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1、Diffusional Kurtosis ImagingDKIContents DWI(diffusion weighted imaging) DTI(diffusion tensor imaging)DKI(diffusion kurtosis imaging) DWI原理MR图像的信号 组织T1、T2驰豫时间、H1的密度、分子弥散运动DWI图像 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 DWI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 coe
2、fficient ADC） 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 ADCADC反映了水分子的扩散运动的能力反映了水分子的扩散运动的能力反映了水分子的扩散运动的能力反映了水分子的
3、扩散运动的能力, ,指水分子单位时间指水分子单位时间指水分子单位时间指水分子单位时间内扩散运动的范围，越高代表水分子扩散能力越强内扩散运动的范围，越高代表水分子扩散能力越强内扩散运动的范围，越高代表水分子扩散能力越强内扩散运动的范围，越高代表水分子扩散能力越强。 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 1=2=3 在脑白质中由于髓鞘的阻挡，在脑白质中由于髓鞘的阻挡，水分子的弥散被限制在与纤维水分子的弥散被限制在与纤维走行一致的方向上，具有较高走行一致的方向上，具有较高的各向异性，此时弥散张量可的各向异性，
4、此时弥散张量可表示为椭球形，其特征值表示为椭球形，其特征值 1 12 23 3，最大特征值对应的，最大特征值对应的方向与经过该体素的纤维束走方向与经过该体素的纤维束走行平行行平行defectsofDTIConventional 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
5、) MR signal has a monoexponential dependence on the diffusion factor (b-value).DTI implicitly assumes that water molecule diffusion occurs in a free and unrestricted environment with a Gaussian distribution of diffusion displacement. defectsofDTI In biological tissue, complex cellular microstructure
6、s make water diffusion a highly hindered or restricted process. Non-monoexponential 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 effecti
7、ve in characterizing relatively isotropic tissue such as GM. Even in WM, the DTI model can fail if the tissue contains substantial crossing or diverging fibers . defectsofDTIAs a result, DTI quantitation is b-value dependent and DTI fails to fully utilize the diffusion measurements that are inherent
8、 to tissue microstructure.KurtosisKurtosis here refers to the excess 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 Gaussi
9、an distribution of unrestricted diffusion, providing a measure of the 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 exc
10、ess diffusional kurtosis can be regarded as a measure of a tissues degree of structure.OtheradvantagesofDKIMean kurtosis (MK), the average apparent kurtosis along all diffusion gradient encoding directions, has been measured and demonstrated to offer an improved sensitivity in detecting developmenta
11、l and pathological changes in neural tissues as compared to conventional 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 diffusi
12、on direction as determined by the 2nd-order diffusion tensorDKI 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).ConditionsThe method is based on the same type
13、of pulse sequences employed for conventional diffusion-weighted 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
14、required to construct KT.DKIvsq-spaceimagingtechniquesDKI 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 diffus
15、ion displacement probability distribution rather than just 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 requi
16、rements and postprocessing effort.Kurtosistensor(KT)derivedparametersMK(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 p
17、arallel and perpendicular to the principle diffusion 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DKIparametricmapsDKIpa
18、rametricmapsTypical DKI-derived parametric 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)
19、, fractional anisotropy (FA), directionally encoded colour FA (DEC-FA) and fractional anisotropy of kurtosis (FAK) maps are computed from DKI model.DKIparametricmapsFor (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
20、filled to 256256), NEX=4, 6 b-values (0.0, 0.5, 1.0, 1.5, 2.0 and 2.5ms/m2) and along 30 directions using 7T scannerDKIparametricmapsFor (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-v
21、alue range was used in ex vivo experiment due to the generally lower diffusivities.DKIparametricmaps 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 directio
22、ns using a 3T Siemens scanner DKIparametricmaps 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 existe
23、nce of heterogeneity and restricted diffusion in axonal structuresBoth MK and K exhibit strong contrast between WM and GM structures.DKIparametricmapsBoth MK and K exhibit strong contrast between WM and GM structures. Positive mean and directional kurtoses are observed in both WM and GM, indicating
24、faster DW signal decay at lower b-values and restricted diffusion environment in both WM and GM under in vivo and formalin-fixed conditions.DKI shows a general decrease indiffusivityandincreaseinkurtosisinWMandGMofthefixedbrainsThe breakdowns of neurofilaments and microtubules caused by fixatives ar
25、e 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
26、nificant decrease and K increase.Directionalkurtosisanalysisoffixedexperimentalautoimmuneencephalitis(EAE)spinalcordThe inflammatory neurodegenerative disease EAE is characterized by both axonal loss and demyelinationIn recent DKI studies, there are promising results of using MK to detect changes in
27、 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 tissueEAEspinalcordK/ is found to be significantly increased and / decreased in the lesion area/ reducti
28、on 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.EAEspinalcordThe directionally averag
29、ed 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.MonitoringpostnatalbrainmaturationbyconventionalDTICC: corpus callosum（胼胝体）; EC: external capsule（外囊）; CP: cerebral peduncle（大脑脚）; AC: anterior co
30、mmissure;（前联合） CT: cerebral cortex（脑皮质）; HP: hippocampus（海马）; CPu: caudate putamen（新纹状体）MonitoringpostnatalbrainmaturationbyconventionalDTIThe sensitivity of / in detecting rat brain WM maturation is generally observed to be the highest at low b-value At relatively low b-values, the apparent diffusi
31、vity 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 observed in the current study suggests the a
32、lterations 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 complexity of extracellular matrix .Monito
33、ringpostnatalbrainmaturationbyconventionalDTIWhereas 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 traversing the membranes and myelin sheathsThe high se
34、nsitivity 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.MonitoringpostnatalbrainmaturationbyconventionalDTIFA quantitation is also
35、 affected by the b-value and its ability in detecting brain maturational changes varies among different structures.MonitoringpostnatalbrainmaturationbyDKIFigure 7a shows that the sensitivity of fitting all the multi-b-value DWIs to DTI model is generally similar to that of employing a medium b-value
36、 (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 diffusivity and kurtosis indices are highly sensitive to brain develo
37、pmental changes.MonitoringpostnatalbrainmaturationbyDKI 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 caused by axoplasmic flow during the myelination periodneuronal loss
38、and axonal pruning that shortens the axon length can lead to an increase of restrictionMonitoringpostnatalbrainmaturationbyDKIThe increase of K in WM is likely ascribed to the myelination and modification of axonal structures that increases restriction in the radial direction. DKI analysis also reve
39、als 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 DTIVSDKIinmonitoringpostnatalbrainmaturation When there is a large K, the estimated diffusivity in conventional DTI
40、 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 the in monoexponential DTI model is mainly a result of increasing K with age (while th
41、e changes of in DKI are moderate). DTIVSDKIinmonitoringpostnatalbrainmaturationDTI-derived / is related to the increase of both K/ and / derived in DKI that manifests opposite and competing effects.herefore diminished sensitivity in detecting maturational changes of / in conventional DTI are observe
42、d. 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 and kurtosis, information obtained in conventional DTI is inadequate to fully infer the microst
43、ructural changes during brain maturation.OtherapplicationsDKI 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 disorderDKI has also been sought to resolve the crossing of WM fibers and possibly lead to more accurate tracking and characterization.From:WU Menglin
