that demonstrate neural activation induced by environmental stimuli.  Provides single-cell resolution of complete adult brains.
  • Disadvantages: Unable to remove naturally-occuring pigments (e.g. heme), which absorb light and limit imagery.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24746791

Nanoscale Neuroimaging (2015)

A new tool has allowed researchers to develop a high-resolution map of the brain with nanoscale resolution.  The newly developed nanoscale neuroimaging has allowed researchers to study connectivity between neurons, and pinpoint abnormalities associated with psychiatric disorders.  The imagery generated by nanoscale neuroimaging allows researchers to see parts of the brain down to the molecular level.

  • How it works: A device was built that slices open a brain into thousands of tiny sections. The slices are stained based on tissue, and electron microscopes are able to capture snapshot pictures of each slice.  Once pictures are taken, they are transmitted to a computer and individually assigned a color based on structure.  The structures are then compiled and formatted into a collective 3D map.
  • Advantages: Shows tiny structures within the brain that are the size of “millions of a millimeter” in 3D. Allows for new discoveries within the brain on a nanoscale level that wouldn’t be detected by other forms of neuroimaging.
  • Disadvantages: The technique is new and thus unrefined. It can only be used to take pictures of the brain post-mortem.  Many scientists believe that viewing portions of the brain on a nanoscale level is a complete waste of time.

This technique will allow researchers to collect details of individual brain cells and understand both connectivity and contents.  By comparison, one pixel of an MRI is equal to a billion pixels of the nanoscale neuroimaging.  The goal of researchers who developed the technology is to start by mapping a rodent (rat) brain, and eventually map human brains to determine abnormal connectivity.

It will initially prove difficult to use nanoscale imaging, but as refinements are made and computing power increases – this technology has significant promise for the field of neuroscience.  It is estimated that it will take approximately 10 years to map out an entire human brain with this technology based on increases in speeds of computing power.

Personal experience with brain scans

I’ve personally experienced a CT scan prior to a surgery, as well as an fMRI following Paxil withdrawal because I was convinced that I had a brain tumor.  The CT scan was used by my surgeon to collect pre-surgical information and the fMRI revealed that my brain was healthy – despite experiencing an array of abnormal symptoms (dizziness, migraines, insomnia, brain zaps, etc.).

I hated getting the fMRI due to the fact that I felt claustrophobic.  The first time I went to get the MRI, I panicked and told the radiologist that I couldn’t tolerate it (plus I had to use the restroom).  He prescribed some Valium for the next scan and I was able to survive as the machine generated pulses of loud (annoying) noises during the scan.

In future years, I expect the advancement of technology to further refine the fMRI, potentially eliminating some of the annoyances associated with current scans (e.g. loud noise).  In addition, there may be an emergence of new scanning techniques in addition to the newly introduced nanoscale neuroimaging.

Have you ever experienced a brain scan?

If you’ve had a brain scan (or multiple brain scans), be sure to leave a comment below mentioning which one you’ve experienced as well as what the experience was like.  What was the purpose for your specific brain scan?  If you don’t mind sharing, feel free to document the results of the scan as interpreted by a medical professional.

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