Enhanced CEST MRI Using the Residual of Inversed Z-Spectra for Ischemia Detection

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) had shown potential in sensing pH changes that occurs early in ischemic stroke. However, detection of mild acidosis is still challenging. To enhance CEST detection for ischemia, we proposed a quantification approach using the residual of inversed Z-spectra, i.e. $MTR_{Rex}^{VOPVP} =1/{Z}_{exp} -1/{Z}_{ref}$ , where the reference Z-spectra ${Z}_{ref}$ was calculated using our previously developed Voxel-wise Optimization of Pseudo Voigt Profile (VOPVP). Simulations were performed at two different exchange rates of amide, representing different pH values. Among all tested quantification methods, including MTRasym, Lorentzian Difference (LD), VOPVP residual ( $Z_{residual}^{VOPVP}$ ), the analytical solution and $MTR_{Rex}^{VOPVP} $ , $MTR_{Rex}^{VOPVP} $ exhibited the largest difference between the two exchange rates. In vivo CEST-MRI was performed at 7 Tesla in rat brain, at 2 hours after transient ischemia by middle cerebral artery occlusion. Firstly, Z-spectra images were assessed at multiple offsets using histogram analysis, with 3.5 and -3.5 ppm exhibiting significant changes between normal rats and stroke rats (n = 5 each). For all stroke rats, $MTR_{Rex}^{VOPVP} $ images (3.5 ppm) exhibited a large area of hypointensity in the lesion hemisphere. In contrast, ${MTR}_{asym}$ and the three-offsets method failed in detecting such changes, particularly for rats with little changes on T2w and DWI images. Among all tested methods, $MTR_{Rex}^{VOPVP} $ achieved the highest contrast-to-noise ratio between lesion striatum and the contralateral. For amide, amine and NOE, $Z_{residual}^{VOPVP} \mathbf {}$ and $MTR_{Rex}^{VOPVP} $ showed significant reduced signals in lesions compared to the contralateral, indicating lower pH with slower exchange. But Z-spectra and ${MTR}_{asym}$ signal did not show such difference. At later time points (6 hrs and 24 hrs), all methods displayed contrast between two hemispheres and $MTR_{Rex}^{VOPVP} $ still show the largest contrast between the two hemisphere. Histology confirmed the edema and other damage in the ipsilateral hemisphere at 2 hours post transient ischemia. In summary, $MTR_{Rex}^{VOPVP} $ may enhance CEST detection for ischemia.