Pearls and Pitfalls of MR Diffusion in Clinical NeurologyDr. Alberto Bizzi Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan, Italy Email: firstname.lastname@example.org Diffusion Tensor Imaging (DTI)(1) measures the effects of tissue microstructure on the random walks (brownian motion) of water molecules in the brain. In tissues with an orderly oriented microstructure, such as the cerebral white matter, the measured diffusivity of water varies with the tissue’s orientation (anisotropic diffusion). Water diffuses fastest along the principal direction of the fibers, and slowest along the cross-‐sectional plane. The DTI model provides the required information to construct a diffusion ellipsoid in each voxel of an imaging volume. DTI measures the diffusivities of water molecules along the three orthogonal axes of the ellipsoid (eigenvalues) and their average (mean diffusivity). Fractional anisotropy is a measure of eccentricity of the displacement of water molecules. In the healthy human brain probably the most relevant factor affecting fractional anisotropy is the intravoxel orientation coherence of white matter fibers(2). There are three main imaging output of DTI MR imaging: quantitative parametric maps displayed in gray scale (i.e. fractional anisotropy maps), color maps showing the principal orientation of diffusion for each voxel and 3 dimensional maps showing virtual dissection of tracts with streamline tracking methods. In the interest of time in the oral presentation we’ll focus on diffusion MR Tractography and its clinical application in brain tumors, stroke, multiple sclerosis, prion disorders and neurodegenerative diseases (Alzheimer, Amyotrophic Lateral Sclerosis). The aim of MR Tractography or fiber tracking is to infer the three-‐dimensional trajectories of white matter bundles by piecing
together discrete estimates of the underlying continuous fiber orientation field measured non-‐invasively with DTI data(3, 4). Fiber tracking algorithms can be broadly classified into two types: deterministic and probabilistic. Few DTI Tractography atlases for virtual in vivo dissection of the principal human white matter tracts using a deterministic approach have been recently published(5-‐7). Few limitations of fiber tracking performed with the deterministic approach motivated the development of probabilistic tracking algorithms(5). It is very important to understand well the inherent limitations of all methods of DTI-‐based virtual dissections and measurements. One important limitation is that in each voxel the eigen vector is the average of the orientation of all bundles included in the voxel. In volumes of white matter with many crossing bundles, as in the frontal and parietal paraventricular white matter, fractional anisotropy is low and the degree of uncertainty in the estimation of bundle orientation increases. An attempt to overcome the limitation of crossing fibers has been addressed with the development of more sophisticated imaging acquisition schemes using high angular resolution diffusion imaging (HARDI)(6). It is important to emphasize that, given the relative size differences between the individual axons (1–5 micron) and voxels (2–3 mm) size, it is possible to observe white matter anatomy only from a macroscopic point of view with MR Tractography. Notwithstanding, the anatomic detail provided by MR Tractography with 10-‐15 min of MR acquisition is unparalleled. Encouraging results with DTI have been reported in several neurological disorders: brain tumors, stroke, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease and other dementias. In the interest of time we’ll focus on the application that is probably closer to become of clinical use: diffusion MR Tractography in presurgical planning. The integration of functional data acquired with fMRI and MEG into the navigational data sets has improved quick identification of eloquent cortex with intraoperative ESM in the operating room. To avoid postoperative neurological deficits, however, it is also necessary to preserve the white matter tracts connecting eloquent cortex.
