1、Diffusional Kurtosis Imaging DKI1Contents DWI(diffusion weighted imaging) DTI(diffusion tensor imaging)DKI(diffusion kurtosis imaging) 2DWI原理组织T1、T2驰豫时间、H1的密度、分子弥散运动利用扩散敏感梯度脉冲将水分子弥散效应扩大，来研究不同组织中水分子扩散运动的差异 3DWI评估弥散的参数 通过两个以上不同弥散敏感梯度值（ b值）的弥散加权象，可计算出弥散敏感梯度方向上水分子的表观弥散系数（apparent diffusion coefficient A
2、DC） ADC=In(S低/S高)/(b高-b低)弥散敏感系数(b)值= =r22g2(-/3) b 值的取值范围为010 000s/mm2，较大的b 值具有较大的弥散权重，对水分子的弥散运动越敏感，并引起较大的信号下降，但b 值越大，图像信噪比也相应下降，如果b 值太小，易受T2 加权的影像，产生所谓的T2 透射效应(T2 shine through effect)，一般来说用大b 值差的图像测得的ADC 值较准确，故侧ADC 值时宜选较高b 值和较大的b 值差4 均质介质中可以水分子的自由运动为各向同性，即在各个方向上的弥散强度大小一致，弥散张量D描述为球形，沿磁共振的三个主坐标的特征值为
3、 1=2=35defects of DTI Conventional DTI fails to fully utilize the MR diffusion measurements that are inherent to tissue microstructure. DTI computes apparent diffusivity based on the assumption that diffusion weighted (DW) MR signal has a monoexponential dependence on the diffusion factor (b-value).
4、 DTI implicitly assumes that water molecule diffusion occurs in a free and unrestricted environment with a Gaussian distribution of diffusion displacement. 6defects of DTI In biological tissue, complex cellular microstructures make water diffusion a highly hindered or restricted process. Non-monoexp
5、onential decays are experimentally observed in both white matter and gray matter. Moreover, the simplified description of the diffusion process in vivo by a 2nd-order 3D diffusivity tensor prevents DTI from being truly effective in characterizing relatively isotropic tissue such as GM. Even in WM, t
6、he DTI model can fail if the tissue contains substantial crossing or diverging fibers . 7defects of DTI As a result, DTI quantitation is b-value dependent and DTI fails to fully utilize the diffusion measurements that are inherent to tissue microstructure.8KurtosisKurtosis here refers to the excess
7、kurtosis that is the normalized and standardized fourth central moment of the water displacement distribution . It is a dimensionless measure that quantifies the deviation of the water diffusion displacement profile from the Gaussian distribution of unrestricted diffusion, providing a measure of the
8、 degree of diffusion hindrance or restriction.fourth central moment:四阶中心距，主要用来衡量随机分布变量的分布在均值附近的陡峭程度Since the deviation from Gaussian behavior is governed by the complexity of the tissue within which the water is diffusing, this excess diffusional kurtosis can be regarded as a measure of a tissues de
9、gree of structure.9Other advantages of DKIMean kurtosis (MK), the average apparent kurtosis along all diffusion gradient encoding directions, has been measured and demonstrated to offer an improved sensitivity in detecting developmental and pathological changes in neural tissues as compared to conve
10、ntional DTI .In addition, directional kurtosis analysis has been formulated to reveal directionally specific information, such as the water diffusion kurtoses along the direction parallel or perpendicular to the principle water diffusion direction as determined by the 2nd-order diffusion tensor10DKI
11、 provides a higher-order description of restricted water diffusion process by a 2nd-order 3D diffusivity tensor (DT as in conventional DTI) together with a 4th-order 3D kurtosis tensor (KT).11ConditionsThe method is based on the same type of pulse sequences employed for conventional diffusion-weight
12、ed imaging (DWI), but the required b values are somewhat larger than those usually used to measure diffusion coefficients. In the brain, b values of about 2000 s/mm2 are sufficient.At least 15 non-collinear and non-coplanar directions are required to construct KT.12DKI vs q-space imaging techniquesD
13、KI has a close relationship to q-space imaging techniques.q-space imaging methods have indeed recently been employed to estimate diffusional kurtosis.The principal difference between them is that q-space imaging seeks to estimate the full diffusion displacement probability distribution rather than j
14、ust the kurtosis.As a consequence,q-space imaging is more demanding in terms of imaging time and gradient strengths.Measuring the diffusional kurtosis requires only modest increases in b valuesAnd DKI is less demanding in terms of hardware requirements and postprocessing effort.13Kurtosis tensor (KT
