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The DTI parameters showed age-related changes in healthy

volunteers. FA increased and RD and MD decreased in all VOIs

(

P

<

.001). AD in CST and ML did not show significant changes

(

P

>

.126) but decreased in other regions (

P

<

.006). FA of the

patient group negatively deviated from the normal age-related

change (ie,

a

2

<

0) and was statistically significant in the entire

pons, dTPF, vTPF, and MCP (

P

<

.004). AD and RD also showed

negative deviations for all VOIs (

P

<

.034) except for dTPF and

vTPF, where RD deviated positively (

a

2

>

0,

P

<

.023). The

deviation from the normal pattern was not strongly dependent on

individual differences of dose (ie,

a

3

dose was not significant)

for most VOIs. Only CST showed a significant relation between

AD reduction and dose (

a

3

<

0,

P

Z

.03).

The pairwise comparison between the pons and midbrain

showed that the decrease of FA in the pons was more pronounced

than that in the midbrain

( Fig. 3 a

). The ratio of the normalized FA

between the pons and midbrain showed a negative trend (

b

3

Z

0.065,

P

<

.001). The ratios of the normalized AD and MD also

showed significantly negative trends (

P

<

.001).

Further pairwise comparisons on substructures revealed that

the temporal changes of DTI parameters were not uniform within

the pons.

Figure 4

shows the FA maps of the pons for a patient at

baseline and the 2 follow-up times. The decrease of FA in TPF

was manifested 18 and 45 months from the baseline. By contrast,

FA in the CST and ML showed smaller reductions at 18 months

and recovered to the baseline level at 45 months.

Figure 5

shows

comparisons of the temporal changes of the normalized FA of the

CST and dTPF for all 42 patients. In most cases, dTPF showed

a greater drop than CST and remained at the lower value, whereas

CST either showed a smaller reduction or eventually recovered to

the baseline level.

The statistical analysis confirmed that the ratio of normal-

ized FA between the dTPF and CST showed a significantly

negative trend (

b

3

Z

0.135,

P

<

.001)

( Fig. 3 b

). The analysis

with other DTI parameters was consistent with this result.

Taken together, these results suggest that compromised struc-

tural integrity is more pronounced in the dTPF than in CST:

dTPF showed more significant decrease in AD, increase in RD,

and increase in MD than did the CST (

P

<

.001 for all

comparisons)

( Fig. 3

b). Similar results were found when the

dTPF was compared with the ML or the MCP

( Fig. 3 c

, d). On

the other hand, no significant differences were observed for the

pairs dTPF/vTPF, ML/CST, and MCP/CST in any of the DTI

parameters

( Fig. 3 e

-g). In summary, the TPF showed more

changes reflecting white matter injury than did the CST, ML,

and MCP at the level of pons, regardless of dorsal or ventral

compartments, whereas there were no significant differences

among the other 3 VOIs.

This regional variation of the temporal changes could not

be explained unequivocally by the dose distribution. Although

Fig. 2.

Average doses in the volumes of interest over the 42

patients. Error bars indicate standard deviation. CST

Z

cortico-

spinal tract; dTPF

Z

dorsal transverse pontine fiber; MCP

Z

middle cerebral peduncle; ML

Z

medial lemniscus; vTPF

Z

ventral transverse pontine fiber.

Fig. 3.

Pairwise statistical comparison of the temporal changes of diffusion tensor imaging parameters between pairs of volumes of

interest. Comparisons between (a) Pons and Midbrain, (b) dTPF and CST, (c) dTPF and ML, (d) dTPF and MCP, (e) dTPF and vTPF, (f) ML

and CST, and (g) MCP and CST are presented. The number in the ordinate is

b

3

in the statistical model equation (see text) that indicates the

temporal change of the volume of interest in numerator with respect to the one in denominator. Error bars indicate standard error. AD

Z

axial diffusivity; CST

Z

corticospinal tract; dTPF

Z

dorsal transverse pontine fiber; FA

Z

fractional anisotropy; MCP

Z

middle cerebral

peduncle; MD

Z

mean diffusivity; ML

Z

medial lemniscus; RD

Z

radial diffusivity; vTPF

Z

ventral transverse pontine fiber.

Volume 86 Number 2 2013

Differences in brainstem fiber tract response

295