Susceptibility Tensor Imaging (STI)

STI is a new MRI”technology in development. It consists on creating images and ┬ácontrast based on the susceptibility of the tissue to the magnetic field. This susceptibility seems to be based to the anisotropic alignment of the molecules. The tissue ismore susceptible when the angle to the magnetic field is smaller. A recent study in mouse, (Chunlei L. et al. 3D fiber tractography with susceptibility tensor imaging. NeuroImage (2012) 59: 1290-1298), shows a similar contrast to Diffusion Tensor Imaging (DTI), although DTI seems to be superior in small and complex fibers.

It would be interesting to compare STI to neuroanatomical tract tracing, since pathology is still the gold standard. This is a new technology that needs more development althoughthe initial results look promising.

Adolfo Cotter, MD

Feb 12/2012

Transcranial Doppler (TCD)

TCD  is the only non-invasive real-time neuroimaging study that can evaluate the characteristics of cerebral blood flow continuously. CT Angiography (CTA ) and Magnetic Resonance Angiography (MRA ) can do snapshots in time. Fluoroscopic angiography is the gold standard and can be used as a confirmatory tool.

Some of the applications of TCD are: stroke, vasomotor reactivity testing, emboli monitoring, shunt detection, increased intracranial pressure, circulatory arrest, monitoring vasospasm after spontaneous subarachnoid hemorrhage, and sickle cell anemia.

In my opinion TCD can be a good test in the assessment of brain death when the diagnosis is doubtful.

A good review paper in this topic is the following:

Tsivgoulis G, et al, Advances in Transcranial Doppler Ultrasonography. Current Neurology and Neuroscience Reports, 2009, 9:46-54

Adolfo Cotter, MD

Jun 28/2011

Magnetic Resonance Force Microscopy (MRFM)

Very impressive advancements have been made in this field. The goal is ultimately to visualize matter at the molecular and atomic level. This of course will resolve and hopefully prove many of the questions and mysteries of atomic physics. Ultrahigh resolution 3D images are currently available and they promise to continue to improve. The key elements of this technology are: 1) Ultra small magnetic tips with high moment materials, 2) Ultrasensitive micromechanical cantilevers, 3) Displacement transducers.

MRFM currently surpasses conventional, inductive nuclear resonance detectors by eight times in magnitude. MRFM can continue to improve by further decreasing the size of the magnetic tips and bringing the sample closer to them. 

A good recent review of this technology is the following:

Peggio M., Degen C.L., Force-detected nuclear magnetic resonance: recent advances and future challenges. Nanotechnology. 21 (2010) 1-13

Adolfo Cotter, MD

May 11/2011

Diffusion MRI Tractography as a diagnostic tool for Brain Pathology

Diffusion MRI tractography can be used to evaluate for brain pathology by measuring for pathlength, for example. The pathlength constitutes neuronal brain connectivity between two specified brain locations. An abnormal pathlength could be increased or decreased. A significant change in pathlength should point to a specific brain pathology depending on the location of the path. A recent study on Traumatic Brain Injury shows a significant decrease in path length between the genu of the corpus callosum and the frontal lobe. This white matter structure is often related to diffuse axonal injury (Pannek K, etal. The average pathlength map: A diffusion MRI Tractography-derived index for study of brain pathology. NeuroImage. 55 (2011) 133-141).

Diffusion MRI Tractography is related to structural brain changes. It would be interesting to evaluate for functional brain changes and its relation to functional connectivity. Also, it would be interesting to evaluate for structural connectivity in the so-called functional brain disorders, and find out if they also have a structural component.

Adolfo Cotter, MD

May 11/2011

Diffraction Enhanced Imaging (DEI)

This is a relatively new imaging technology that uses three “physical mechanisms” to generate contrast. Those mechanisms are: 1) X-Ray absorption, 2) Refraction, 3) Ultra small angle scatter rejection. This technology can produce high contrast images with much lower radiation dose compared to conventional radiography.

One of the applications this technique might be useful for is to image amyloid plaques in Alzheimer’s disease. Those plaques are usually very small and difficult to visualize with other methods.  This technique showed to be useful in a study imaging amyloid plaques in mice.

An interesting paper in the topic is the following:

Parham C, et al. Design and implementation of a compact low-dose Diffraction Enhanced Medical Imaging System. Academic Radiology (2009) August; 16(8): 911-917.

Adolfo Cotter, MD

Feb 10/2011

Track Density Imaging (TDI)

When using MRI, in order to increase spatial resolution we need a longer acquisition time. We also need the same to increase signal to noise ratio (SNR). High tesla MRI, although it increases SNR, it has a problem with deep penetration called the skin effect. Deep structures might be difficult to visualize.

