Too Good to be True

You hear it often: that’s too good to be true. A long list of hucksters and criminals have used the method of offering exceptionally good opportunities in order to steal people’s money in the past, and so our society does not believe in fantastic opportunities anymore. This is very sad and dangerous for true and generous people who are now usually mistaken for being liars and criminals whenever they might “go too far” in presenting the virtues of an opportunity. In other words, true criminals who have been using this method, not only have committed the criminal act, but have deeply hurt our society by not allowing truly exceptional people to prosper. This in consequence has diminished the number of real outstanding opportunities.

At NeuroImage we thrive to provide exceptional service. We do hope our clients will not think about us as “Too good to be true”

Adolfo Cotter, MD

Nov 26/2011

Imaging Genetics

Imaging genetics has been focused so far in imaging the phenotype. Most of the research done has been related to human behavior.  The phenotype constitutes the biological basis of the clinical manifestation of the specific gene. For example, we could image brain circuitry by using MRI in order to understand the biological basis of schizophrenia and its relation to the genotype. After the circuit has been understood, we can perform statistical analysis between these findings and the clinical manifestations. We have to understand that phenotype is also related to non-genetic factors such as: diet, age, smoking habits, sleep, medications, etc. We have to include those as covariates when we perform”the statistical analysis.

In my opinion imaging genetics might include not only phenotype imaging but also genetic imaging itself such as with MRI Spectroscopy.   Other areas besides behavior will most likely be explored in the future 

This is a good article related to this topic:

Bigos KL, Weinberg DR. Imaging Genetics- days of future and””past.  NeuroImage. 2010; 53:  804-809.

Adolfo Cotter, MD

Oct 21/2010

Nanoantibodies

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

Longevity and Genomics

Methylation/demethylation of DNA  and/or histones, acethylation/deacethylation of histones and shortening of telomeres appear to be some of the epigenetic factors controlling gene expression over time. The epigenetic control mechanism is affected by the environment and seems to become progressively relaxed or disrupted as we age. Because of this disruption illnesses of aging can appear, including cancer. In fact, aging is one of the highest risk factors for cancer. Because cancer involves an uncontrolled cell replication, senescence of replication might appear as a compensatory mechanism. This seems to be at least partially mediated through changes in telomeres.

In a previous blog entry I mentioned that life events can change gene expression. The mechanism could be the one explained here. Because of this interaction with the environment, in my opinion, it seems that the control mechanism might respond to drug manipulations or specific changes in the environment. By doing this we could hope to delay or even stop the aging process and its consequences. One of the difficulties for doing this is the heterogeneity in different cells. There seems not to be a uniform response to epigenetic manipulations, and each cell seems to behave differently. A good paper in this topic is the following:

Gravina Silvia, etal, Epigenetic factors in aging and longevity, Pflugers Arch- Eur J Physiol 2010 459: 247-258

Adolfo Cotter, MD

Jul 26/2010

Nanoparticles (NPs)

Nanotechnology has made possible the production of Nanoparticles. NPs can be made of different materials such as ceramics, carbon and various metals. It also can take different shapes. They can be used in imaging and also to transport drugs. They can be widely used in imaging but in the case of Brain Imaging, its main use is to facilitate the passage of a tracer or drug across the blood brain barrier BBB. The basic mechanism of action is that the NPs bind to a receptor at the surface of the cell and the whole structure (NPs+tracer or NPs+drug) is transported by endocytosis and then released to the brain. NPs can be also targeted to specific molecules. In the case of tumors there is an extra advantage since the vascular leakage is higher and the lymphatic drainage is impaired, which promotes accumulation of the NPs.

In my opinion, Nanoparticles are a new technology with great promise, since imaging and drug delivery to the brain has long been hampered by the problem of BBB impermeability. Many drugs and tracers with great potential usefulness have had to be discarded in the past because they were unable to reach their target due to BBB impermeability. Hopefully this will no longer be a problem when using NPs in many instances. The following is a good paper on the topic:

Provenzale, JM etal., Uses of Nanoparticles for Central Nervous System  

Imaging and Therapy, Am J Neuroradiol 2009 Aug 30(7) 1293-301.

