Preclinical multi-physiologic monitoring of immediate-early responses to diverse treatment strategies in breast cancer by optoacoustic imaging.

Optoacoustic imaging enables the measurement of tissue oxygen saturation (sO2) and blood perfusion while being utilized for detecting tumor microenvironments. Our aim was to employ multispectral optoacoustic tomography (MSOT) to assess immediate-early changes of hemoglobin level and sO2 within breast tumors during diverse treatments. Mouse breast cancer models were allocated into four groups: control, everolimus (EVE), paclitaxel (PTX), and photodynamic therapy (PDT). Hemoglobin was quantified daily, as well as sO2 and blood perfusion were verified by immunohistochemical (IHC) staining. MSOT showed a temporal window of enhanced oxygenation and improved perfusion in EVE and PTX groups, while sO2 consistently remained below baseline in PDT. The same results were obtained for the IHC. Therefore, MSOT can monitor tumor hypoxia and indirectly reflect blood perfusion in a non-invasive and non-labeled way, which has the potential to monitor breast cancer progression early and enable individualized treatment in clinical practice.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI to Evaluate the Rapid Antidepressant Effects of Ketamine in the Hippocampus of Rat Depression Model.

BACKGROUND: Ketamine is a quick acting antidepressant drug, and an accurate detection method is lacking. Ketamine's effects in a rat depression model have not previously been well explored using glutamate chemical exchange saturation transfer (GluCEST). PURPOSE: To investigate the GluCEST changes of chronic unpredictable mild stress (CUMS) rats after receiving either ketamine or saline injection. STUDY TYPE: Randomized animal model trial. ANIMAL MODEL: 12 CUMS and 6 Sprague-Dawley rats. Divided into three groups: ketamine (N = 6), saline (N = 6), and control (N = 6). FIELD STRENGTH/SEQUENCE: 7.0 T/the sequence is GluCEST and 1 H MR spectroscopy (MRS). ASSESSMENT: The CUMS rats were exposed to different stress factors for 8 weeks. The glutamate concentration in the hippocampus was assessed by the GluCEST,1 H MRS, and the high-performance liquid chromatography (HPLC). STATISTICAL TESTS: The t-test, Mann-Whitney U test, and Pearson's correlation. RESULTS: In depression conditions, GluCEST signals were lower in the bilateral hippocampus than in control group. Thirty minutes after ketamine injection, the GluCEST signals in the bilateral hippocampus were higher compared with the saline group (left: 2.99 ± 0.34 [Control] vs. 2.44 ± 0.20 [Saline] vs. 2.85 ± 0.11 [Ketamine]; right: 2.97 ± 0.28 [Control] vs. 2.49 ± 0.25 [Saline] vs. 2.86 ± 0.19 [Ketamine]). In 1 H MRS, significant changes were only observed in the left hippocampus (2.00 ± 0.16 [Control] vs. 1.81 ± 0.09 [Saline] vs. 2.04 ± 0.14 [Ketamine]). Furthermore, HPLC results showed similar trends to those observed in the GluCEST results (left: 2.32 ± 0.22 [Control] vs. 1.96 ± 0.11 [Saline] vs. 2.18 ± 0.11 [Ketamine]; right: 2.35 ± 0.18 [Control] vs. 1.87 ± 0.16 [Saline] vs. 2.09 ± 0.08 [Ketamine]). DATA CONCLUSION: GluCEST can sensitively evaluate the ketamine's antidepressant effects by detecting the fast increase in glutamate concentration. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Design and Optimization of Linking Matrix for a JSCC System Based on DP-LDPC Codes.

Although extensive optimization of encoding and decoding schemes for joint source-channel coding (JSCC) systems has been conducted, efficient optimization schemes are still required for designing and optimizing the linking matrix between variable nodes of the source code and check nodes of the channel code. A scheme has been proposed for design and optimization of linking matrix with multi-edges by analyzing the performance of the JSCC system using the joint protograph extrinsic information transfer algorithm to calculate decoding thresholds. The proposed scheme incorporates structural constraints and is effective in designing and optimizing the multi-edges in linking matrix for the JSCC system. Experimental results have demonstrated that the designed and optimized linking matrix significantly improves the performance of the JSCC system. Furthermore, the proposed scheme reduces the complexity of the solution space for the optimized example.

Design of Low-Density Parity-Check Code Pair for Joint Source-Channel Coding Systems Based on Graph Theory.

In this article, a graph-theoretic method (taking advantage of constraints among sets associated with the corresponding parity-check matrices) is applied for the construction of a double low-density parity-check (D-LDPC) code (also known as LDPC code pair) in a joint source-channel coding (JSCC) system. Specifically, we pre-set the girth of the parity-check matrix for the LDPC code pair when jointly designing the two LDPC codes, which are constructed by following the set constraints. The constructed parity-check matrices for channel codes comprise an identity submatrix and an additional submatrix, whose column weights can be pre-set to be any positive integer numbers. Simulation results illustrate that the constructed D-LDPC codes exhibit significant performance improvement and enhanced flexible frame length (i.e., adaptability under various channel conditions) compared with the benchmark code pair.

Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy.

Introduction: Accurate tumor diagnosis is essential to achieve the ideal therapeutic effect. However, it is difficult to accurately diagnose cancer using a single imaging method because of the technical limitations. Multimodal imaging plays an increasingly important role in tumor treatment. Photodynamic therapy (PDT) has received widespread attention in tumor treatment due to its high specificity and controllable photocytotoxicity. Nevertheless, PDT is susceptible to tumor microenvironment (TME) hypoxia, which greatly reduces the therapeutic effect of tumor treatment. Methods: In this study, a novel multifunctional nano-snowflake probe (USPIO@MnO2@Ce6, UMC) for oxygen-enhanced photodynamic therapy was developed. We have fabricated the honeycomb-like MnO2 to co-load chlorin e6 (Ce6, a photosensitizer) and ultrasmall superparamagnetic iron oxide (USPIO, T1-T2 double contrast agent). Under the high H2O2 level of tumor cells, UMC efficiently degraded and triggered the exposure of photosensitizers to the generated oxygen, accelerating the production of reactive oxygen species (ROS) during PDT. Moreover, the resulting USPIO and Mn2+ allow for MR T1-T2 imaging and transformable PAI for multimodal imaging-guided tumor therapy. Results: TEM and UV-vis spectroscopy results showed that nano-snowflake probe (UMC) was successfully synthesized, and the degradation of UMC was due to the pH/ H2O2 responsive properties. In vitro results indicated good uptake of UMC in 4T-1 cells, with maximal accumulation at 4 h. In vitro and in vivo experimental results showed their imaging capability for both T1-T2 MR and PA imaging, providing the potential for multimodal imaging-guided tumor therapy. Compared to the free Ce6, UMC exhibited enhanced treatment efficiency due to the production of O2 with the assistance of 660 nm laser irradiation. In vivo experiments confirmed that UMC achieved oxygenated PDT under MR/PA imaging guidance in tumor-bearing mice and significantly inhibited tumor growth in tumor-bearing mice, exhibiting good biocompatibility and minimal side effects. Conclusion: The multimodal imaging contrast agent (UMC) not only can be used for MR and PA imaging but also has oxygen-enhanced PDT capabilities. These results suggest that UMC may have a good potential for further clinical application in the future.

Developing Smart Nanoparticles Responsive to the Tumor Micro-Environment for Enhanced Synergism of Thermo-Chemotherapy With PA/MR Bimodal Imaging.

With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO2@DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO2), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.

Glutamate Chemical Exchange Saturation Transfer Imaging and Functional Alterations of Hippocampus in Rat Depression Model: A Pilot Study.

BACKGROUND: Adjusting abnormal glutamate neurotransmission is a crucial mechanism in the treatment of depression. However, few non-invasive techniques could effectively detect changes in glutamate neurotransmitters, and no consensus exists on whether glutamate could affect resting-state function changes in depression. PURPOSE: To study the changes in glutamate chemical exchange saturation transfer (GluCEST) value in the hippocampus of rat model exposed to chronic unpredictable mild stress (CUMS), and to explore the effect of this change on the activity of hippocampal glutamatergic neurons. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Twenty male Sprague-Dawley rats (200-300 g). FIELD STRENGTH/SEQUENCE: 7.0 T scanner. Fat rapid acquisition relaxation enhancement sequence for GluCEST, and echo planner imaging sequence for resting-state functional magnetic resonance imaging (rs_fMRI). ASSESSMENT: Rats were divided into two groups: CUMS group (N = 10) and control group (CTRL, N = 10). The magnetization transfer ratio asymmetry analysis was used to quantify the GluCEST data, and evaluate the rs_fMRI data through the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis. STATISTICAL TESTS: A t-test was used to compare the difference in GluCEST or rs_fMRI between CUMS and CTRL groups. Spearman's correlation was applied to explore the correlation between GluCEST values and abnormal fMRI values in hippocampus. Statistical significance was set at P < 0.05. RESULTS: The GluCEST value in the left hippocampus has changed significantly (3.3 ± 0.3 [CUMS] vs. 3.9 ± 0.4 [CTRL], P < 0.05). In addition, the GluCEST value was significantly positively correlated with the ALFF values (r = 0.5, P < 0. 05, df = 7) and negatively correlated with the ReHo values (r = -0.6, P < 0.05, df = 7). DATA CONCLUSION: GluCEST technique has the feasibility of mapping glutamate changes in rat depression. Glutamate neurotransmitters are important factors affecting the abnormal function of neural activity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.