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The impact of chronic cerebral hypoperfusion on resting-state blood oxygen level-dependent signal fluctuations remains unknown. We aimed to determine whether chronic ischemia induces changes in amplitude of low-frequency fluctuations (ALFF) and to investigate the correlation between ALFF and perfusion-weighted magnetic resonance imaging (PWI) parameters in patients with moyamoya disease (MMD). Thirty patients with pre- and postoperative resting-state functional magnetic resonance imaging and PWI were included, and thirty normal controls underwent resting-state functional magnetic resonance imaging. A decrease in preoperative frontal lobe ALFF was observed in patients with MMD. Postoperative frontal lobe ALFF showed moderate improvement but still remained lower than those in normal controls. The values of mean transit time and time-to-peak, but not cerebral blood volume and cerebral blood flow, correlated significantly with frontal lobe ALFF. Moreover, there were significant negative correlations between changes in frontal lobe PWI parameters and changes in frontal lobe ALFF on both operated side and contralateral side after the unilateral revascularization surgery. Our results demonstrate that reduced ALFF are closely related to the abnormal PWI parameters and vary with the alteration of cerebral perfusion in patients with MMD. [ABSTRACT FROM AUTHOR]

Purpose: In clinical work, accurately measuring the volume and the size of breast cancer is significant to develop a treatment plan. However, it is time-consuming, and inter- and intra-observer variations among radiologists exist. The purpose of this study was to assess the performance of a Res-UNet convolutional neural network based on automatic segmentation for size and volumetric measurement of mass enhancement breast cancer on magnetic resonance imaging (MRI)., Materials and Methods: A total of 1,000 female breast cancer patients who underwent preoperative 1.5-T dynamic contrast-enhanced MRI prior to treatment were selected from January 2015 to October 2021 and randomly divided into a training cohort ( n = 800) and a testing cohort ( n = 200). Compared with the masks named ground truth delineated manually by radiologists, the model performance on segmentation was evaluated with dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). The performance of tumor (T) stage classification was evaluated with accuracy, sensitivity, and specificity., Results: In the test cohort, the DSC of automatic segmentation reached 0.89. Excellent concordance (ICC > 0.95) of the maximal and minimal diameter and good concordance (ICC > 0.80) of volumetric measurement were shown between the model and the radiologists. The trained model took approximately 10-15 s to provide automatic segmentation and classified the T stage with an overall accuracy of 0.93, sensitivity of 0.94, 0.94, and 0.75, and specificity of 0.95, 0.92, and 0.99, respectively, in T1, T2, and T3., Conclusions: Our model demonstrated good performance and reliability for automatic segmentation for size and volumetric measurement of breast cancer, which can be time-saving and effective in clinical decision-making., Competing Interests: Author GL, ZT and ZS were employed by Keya Medical Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yue, Zhang, Zhou, Li, Tang, Sun, Cai, Tian, Gao, Dong, Liu, Bai and Sheng.)

Background and Purpose: 3D pseudo-continuous arterial spin labeling (3D pCASL) is commonly used to measure arterial cerebral blood flow (CBF). The aim of this study was to assess the clinical feasibility and accuracy of 3D pCASL in comparison with dynamic susceptibility contrast (DSC) perfusion imaging in moyamoya disease (MMD)., Materials and Methods: A total of 174 MMD patients underwent 3D pCASL and DSC-MRI for evaluating cerebral blood perfusion. 3D-pCASL with two single post-labeling delay (PLD) times (1,500 and 2,500 ms) was used to measure CBF. The values of DSC-CBF and ASL-CBF were calculated for major arterial territories including the anterior, middle, and posterior cerebral arteries as well as the areas based on the Alberta Stroke Program Early CT Score (ASPECTS) template. The correlation between DSC-CBF and ASL-CBF was analyzed. The consistency and accuracy between the two methods in assessing the cerebral ischemic state before and after surgery were analyzed., Results: The correlation between ASL (2,500 ms) and DSC-MRI was slightly better than the correlation between ASL (1,500 ms) and DSC-MRI in major vascular territories before revascularization. Significant correlations were observed between ASL (2,500 ms) and DSC-MRI and between ASL (1,500 ms) and DSC-MRI in major vascular territories after revascularization. For 44 surgically treated patients, the scores of ASPECTS for CBF on the operated side were significantly different before and after revascularization ( p < 0.05) and showed good consistency on all the examination methods. A comparison of the scores of ASPECTS of the three parameters before and after revascularization showed that there was no statistical difference between them ( p > 0.05)., Conclusion: Compared to DSC-MRI, 3D pCASL can assess the cerebral blood perfusion in MMD before and after revascularization effectively. 3D pCASL showed the feasibility and clinical utility value in patients with MMD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Lu, Liu, Liu, Shen, Sheng, Han and Cai.)

