The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the intriguing blood−brain barrier (BBB)-penetrating ability of 4T1 cancer cells upon their brain metastasis, we herein designed a promising biomimetic nanoplatform by camouflaging a succinobucol-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB), aiming to promote the preferential targeting of cerebral ischemic lesions to attenuate the ischemia/ reperfusion injury. In transient middle cerebral artery occlusion (tMCAO) rat models, MPP/SCB could be preferentially delivered to the ischemic hemisphere with a 4.79-fold higher than that in the normal hemisphere. Moreover, MPP/SCB produced notable enhancement of microvascular reperfusion in the ischemic hemisphere, resulting in a 69.9% reduction of infarct volume and showing remarkable neuroprotective effects of tMCAO rats, which was superior to the counterpart uncamouflaged nanovehicles (PP/SCB). Therefore, this design provides a promising nanoplatform to target the cerebral ischemic lesions for ischemic stroke therapy.

Chemical exchange saturation transfer (CEST) MRI is versatile for measuring the dilute labile protons and microenvironment properties. However, the use of insufficiently long RF saturation duration (Ts) and relaxation delay (Td) may underestimate the CEST measurement. This study proposed a quasi-steady-state (QUASS) CEST analysis for robust CEST quantification. Methods: The CEST signal evolution was modeled as a function of the longitudinal relaxation rate during Td and spin-lock relaxation rate during Ts, from which the QUASS-CEST effect is derived. Numerical simulation and in vivo rat glioma MRI experiments were conducted at 11.7 T to compare the apparent and QUASS-CEST results obtained under different Ts/Td of 2 seconds/2 seconds and 4 seconds/4 seconds. Magnetization transfer and amide proton transfer effects were resolved using a multipool Lorentzian fitting and evaluated in contralateral normal tissue and tumor regions. Results: The simulation showed the dependence of the apparent CEST effect on Ts and Td, and such reliance was mitigated with the QUASS algorithm. Animal experiment results showed that the apparent magnetization transfer and amide proton transfer effects and their contrast between contralateral normal tissue and tumor regions increased substantially with Ts and Td. In comparison, the QUASS magnetization transfer and amide proton transfer effects and their difference between contralateral normal tissue and tumor exhibited little dependence on Ts and Td. In addition, the apparent magnetization transfer and amide proton transfer were significantly smaller than the corresponding QUASS indices (P < .05). |ZHANG et Al. | INTRODUCTIONChemical exchange saturation transfer MRI has emerged as a sensitive method for detecting dilute labile protons and microenvironment properties such as pH and temperature. [1][2][3][4] It has shown promise in measuring endogenous metabolites and compounds (eg, glucose, glycogen, amide protons) and exogenous diamagnetic/paramagnetic CEST agents, offering a novel means to image a host of disorders, including acute stroke, tumor, and epilepsy. [5][6][7][8][9][10] Although CEST MRI is versatile, its contrast is quite complicated. The measurable CEST effect depends not only on the labile proton concentration and exchange rate, but also on experimental parameters, 11,12 such as the duration of RF irradiation and the relaxation delay (Td) between RF saturation. [13][14][15][16] Indeed, the CEST effect reflects two competing processes, namely, the signal reduction due to saturation transfer from irradiated labile protons and the signal recovery through relaxation. The CEST-MRI effect has a complicated dependence on bulk water T 1 . 17 This is further confounded in the presence of T 1 changes in diseased tissues. 18 Recently, Tanoue et al demonstrated the effect of RF saturation duration (Ts) on the CEST effect at 11.7 T. 19 It takes prolonged saturation and recovery time to reach the steady state. A trade-off has to be made between the magnitudes of the CEST effect and scan tim...