Despite its improved sensitivity in the detection of micro-hemorrhages, SWI is still a qualitative instead of quantitative approach. Theoretically, blood products at different stages, from deoxyhemoglobin, to extracellular methemoglobin and then hemosiderin, has different susceptibilities. As a natural extension, susceptibility-weighted imaging and mapping (SWIM), also called quantitative susceptibility mapping (QSM), is the next generation of SWI development, which could quantify the susceptibility values of blood products. Ideally SWIM/QSM could have the following potential usage in mTBI:

In summary, there is still a need to investigate TVI in a large number of mTBI patients by using SWI/SWIM. This may represent a promising direction for mTBI research in the coming years.

Diffusion imaging sequences are sensitive to TAI secondary to stretch and shear forces. DTI measures the bulk motion of water molecular diffusion in biological tissues. It is most useful when diffusion is anisotropic, i.e., when diffusion is not equivalent in all directions, such as in skeletal muscle or axons in the white matter of the CNS. Histological studies have validated DTI’s sensitivity to brain injury in both focal injury [43] and DAI [44] models. Two parameters derived from DTI, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) [45, 46], have been extensively studied in TBI. ADC is an estimate of the average magnitude of water movement in a voxel (regardless of direction), while FA is an index of the directional nonuniformity, or anisotropy, of water diffusion within a voxel.

FA has been used to detect alterations in directional diffusion resulting from tissue damage. FA in white matter is highest when fibers are long (relative to voxel dimension) and oriented uniformly (collinear) within a voxel and lowest when fibers are not collinear (e.g., “crossing fibers”) or have been damaged. When axons are injured, as in acceleration/deceleration injuries (such as MVCs), diffusion anisotropy typically decreases. Loss of diffusion anisotropy is the result of a number of axonal changes after injury including: (1) increased permeability of the axonal membrane; (2) swelling of axons; (3) decreased diffusion in the axial (long axis) direction; and (4) degeneration and loss of axons in the chronic stage. In general, any pathological alteration of white matter fibers will result in FA decrease, because one or more of these axonal changes occur in disorders of white matter. Not surprisingly, most clinical studies of moderate and severe TBI have shown FA to be more sensitive than ADC to traumatic injury. On the other hand, ADC, FA, and directionally selective diffusivities (principal, intermediate, and minor components of diffusion) can help to better characterize brain injury pathologies. Trace and mean diffusivity (MD) are two other measurements similar to ADC and vary similarly. Changes in FA in association with ADC changes can differentiate the type of edema. For example, in the acute stage, decreased FA in association with increased ADC suggests vasogenic edema, while increased FA in association with decreased ADC suggests cytotoxic edema. Decreased FA in association with decreased ADC and decreased longitudinal (parallel to the long axis of the axons) water diffusivity suggests axonal transport failure as occurs in degenerative neurological diseases such as in ALS.

Regarding the location of brain lesions detected by DTI, Niogi and Mukherjee [47] summarized that the frontal association pathways, including anterior corona radiata, uncinate fasciculus, superior longitudinal fasciculus, and genu of corpus callosum (CC), are the mostly frequently injured WM structures in mTBI patients. Single subject results were not reported but it can be assumed that significant interindividual variability for location and extent of WM injury exists due to varying injury mechanisms (and forces) and biological (neural and non-neural) differences across patients.

Interestingly, despite the higher incidence of milder TBI compared with more severe TBI in western countries, there are many fewer mTBI imaging studies reported in the literature. One reason is the fact that recruitment of mTBI patients is more difficult, since they are typically outpatients. Another reason is the common conception that mTBI is a transient problem from which virtually all who are afflicted will recover fully. Therefore, some question the clinical importance of studying mTBI. Certainly, insurance reimbursement for MRI scanning of mTBI is rare and even rarer in the acute setting, so that “adding on research sequences” is not possible.

With these limitations in mind, a growing literature on DTI in TBI has begun to address the DTI findings at different stages.

