Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

Effect of Cyclosporin H on ischemic injury and neutrophil infiltration in cerebral infarct model of rats via PET imaging.

BACKGROUND: Brain ischemia-reperfusion injury is a complex process, and neuroinflammation is an important secondary contributing pathological event. Neutrophils play major roles in ischemic neuroinflammation. Once activated, neutrophils express formyl peptide receptors (FPRs), which are special receptors of a class of chemoattractants and may be potential targets to regulate the activity of neutrophils and control cerebral ischemic injury. This study was aimed to explore the ameliorating effect of Cyclosporin H (CsH), a potent FPR antagonist, on brain ischemic injury by inhibiting the activation and migration of neutrophils, and improving cerebral blood flow. METHODS: We employed a middle cerebral artery occlusion (MCAO) Model on rats and performed behavioral, morphological, and microPET imaging assays to investigate the potential restoring efficacy of CsH on cerebral ischemic damages. Peptide N-cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), an antagonist to the neutrophil FPR with a high binding affinity, was used for imaging neutrophil distribution. RESULTS: We found that CsH had similar effect with edaravone on improving the neurobehavioral deficient symptoms after cerebral ischemia-reperfusion, and treatment with CsH also alleviated ischemic cerebral infarction. Compared with the MCAO Model group, [18F]FDG uptake ratios of the CsH and edaravone treatment groups were significantly higher. The CsH-treated groups also showed significant increases in [18F]FDG uptake at 144 h when compared with that of 24 h. This result indicates that like edaravone, treatment with both doses of CsH promoted the recovery of blood supply after cerebral ischemic event. Moreover, MCAO-induced cerebral ischemia significantly increased the radiouptake of [68Ga]Ga-cFLFLF at 72 h after ischemia-reperfusion operation. Compared with MCAO Model group, radiouptake values of [68Ga]-cFLFLF in both doses of CsH and edaravone groups were all decreased significantly. These results showed that both doses of CsH resulted in a similar therapeutic effect with edaravone on inhibiting neutrophil infiltration in cerebral infarction. CONCLUSION: Potent FPR antagonist CsH is promisingly beneficial in attenuating neuroinflammation and improving neurobehavioral function against cerebral infarction. Therefore, FPR may become a novel target for regulating neuroinflammation and improving prognosis for ischemic cerebrovascular disorders.

Evaluation of renal ischemia-reperfusion injury using CEUS in mice.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) frequently occurs clinically. We investigated the value of contrast-enhanced ultrasonography (CEUS) in the evaluation of renal IRI levels in mice. METHODS: Thirty-six healthy adult male C57BL/6 mice (20-22 g) were randomly divided into the sham, 10 min, 20 min, 30 min, 40 min, and 50 min groups based on the time of renal warm ischemia by blocking the left renal pedicle, approved by the Institutional Animal Ethics Committee. Time-intensity curve (TIC)-derived parameters such as peak enhancement (PE) and wash-in perfusion index (WiPI) were produced using CEUS at 1 h and 24 h after IRI. The severity of kidney injury was detected by the renal tubular necrosis rate which was analyzed by hematoxylin and eosin staining at 24 h after IRI. The Spearman correlation coefficient was used to describe the correlations between PE and WiPI values and the renal tubular necrosis rate. RESULTS: The PE and WiPI values decreased after IRI in the groups with a warm ischemia time ≥ 20 min. The renal tubular necrosis rate was significantly correlated with the PE value at 1 h (ρ = -0.802) and 24 h (ρ = -0.861) after IRI and the WiPI value at 1 h (ρ = -0.814) and 24 h (ρ = -0.853) after IRI (all p < 0.001). CONCLUSION: TIC-derived parameters, including PE and WiPI values, can be used to evaluate the severity of renal IRI in mice. CEUS is a safe and effective technology for the detection of renal IRI. RELEVANCE STATEMENT: CEUS can evaluate the severity of renal ischemia-reperfusion injury by peak enhancement and wash-in perfusion index values selected from various time-intensity curve-derived parameters. KEY POINTS: • Contrast-enhanced ultrasonography can evaluate the level of renal ischemia-reperfusion injury. • Peak enhancement and wash-in perfusion index are correlated with the renal tubular necrosis rate. • CEUS can detect changes in unilateral renal function without radiation.

Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia/reperfusion injury.

OBJECTIVES: Multi-parametric magnetic resonance imaging (MRI) can provide comprehensive and valuable information for precise diagnosis and treatment evaluation of a number of diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microenvironment. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into three groups: the Sham, CIRI and CIRI + Mel groups. At multiple time points after ischemia, MRI scanning was performed on a 7.0 Tesla MRI scanner. Multi-parametric MRI includes T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and chemical exchange saturation transfer (CEST)-MRI. CEST effects were calculated by the Lorentzian difference method, 3.5 ppm indicates amide protons of mobile proteins/peptide (Amide-CEST) and 2.0 ppm indicates amine protons (Guan-CEST). Multiple histopathological techniques were used to examine the histopathological changes and explore the therapeutic effects of Mel. RESULTS: T2WI and DWI-MRI could localize the infarct foci and areas in CIRI rats, which was further validated by staining, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining. After Mel treatment, T2WI and DWI-MRI showed smaller infarct volume, and neurons displayed improved morphology with less apoptosis rates. Notably, Amide-CEST and Guan-CEST signal decreased as early as 2 h after CIRI (all P <0.001), reflecting the change of pH after ischemia. After Mel treatment, both Amide-CEST and Guan-CEST signal increased in ischemic cortex and striatum compared with control group (all P < 0.001). The immunofluorescence staining and western blotting analysis suggested the expression of M2 microglia increased after Mel treatment; While，after Mel treatment the inflammatory factor interleukin-1ß (IL-1ß) decreased compared with control CIRI rats. CONCLUSIONS: Multi-parametric MRI was shown to be an effective method to monitor the brain damage in a rat model of CIRI and assess the therapeutic effects of Mel treatment. Amide-CEST and Guan-CEST were especially sensitive to the changes in brain microenvironment during the early stage after CIRI. Furthermore, the neuroprotective effect of Mel treatment is associated with its promotion of the microglia polarized to M2 type in CIRI rats.

Targeted echogenic and anti-inflammatory polymeric prodrug nanoparticles for the management of renal ischemia/reperfusion injury.

Ischemia/reperfusion (IR) injury is an inevitable pathological event occurring when blood is resupplied to the tissues after a period of ischemia. One of major causes of IR injury is the overproduction of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), which mediates the expression of various inflammatory cytokines to exacerbate tissue damages. The overproduced H2O2 could therefore serve as a diagnostic and therapeutic biomarker of IR injury. In this study, poly(boronated methacrylate) (pBMA) nanoparticles were developed as nanotheranostic agents for renal IR injury, which not only generate CO2 bubbles to enhance the ultrasound contrast but also provide potent preventive effects in a H2O2-triggered manner. The surface of pBMA nanoparticles was decorated with taurodeoxycholic acid (TUDCA) that binds P-selectin overexpressed in inflamed tissues. In the mouse model of renal IR injury, TUDCA-coated pBMA (T-pBMA) nanoparticles preferentially accumulated in the injured kidney and markedly enhanced the ultrasound contrast. T-pBMA nanoparticles also effectively prevented renal IR injury by scavenging H2O2 and suppressing the expression of inflammatory cytokines. Treatment progress of IR injury could be also monitored by echogenic T-pBMA nanoparticles. Given their targeting ability, excellent H2O2-responsiveness, anti-inflammatory activity and H2O2-triggered echogenicity, T-pBMA nanoparticles have excellent translational potential for the management of various H2O2-related diseases including IR injury.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

PURPOSE: Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. METHODS: Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. RESULTS: Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CONCLUSIONS: CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

Unveiling the Crucial Roles of O2•- and ATP in Hepatic Ischemia-Reperfusion Injury Using Dual-Color/Reversible Fluorescence Imaging.