15、) derived parametersMK(mean kurtosis):MK is a measure of the overall kurtosis. It does not have any directional specificity. MK 的大小取决于感兴趣区内组织的结构复杂程度，结构越复杂非正态分布水分子扩散受限越显著，MK 也即越大K (Axial kurtosis)and K(Radial kurtosis) :can be defined as the kurtosis parallel and perpendicular to the principle diffus
16、ion eigenvector (e1) K越大表明在该方向非正态分布水分子扩散受限越明显，反之则表明扩散受限越弱FAK (fractional anisotropy of kurtosis )Similar to FA in DTI, the anisotropy of directional kurtosis can be conveniently defined as FAK KA 越小即表示越趋于各向同性扩散; 若组织结构越紧密越规则，KA 越大14DKI parametric maps15DKI parametric maps Typical DKI-derived parametr
17、ic maps from a single slice of a) in vivo, b) formalin-fixed adult rat brains and c) a normal human subject (male, 44 years old). Axial diffusivity (/), radial diffusivity (), mean diffusivity (MD), axial kurtosis (K/), radial kurtosis (K ), mean kurtosis (MK), fractional anisotropy (FA), directiona
18、lly encoded colour FA (DEC-FA) and fractional anisotropy of kurtosis (FAK) maps are computed from DKI model.16DKI parametric maps For (a), raw DWIs were acquired by SE EPI with TR/TE=3000/30.3ms, /=5/17ms, slice thickness=1mm, FOV=3030mm2, data matrix=128128 (zero filled to 256256), NEX=4, 6 b-value
19、s (0.0, 0.5, 1.0, 1.5, 2.0 and 2.5ms/m2) and along 30 directions using 7T scanner17DKI parametric maps For (b), raw DWIs were acquired with the same parameters as those for in vivo except TE=34.3ms, =9ms and b-values of 0.0, 1.0, 2.0, 3.0, 4.0 and 5.0ms/m2. A larger b-value range was used in ex vivo
20、 experiment due to the generally lower diffusivities.18DKI parametric maps For (c), raw DWIs were acquired by SE EPI with TR/TE=2300/109ms, slice thickness=2mm, FOV=256256mm2, data matrix=128128, NEX=2, 6 b-values (0.0, 0.5, 1.0, 1.5, 2.0 and 2.5ms/m2) and along 30 directions using a 3T Siemens scan
21、ner 19DKI parametric maps Higher MK is found in WM, indicating a generally higher degree of diffusion complexity and restriction in the WM structures. It can be seen from the directional kurtosis maps that such high MK in WM is mainly contributed by K . This suggests the existence of heterogeneity a
22、nd restricted diffusion in axonal structuresBoth MK and K exhibit strong contrast between WM and GM structures.20DKI parametric maps Both MK and K exhibit strong contrast between WM and GM structures. Positive mean and directional kurtoses are observed in both WM and GM, indicating faster DW signal
23、decay at lower b-values and restricted diffusion environment in both WM and GM under in vivo and formalin-fixed conditions.21DKI shows a general decrease in diffusivity and increase in kurtosis in WM and GM of the fixed brains The breakdowns of neurofilaments and microtubules caused by fixatives are
24、 believed to produce more diffusion barriers and hence lead to the / decrease and K/ increase. Other fixation effects such as tissue shrinkage , decrease in membrane permeability , increase in axonal packing density and reduction of extracellular space in parenchyma also likely contribute to the sig
25、nificant decrease and K increase.22Directional kurtosis analysis of fixed experimental autoimmune encephalitis (EAE) spinal cord The inflammatory neurodegenerative disease EAE is characterized by both axonal loss and demyelination In recent DKI studies, there are promising results of using MK to det
26、ect changes in normal or pathological neural tissue However, as an average of kurtoses along all the diffusion directions, MK can lose sensitivity and specificity in probing directional changes of pathological tissue23EAE spinal cordK/ is found to be significantly increased and / decreased in the le
27、sion area/ reduction is likely due to cytoskeletal perturbation or debris formation when the axonal structures break downIn addition, increases whereas K decreases likely because of the demyelination and axonal loss that also lead to less diffusion restriction in radial direction.24EAE spinal cord T
28、he directionally averaged MD and MK are found to be less sensitive to EAE pathology due to the opposite trends of diffusivity and kurtosis changes in axial and radial direction.25Monitoring postnatal brain maturation by conventional DTICC: corpus callosum（胼胝体）; EC: external capsule（外囊）; CP: cerebral
29、 peduncle（大脑脚）; AC: anterior commissure;（前联合） CT: cerebral cortex（脑皮质）; HP: hippocampus（海马）; CPu: caudate putamen（新纹状体）26Monitoring postnatal brain maturation by conventional DTIThe sensitivity of / in detecting rat brain WM maturation is generally observed to be the highest at low b-value At relati