Mild TBI patients often develop a constellation of physical, cognitive, and emotional symptoms that are collectively known as PCS. In terms of neurocognitive symptoms, there are four key domains implicated in chronic neuropsychological impairment after mTBI. These domains include: (1) higher-order attention, (2) executive function, (3) episodic memory, and (4) speed of information processing. To date, several studies have demonstrated typical mTBI cognitive profiles and association with DTI findings. Niogi and Mukherjee summarized the topographic and neurocognitive deficits [47].

Damage to the frontal WM has been reported to be associated with impaired executive function. Lipton et al. [58] studied 20 acute to subacute patients and reported that reduced FA in WM of dorsolateral prefrontal cortex (DLPRC) is correlated with worse executive function.

Frontal WM injury is also associated with attention deficit. Niogi et al. [72] reported that reduced FA in the left anterior corona radiata is correlated with attention control in chronic mild TBI patients.

Injury at the temporal WM tracts or cingulum bundle may cause memory problems. Niogi et al. reported that reduced FA in the uncinate fasciculus correlated with memory performance [72]. Wu et al. [49] reported that an FA measure of left cingulum bundle correlated with delayed recall.

Injury of the callosal fibers has been reported to be associated with PCS scores. Wilde et al. [50] studied ten adolescent mTBI patients in the acute stage and reported that increased FA and decreased ADC and MD in corpus callosum is correlated with patients’ PCS score. Bazarian et al. [51] studied six mild TBI patients in the acute stage and reported a lower mean trace in the left anterior IC and a higher FA in the posterior CC. FA values correlated with patients’ 72 h PCS score and visual motor speed and impulse control.

The overall burden or extent of WM injury is associated with both speed of information processing and overall functional outcome. Niogi et al. [62] studied 34 subacute to chronic mTBI patients and reported that FA decreased in several WM regions, including anterior corona radiata, uncinate fasciculus, CC genu, and cingulum bundle. They demonstrated that the number of damaged WM regions is correlated with patient’s reaction time. Miles et al. [59] studied 17 mTBI patients at the acute stage and followed them up to 6 months after injury. They reported that, at the acute stage, the increased mean diffusivity (MD) in the central semiovale, the genu and splenium of CC, and the posterior limb of IC tended to correlate with a patient’s response speed at 6 months after injury. Regarding the overall outcome, Messé et al. [57] divided mTBI patients into two outcome groups: poor outcome (PO) vs. good outcome (GO). PO patients showed significantly higher mean diffusivity (MD) values than both controls and GO patients in the corpus callosum, the right anterior thalamic radiations, the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the fronto-occipital fasciculus bilaterally.

Interestingly, injury or reduced blood supply in the thalamus, which is the relay station of neuronal pathways, may cause a constellation of symptoms in the speed of information processing, memory, verbal, and executive function. Grossman et al. studied 22 subacute to chronic mTBI patients by using diffusion kurtosis imaging, which is a more advanced form of diffusion analysis, and demonstrated that overall cognitive impairment is associated with the diffusion measurement in the thalamus and internal capsule [73]. This work is along the same line of a perfusion study by the same group, which demonstrated that reduced blood flow in the thalamus correlated with patient’s overall neurocognitive function [74]. See Fig. 12.4 as an example of axonal injury. In summary, significant progress has been made by researchers in recent years regarding the prognostic value of DTI in the form of FA for mTBI patients’ neurocognitive outcome. However, more and more evidence suggests that a tensor model may not be the ideal approach to the complicated pathophysiological process in TBI. Particularly, despite its high sensitivity, DTI suffers low specificity to trauma. Numerous medical reasons could cause water diffusivity changes and lead to changed FA; examples include neurodegenerative diseases, stroke, cancer, multiple sclerosis, hypertension, and diabetes, to name a few. Any preexisting conditions in the brain could affect the diffusivity and FA changes. Conflicting data on FA changes at the acute stage suggest that the field needs a better approach to characterizing the injury pathology than the current DTI model. This approach should be more specific to a TBI pathological process. It could be used to evaluate the neural basis of patients’ injury to recovery process in longitudinal studies over a large number of patients.