Autofocus Fourier single-pixel microscopy.

Single-pixel microscopy enables observation of micro samples in invisible wave bands. Finding the focus position is essential to capture a clear image of a sample but could be difficult for single-pixel microscopy particularly in invisible wave bands. It is because the structured patterns projected onto the sample would be invisible and searching for the focus position manually could be exhausting. Here, we report an autofocus method for Fourier single-pixel microscopy. The reported method allows one to find the focus position without recording or reconstructing a complete image. The focus position is determined by the magnitude summation of a small number of Fourier coefficients, which enables fast autofocus. The reported method is experimentally demonstrated in imaging various objects in both visible and near-infrared wave bands. The method adds practicability to a single-pixel microscopy.

Image-free active autofocusing with dual modulation and its application to Fourier single-pixel imaging.

Autofocusing is widely used in applications where sharp image acquisition or projection is needed. Here we report an active autofocusing method for sharp image projection. The method works with wide-field structured illumination and single-pixel detection. To find the focus position, the method illuminates the target object with a set of 3-step phase-shifting Fourier basis patterns repeatedly and collects the backscattered light by using a single-pixel detector through a grating. Dual modulation-dynamic modulation by the time-varying structured illumination and static modulation by the grating-embeds the depth information for the target object in the resulting single-pixel measurements. As such, the focus position can be determined by recovering the Fourier coefficients from the single-pixel measurements and searching for the coefficient with the maximum magnitude. High-speed spatial light modulation not only enables rapid autofocusing but also makes the method work even when the lens system is in continuous motion or the focal length of the lens is continuously adjusted. We experimentally validate the reported method in a self-built digital projector and demonstrate the application of the method in Fourier single-pixel imaging.

Leveraging a disulfidptosis/ferroptosis-based signature to predict the prognosis of lung adenocarcinoma.

BACKGROUND: Disulfidptosis and Ferroptosis are two novel forms of cell death. Although their mechanisms differ, research has shown that there is a relationship between the two. Investigating the connection between these two forms of cell death can further deepen our understanding of the development and progression of cancer, and provide better prediction models for accurate prognosis. METHODS: In this study, RNA sequencing (RNA-seq) data, clinical data, single nucleotide polymorphism (SNP) data, and single-cell sequencing data were obtained from public databases. We used weighted gene co-expression network analysis (WGCNA) and unsupervised clustering to identify new Disulfidptosis/Ferroptosis-Related Genes (DFRG), and constructed a LASSO COX prognosis model that was externally validated. To further explore this novel signature, pathway and function analysis was performed, and differences in gene mutation frequency between high- and low-risk groups were studied. Importantly, we also conducted research on immune checkpoint, immune cell infiltration levels and immune resistance indicators, in addition to analyzing real clinical immunotherapy data. RESULTS: We have identified four optimal disulfidptosis/ferroptosis-related genes (ODFRGs) that are differentially expressed and associated with the prognosis of Lung Adenocarcinoma (LUAD). These genes include GMPR, MCFD2, MRPL13, and SALL2. Based on these ODFRGs, we constructed a robust prognostic model in this study, and the high-risk group showed significantly lower overall survival (OS) compared to the low-risk group. Furthermore, this model can also predict the immunotherapy outcomes of LUAD patients to some extent.

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.

The incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal diseases, this review focuses on understanding the contribution of ion channels/transporters to protecting the GI mucosal barrier and the relationship between GI mucosal disease and ion channels/transporters, including Cl-/HCO3- exchangers, Cl- channels, aquaporins, Na+/H+ exchangers, and K+ channels. Here, we provide novel prospects for the treatment of GI mucosal diseases.

Total-body 18F-FDG PET/CT scan in oncology patients: how fast could it be?

PURPOSE: The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. METHODS: A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3 min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). RESULTS: In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). CONCLUSIONS: This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.

SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

Gastric immune homeostasis imbalance: An important factor in the development of gastric mucosal diseases.

The gastric mucosal immune system is a unique immune organ independent of systemic immunity that not only maintains nutrient absorption but also plays a role in resisting the external environment. Gastric mucosal immune disorder leads to a series of gastric mucosal diseases, including autoimmune gastritis (AIG)-related diseases, Helicobacter pylori (H. pylori)-induced diseases, and various types of gastric cancer (GC). Therefore, understanding the role of gastric mucosal immune homeostasis in gastric mucosal protection and the relationship between mucosal immunity and gastric mucosal diseases is very important. This review focuses on the protective effect of gastric mucosal immune homeostasis on the gastric mucosa, as well as multiple gastric mucosal diseases caused by gastric immune disorders. We hope to offer new prospects for the prevention and treatment of gastric mucosal diseases.

The mechanisms of gastric mucosal injury: focus on initial chief cell loss as a key target.

