Diffusion kurtosis imaging (DKI) can offer a useful complementary tool to routine diffusion MRI for improved stratification of tissue damage in acute ischemic stroke ¹. However its relatively long imaging time has hampered its clinical applications. Recently proposed fast DKI approach substantially shortens the imaging time ², but its sensitivity for imaging acute stroke has yet been fully described. In this study, we compared the conventional tensor-model DKI and fast DKI methods by means of the contrast-to-noise ratio (CNR) and CNR efficiency to elucidate its diagnostic value in the acute stroke setting.

MRI: Eleven rats were induced unilateral stroke with a standard intraluminal MCAO procedure and imaged with a 4.7 T MR scanner 60 minutes after the procedure. Five slices (slice thickness/gap = 1.8/0.2 mm) were acquired with a single-shot EPI sequence. Imaging parameters include: FOV = 20x20 mm², matrix size = 48x48, diffusion duration/diffusion time = 6/20 ms, TR/TE = 2500/36.6 ms, one reference image of b = 0 s/mm², NSA = 4. For the conventional DKI protocol, two b-values of 1000 and 2500 s/mm² were applied in fifteen diffusion directions. The scan time was 5 min and 10 s. For the fast DKI protocol, three images of b = 1000 s/mm² were applied along gradient directions of (1,0,0), (0,1,0) and (0,0,1), and nine images of b = 2500 s/mm² along diffusion directions of $$$\widehat{n}^{(1)}=(1,0,0)^T$$$, $$$\widehat{n}^{(1+)}=(0,1,1)^T$$$ and $$$\widehat{n}^{(1-)}=(0,1,-1)^T$$$, and similarly for i =2 and 3. Note that the superscript i in $$$\widehat{n}^{(i)}$$$ labels the position of the “1”, while in $$$\widehat{n}^{(i+)}$$$ and $$$\widehat{n}^{(i-)}$$$ it labels the position of the “0”. The fast DKI scan time was 2 min and 10 s.

Image analysis: For conventional DKI, fractional anisotropy (FA), axial (D_∥) and radial (D_⊥) diffusivity, axial (K_∥) and radial (K_⊥) kurtosis, and tensor-based MD_tensor and MK_tensor were obtained using DKE. For the fast DKI, MD_fast was calculated as the mean of MD_x,y,z as ³: $$$MD\scriptsize x,y,z \normalsize = \frac{(b_{1}+b_{3})D_{x,y,z}^{(12)}-(b_{1}+b_{2})D_{x,y,z}^{(13)}}{b_{3}-b_{2}}$$$, where $$$D_{x,y,z}^{(ij)}=\frac{lnS(b_i)/S(0)-lnS(b_j)/S(0)}{b_j-b_i}$$$, i = 1, j = 2, 3, and b₁ = 0, b₂ = 1000, and b₃ = 2500 s/mm². Furthermore, MK_fast was obtained from ²: $$ MK_{fast}=\frac{\frac{6}{15}[\sum_{i=1}^3ln\frac{S(b_3,\widehat{n}^{(i)})}{S(0)}+2\sum_{i=1}^3ln\frac{S(b_3,\widehat{n}^{{(i+)}})}{S(0)}+2\sum_{i=1}^3ln\frac{S(b_3,\widehat{n}^{(i-)})}{S(0)}]+6\cdot b_3\cdot MD_{fast}}{b_3^2\cdot MD_{fast}^2}.$$

Image segmentation: The ischemic lesion was defined by thresholding at two standard deviations (SD) below the baseline MD of the contralateral normal brain. The reference ROI was designated by mirroring the segmented lesion into the contralateral brain. The MK_tensor, MD_fast and MK_fast lesions were similarly defined.

Data Analysis: The CNR and CNR efficiency were calculated as ⁴: $$$CNR=(S_{ischemia}-S_{contralateral})/{\sqrt{{(\sigma_{ischemia}^2+\sigma_{contralateral}^2)}/2}}$$$ and $$$CNR/\sqrt{scan time}$$$. Two-tailed Student’s t-test was performed between paired measurements in ipsilateral ischemic and contralateral normal regions. Measurement differences across the ROIs were tested using one-way ANOVA with Bonferroni correction.

Ischemic regions showed significant decrease in diffusion indices (MD_tensor: 32.1±2.1%, D_∥: 28.4±2.1%, and D_⊥: 34.9±2.3%), and increase of FA (22.5±4.5%) and kurtosis indices (MK_tensor: 47.1±7.3%, K_∥: 50.6±6.2%, and K_⊥: 37.4±7.6%) compared to those in the contralateral regions. The magnitude of percentage changes were significantly higher in MK_tensor and K_∥ than other indices. In addition, the difference between the percentage changes of MK_tensor and K_∥ was insignificant. Fig. 1 compares MD and MK maps between the two DKI methods. MD and MK lesions were overlaid on a diffusion-weighted image and were respectively colored in red and green, exhibiting noticeable mismatch. MK_fast map shows significantly higher CNR between the reference and ischemic regions (1.6±0.2), compared to that of MK_tensor map (1.3±0.2). The acquisition time of the fast DKI method was about 50% shorter than that of the conventional DKI protocol, leading to 1.9 times higher gain of CNR efficiency. Lesion sizes of MD and MK are highly correlated between the two DKI methods (Fig. 2). Multi-slice and 3D volume rendering of typical ischemic diffusion and kurtosis lesions derived from the fast DKI method shows MK_fast lesion significantly smaller than MD_fast lesion, with their normalized lesion area ratio being 0.75±0.11. Although MD_fast values were significantly reduced in all ischemic lesions from the contralateral normal area, differences of MD_fast values across the three lesions were statistically insignificant (Table 1). In comparison, MK_fast across the three lesion areas was significantly elevated from the normal area, with significant difference of MK_fast across the three lesion areas.Our study recapitulated that mean kurtosis is one of the most sensitive parameters to detect acute stroke injury, and demonstrated the enhanced sensitivity and efficiency of the fast DKI method for stratification of ischemic tissue injury during acute stroke. The fast DKI method provides important information for resolving heterogeneous DWI lesion, particularly translatable in the acute stroke setting.