Diffusion tensor imaging delivers crucial information

Tensor imaging and tractography are diffusion-based MR techniques for advanced functional imaging of brain white matter.¹ Imaging brain anisotropy can yield useful information about white matter integrity and demonstrate pathology occult to conventional imaging techniques. Anisotropy imaging can also provide information about ordered white matter (WM) tracts such as directional orientation and connectivity, which can be critical in surgical planning and useful in the understanding of certain developmental and acquired disease states.

With appropriately applied magnetic field gradients, MR images can be sensitized to diffusion, or the random thermally driven motion of water molecules in tissue. Water movement is essentially random in brain gray matter, but diffusion is anisotropic, or directionally oriented, in WM tracts. There, axonal membranes and myelin sheaths present barriers to water motion in directions other than parallel to fiber orientation. The direction of maximum diffusivity coincides with WM fiber tract orientation.

This information is contained in the diffusion tensor, a mathematical model of diffusion in 3D space. The tensor is a matrix of numbers derived from diffusion measurements in at least six different directions from which diffusivity in any direction can be estimated and the direction of maximum diffusivity can be determined.

The tensor matrix can be visualized as an ellipsoid. The diameter in any direction estimates the diffusivity in that direction, and the major principal axis is oriented in the direction of maximum diffusivity. The degree to which the diffusion tensor shape differs from that of a sphere (random motion) represents anisotropy (ordered motion).

With diffusion tensor imaging (DTI), the degree of anisotropy as well as local fiber orientation can be mapped, providing an opportunity to study WM architecture and evaluate fiber integrity.

WM fiber tracts are classified as association, projection, or commissural fibers. Association fibers connect cortical areas in each hemisphere (Table 1). Projection fibers connect cortical areas with deep nuclei, brain stem, cerebellum, and spinal cord (Table 2). Commissural fibers connect similar cortical areas between opposite hemispheres (Table 3). Three-D tract rendering is accomplished with commercially available software that can be found on the scanner or workstation. While individual tract parsing is imperfect, in some circumstances incompletely extracting individual tracts, these techniques are still quite efficacious at display and evaluation of the ordered WM.

CLINICAL UTILITY

Parameters derived from the diffusion tensor, such as relative and fractional anisotropy, have been used to evaluate multiple disease states, including adrenoleukodystrophy, multiple sclerosis, and AIDS. Anisotropy imaging (AI) has been studied in the evaluation of hypertensive encephalopathy, leukoariosis, and aging changes.

Use in neuropsychiatric disorders such as traumatic brain injury reveals reductions in anisotropy corresponding to regions of injured brain. Schizophrenic patients show reduction in anisotropy in frontal white matter pathways similar to the pattern of reduction seen with perfusion imaging. In Alzheimer's disease, reduced anisotropy that has been reported in the corpus callosum, as well as in the fronto-occipital and thalamofrontal tracts, corresponds to the loss of coherence between the frontal and occipital lobes seen on electroencephalogram testing.²

AI and DTI have been used in the workup of patients with epilepsy, revealing loss of anisotropy in tracts such as the fornix and hippocampal stria. These results supplement information obtained with structural MR imaging and EEG testing and guide the localization of atrophic lesions such as hippocampal sclerosis.

DTI has also been used to investigate brain development and assist in understanding the organization of the brain white matter in developmental brain abnormalities, often demonstrating additional findings beyond those seen with conventional MR imaging (Figure 1).³

SURGICAL PLANNING

The preservation of vital cerebral function while maximizing lesion resection is the principal goal in brain neurosurgery. Cortical mapping can be accomplished intraoperatively with electrocortical stimulation. Preoperatively, functional MR techniques such as blood oxygen level-dependent (BOLD) imaging are used in the localization of eloquent cerebral cortex. Neither cortical mapping nor BOLD imaging provides information about WM tracts in or adjacent to brain lesions, however. Two-D and 3D WM tractography techniques can be very powerful in elucidating relationships of deep brain lesions to eloquent brain structures, assisting in the estimation of the impact of surgical intervention and lesion resection on brain function.⁴

At New Jersey Neuroscience Institute, DTI is part of the imaging workup of all lesions being considered for surgical resection. White matter imaging is used to estimate the relationship of the lesion to tracts responsible for brain activity such as motor function (corticospinal tracts). DTI techniques are also employed to estimate the effect of surgical intervention on residual language (superior longitudinal and arcuate fasciculus) or vision function (geniculocalcarine tracts, or optic radiations). DT tractography, which requires five to seven minutes to scan and is easily processed with commercially available software, is practical and easily integrated into the armamentarium of techniques of the high-end neurologically oriented clinical practice, as shown in the following examples.