Adolfo Cotter, MD

Jul 05/2010

Multispectral Optoacustic Tomography (MSOT)

MSOT uses the photoacoustic principle I explained in a previous blog entry. With this technique one is able to visualize in vivo cellular events with high sensitivity, at a resolution of 100 micrometers. It has a big advantage of being able to visualize physiology and anatomy at the same time without combining two different technologies. It is also a portable technique. It can be used for molecular imaging, biomarkers, and it allows the use of contrast agents. It is currently used in small animal imaging and it can be very helpful in studies of drug development.

Its usefulness is however limited by its inability to penetrate tissue as well some other older technologies such as PET.

In my opinion this is new and revolutionary technology because of its high resolution and the ability to evaluate in vivo processes. It will be very useful in evaluating the mechanism of action of a drug, side effects of a drug in detail, pharmacodynamics, etc.

A good paper in this topic is-

Ntziachristos, V etal. Molecular Imaging by means of Mutispectral Optoacustic Tomography (MSOT); Chem Rev 2010, 110, 2783-2794

Adolfo Cotter, MD

Jun 27/2010

Microscopic Diffusion Tensor Imaging

Resolution is always a limitation when detailed analysis of the brain anatomy is needed. A partial solution for this problem is the use of Microscopic Diffusion Tensor Imaging.

Diffusion Tensor Imaging (DTI) is an MRI technique that displays the white matter tracts by using the diffusion of water as a technique. The applicability of this technique can be to build a detailed anatomical atlas of brain connectivity or the analysis of brain connectivity in pathological states. In my opinion, we would be able at some point to characterize some brain diseases by connectivity abnormalities, and DTI can be a test for those conditions. The problem I see is lack of resolution, and this can be overcome by the use of microscopy. On the other hand microscopic DTI uses in vitro specimens, so the microscopic test would be used for research applications and possible as a test used in autopsy. Microscopy increases resolution, but scanning time although long, it is being shortened by acquisition and processing techniques, such as- dynamic image acquisition and automated registration. Here is a good paper on this topic:

Jiang Yi, Microscopic diffusion tensor imaging of the mouse brain, NeuroImage, 50, 465-471.

Adolfo Cotter, MD

Jun 17/2010

Neurogenomics and Human Cognition

Our cognitive abilities are partially explained by our genes; The rest is explained by the environment. Because the interaction between genes and environment is complex, scientists have, so far, been able to identify only about 5% of the genes responsible for our cognition. Our genes can affect how much the environment is going to influence us, and the environment can affect the expression of our genes. Interestingly, life events such as break-ups, deaths, the birth of a child, etc.. can affect how our genes and the environment influence us. This is a fascinating field, and it can explain what I had discussed on Creativity. We are born with a creative ability but if the environment doesn’t allow it to develop, we will not be able to express our creativity in life. It is a pity that this is happening even in the developed world. A good up-to-date short paper on this topic is-

Vinkhuyzen, AAE, etal, LIfe events moderate variation in cognitive ability (g) in adults, Molecular Psychiatry Feb 16 2010 Epub

Adolfo Cotter, MD

Jun 08/2010

Acting without Comprehending

In my opinion action without theory or theory without action is useless. What I see happening presently is that people just do actions without understanding the why and how the underlying processes occur. Although this can be alleviating in the short term, it can be very dangerous in the long run.

By acting without understanding, people if they are lucky, they might hit the ball, but most likely they will miss it. If they fail, the consequences might not be apparent in the short term but they will be in the long run. By understanding, we for sure will decrease the likelihood of failure. This applies to any field of human knowledge including: science, medicine, business, politics, administration, the economy, etc. I think this is in big part the reason of the malaise we see these days.

Adolfo Cotter, MD

Jul 02/2012