(Stroke. 2004;35:92.)
© 2004 American Heart Association, Inc.
Original Contributions |
Editorial Comment— Finding Landmarks for Understanding White Matter Stroke
Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, United Kingdom
Stroke care has entered a new era of treatment rather than simply supportive care. However, the benefits of treatment also bring new risks. Considerable attention has been given to the problem of identifying features that may minimize risks of intracerebral hemorrhage with tissue plasminogen activator in consequence. It also is important to maximize benefit. One approach to this is establishing the prognosis for an untreated stroke at the earliest possible time after onset.
For 150 years, clinical-pathological correlations have been based on cortical localization; outcomes have been anticipated based on the location and extent of lesion involvement of the cortex. However, this powerful strategy has not addressed the problems posed by patients with predominantly white matter lesions. Unlike cortical anatomy, which can be defined from gyral surface structure, the anatomy of white matter has not been able to be defined clearly in individual brains. Because white matter has well-defined tracts leading between major cortical and subcortical regions and these show regular patterns of organization (eg, a region of somatotopically organized fiber bundles in the posterior limb of the internal capsule), important clinicopathological information would come from relating white matter organization to stroke localization directly.
There have been previous attempts to use a general template of white matter anatomy for understanding the relationship between stroke lesion distributions and outcomes. For example, Pineiro et al estimated the path of the corticospinal tract based on the major anatomic landmarks of the precentral gyrus and basal ganglia.1 Using a population-based, probabilistic description of the corticospinal tract defined in this way, they were able to demonstrate a good correlation between functional impairments in the contralateral limb and cross-sectional areas of lesions within the tract. More sophisticated and general models for segmenting white matter tracts based on surface anatomy have been proposed that could extend this type of analysis.2
Diffusion-weighted imaging (DWI) has been shown to be sensitive to early, largely irreversible brain tissue changes with ischemia.3 DWI provides a way of identifying the extent of lesions even within hours of onset. It is performed with application of a magnetic field gradient during the readout period in the MRI sequence: signal is lost (because the frequency of the signal, which is proportional to the magnetic field experienced, is dispersed) from water molecules with greater relative diffusion through the field gradient during this period. With the application of multiple gradients along different axes in rapidly acquired, serial images, the relative anisotropy and preferred directions for diffusion can be assessed from the relation between the relative magnitudes of signals and the directions of the field gradients applied. As the physical barriers of cell membranes constrain the diffusion of water molecules, water preferentially diffuses longitudinally along axons in white matter. Thus, by defining the preferred directions for diffusion, the net orientation of included white matter tracts can be estimated at each voxel (one common approach is to express the preferred diffusion direction as a "tensor," which is simply a 3-dimensional vector). From these voxel-by-voxel estimates, maps of white matter anatomy are generated in diffusion tensor imaging (DTI) (or with other, more general methods of diffusion tractography).4
In this issue, Lie et al provide a carefully considered and informative example of how this information could be used in clinicopathological correlations for stroke.5 They demonstrate that sufficiently precise descriptions of white matter anatomy can be defined with DTI to delineate the extent to which lesions (defined by DWI) impinge upon specific white matter tracts. This allows direct matching of lesion location with individual white matter anatomy. Fifteen patients with pyramidal tract syndromes were imaged in the subacute phase (3 to 7 days) after an ischemic stroke. The anatomic localizations and extent of lesions defined by DWI were visualized with respect to the major white matter landmark of the corticospinal tract, which was visualized by DTI, as well as the basal ganglia and thalamus.
Five distinct anatomic patterns for subcortical strokes were identified in the group. Not surprisingly, anatomic variations in stroke locations were associated with distinct clinical syndromes. More significant, however, was that the distribution of lesions could be related to outcome. Two clear subgroups were identified: those with marked deficits and poor recovery, who had long lesions centered on the corticospinal tract (often involving the basal ganglia), and those who showed a good spontaneous recovery and had smaller lesions located more anteriorly or medially. With the increasingly widespread availability of fast imaging at higher fields, diffusion MRI eventually should become commonly available routinely even in emergent situations, making this a potentially practical strategy outside of a research context. The major limitation to its use may be the sensitivity of the method to artefacts from subject movement.
While the method described involves substantial operator input for definition of the lesions and assessment of their relative localizations, improvements in image registration offer the potential for developing templates that could be matched automatically to individual DTI images and optimized for labeling of white matter structures. This would allow the relationship between lesions and white matter anatomy to be defined in an entirely automated fashion and provide a potentially practical method for establishing the likely prognosis soon after presentation. Explicitly probabilistic descriptions of tract anatomy could allow uncertainties in correlations between lesion and white matter anatomy to be quantified to better guide clinical decision-making. Just as approaches based on CT now are used to help identify patients with larger strokes involving the cortex who may best benefit from tissue plasminogen activator,6 a DTI-based approach could increase the precision with which this could be done for patients with subcortical infarctions.
The approach has even more general significance. A concern with the definition of lesions by DWI is that the contrast may not be sufficient at the earliest stages and before the onset of irreversible changes. However, subcortical clinical-anatomic localization can be performed using other mechanisms for generating lesion contrast, such as perfusion imaging.7 This potentially would allow useful prognostic data for subcortical strokes to become available at the time of first symptoms for rational risk-benefit assessments to guide new treatments.
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 Top References |
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- Pineiro R, Pendlebury ST, Smith S, Flitney D, Blamire AM, Styles P, et al. Relating MRI changes to motor deficit after ischemic stroke by segmentation of functional motor pathways. Stroke. 2000; 31: 672–679.
[Abstract/Free Full Text] - Meyer JW, Makris N, Bates JF, Caviness VS, Kennedy DN. MRI-based topographic parcellation of human cerebral white matter. Neuroimage. 1999; 9: 1–17.[CrossRef][Medline] [Order article via Infotrieve]
- Sotak CH. The role of diffusion tensor imaging in the evaluation of ischemic brain injury: a review. NMR Biomed. 2002; 15: 561–569.[CrossRef][Medline] [Order article via Infotrieve]
- Behrens TE, Johansen-Berg H, Woolrich MW, Smith SM, Wheeler-Kingshott CA, Boulby PA, et al. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci. 2003; 6: 750–757.[CrossRef][Medline] [Order article via Infotrieve]
- Lie C, Hirsch JG, Roßmanith C, Hennerici MG, Gass A. Clinicotopographical correlation of cortical spinal tract stroke: a color-coded diffusion tensor imaging study. Stroke. 2003; 35: 86–93.[CrossRef][Medline] [Order article via Infotrieve]
- Hill MD, Rowley HA, Adler F, Eliasziw M, Furlan A, Higashida RT, Wechsler LR, Roberts HC, Dillon WP, Fischbein NJ, et al, for the PROACT-II Investigators. Selection of acute ischemic stroke patients for intra-arterial thrombolysis with pro-urokinase ASPECTS. Stroke. 2003; 34: 1925–1931.
[Abstract/Free Full Text] - Yang Y, Frank JA, Hou L, Ye FQ, McLaughlin AC, Duyn JH. Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling. Magn Reson Med. 1998; 39: 825–832.[Medline] [Order article via Infotrieve]
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