A new post-processing method called TDI seems to be useful to increase spatial resolution and it has a high SNR when imaging the brain white matter. It is also an objective technique and able to be automated. It basically calculates the number of tracts throughout the brain. It seems to help with the crossing fiber problem of fiber tracking by the use of high angular resolution diffusion imaging (HARDI). 

A good paper in the topic is the following:

Calamante F, etal. Track-Density imaging (TDI): Super-resolution white matter imaging using whole-brain track-density mapping. NeuroImage, 53 (2010) 1233-1243.

Adolfo Cotter, MD

Dec 24/2010

Magnetic Resonance Elastography

The elastic properties of human tissues have been evaluated in a clinical setting by palpation. Although this procedure has often helped clinical diagnosis, it is a subjective procedure and cannot be quantified.

More recently a quantifiable technique has been developed using imaging technologies such as  MRI, Ultrasound, Optical Imaging and so forth, whereby the degree of elasticity can be observed has hard data after administering vibrations to the tissue.

For the brain, the preferred technology has been MRI . Vibrations of 60 Hz have been applied at the base of the brain and elastic properties then measured. We can envision a wide range of applications of this technique for the brain, including but not limited to: Alzheimer’s disease, Brain Tumours, Multiple Sclerosis, and Stroke. The vibratory frequency used seems to be safe and unable to produce damage such as the rupture of brain vessels.

In my opinion this technique can be very useful for the differential diagnosis of brain disorders in conjunction with the already known anatomical information that  MRI can provide.

This is a good paper on the subject:

Mariappan YK, etc al. Magnetic Resonance Elastography: A Review. Clinical Anatomy, 2010, 23: 497-11.

Adolfo Cotter, MD

Nov 28/2010

Mapping the Mind

As I mentioned on previous blog entries, I believe the brain and the mind overlap to some degree but also there should be a free brain area without mind and a free mind area without brain. Because our medications act on the brain but not on the mind itself, our knowledge of this interface is most useful to treat psychological and psychiatric conditions, in my opinion.

The Allen Brain Science Institute has identified over 20,000 genes responsible of brain activity and has created an atlas. Having this important knowledge, the next step would be to understand the effect and the functioning of these genes. Imaging studies such as fMRI and  MRI Spectroscopy could help understand these cellular processes by evaluating brain function and brain chemistry.

The NIH has started working on the Human Connectome Project looking for brain circuitry. In my opinion, understanding the brain circuitry related to mental processes and states as well as the cellular mechanisms involved, will help us develop drugs that will target more specifically mental activity with less side effects. Also, if we apply Pharmacogenomics to psychiatric medications, we will be able to more efficiently treat psychiatric conditions.

An interesting paper related to this topic is the following:

Jones, AR, etal, Mapping The Mind, Scientific American Mind, September/October 2010, pp 57 – 63.

Adolfo Cotter, MD

Oct 14/2010

Measures of Cortical Brain Thickness

Anatomical MRI measures of cortical brain thickness have been recently evaluated. In normal aging there is a decrease in cortical thickness, which presents an anterior-posterior gradient, being more prominent in Frontal and Parietal than in Temporal and Occipital lobes. There are regional differences between both sexes. In Alzheimer’s disease the reduction in cortical thickness is significantly greater. The sensitivity of AD diagnosis by measurements of cortical thickness is close to 90%, which is higher than with other anatomical measures. In early AD the regions affected are usually medial temporal lobe regions, such as: the hippocampus and entorhinal cortices.

In my opinion, if we combine these anatomical MRI measures with functional ones such as with PET or SPECT, we should obtain higher sensitivity values approaching 100%. This is because anatomical and functional measures are usually synergistic.

The following is a good paper related to this subject:

Thambisetty M, etal., Longitudinal changes in cortical thickness associated with normal aging, NeuroImage, 52 (2010) 1215-1223.

Adolfo Cotter, MD

Aug 16/2010


Nanoantibodies also known as nanobodies, have advantage over full size antibodies that they are more stable, aggregate less, and they can penetrate very small locations. There are currently attempts to make them cross the blood brain barrier ( BBB ). An idea that I suggest is to bind a nanobody to a nanoparticle, so the nanoparticle can help them cross the BBB. I think this is doable and I invite interested scientists to try it.

They also show very good specificity, which can be useful to treat cancer for example. One of the problems with chemotherapy for cancer is its lack of specificity, and in consequence it shows many side effects. Other therapeutic applications that look promising are: Alzheimer’s disease by targeting amyloid plaques, and Parkinson’s disease by targeting alpha-synuclein. 

They also seem useful for molecular imaging as a probe for PET or SPECT. They seem to show a good uptake. A good paper in the topic is the following:

Dmitrov DS, Engineered CH2 domains (nanoantibodies), MAbs 2009 Vol 1 Issue 1 26-28

Adolfo Cotter, MD

Aug 08/2010