Diffusion MR Tractography has recently emerged as potentially valuable clinical tool for presurgical planning(7-‐9) and intraoperative imaging-‐guided navigation in the operating room(10). Diffusion MR Tractography can provide the neurosurgeon with additional information about brain anatomy, pathology and architecture that conventional MRI methods cannot. Fig. 1 -‐ Directionally encoded color maps in a 65 years old male with glioblastoma multiforme in the left dorsolateral prefrontal region. The mass has infiltrated the superior longitudinal fasciculus, including the arcuate fasciculus (displayed in green, see cursor). The directionally encoded color maps, with hues reflecting tensor orientation and intensity weighted by fractional anisotropy, provides an aesthetic and informative synthesis of tissue microstructure and architecture. The color maps are a promising tool for delineation of tumor extent and infiltration. DTI color maps indicate whether a mass is displacing, infiltrating or destroying the main white matter tracts(11). MR Tractography can be used to virtually dissect functionally critical white matter tracts, such as the corticospinal tract and the arcuate fasciculus (AF), enabling the neurosurgeon to identify and preserve the tract during resection(12). It has been shown that acquisition of DTI color maps is feasible also in the operating room with intraoperative 1.5 Tesla MR scanners. Intraoperative DTI can depict shifting of major white matter tracts that may occur during surgical removal of the mass. It has been shown that shifting of brain structures may be
unpredictable, therefore intraoperative updating of the navigation system is strongly recommended(10). Fig. 2 – Streamlines of the three segments of the left arcuate fasciculus (AF: long segment in red, anterior in green, posterior in yellow) are displied on the diffusion-‐weighted image at the level of a mass in the left posterior mesial temporal lobe. In this 70 years-‐old male with glioblastoma multiforme, MR Tractography was essential to demonstrate that the mass had not destroyed but only displaced the AF posteriorly and laterally. Streamlines of the AF confirmed that most of the fasciculus was intact. Three dimensional objects of preoperative virtually dissected tracts can be reliably integrated into a standard neuronavigation system, allowing for intraoperative visualization and localization of the main tracts(13). MR Tractography may show the relationship of the mass to the virtually dissected AF. Virtual dissection of the three segments of the AF may show whether the mass has partially interrupted or only displaced each of the three segments of the AF. Display of MR Tractography results may also be useful in the operating room when the neurosurgeon is approaching an important bundle and he wants to reinforce his anatomical orientation in the operating field and consider
whether to use subcortical ESM to test the functional relevance of a specific tract(14). Fig. 3 – Streamlines of the left inferior frontal occipital fasciculus (IFOF) and fMRI (sentence comprehension task) are overlaid on FLAIR images, neuronavigator-‐ready for guiding surgery in the operating room. In this 62 years-‐old woman with fibrillary astrocytoma in the left temporal pole, MR Tractography demonstrated that the mass had partially interrupted the uncinate fasciculus (UF, not shown), while the IFOF (in pink) appears intact. Note the close relationship of the left IFOF with the hyperintense mass in the temporal pole. Modern cognitive models of language have shown that there is a lot of redundancy in the language network. It is of paramount importance to identify those bundles that if severed may cause permanent language deficits. Definition of which bundles are functionally eloquent and have to be absolutely spared during resection remains an important issue. There is a long list of important limitations(15). Few are inherent to the DTI and the MR Tractography technology and they must be well understood
before the results of presurgical MR Tractography dissections can be safely exported to the operating room. It is not yet established whether resection of fibers apparently infiltrated by the tumor that appear to be interrupted or destroyed on diffusion MR Tractography will result in permanent postoperative neurologic deficits(15). Nevertheless, it should be established whether resection of fibers that on MR Tractography appear to be interrupted within the tumor will cause permanent postoperative deficits. On the contrary, it has been shown many times that severing of the pyramidal tract will cause hemiplegia. Whether severing of one of the many language connections will cause aphasia is currently a controversial issue(16). In conclusion, diffusion MR Tractography has emerged as a valuable tool in the evaluation of motor and language pathways both in healthy individuals and in patients with neurological disorders. In healthy subjects they are contributing to refine current cognitive and anatomic models. Not only they have confirmed several theories about language processing, but they have also raised unexpected important questions. In patients with brain tumors they have obtained recognition as valuable presurgical clinical tools in the determination of hemispheric dominance and in the selection of candidates who may benefit from awake craniotomy.
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