Case study one. A 13-year-old girl, diagnosed at an outside institution with a low-grade thalamic glioma, was referred to the New Jersey Neuroscience Institute for evaluation for resection. As a critical part of the planning process, surgeons requested a 3T MR study for detailed anatomic delineation and functional localization. Imaging revealed a well-circumscribed, nonenhancing left thalamic mass distorting local anatomy and obscuring relationships with the adjacent internal capsule. Definitive localization of the blue corticospinal fibers coursing in a cephalocaudal direction was made possible by the directionally encoded 2D tensor images (Figures 2 and 3).

These images, along with 3D tractograms seeded and grown from the ipsilateral precentral gyrus WM, showed that the lesion displaced the posterior limb of the internal capsule laterally and inferiorly. The anterior limb of the internal capsule, coded in green as its fibers course anteroposteriorly, was displaced anteromedially. Armed with this functional information, the surgeon resected from a medial approach. After several days, the patient was discharged with no motor deficit after resection.

Case study two. A 35-year-old woman with seizures presented with an outside institution MR study showing a left temporal lobe hemorrhage and other findings suspicious for the presence of an arteriovenous malformation. The patient was referred to Edison Imaging for definitive 3T MR evaluation of the presence of an AVM as well as estimation of the functional significance of lesion resection. Time-resolved contrast-enhanced MRA confirmed the presence of an AVM within the left temporal lobe. Functional MR with BOLD imaging clearly defined the central sulcus and sensorimotor cortex on the surface of the brain but yielded little information related to the surgical approach to the temporal lobe lesion (Figures 4 and 5).

Three-D tractography demonstrated that the lesion and hematoma were separate from the superior longitudinal fasciculus. The optic radiations and inferior longitudinal fasciculi had been destroyed by the lesion, and thus function was not likely to deteriorate further as a result of surgical treatment of the AVM.

Case study three. A 60-year-old patient with a solitary metastatic focus was referred for consideration of resection. Routine anatomic imaging at 3T showed a hypointense metastasis in the vicinity of eloquent cortex. Three-D tractograms obtained by seeding the pre- and postcentral gyri, as determined by BOLD imaging, confirmed the lesion was posterior to the sensory cortex, allowing lesion resection without deficit (Figure 6).

Case study four. A 40-year-old patient with a recurrent high-grade glioma was referred for consideration of lesion debulking. BOLD imaging readily marked the central sulcus, showing that the enhancing portion of the lesion was well posterior to eloquent cortex. Localization of WM fibers with respect to the deeper portions of this large neoplasm was facilitated by 3D tractography. The corticospinal fibers were clearly displaced and bowed anteriorly by the tumor. Lesion debulking did not produce a motor deficit (Figure 7).

Case study five. A 42-year-old man presented with seizures, and 3T MR imaging revealed a cavernous malformation within the occipital lobe. The goal of neurosurgery was to resect the lesion with minimal disruption of visual function. Tractography demonstrated that the lesion was lateral to the optic radiations and largely inferior and posterior to the inferior longitudinal and inferior occipitofrontal fasciculi, leading to an inferiorly angled superior and posterior approach to lesion removal (Figures 8 and 9).

CLINICAL IMPACT

Advanced imaging tools using diffusion tensor imaging and tractography are poised to make a significant impact in the clinical imaging of patients with neurological disease. Yielding structural and functional information about ordered white matter pathways in the brain, DTI assists in the understanding of various disease states, identifying conditions occult to structural imaging, and providing relational information critical to neurosurgical decision making. The studies, which can be acquired and processed in a practical and efficient manner, are applicable in any setting involving the high-level practice of neuroimaging.

Dr. Tanenbaum is section chief for MR, CT, and neuroradiology at Edison Imaging-JFK Medical Center, New Jersey Neuroscience Institute, Seton Hall School of Graduate Medical Education.

References

1, Jellison BJ, Field AS, Medow J et. al. Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. AJNR 2004;25:356-369.

2. Benziger TLS. Radiologic Approach to Alzheimer's disease and other dementias. Applied Radiology 2005;Suppl:25-33.

3. Lee SK, Kim DI, Kim J et. al. Diffusion-tensor MR imaging and fiber tractography: A new method of describing aberrant fiber connections in developmental CNS anomalies. Radiographics 2005;25:53-68.

4. Witwer BP, Moftakhar R, Hasan KM, et. al. Diffusion tensor imaging of white matter tracts in patients with cerebral neoplasm. J Neurosurg. 2002;97(3):568-575.

Fiber Types and Location

Association Fibers

- Cingulum

- Superior occipitofrontal fasciculus

- Inferior occipitofrontal fasciculus

- Uncinate fasciculus

- Superior longitudinal (arcuate) fasciculus

- Inferior longitudinal (occipitotemporal) fasciculus

Projection Fibers

- Corticospinal tracts

- Corticobulbar tracts

- Corticopontine tracts

- Geniculocalcarine tracts (optic radiations)

Commissural Fibers

- Corpus callosum

- Anterior commissure