Neuroimaging

The first entries of this blog, start with impressive, yet simple, inventions that were indispensable to the advance of Neuroscinece. We started contemplating Golgi’s technique, and now we are going to see the brain trough a computer.

The advance is notorious and impressive, but the motivation behind this creation, in the end, is the same, to look inside our brain, to see, and understand. To obtain a rich image full of information, and in this case, make that image dynamic.

The term, neuroimaging, embraces a variety of different methods and technologies. It’s similar to the concept “brain scans”, and also “in vivo imaging”. This last term specifies, that this technique is performed in living animals, specially humans.

The history of neuroimage goes back to the origins of radiology. Discipline that started its path, in 1895, with the discovery of X rays, in the hands of Wilhelm Conrad Röntgen.
X rays, were born in the field of physics, but rapidly extended to other disciplines, and were applied to the medical sciences. The exploration of the organism was now possible, the structure and tissue of the body were visible. This was a huge breakthrough in medicine and its subspecialties.

In 1918, Walter Dandy, from the University John Hopkins, officially inaugurated neuroradiology, when he introduced ventriculography and gaseous pneumoencephalography.

Egas Moniz, the Portuguese neurosurgeon and psychiatrist, that received the Nobel Prize in 1949, for the discovery of the therapeutical value of lobotomy in specific forms of psychosis, is also relevant in the history of neuroimaging.
Before winning the Nobel prize, in the 30s, he invented the cerebral angiography, a diagnostic technique that permitted the visualization of blood flow, with a simple method applying the use of X rays.

Fig 1. Cerebral angiography

During the first half of the XXth century, techniques were mainly morphological, so the knowledge obtained during this time, was about the anatomy of the brain.

In 1948, George Moore, from the Universitiy of Minessota, introduced nuclear medicine, when he used radioactive isotopes. Around this time, Gordon Brownell and William Sweet, two researchers and clinicians at the General Hospital at Boston, applied the same technique for the localization of tumors in the brain.

Structural imaging

This advance, the creation of the field of nuclear medicine, and another set of scientific steps lead to the creation of the computerized tomography (CT) in the 70s. This marked the change of the analogical image to the digital format.

CT Scan

Allan M. Cormack and Godfrey N. Hounsfield shared the Nobel prize for Physiology or medicine in 1979, for the creation of the CT scan in 1972.
A CT is composed by a computer which processes combinations of many X-ray measurements taken from different angles, to produce cross-sectional (tomographic) images of specific areas of the body.
This extraordinary advance, offered virtual images, multiplane and tridimensional, in real time.
CAT is a structural imaging technique, wich offered incredible options, and revolutionized brain study after its creation. It is still used nowadays.

Fig 2. Image obtained with a CT scan (left) and a MRI (right).

MRI

Raymond Damadian, developed the magnetic resonance imaging (MRI) in 1972, and performed the first scan in 1977.
This machine produces detailed, high quality and high-resolution images of the brain, and it doesn’t need to expose subjects to radiation.
An MRI is composed by a big magnet with an opening, where subjects lie during the examination. The magnetism produced by the MRI realigns the protons found in the tissue of the brain. A radio pulse produced by the machine, forces some of this protons to move at a particular frequency. When this pulse ends, the protons go back to their original position and return the energy of this replacement, which is obtained by the MRI.
A computer generates scans of the tissue using the values of this energy and reproduces an image of the brain’s structure with great detail.

Functional Imaging

One of the biggest contributions from neuroimaging to Modern Neuroscience, has a clear protagonist, Seiji Ogawa, a Japanese researcher, the father of modern functional brain imaging.

He proposed the following principle:
Since changes in blood oxygen level cause the magnetic resonance imaging properties to change, a map of blood can be obtained, and therefore, a functional map of the activity in the brain can be created.

He discovered the BOLD effect, that is, the level of oxygen in blood that determines the functional brain image. For this reason, the technique he invited is called BOLD contrast (blood oxygenation level-dependent).

Fig 3. Scans obtained with fMRI.

This is the thought behind functional MRI (fMRI). The hemodynamic response. Neuronal activity and blood flow are related, the more neuronal activity, the more blood flow to the area.

The map of the activity in the brain indicates the neurons in the brain that respond in certain mental processes with electrochemical signals.
Functional MRI (fMRI) allowed the mapping of the visual, auditory and sensory regions in the brain, and even higher brain functions, cognitive processes. fMRI is the principal technique that made possible the emergence of Cognitive Neuroscience.

PET

Fig 4. PET Scan obtained images. (From:IDEAS-Study)

PET scans measure blood flow in the brain by injecting small amounts of radioactive substances, and then scanning the absorption of the radioactivity. More active regions of the brain have increased blood flow, carrying more of the radioactive substance to those active areas. Less active areas of the brain consume less of the substance.
As the radioactive substances decay, they release gamma rays that the PET technology measures, providing pictures that contrast the more and less active parts of the brain. A computer demonstrates the areas by colors: red indicates more active areas; blue indicates less active areas. The computer shows cross-sectional slices of the brain. These images display deep structures within the brain, and demonstrate functional responses within these structures. PET scans do not measure neuronal processes taking place, only levels of change in different brain areas under different conditions.

Regional cerebral blood flow (rCBF)

Fig 5. rCBF obtained images.

rCBF is a type of PET scan that also measures more and less active brain regions based on radioactive substances transported through blood flow. Patients inhale a small amount of radioactive gas such as xenon, which the blood carries to the brain.
Patients sit under devices resembling hair dryers that cover their head. These “caps” have sensors that measure the radioactivity transported to the brain, identifying the more active areas.

As happens with PET scans, rCBF does not measure neuronal activity but only changes in blood-flow activity.

New technologies to come!

The evolution of imaging technologies continues to grow in the XXIth century. Stanford Michael Moseley, invented the diffusion tensor imaging technique, a measure of movement and directionality of water trough the fibers in the brain. This provides a vision of the white matter, and therefore, a map of the brain’s connectivity.

Another new technique of MRI machines is magnetic resonance spectroscopy (MRS), used mainly by researchers rather than clinicians. MRS studies the biochemistry of brain tissues without the need for a biopsy.

References

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