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26 BAKER ET AL.

segment of the cingulum compared with their MM fiber length was additionally associated with worse
counterparts (44). Our group has also revealed that performance on tests of executive functioning and
higher body mass index (BMI) was independently processing speed in the SIVD group. Effect sizes were
and significantly associated with shorter white mat- consistently smaller for average FA values compared
ter FBL in the temporal lobe (9). with qtDTI metrics, suggesting that qtDTI may be a
While age may represent a salient factor in white more robust indicator of white matter tract damage
matter integrity of a healthy older adult population, in SIVD compared with traditional DTI scalar met-
additional factors such as BMI and genetic poly- rics.
morphisms can contribute to subtle, yet identifiable,
alterations to white matter fiber bundles that are STRENGTHS AND LIMITATIONS OF qtDTI
detectable with qtDTI. Collectively, these three TECHNOLOGY
studies lend support to the utility of qtDTI in the The first major strength is that qtDTI provides
assessment of cerebral white matter changes asso- multi-faceted measurements of fiber bundles that pro-
ciated with common risk factors that often lead to vide complementary measures, such as FBL, volume,
suboptimal brain health in older adults. FA, and MD, that can detect and gauge the magni-
tude of various aspects of white matter anatomy. As
APPLICATION OF qtDTI TECHNOLOGY TO discussed earlier, FBL can provide a valuable signal
DETERMINE WHITE MATTER INTEGRITY that goes beyond diffusivity measurements alone.
IN A CLINICAL POPULATION Furthermore, composite measures such as anisot-
qtDTI technology has also been used to examine ropy-weighted FBL are potentially more sensitive to
white matter fiber lengths in individuals with sub- pathology than any one alone, as they can reflect both
cortical ischemic vascular disease (SIVD) compared fiber termination and overall changes in anisotropy
with healthy controls to determine the sensitivity of (17). The second major strength is the anatomical
qtDTI to detect white matter changes in a clinical specificity of qtDTI, which is valuable for localizing
population. SIVD is a condition that is associated pathological effects that would be undetectable when
with significant white matter microstructural damage simpler whole-brain analysis is performed. Together,
in the brain (12,20-21,28). Prior studies have demon- these aspects make qtDTI a unique and powerful tool
strated the sensitivity of traditional DTI indices to for understanding structural aspects of fiber bundles.
the white matter alterations associated with SIVD Several limitations of qtDTI technology warrant
in specifically defined regions of interest, such as discussion. First, qtDTI is sensitive to imaging arti-
the corpus callosum and the corona radiate, in addi- facts such as partial-volume averaging of fiber bundle
tion to the presence of white matter hyperintensities populations with varying degrees of myelination, fiber
(WMH) that are characteristic of the disease (20- orientation, and/or axon caliber. Partial-volume con-
21). Members of our group investigated the utility founds can be somewhat managed by decreasing the
of qtDTI metrics, particularly those associated with voxel size and increasing the gradient strengths and
length (e.g., average fiber length, FA-weighted fiber number of directions. However, these adjustments
length, normalized fiber length), to examine white reduce signal-to-noise ratios and increase scan time
matter tract integrity and its relation to cognitive and post-processing complexity. Additional artifacts
performance in a group of individuals with SIVD include subject motion, magnetic susceptibility, and
(17). Average FA was included to investigate the rel- echo planar imaging distortion. While these arti-
ative performance of traditional DTI compared to facts are often difficult to avoid, they can be readily
qtDTI in identifying white matter alterations. Both detected by inspection, and negative effects on bun-
average FA and qtDTI metrics, particularly those dle reconstruction can often be avoided by quality
associated with fiber length, revealed poorer white control (51).
matter integrity of transcallosal fibers in individuals
with SIVD compared with healthy controls. Reduced