About me

Juan Eugenio Iglesias is a postdoctoral researcher at the Basque Center on Cognition, Brain and Language (BCBL). He did his Ph.D. at the Laboratory of Neuro Imaging at UCLA. His research interests lie mainly within the computerized analysis of brain MRI scans. You can visit his research website here: http://www.jeiglesias.com

Hay una versión de este blog en Español; puedes encontrarla aquí: http://analisis-imagenes-medicas.blogspot.com

Thursday, November 19, 2015

Ex vivo MRI scanning (a.k.a. scanning dead brains)

Imagine you were taking a photograph in a room with very dim lightning. You could still take a picture if you use a very long exposure: by keeping the shutter open for a long time, you can collect enough light to create your image. A problem with this approach is that it only works if the object we’re imaging remains completely still. If the object (or person) or the camera moves, we obtain a blurry picture.

A blurry photograph

A similar thing happens with MRI. Obtaining MRI images al ultra-high resolution requires very long scanning times (tens of hours), so it is inevitable that the subject being scanned moves during that period of time. For that reason, practical MRI scanning protocols are usually shorter than 10 minutes. However, if we want to build accurate, high resolution models of brain anatomy, there is a way of overcoming the restrictions imposed by subject motion: using ex vivo brains from cadavers. 

The idea is as simple as this: dead brains don’t move, so we can scan them as long as we want without motion artifacts. Unfortunately, scanning ex vivo brains the same way we scan in vivo (meaning, living brains in living people) does not work. The reason is that the fixation process (immersion in formalin for preservation of the sample) changes the magnetic properties of the tissue. Moreover, the formalin and air bubbles introduce image artifacts that degrade the quality of the scan. 

An ex vivo brain scanned in formalin. The red arrows point at artifacts created by air bubbles

What can we do to fix this? One way is to replace the formalin by a fluid that is transparent to MRI. Since MRI is based on detecting and measuring protons, we can use a proton-free fluid. Many studies use a lubricant called Fomblin. We use a cheaper (and less slippery) alternative called Fluorinert. 

Slice of a ex vivo brain scanned in Fluorinert

Once we have fixed the problem with the artifacts, we have yet another problem. The hardware of clinical scanners like the one we have at the BCBL is not meant to acquire images at ultra-high resolution. For this reason, when we try to acquire a big 3D scan, the machine runs out of memory during the reconstruction (the process of transforming MRI measurements into images). This problem can be overcome by acquiring different parts of the image separately and then stitching them together. The strategy is normally to acquire several slabs that can subsequently be stacked to create our final scan. 

Stacking slabs to create a MRI scan

 Stacking slabs enables us to bypass the memory limitations of the scanner, but it introduces yet another artifact: the Venetian blind. This is because the sensitivity of the scanner is not uniform across each slab; instead, it is lower in the first and last couple of slices of each slab. If we acquire the whole 3D scan in one shot, this is not a problem, because the first and last slabs do not cover the brain anyway. But when we stack slabs, we get patterns that resemble a Venetian blind.

Venetian blind artifact

As bad as this might look, there is a bunch of image analysis algorithms you can use to correct for this artifact. Here I’ll show you the output from an algorithm that we have developed ourselves, and which also corrects for intensity inhomogeneities (more on that another day; for now, let’s just say that it’s an artifact that makes some regions brighter than others).

Before (left) and after correction with our method (right)

These are pretty pictures, right? Let’s look at a close-up of the hippocampus, and compare with a standard resolution in vivo scan.

Left: standard resolution (1 mm). Right: ex vivo scan (0.25 mm)

What will we do with these beautiful scans? That remains for a future post ;-)

Thursday, July 2, 2015

The THALAMODEL project: visiting Dr. Insausti

A couple of days ago, we went to Albacete to visit Dr. Ricardo Insausti, full professor in human anatomy and embryology at the University of Castilla - La Mancha (UCLM). Dr. Insausti is going to be an instrumental part of the THALAMODEL project. He is going to find the donors whose brains we will use to build our models; and then he is going to extract the brains and carry out their fixation with formalin.

