The neuroprotective effect of oxygen leads to recent interest in normobaric oxygen (NBO) therapy after acute ischemic stroke. However, the mechanism remains unclear and inconsistent outcomes were reported in human studies. Because NBO aims to improve brain tissue oxygenation by enhancing oxygen delivery to ischemic tissue, monitoring the oxygenation level changes in response to NBO becomes necessary to elucidate the mechanism and to assess the efficacy. Susceptibility weighted imaging (SWI) which provides a new MRI contrast by combining the magnitude and phase images is fit for purpose. SWI is sensitive to deoxyhemoglobin level changes and thus can be used to evaluate the cerebral metabolic rate of oxygen. In this study, SWI was used for in vivo monitoring of oxygenation changes in a rat model of permanent middle cerebral artery occlusion (MCAO) before, during and after 30 min of NBO treatment. Regions of interest in ischemic core, penumbra and contralateral normal area were generated based on diffusionweighted imaging and perfusion imaging. Significant differences in SWI indicating different oxygenation levels were generally found: contralateral normal > penumbra > ischemic core. Ischemic core showed insignificant increase in oxygenation during NBO and returned to pre-treatment level after termination of NBO. Meanwhile, the oxygenation levels slightly increased in contralateral normal and penumbra regions during NBO and significantly decreased to a level lower than pre-treatment after termination of NBO, indicating secondary metabolic disruption upon the termination of transient metabolic support from oxygen. Further investigation of NBO effect combined with reperfusion is necessary while SWI can be used to detect hemorrhagic transformation after reperfusion.
Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange.The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTR<sub>asym</sub>) may reasonably compensate for direct RF saturation, in vivo MTR<sub>asym</sub> is however, susceptible to an intrinsically asymmetric shift (MTR’<sub>asym</sub>). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTR<sub>asym</sub> has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTR<sub>asym</sub> between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the <i>in vivo</i> MTR’<sub>asym</sub> can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR’<sub>asym</sub> =MTR<sub>asym</sub>-APTR). In addition, MTR’<sub>asym</sub> can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTR<sub>asym</sub> contrast so that pHspecific contrast can be obtained for imaging ischemic tissue acidosis.
Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute exchangeable protons and local properties such as pH and temperate, yet its susceptibility to field inhomogeneity limits its in vivo applications. Particularly, CEST measurement varies with RF irradiation power, the dependence of which is complex due to concomitant direct RF saturation (RF spillover) effect. Because the volume transmitters provide relatively homogeneous RF field, they have been conventionally used for CEST imaging despite of their elevated specific absorption rate (SAR) and relatively low sensitivity than surface coils. To address this limitation, we developed an efficient B<sub>1</sub> inhomogeneity correction algorithm that enables CEST MRI using surface transceiver coils. This is built on recent work that showed the inverse CEST asymmetry analysis (CESTR<sub>ind</sub>) is not susceptible to confounding RF spillover effect. We here postulated that the linear relationship between RF power level and CESTR<sub>ind</sub> can be extended for correcting B<sub>1</sub> inhomogeneity induced CEST MRI artifacts. Briefly, we prepared a tissue-like Creatine gel pH phantom and collected multiparametric MRI including relaxation, field map and CEST MRI under multiple RF power levels, using a conventional surface transceiver coil. The raw CEST images showed substantial heterogeneity due to B1 inhomogeneity, with pH contrast to noise ratio (CNR) being 8.8. In comparison, pH MRI CNR of the fieldinhomogeneity corrected CEST MRI was found to be 17.2, substantially higher than that without correction. To summarize, our study validated an efficient field inhomogeneity correction that enables sensitive CEST MRI with surface transceiver, promising for in vivo translation.