Hepatic ischemia-reperfusion injury (HIRI) is mainly responsible for morbidity or death due to graft rejection after liver transplantation. During HIRI, superoxide anion (O2•-) and adenosine-5'-triphosphate (ATP) have been identified as pivotal biomarkers associated with oxidative stress and energy metabolism, respectively. However, how the temporal and spatial fluctuations of O2•- and ATP coordinate changes in HIRI and particularly how they synergistically regulate each other in the pathological mechanism of HIRI remains unclear. Herein, we rationally designed and successfully synthesized a dual-color and dual-reversible molecular fluorescent probe (UDP) for dynamic and simultaneous visualization of O2•- and ATP in real-time, and uncovered their interrelationship and synergy in HIRI. UDP featured excellent sensitivity, selectivity, and reversibility in response to O2•- and ATP, which rendered UDP suitable for detecting O2•- and ATP and generating independent responses in the blue and red fluorescence channels without spectral crosstalk. Notably, in situ imaging with UDP revealed for the first time synchronous O2•- bursts and ATP depletion in hepatocytes and mouse livers during the process of HIRI. Surprisingly, a slight increase in ATP was observed during reperfusion. More importantly, intracellular O2•-─succinate dehydrogenase (SDH)─mitochondrial (Mito) reduced nicotinamide adenine dinucleotide (NADH)─Mito ATP─intracellular ATP cascade signaling pathway in the HIRI process was unveiled which illustrated the correlation between O2•- and ATP for the first time. This research confirms the potential of UDP for the dynamic monitoring of HIRI and provides a clear illustration of HIRI pathogenesis.

Magnetic Resonance Diffusion Tensor Imaging Characterize the Hepatic Ischemia-Reperfusion Injury in an Animal Study.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is the main cause of morbidity and mortality after hepatectomy; thus, new methods for reducing I/R injury are required. The aim of this study is to evaluate changes in the average apparent diffusion coefficient (ADCavg) and fractional anisotropy (FA) in rabbits with partial hepatic I/R injury with magnetic resonance diffusion tensor imaging (DTI). METHODS: The left lobe of the rabbit liver underwent 60 minutes of ischemia followed by 0.5, 2, 6, 12, 24, and 48 hours of reperfusion. T2-weighted images (T2WI), T1-weighted images (T1WI), DTI, and contrast-enhanced T1WI were performed; 6 b values were used for DTI on 6 diffusion directions. The serum levels of transaminases and liver histopathology findings were examined. RESULTS: In the early stage of I/R (0.5 hour), ADCavg decreased significantly and increased sharply to 2 hours, then increased from 6 hours to 48 hours of reperfusion, except for a transient decrease (24 hours). Meanwhile, FA showed almost the opposite trend, drastically increasing during the first 0.5 hour and then slightly decreasing until 48 hours of reperfusion, except for an obvious decrease in the 2-hours group. The serum levels of liver markers and the pathologic scores were sharply increased in the I/R group after reperfusion and correlated with DTI of hepatic tissue after I/R. CONCLUSIONS: Diffusion tensor imaging is feasible for imaging I/R-induced liver damage and can discriminate isotropic properties of the liver after I/R injury with objective changes in the ADCavg and FA. Diffusion tensor imaging can be a promising novel approach for use in clinical management after liver surgery.

Uncovering Endoplasmic Reticulum Superoxide Regulating Hepatic Ischemia-Reperfusion Injury by Dynamic Reversible Fluorescence Imaging.

Hepatic ischemia-reperfusion injury (HIRI) is a relatively common complication of liver resection and transplantation that is intimately connected to oxidative stress. The superoxide anion radical (O2•-), as the first reactive oxygen species produced by organisms, is an important marker of HIRI. The endoplasmic reticulum (ER) is an essential site for O2•- production, especially ER oxidative stress, which is closely linked to HIRI. Thus, dynamic variations in ER O2•- may accurately indicate the HIRI extent. However, there is still a lack of tools for the dynamic reversible detection of ER O2•-. Therefore, we designed and prepared an ER-targeted fluorescent reversible probe DPC for real-time tracing of O2•- fluctuations. We successfully observed a marked increase in ER O2•- levels in HIRI mice. A potential NADPH oxidase 4-ER O2•--SERCA2b-caspase 4 signaling pathway in HIRI mice was also revealed. Attractively, DPC was successfully used for precise fluorescent navigation and excision of HIRI sites.

