Saturday, September 25, 2010

Quantitative white matter fiber analysis: a short history (Part II)

Part II: Imaging

This is the second of three parts. Parts I and III are here and here.

With the advent of soft tissue imaging technology--computed tomography (CT) in 1972 and magnetic resonance imaging (MRI) in 1977--it was possible to examine living brains. In 1982, physicians saw multiple sclerosis (MS) lesions for the first time in a live patient. Since then, clinicians have increasingly relied on brain scans for diagnosis and treatment. With this in vivo technology, disease progression in patients could be tracked by physicians and researchers, either individually, or as part of a longitudinal study of cohorts. This has led to a better understanding of white matter degenerative disease and has improved treatment options.

The MR signal can be assessed in different ways and the 1990s saw the emergence of two important MRI modalities. The first, Seiji Ogawa's 1990 proposal to use contrasts in blood oxygen response to map changes in brain activity, led to the development of functional magnetic resonance imaging (fMRI). The ability to view the brain in real time was a big step forward; it enabled us to study brain function and is responsible for the widespread use of fMRI among clinical neurologists, behavioral scientists, neuroscientists and others.

Diffusion tensor magnetic resonance imaging (DTI) was the second important MRI modality introduced. Water constitutes a big part of living tissue--white matter is 72% water--and the physical flow of fluid is described by a diffusion process. In 1994, Peter Basser, James Matiello and Denis Le Bihan, in a landmark paper, proposed a tensor model for diffusion where the flow of water was described by the magnitude and direction of the principal eigenvector at each image voxel. White matter fibers are inherently anisotropic and the first applications of DTI were studies of neural connectivity where fibers were tracked from end to end. Since the resolution of DTI is at the cellular level, it was also possible to detect disease--through indices such as fractional anisotropy (FA)--before it appeared in conventional MRI scans. Normal appearing white matter (NAWM) in MS is one example where compromised integrity manifests through lower FA values.

A second-order tensor model is adequate for DTI reproductions of coherent fiber tracks but in cases where fibers meet or cross, only one of these directions is retained. DTI tractography of callosal fibers, where the lateral projections are attenuated, is illustrative of this limitation. To overcome this shortcoming, high angular resolution diffusion imaging (HARDI) images acquired in several spatially uniform directions has been used. An orientation distribution function (ODF) that can model multiple maxima representing the different fiber directions replaces the simple tensor model at each voxel. HARDI datasets offer better resolution for important DTI applications such as connectivity studies and preoperative investigations.

Saturday, September 18, 2010

Quantitative white matter fiber analysis: a short history (Part I)

Part I: Histological investigation
This is the first post in a three part series. Parts II and III are here and here.

The modern scientific study of white matter has its roots in the 19th century when links were being established between mental dysfunction and neuroanatomy. Correlations made between postmortem abnormalities in the brains of mental patients and clinical evaluations while they were living led to important discoveries. The identification of the arcuate fasciculus as a language pathway that connected the two language centers, the Broca and Wernicke regions, is one famous example. In that case, Carl Wernicke, who was developing language network models, made the association between lesions in the arcuate fasciculus and the various aphasias he had observed.

The impetus from these investigations crossed over to other developments. Theodor Meynert, the reputed neuroanatomist, had classified prominent white matter tracts or fasciculi, as they were known, based on the kinds of connections they made. Burdach and Déjérine published postmortem atlases, and both prominently included white matter dissections. New techniques for histopathological analysis were introduced. Notable among these was Camilio Golgi's staining method and Santiago Ramón y Cajal's use of it in his histolgical studies of nerve fibers.

Quantitative white matter fiber analysis benefited from these cumulative efforts which made studies in fiber thinning, demyelination and microstuctural damage possible. Today, postmortem dissections still give the most precise quantitative assessments.

Note of appreciation: This write-up was compiled based partly on Marco Catani's--I have pointed him out before--voluminous publications. He writes exceedingly well on the subject of language networks and related themes.