30、vely low b-values, the apparent diffusivity is primarily contributed from the fast water diffusion activities in extracellular space that depend on both cellular microstructure and membrane permeability. The use of low b-value can best detect these changes.The high / sensitivity at low b-value obser
31、ved in the current study suggests the alterations of these fast water diffusion activities along axonal direction during brain maturation. Such alterations may result from the increase in packing density of fiber bundles and axons, axonal diameter increase, changes in neurofibrils, and increased com
32、plexity of extracellular matrix .27Monitoring postnatal brain maturation by conventional DTIWhereas that of is the highest at high b-valueThe diffusion changes probed in WM using high b-values are ascribed more to the slow water molecule diffusion particularly along the radial direction when travers
33、ing the membranes and myelin sheathsThe high sensitivity of at high b-value in detecting brain maturation shown in the figure likely reflects these WM microstructural changes, including myelination and axonal density and diameter changes during postnatal brain development.28Monitoring postnatal brai
34、n maturation by conventional DTIFA quantitation is also affected by the b-value and its ability in detecting brain maturational changes varies among different structures.29Monitoring postnatal brain maturation by DKIFigure 7a shows that the sensitivity of fitting all the multi-b-value DWIs to DTI mo
35、del is generally similar to that of employing a medium b-value (b=1.5ms/m2) shown in Figure 6In Figure 7b, the general and continual kurtosis increase with age is observed, indicating that more diffusion restriction occurs during brain maturation in both WM and GM structures. The DKI-derived diffusi
36、vity and kurtosis indices are highly sensitive to brain developmental changes.30Monitoring postnatal brain maturation by DKI Both / and K/ of WM are found to increases with age, which may arise from various biological events during early postnatal brain maturation.The increase of diffusivity can be
37、caused by axoplasmic flow during the myelination periodneuronal loss and axonal pruning that shortens the axon length can lead to an increase of restriction31Monitoring postnatal brain maturation by DKI The increase of K in WM is likely ascribed to the myelination and modification of axonal structur
38、es that increases restriction in the radial direction. DKI analysis also reveals that diffusion restriction in the relatively isotropic GM increases with age. This may reflect the more densely packed structures and the dendritic architectural modification in GM 32DTI VS DKI in monitoring postnatal b
39、rain maturation When there is a large K, the estimated diffusivity in conventional DTI shows a large discrepancy with the diffusivity estimated in DKI approach. As K in all the structures is positive, DTI-derived diffusivities are generally lower than those by DKI.The relatively high sensitivity of
40、the in monoexponential DTI model is mainly a result of increasing K with age (while the changes of in DKI are moderate). 33DTI VS DKI in monitoring postnatal brain maturationDTI-derived / is related to the increase of both K/ and / derived in DKI that manifests opposite and competing effects.herefor
41、e diminished sensitivity in detecting maturational changes of / in conventional DTI are observed. The separation of / and K/ can improve the characterization of neural tissue along the axial direction. Because the complex biological modification of WM along axonal direction affects both diffusivity
42、and kurtosis, information obtained in conventional DTI is inadequate to fully infer the microstructural changes during brain maturation.34Other applications DKI may serve as a more sensitive tool to detect and characterize such subtle changes in both WM and GM. DKI has also been applied in various pathological states, including Alzheimers disease , schizophrenia and attention deficit and hyperactivity disorder DKI has also been sought to resolve the crossing of WM fibers and possibly lead to more accurate tracking and characterization.35From:WU Menglin36