In vivo imaging of renal microvasculature in a murine ischemia-reperfusion injury model using optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) provides three-dimensional structural and semiquantitative imaging of microvasculature in vivo. We developed an OCTA imaging protocol for a murine kidney ischemia-reperfusion injury (IRI) model to investigate the correlation between renal microvascular changes and ischemic damage. Mice were divided into mild and moderate IRI groups according to the duration of ischemia (10 and 35 mins, respectively). Each animal was imaged at baseline; during ischemia; and at 1, 15, 30, 45, and 60 mins after ischemia. Amplitude decorrelation OCTA images were constructed with 1.5-, 3.0-, and 5.8-ms interscan times, to calculate the semiquantitative flow index in the superficial (50-70 µm) and the deep (220-340 µm) capillaries of the renal cortex. The mild IRI group showed no significant flow index change in both the superfial and the deep layers. The moderate IRI group showed a significantly decreased flow index from 15 and 45 mins in the superficial and deep layers, respectively. Seven weeks after IRI induction, the moderate IRI group showed lower kidney function and higher collagen deposition than the mild IRI group. OCTA imaging of the murine IRI model revealed changes in superficial blood flow after ischemic injury. A more pronounced decrease in superficial blood flow than in deep blood flow was associated with sustained dysfunction after IRI. Further investigation on post-IRI renal microvascular response using OCTA may improve our understanding of the relationship between the degree of ischemic insult and kidney function.

Assessment of focal renal ischemia-reperfusion injury in a porcine model using hyperpolarized [1-13 C]pyruvate MRI.

PURPOSE: Ischemic injury in the kidney is a common pathophysiological event associated with both acute kidney injury and chronic kidney disease; however, regional ischemia-reperfusion as seen in thromboembolic renal disease is often undetectable and thus subclinical. Here, we assessed the metabolic alterations following subclinical focal ischemia-reperfusion injury with hyperpolarized [1-13 C]pyruvate MRI in a porcine model. METHODS: Five pigs were subjected to 60 min of focal kidney ischemia. After 90 min of reperfusion, a multiparametric proton MRI protocol was performed on a clinical 3T scanner system. Metabolism was evaluated using 13 C MRI following infusion of hyperpolarized [1-13 C]pyruvate. Ratios of pyruvate to its detectable metabolites (lactate, bicarbonate, and alanine) were used to quantify metabolism. RESULTS: The focal ischemia-reperfusion injury resulted in injured areas with a mean size of 0.971 cm3 (±1.019). Compared with the contralateral kidney, the injured areas demonstrated restricted diffusion (1269 ± 83.59 × 10-6 mm2 /s vs. 1530 ± 52.73 × 10-6 mm2 /s; p = 0.006) and decreased perfusion (158.8 ± 29.4 mL/100 mL/min vs. 274 ± 63.1 mL/100 mL/min; p = 0.014). In the metabolic assessment, the injured areas displayed increased lactate/pyruvate ratios compared with the entire ipsilateral and the contralateral kidney (0.35 ± 0.13 vs. 0.27 ± 0.1 vs. 0.25 ± 0.1; p = 0.0086). Alanine/pyruvate ratio was unaltered, and we were unable to quantify bicarbonate due to low signal. CONCLUSION: MRI with hyperpolarized [1-13 C]pyruvate in a clinical setup is capable of detecting the acute, subtle, focal metabolic changes following ischemia. This may prove to be a valuable future addition to the renal MRI suite.

Magnetic Response Combined with Bioactive Ion Therapy: A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal Ischemia-Reperfusion Injury.

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia-reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe3O4 and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a "diagnosis-therapy-protection" approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.

A biomarker-responsive nanoprobe for detecting hepatic ischemia-reperfusion injury via optoacoustic/NIR-II fluorescence imaging.

A nanoprobe for detecting hepatic ischemia-reperfusion injury has been developed. Apparent optoacoustic and NIR-II fluorescent signals are given out upon the nanoprobe's response to the in situ biomarker H2O2 in the liver in the case of ischemia-reperfusion injury.

Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. RESULTS: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. CONCLUSIONS: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

'White Cord Syndrome': A Rare Catastrophic Complication Following Anterior Cervical Discectomy and Fusion.

Background: 'White-cord syndrome' is an extremely rare entity following decompression of cervical cord in which post-operative reperfusion injury results in worsening of patient's neurology and MRI reveals signal changes in spinal cord in absence of cord compression. We wish to report a case of 'white-cord syndrome' following a 'routine' ACDF. Case Description: A 39-year-old woman with paresthesias and spastic quadriparesis was found to have C5-C6 PIVD on MRI. ACDF was performed at C5-C6, after which worsening of quadriparesis was noted, for which intravenous high-dose steroids were started. An urgent MRI was done, which revealed findings of white-cord syndrome, without compression on underlying cord. With conservative management, her ASIA grade improved from C to D and the features of white-cord syndrome disappeared on follow-up imaging. Conclusion: It is important for surgeons and patients to be aware of this rare but potentially catastrophic entity as this needs to be discussed while taking consent for surgery.