Nanozymes that mimic natural enzyme-like activities have gradually emerged in cancer therapy. To overcome the bottlenecks of single-mode nanozymes, including "off-target" toxicity and ineffectiveness toward metastatic cancers, we designed magnetic nanoparticle-based multifunctional visualized immunomodulatory nanozymes. Besides the partial initiation of the prime immune response by intrinsic immunogenicity, as a smart drug delivery system with a temperature- and pH-sensitive dual response to the tumor microenvironment, these nanozymes released immune agonists to boost enhanced systemic immune response, eventually ameliorating the cancer immune microenvironment through many aspects: activating dendritic cells, improving the function of CD8 + T cells, and decreasing the population of myeloid-derived suppressor cells, which inhibited both primary and metastatic cancers. Mechanistically, these nanozymes regulated the reactive oxygen species-related Akt signaling pathway and consequently activated cell apoptosis-related signaling pathways, which provided a deeper understanding of the synergistic mechanism of multifunctional nanozymes. Our findings offer a promising imaging-guided cocktail therapy strategy through immunomodulatory nanozymes.

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer therapy. However, it remains a great challenge to design nanozymes that precisely exert its activity in tumor without producing off-target toxicity to surrounding normal tissues. Here, we report a synergetic enhancement strategy through the combination between nanozyme and tumor vascular normalization to destruct tumors, which was based on tumor microenvironment (TME) "unlocking." This nanozyme that we developed not only has photothermal properties but also can produce reactive oxygen species efficiently under the stimulation of TME. Moreover, this nanozyme also showed remarkable imaging performance in fluorescence imaging in the second near-infrared region and magnetic resonance imaging for visualization tracing in vivo. The process of combination therapy showed remarkable therapeutic effect for breast cancer. This study provides a therapeutic strategy by the cooperation between multifunctional nanozyme and tumor vascular normalization for intensive combination therapy of breast cancer., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Clinically diagnosing low-grade gliomas and microscopic metastatic tumors in the spinal cord using magnetic resonance imaging (MRI) is challenging, as the blood-brain barrier (BBB) almost completely excludes the MRI contrast agent gadopentetate dimeglumine, GdDTPA (Magnevist), from the brain. The development of a more efficient, safe, and broad-spectrum glioma diagnosis and treatment would therefore have a great clinical value. Based on the high expression levels of both transferrin receptor 1 (TfR1) and low-density lipoprotein receptor-related protein 1 (LRP1) in BBB-related cells and glioma cells, we designed a novel protein nanoparticle, ferritin-HREV107-Angiopep-2 (Fn-Rev-Ang). We found that Fn-Rev-Ang rapidly crossed the BBB in mice and had drug-loading properties. Moreover, the brain MRI signal intensity ratio associated with Fn-Rev-Ang-GdDTPA was higher than that associated with Fn-GdDTPA alone. Importantly, gliomas with diameters below 1 mm and microscopic metastatic tumors in the spinal cord were successfully detected in mice by MRI with Fn-Rev-Ang-GdDTPA, which is not possible using the current clinical MRI technology. In addition, Fn-Rev-Ang-loaded doxorubicin had a strong inhibitory effect on mouse brain gliomas and their metastasis, which significantly prolonged the animal survival time. Thus, our newly constructed Fn-Rev-Ang nanodelivery carrier may help expand the use of MRI to the early diagnosis and treatment of microscopic tumors, thereby offering a possible basis for improving the survival rate of patients with gliomas and microscopic spinal metastatic tumors., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Transition metal copper (Cu) can exist in oxidized or reduced states in cells, leading to cytotoxicity in cancer cells through oxidative stress. Recently, copper complexes are emerging as a new class of anticancer compounds. Here, we report that a novel anticancer copper complex (HYF127c/Cu) induces oxidative stress-dependent cell death in cancer cells. Further, transcriptional analysis revealed that oxidative stress elicits broad transcriptional changes of genes, in which autophagy-related genes are significantly changed in HYF127c/Cu-treated cells. Consistently, autophagy was induced in HYF127c/Cu-treated cells and inhibitors of autophagy promoted cell death induced by HYF127c/Cu. Further analysis identified that the MAPK11/12/13/14 (formerly known as p38 MAPK) pathway was also activated in HYF127c/Cu-treated cells. Meanwhile, the MAPK11/12/13/14 inhibitor SB203580 downregulated autophagy by inhibiting the transcription of the autophagy genes MAP1LC3B, BAG3, and HSPA1A, and promoted HYF127c/Cu-induced cell death. These data suggest that copper-induced oxidative stress will induce protective autophagy through transcriptional regulation of autophagy genes by activation of the MAPK11/12/13/14 pathway in HeLa cells.