Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice

Abstract

Diffusion tensor imaging (DTI) using variable diffusion times (t diff ) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At t diff = 30 ms, the diffusion anisotropy "volume ratio" (VR), diffusion perpendicular to the fibers (λ ⊥ ), and mean apparent diffusion coefficient (〈D〉) of the corpus callosum of shi mice were significantly higher than those of wt mice by 12 ± 2%, 13 ± 2%, and 10 ± 1%, respectively; fractional anisotropy (FA) and relative anisotropy (RA) were lower by 10 ± 1% and 11 ± 3%, respectively. Diffusion parallel to the fibers (λ // ) was not statistically different between shi and wt mice. Normalized T 2 -weighted signal intensities showed obvious differences (27 ± 4%) between wt and shi mice in the corpus callosum but surprisingly did not detect transplant-derived myelination. In contrast, diffusion anisotropy maps detected transplant-derived myelination in the corpus callosum and its spatial distribution was consistent with the donor-derived myelination determined by immunohistochemical staining. Anisotropy indices (except λ // ) in the corpus callosum showed strong t diff dependence (30-280 ms), and the differences in λ ⊥ and VR between wt and shi mice became significantly larger at longer t diff , indicative of improved DTI sensitivity at long t diff . In contrast, anisotropy indices in the hippocampus showed very weak t diff dependence and were not significantly different between wt and shi mice across different t diff . This study provides insights into the biological signal sources and measurement parameters influencing DTI contrast, which could lead to developing more sensitive techniques for detection of demyelinating diseases.

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

“…The FA values for the corpus callosum reported here from both ROI and fiber tracking analyses fall within the range of published values in rodents from ROI analysis (range: 32 to 75%) (Guilfoyle, et al, 2003;Harsan, et al, 2006;Nair, et al, 2005;Tyszka, et al, 2006;Verma, et al, 2005). The few studies in humans that have compared diffusion parameters calculated from fiber tracking and ROI analysis reveal that FA values obtained using the former method tend to be lower (Dubois, et al, 2006;Thomas, et al, 2005).…”

“…To date, the mainstay of diffusion imaging studies of the rodent brain have used high-field animal scanners (4.7-11.7T) (Guilfoyle, et al, 2003;Harsan, et al, 2006;Hoehn-Berlage, et al, 1999;Nair, et al, 2005;Tyszka, et al, 2006;Verma, et al, 2005;Zhang, et al, 2002). Additionally, because adequate signal-to-noise ratio (SNR) requires prolonged scan times, many of these experiments have been conducted on in vitro brain tissue.…”

“…Additionally, because adequate signal-to-noise ratio (SNR) requires prolonged scan times, many of these experiments have been conducted on in vitro brain tissue. Only a few studies report in vivo results (mice: (Guilfoyle, et al, 2003;Harsan, et al, 2006;Nair, et al, 2005); rats: (Boretius, et al, 2004;Hoehn-Berlage, et al, 1999;Lee, et al, 2006;Lin, et al, 2005;Numano, et al, ;). Most reports have displayed color orientation maps rather than fiber tracking, with exceptions being Xue et al , who demonstrated fiber reconstruction at 4.7T with 0.22 × 0.31 × 0.50-mm 3 resolution in 2 h, and Lee et al (Lee, et al, 2006), who reported quantitative fiber tracking at 1.5T in which 0.63 × 0.63 × 0.50-mm 3 resolution required 110 min of scanning.…”

Quantitative Differentiation Between Healthy and Disordered Brain Matter in Patients with Neurofibromatosis Type I Using Diffusion Tensor Imaging

“…Animal studies have shown that an increment of axial diffusivity ( 2 and 3 ) is related to myelin deficiency, whereas a decrease of parallel diffusivity ( 1 ) indicates axonal disturbance. [26][27][28] Our findings of higher values for 2 and 3 indicate that diffusion perpendicular to the white matter structure is higher. Because we did not find lower values for 1 in NF-1 regions with UBOs than in NF-1 regions without UBOs, we hypothesize that the observed changes of the brain tissue in NF-1 are not caused by damage to the axon, but relate to myelin deficiency.…”

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

“…DTI is likely to have similar properties in humans and experimental animals, as shown by comparisons between humans with multiple sclerosis and animal models of demyelinating diseases (Bammer et al, 2000;Filippi et al, 2001;Kim et al, 2006;Song et al, 2005). This method has been used to detect white matter pathology in experimental animal models of neurological diseases (Gaviria et al, 2006;Gulani et al, 2001;Nair et al, 2005;Ono et al, 1995;Song et al, 2004;Song et al, 2003;Song et al, 2005), including traumatic spinal cord injury (Deo et al, 2006;Nevo et al, 2001;Schwartz et al, 2005) by exploiting its sensitivity to white matter orientation. It can provide information about brain microstructure by quantifying isotropic and anisotropic water diffusion (Huisman et al, 2003;Neil et al, 2002;Sundgren et al, 2004).…”