Deep-Depth Imaging of Hepatic Ischemia/Reperfusion Injury Using a Carbon Monoxide-Activated Upconversion Luminescence Nanosystem.

Exploring a chemical imaging tool for visualizing the endogenous CO biosignaling molecule is of great importance in understanding the pathophysiological functions of CO in complex biological systems. Most of the existing CO fluorescent probes show excitation and emission in the region of ultraviolet and visible light, which are not suitable for application in in vivo deep-depth imaging of CO. Herein, a new near-infrared (NIR) to NIR upconversion luminescence (UCL) nanosystem for in vivo visualization of CO was developed, which possesses the merits of high selectivity and sensitivity, a deep tissue penetration depth, and a high signal-to-noise ratio. In this design, upon interaction with CO, the maxima absorption peak of the nanosystem showed a significant blue shift from 795 nm to 621 nm and triggered a remarkable turn-on NIR UCL signal due to the luminescence resonance energy transfer process. Leveraging this nanosystem, we achieved an NIR UCL visualization of the generation of CO biosignals caused by hypoxic, acute inflammation, or ischemic injury in living cells, zebrafish, and mice. Moreover, the protective effect of CO in zebrafish models of oxygen and glucose deprivation/reperfusion (OGD/R) and mice models of lipopolysaccharide-induced oxidative stress (LOS) and hepatic ischemia/reperfusion (HI/R) was also further verified. Therefore, this work discloses that the nanosystem not only serves as a promising nanoplatform to study biological signaling pathways of CO in pathophysiological events, but may also provide a powerful tool for HI/R injury diagnosis.

Intraoperative evaluation of testicular vascularization and perfusion in rat testicles with indocyanine green (ICG)/near-infrared (NIR) fluorescent imaging after torsion-detorsion and reperfusion.

INTRODUCTION: The aim of this study was to evaluate testicular perfusion and vascularization with intraoperative ICG/NIR imaging in a testicular ischemia-reperfusion model and to investigate the effects of ICG on testicular tissue. MATERIALS AND METHODS: 24 male rats were divided into four groups. In the ICG group, only ICG was given and images of the testicles were recorded with NIR camera. In the torsion group, the testicles were left in torsion for 4 h. ICG/NIR images were obtained after torsion and detorsion. In the reperfusion group, ICG/NIR images of the testicles were obtained at the 4th hour of reperfusion. After the procedures, testicles were collected and evaluated with histological, immunohistochemical examination and qRT-PCR. RESULTS: There was no histologically negative effect of ICG on testicular tissue. There was no testicular perfusion in the torsion group, but perfusion started after detorsion. At the 4th hour of reperfusion, testicular perfusion continued. TNF-a, IL-6, MCP-1 and caspase-3 immunoreactivity were found to be at low levels in the control and ICG groups, while high in the torsion and reperfusion groups (p < 0.05). In qRT-PCR, TNF-a, IL-6, MCP-1 and caspase-3 expressions were lower in the control and ICG groups, but higher in the torsion and reperfusion groups. CONCLUSION: There was no histologically negative effect of ICG on testicles. The ICG/NIR imaging technique seems to be a feasible method in testicular torsion and may contribute to the surgeon in the intraoperative management of testicular torsion. In testicles that started to be perfused after detorsion, perfusion still continued at the 4th hour of reperfusion. Our next goal is to test whether testicles showing ICG fluorescence in during reperfusion maintain their viability for long term.

Deep Learning Reconstruction Algorithm-Based MRI Image Evaluation of Edaravone in the Treatment of Lower Limb Ischemia-Reperfusion Injury.