Brain fixation is critical to study the brain ex vivo (meaning, outside a living body). If a brain sample is not fixated soon after death, it deteriorates quickly due to the blood supply. After the fixation, the brain can be preserved for a long time.

Dr. Insausti, holding a fixed human brain

 Dr. Insausti is also going to carry the histological study. Such study consists of two different phases: slicing the brain, and staining the slices. In order to slice the brain (or in our case, a block of tissue around the thalamus) into very thin sections, one first freezes the sample with dry ice and then sections it with a machine called "microtome". As opposed to thicker blocks of tissue, these thin slices can be examined under the microscope.

Rather than looking at the slices directly, one enriches their contrast first through a staining process. Different types of stains and dyes can be used to enhance different properties of the tissue. The most popular technique is arguably Nissl staining, invented by Franz Nissl in the late 19th century. After staining, the samples are mounted on slides that protect them, and can then be examined with a microscope.

Nissl-stained slice of human thalamus
Looking at mounted slides with samples of a human hippocampus
 Finally, Dr. Insausti will use the stained slices to manually trace the boundaries of the thalamic nuclei. This information will be critical for us to build the thalamic atlas which is at the core of our project. How we go from slices of the thalamus to a 3D atlas of the thalamic nuclei will be discussed in future posts.

Tuesday, June 2, 2015

The THALAMODEL project: thalamus and dyslexia

Location of the thalamus (in red)
I have recently been awarded a Marie Skłodowska-Curie individual fellowship to build a probabilistic atlas of the thalamus, as well as a set of tools that enable us to use the atlas to automatically analyze the thalamic nuclei brain MRI scans from neuroimaging studies. The title of the project is “Multimodal, high-resolution modeling of the thalamus for neuroimaging studies: application to dyslexia”, and the funding is from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement number 654911.

Why the thalamus? Located between the cortex and the midbrain, this cerebral structure is the main relay station of the brain: it is connected by fibers to virtually the entire cerebral cortex. In addition, the thalamus is related to the regulation of consciousness and sleep, and it is also closely related to language. The relationship with language has been proven in case studies involving thalamic lesions and electrical stimulation of the thalamus. However, it is still unclear whether this relationship is due to the connection between the thalamus with cortical regions related to language, or due to its involvement in the integration of language functions via memory.

Moreover, the thalamus has been linked to some of the most common language disorders, including dyslexia, a condition in which individuals with normal intelligence have serious problems learning to read. Dyslexia is the most common neurobehavioural disorder in children, on which it has a terrible impact: it causes severe disadvantages in school development, education and self-esteem that greatly increases the risk of social marginalization later in their lives.

This project aims for building a detailed atlas of the thalamic nuclei using multimodal imaging data from autopsy brain samples, and for creating companion image analysis tools that can use the atlas to analyze the thalamic nuclei in in vivo brain MRI data (that is, from living people) from neuroimaging studies. The project consists of four major steps. First, we plan to acquire ultra-high resolution MRI data of the autopsy samples. Since these samples don’t move (for obvious reasons), we can make the MRI acquisition very long therefore with very high resolution. Second, we will slice the brains to perform a microscopic anatomical study (known as “histology”) of the samples. The ultra-high resolution MRI and the histology images will allow us to build a thalamic atlas with very high level of detail. Third, we will create the tools that enable us to use the atlas in the analysis of in vivo data. And fourth, we will make the tools publicly available and apply them to a dyslexia study at the BCBL. Hopefully, the new tools will allow us to better understand this disorder, while enabling researchers at other institutions to improve their understanding of this cerebral structure by carrying out analyses at a higher level of detail - compared with current tools.

I will regularly post here with the progress of the project; stay tuned!