Characterization of T(2)* heterogeneity in human brain white matter

Abstract

Recent in vivo MRI studies at 7.0 T have demonstrated extensive heterogeneity of T(2)* relaxation in white matter of the human brain. In order to study the origin of this heterogeneity, we performed T(2)* measurements at 1.5, 3.0, and 7.0 T in normal volunteers. Formalin-fixed brain tissue specimens were also studied using T(2)*-weighted MRI, histologic staining, chemical analysis, and electron microscopy. We found that T(2)* relaxation rate (R(2)* = 1/T(2)*) in white matter in living human brain is linearly dependent on the main magnetic field strength, and the T(2)* heterogeneity in white matter observed at 7.0 T can also be detected, albeit more weakly, at 1.5 and 3.0 T. The T(2)* heterogeneity exists also in white matter of the formalin-fixed brain tissue specimens, with prominent differences between the major fiber bundles such as the cingulum (CG) and the superior corona radiata. The white matter specimen with substantial difference in T(2)* has no significant difference in the total iron content, as determined by chemical analysis. On the other hand, evidence from histologic staining and electron microscopy demonstrates these tissue specimens have apparent difference in myelin content and microstructure.

FIG. 1

A set of T₂*-weighted images acquired at 7T from a normal human brain. The acquisition parameters were: TR/TE=800/30 ms, flip angle=30°, receiver bandwidth=32 kHz, matrix size 1024×768, FOV=220×165 mm², slice thickness=1 mm. Substantial contrast difference is seen between gray matter, CSF, vessels, and white matter. Also remarkable is the contrast difference between the different fiber projections. The labeled white matter bundles include: superior region of corona radiata (SCR); Splenium of corpus callosum (SPL), genu of corpus callosum (GCC), external capsule (EC), superior frontal-occipital fasciculus (SFO), tapetum (Tap), posterior region of coronal radiata (PCR), superior longitudinal fasciculus (SLF), anterior commissar (AC), and cingulum (CG).

FIG. 2

The T₂* relaxation rate (R2* =1/T₂*) for the different white matter fiber bundles as a function of the main magnetic field strength. The lines are least square fit of the equation R₂*=α+β*B₀. The fitting results for each fiber bundles are detailed in Table 2. Increasing the main magnetic field strength from 1.5T to 7.0T, the T₂* relaxation contrast heterogeneity is significantly enhanced by more than 4 times.

FIG. 3

(a) a T₂*-weighted image acquired at 7.0 T in a coronal slab of formalin fixed brain tissue across the cingulate cortex. The acquisition parameters were: TR/TE=800/20 ms, flip angle=30°, receiver bandwidth=32 kHz, matrix size 1024×512, FOV=200×100 mm², and slice thickness=1 mm, NEX=3. As detected in the living human brains, in the fixed brain tissue specimen there is also substantial contrast different between the superior region of corona radiata (SCR) and cingulum (CG). (b) myelin (Luxol fast blue) staining result for the SCR fiber bundle; (c) axonal staining (Bielschowsky's Silver Stain method) result for the SCR region. (d) myelin staining result for cingulum. (e) axonal staining result for the cingulum region. The myelin and axonal stains demonstrate that the white matter fiber bundles SCR and CG differ substantially in myelin content and axonal microstructure.

FIG. 4

(a) Transmission electron micrograph of superior region of corona radiata (SCR) showing less compact myelinated axons. The orientations of the axons are also less coherent. The magnification is 10,000×. (b) Transmission electron micrograph of cingulum showing more compact and coherent oriented axons. The magnification is 10,000×.