Diffuse gastric mucosal injury is a chronic injury with altered cell differentiation, including spasmolytic polypeptide expression metaplasia (SPEM) and intestinal metaplasia (IM), which are considered precancerous lesions of gastric cancer (GC). Previously, most studies have focused on how parietal cell loss causes SPEM through transdifferentiation of chief cells. In theory, alteration or loss of chief cells seems to be a secondary phenomenon due to initial partial cell loss. However, whether initial chief cell loss causes SPEM needs to be further investigated. Currently, increasing evidence shows that initial chief cell loss is sufficient to induce gastric mucosal injury, including SPEM and IM, and ultimately lead to GC. Therefore, we summarized the two main types of models that explain the development of gastric mucosal injury due to initial chief cell loss. We hope to provide a novel perspective for the prevention and treatment of diffuse gastric mucosal injury.

Role of spasmolytic polypeptide-expressing metaplasia in gastric mucosal diseases.

Spasmolytic polypeptide-expressing metaplasia (SPEM) is a trefoil factor 2-expressing metaplasia in the fundic glands that resembles the fundic metaplasia of deep antral glandular cells and arises mainly from transdifferentiation of mature chief cells as well as mucous neck cells or isthmic stem cells. SPEM participates in the regulation of gastric mucosal injury, including focal and diffuse injury. This review focuses on the origin, models, and regulatory mechanisms of SPEM and on its role in the development of gastric mucosal injury. We hope to provide new prospects for the prevention and treatment of gastric mucosal diseases from the perspective of cell differentiation and transformation.

Adaptive synthetic-aperture focusing technique for microvasculature imaging using photoacoustic microscopy.

To improve the lateral resolution of the blood vessels along arbitrary direction out of focus in photoacoustic microscopy (PAM), we propose an adaptive synthetic-aperture focusing technique (ASAFT) for microvasculature imaging which can be automatically applied to each branch of blood vessels, based on our previous two-dimensional (2D) SAFT. The ASAFT is validated both in the phantom study and in vivo imaging. The results demonstrate that ASAFT can provide images of blood vessels with better lateral resolution both at different depths and along various directions compared with one-dimensional and 2D SAFT.

Expression alteration and dysfunction of ion channels/transporters in the parietal cells induces gastric diffused mucosal injury.

Gastric mucosal injuries include focal and diffused injuries, which do and do not change the cell differentiation pattern. Parietal cells loss is related to the occurrence of gastric mucosal diffused injury, with two phenotypes of spasmolytic polypeptide-expressing metaplasia and neuroendocrine cell hyperplasia, which is the basis of gastric cancer and gastric neuroendocrine tumor respectively. Multiple ion channels and transporters are located and expressed in the parietal cells, which is not only regulate the gastric acid-base homeostasis, but also regulate the growth and development of parietal cells. Therefore, alteration and dysregulation of ion channels and transporters in the parietal cells impairs the morphology and physiological functions of stomach, resulted in gastric diffused mucosal damage. In this review, multiple ion channels and transporters in parietal cells, including K+ channels, aquaporins, Cl- channels, Na+/H+ transporters, and Cl-/HCO3- transporters are described, and their roles in gastric diffused mucosal injury are discussed. We hope to drive researcher's attention to focus on the role of ion channels/transporters loss in the parietal cells induced gastric diffused mucosal injury.

The outcomes of acute myocardial infarction patients comorbidity with hypertension and hyperhomocysteinemia.

This study investigated the outcomes and major adverse cardiovascular events (MACEs) incurred by acute myocardial infarction (AMI) patients comorbiding with hypertension and hyperhomocysteinemia (HHcy) during hospitalization and 1-year follow-up. 648 consecutive AMI patients were divided into four categories: (1) hypertension with Hcy ≥ 15 µmol/L; (2) hypertension with Hcy < 15 µmol/L; (3) no-hypertension with Hcy ≥ 15 µmol/L; (4) no-hypertension with Hcy < 15 µmol/L. Information taken from these case files included gender, past medical history, vital signs, laboratory examination, electrocardiogram, coronary angiography, cardiac ultrasound, and medicine treatment. The primary endpoints were duration of coronary care units (CCU) stay, duration of in-hospital stay, and MACEs during follow-up. Our data show that hypertension and HHcy have a synergistic effect in AMI patients, AMI comorbiding with hypertension and HHcy patients had more severe multi-coronary artery disease and more frequent non-culprit coronary lesions complete clogging, had a higher prevalence of pro-brain natriuretic peptide, and significant decreases in the left ventricular ejection fraction. These patients had significant increases in the duration of CCU stay and in-hospital stay, had significant increase in the rate of MACEs, had significant decreases in the survival rate during follow-up.

Role of the posterior mucosal defense barrier in portal hypertensive gastropathy.

Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER.

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of 18F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the 18F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging.

[Micro-CT system based on the flat panel detector for small animal imaging].

A high resolution Micro-CT system for small animal imaging is introduced in this paper. Micro-focus X-ray tube with focal diameter of 100 microm and flat panel detector with imaging area of 13cm x 13cm are adopted in this system. The data acquired in rotation scanning is reconstructed with cone beam algorithm. The resolving power of the detector is measured to be 31 lp/cm at 10% of the MTF. The resolution of the Micro-CT system could achieve 185 m when the magnification factor is 1.94. Thighbone of a rabbit is used as sample imaging with the system. The trabecular bone could be imaged clearly. And the ability of small animal imaging of the system has been demonstrated.

Integrated Histotripsy and Bubble Coalescence Transducer for Thrombolysis.

After the collapse of a cavitation bubble cloud, residual microbubbles can persist for up to seconds and function as weak cavitation nuclei for subsequent pulses in a phenomenon known as cavitation memory effect. In histotripsy, the cavitation memory effect can cause bubble clouds to repeatedly form at the same discrete set of sites. This effect limits the efficacy of histotripsy-based tissue fractionation. Our previous studies have indicated that low-amplitude bubble-coalescing (BC) ultrasound sequences interleaved with high-amplitude histotripsy pulses can coalesce the residual bubbles into one large bubble quickly. This reduces the cavitation memory effect and may increase treatment efficacy. Histotripsy has been investigated for thrombolysis by breaking up clots into debris smaller than red blood cells. However, this treatment has low efficacy for aged or retracted clots. In this study, we investigate the use of histotripsy with BC to improve the efficacy of treatment of retracted clots. An integrated histotripsy and bubble-coalescing (HBC) transducer system with specialized electronic driving system was built in-house. One high-amplitude (32 MPa), one-cycle histotripsy pulse followed by 36 low-amplitude (2.4 MPa), one-cycle BC pulses formed one HBC sequence. Results indicate that HBC sequences successfully generated a flow channel through the retracted clots at scan speeds of 0.2-0.5 mm/s. The channel size created using the HBC sequence was 128% to 480% larger than that created using histotripsy alone. The clot debris particles generated during HBC treatments were within the tolerable range. These results illustrate the concept that BC improves the treatment efficacy of histotripsy thrombolysis for retracted clots.

In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy.

Stroke is a devastating disease. The changes in cerebral hemodynamics and oxygen metabolism associated with stroke play an important role in pathophysiology study. But the changes were difficult to describe with a single imaging modality. Here the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen saturation (SO2) were yielded with laser speckle imaging (LSI) and photoacoustic microscopy (PAM) during and after 3-h acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF). The results indicate that all the hemodynamics except CBV had rapid declines within 40-min occlusion of middle cerebral artery (MCAO). CBV in arteries and veins first increased to the maximum value of 112.42 ± 36.69% and 130.58 ± 31.01% by 15 min MCAO; then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic. When ischemia lasted for 3 h, CBF in arteries, veins decreased to 17 ± 14.65%, 24.52 ± 20.66%, respectively, CBV dropped to 62 ± 18.56% and 59 ± 18.48%. And the absolute SO2 decreased by 40.52 ± 22.42% and 54.24 ± 11.77%. After 180-min MCAO, the changes in hemodynamics and oxygen metabolism were also quantified. The study suggested that combining LSI and PAM provides an attractive approach for stroke detection in small animal studies.

Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy.

Because cerebral hypoperfusion brings damage to the brain, prevention of cerebrovascular diseases correlative to hypoperfusion by studying animal models makes great sense. Since complicated cerebrovascular adaptive changes in hypoperfusion could not be revealed only by cerebral blood flow (CBF) velocity imaging, we performed multi-parameter imaging by combining laser speckle imaging and functional photoacoustic microscopy. The changes in CBF, hemoglobin oxygen saturation (SO(2)), and total hemoglobin concentration (HbT) in single blood vessels of ipsilateral cortex were observed during transient cerebral hypoperfusion by ligating the unilateral common carotid artery in rats. CBF, SO(2), and HbT, respectively, decreased to 37 ± 3%, 71 ± 7.5%, and 92 ± 1.3% of baseline in 6 s immediately after occlusion, and then recovered to 77 ± 4.8%, 84 ± 8%, and 96 ± 2% of baseline in 60 s. These parameters presented the decrease with different degree and the following recovery over time after ligation, the recovery of SO(2) lagged behind those of CBF and HbT, which had the similar response. The results demonstrated that complete monitoring of both cerebral hemodynamic response and oxygen metabolic changes occurred at the earliest period of cerebral hypoperfusion was possible by using the two image modalities with high temporal and spatial resolution.