This research aimed to evaluate the therapeutic effect of edaravone on lower limb ischemia-reperfusion injury by MRI images of graph patch-based directional curvelet transform (GPBDCT), compression reconstruction algorithm. 200 patients with lower limb ischemia-reperfusion injury after replantation of severed limb were randomly divided into the observation group (edaravone treatment) and control group (Mailuoning injection treatment), with 100 cases in each group. MRI scanning and image processing using the GPBDCT algorithm were used to evaluate the therapeutic effect of the two groups of patients. The results showed that the signal noise ratio (SNR) (22.01), relative l 2 norm error (RLNE) (0.0792), and matching degree γ (0.9997) of the compression and reconstruction algorithm based on GPBDCT were superior to those of the conventional compression and reconstruction algorithm (P < 0.05). MRI examination showed that the decrease of bleeding signal after treatment in the observation group was superior to that in the control group. The levels of superoxide dismutase (SOD) (15 ± 2.02), malondialdehyde (MDA) (2.27 ± 1.02), B cell lymphoma-2 (Bcl-2) (8.5 ± 1.02), Bcl-2-associated X (Bax) (3.7 ± 0.42), and Caspase-3 protein (35.9 ± 5.42) in the observation group before and after treatment were significantly higher than those in the control group (P < 0.05). In conclusion, the GPBDCT-based compression reconstruction algorithm has a better effect on MRI image processing, and edaravone can better remove free radicals and alleviate apoptosis.

Precision Navigation of Hepatic Ischemia-Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence.

Hepatic ischemia-reperfusion injury (HIRI) is responsible for postoperative liver dysfunction and liver failure. Precise and rapid navigation of HIRI lesions is critical for early warning and timely development of pretreatment plans. Available methods for assaying liver injury fail to provide the exact location of lesions in real time intraoperatively. HIRI is intimately associated with oxidative stress which impairs lysosomal degradative function, leading to significant changes in lysosomal viscosity. Therefore, lysosomal viscosity is a potential biomarker for the precise targeting of HIRI. Hence, we developed a viscosity-activatable second near-infrared window fluorescent probe (NP-V) for the detection of lysosomal viscosity in hepatocytes and mice during HIRI. A reactive oxygen species-malondialdehyde-cathepsin B signaling pathway during HIRI was established. We further conducted high signal-to-background ratio NIR-II fluorescence imaging of HIRI mice. The contour and boundary of liver lesions were delineated, and as such the precise intraoperative resection of the lesion area was implemented. This research demonstrates the potential of NP-V as a dual-functional probe for the elucidation of HIRI pathogenesis and the direct navigation of HIRI lesions in clinical applications.

Susceptibility-Weighted MRI as an Imaging Marker for Reperfusion Injury in Acute Ischemic Stroke Following Mechanical Thrombectomy.

Background/Purpose: Following endovascular intervention for stroke, hyperattenuated areas are common in brain parenchyma and it is difficult to differentiate on non-contrast CT whether it is contrast staining or reperfusion hemorrhage. Differentiation between contrast staining from reperfusion hemorrhage is of paramount importance for early initiation of antiplatelets and/or anticoagulants to prevent reocclusion of vessel. This study demonstrates signal characteristics of contrast-staining and reperfusion hemorrhage on susceptibility weighted MRI and its role to differentiate between two. Materials/Methods: Between July 2017 to March 2019, 36 patients who presented with acute ischemic stroke due to large vessel occlusion underwent mechanical thrombectomy. Low-osmolar non-ionic (Iopromide 300 mg/L) iodinated contrast was used in all patients who underwent endovascular intervention. All patients underwent noncontrast CT brain and SWI on 3T MRI within 30 minutes of endovascular intervention. MRI was evaluated by two neuroradiologists. Reperfusion hemorrhage was defined as ECASS criteria II. Symptomatic ICH was defined as hemorrhagic transformation temporally related to a negative shift in NIHSS score >/=4. Results: Out of 36 patients, 15 had hyperattenuated areas in brain on NCCT. Out of 15, 13 patients had blooming on SWI, suggestive of bleed. Two patients had no blooming on SWI, suggestive of contrast staining. Two patients didnot show any hyperdensity on NCCT but blooming on SWI, suggestive of bleed. Conclusion: All patients with hyperdensity on NCCT secondary to bleed showed blooming on SWI whereas those with contrast staining didnot show any signal changes on SWI. Thus, it is possible to differentiate reperfusion hemorrhage from contrast staining using SWI MRI. The significance of SWI in normal CT may be low where a small bleed maynot have any clinical significance.