Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

Adhesion molecule-targeted magnetic particle imaging nanoprobe for visualization of inflammation in acute lung injury.

PURPOSE: Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. METHODS: ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. RESULTS: The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial MagImaging® and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1ß, R > 0.7). CONCLUSION: ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation.

[Melatonin alleviates autophagy in cortical neurons of neonatal rats with hypoxic- ischemic brain damage via the PI3K/AKT pathway]. / è¤ªé»‘ç´ é€šè¿‡PI3K/AKTé€šè·¯å‡è½»ç¼ºæ°§ç¼ºè¡€æ€§è„‘æŸä¼¤æ–°ç”Ÿå¤§é¼ å¤§è„‘çš®å±‚ç¥žç»ç»†èƒžè‡ªå™¬çš„ç ”ç©¶.

OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.

Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 BA versus the current routine care. SUMMARY BACKGROUND DATA: Whether steroid therapy post-Kasai portoen-terostomy improves the outcomes of BA remains controversial. Clinical evidence from 2 randomized trials in the UK and USA do not support the routine use of steroid in the treatment of BA. METHODS: In this open-label randomized controlled trial, patients with type 3 BA were randomized to routine postoperative treatment with or without 10 to 12 weeks of adjuvant steroid treatment. The primary outcome was the postoperative jaundice clearance rate with native liver at 6 months. The secondary outcomes included postoperative jaundice clearance rate at 3, 12, and 24 months, survival with native liver at 12 and 24 months, and SAEs within 3 months. RESULTS: Overall, 200 participants were randomized and allocated into either steroid or control group (n = 100/group). The proportion of participants that are jaundice free without liver transplantation was significantly higher in the steroid group than in the control group at 6 months (54.1% vs 31.0%, P = 0.0015). The native liver survival rate was higher postoperatively in the steroid group than in the control group at 12 (66.3% vs 50.0%, P = 0.02) and 24 (57.1% vs 40.0%, P = 0.02) months. The survival time with native liver was significantly longer in the steroid group than in the control group (median survival, steroid vs control: not reached vs 1.21 years, P = 0.02). There were no significant differences between the 2 groups in the mean occurrence of SAEs within 3 months (steroid vs control: 0.63 vs 0.45, P = 0.20). CONCLUSIONS: Postoperative adjuvant steroid intervention improved bile drainage and survival with native liver in type 3 BA patients, without increasing early-stage SAEs.

Colourful fluorescence-based carbon dots for tumour imaging-guided nanosurgery.

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields.

[The TXNIP/Trx-1/GPX4 pathway promotes ferroptosis in hippocampal neurons after hypoxia-ischemia in neonatal rats]. / TXNIP/Trx-1/GPX4é€šè·¯ä¿ƒè¿›æ–°ç”Ÿå¤§é¼ ç¼ºæ°§ç¼ºè¡€åŽæµ·é©¬ç¥žç»å ƒé“æ­»äº¡çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe the change in ferroptosis in hippocampal neurons after hypoxia-ischemia (HI) in neonatal rats and investigate the related mechanism based on the TXNIP/Trx-1/GPX4 signaling pathway. METHODS: Healthy neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into three groups: sham-operation (n=30), hypoxic-ischemic brain damage (HIBD) (n=30) and siRNA (TXNIP siRNA) (n=12). The classic Rice-Vannucci method was used to establish a neonatal rat model of HIBD. At 6 hours, 24 hours, 72 hours, and 7 days after modeling, Western blot was used to measure the protein expression of GPX4 in the hippocampal tissue at the injured side; at 24 hours after modeling, laser speckle imaging combined with hematoxylin-eosin staining was used to determine whether the model was established successfully; NeuN/GPX4 and GFAP/GPX4 immunofluorescence staining combined with Western blot and other methods was used to measure the protein expression of GPX4 and the signal molecules TXNIP and Trx-1 in the hippocampal tissue at the injured side; the kits for determining the content of serum iron and tissue iron were used to measure the change in iron content; quantitative real-time PCR was used to measure the mRNA expression of TXNIP, Trx-1, and GPX4. RESULTS: At 6 hours, 24 hours, 72 hours, and 7 days after modeling, the HIBD group had a significantly lower protein expression level of GPX4 than the sham-operation group (P<0.05). At 24 hours after modeling, the HIBD group had a significantly lower cerebral blood flow of the injured side than the sham-operation group (P<0.05), with loose and disordered arrangement and irregular morphology of hippocampal CA1 neurons at the injured side. Compared with the sham-operation group, the HIBD group had a significantly higher number of TXNIP+ cells and significantly lower numbers of Trx-1+ cells and NeuN+GPX4+/NeuN+ cells in the hippocampal CA1 region at the injured side (P<0.05), with almost no GFAP+GPX4+ cells in the hippocampal CA1 region. Compared with the sham-operation group, the HIBD group and the siRNA group had significantly higher levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). Compared with the HIBD group, the siRNA group had significantly lower levels of serum iron and tissue iron in the hippocampus at the injured side (P<0.05). The HIBD group and the siRNA group had significantly higher mRNA and protein expression levels of TXNIP than the sham-operation group (P<0.05), and the siRNA group had significantly lower expression levels than the HIBD group (P<0.05). The HIBD group and the siRNA group had significantly lower mRNA and protein expression levels of Trx-1 and GPX4 in the hippocampus at the injured side than the sham-operation group (P<0.05), and the siRNA group had significantly higher expression levels than the HIBD group (P<0.05). CONCLUSIONS: HI induces ferroptosis of hippocampal neurons in neonatal rats by activating the TXNIP/Trx-1/GPX4 pathway, thereby resulting in HIBD.

Improving spatial resolution with an edge-enhancement model for low-dose propagation-based X-ray phase-contrast computed tomography.

Propagation-based X-ray phase-contrast computed tomography (PB-PCCT) has been increasingly popular for distinguishing low contrast tissues. Phase retrieval is an important step to quantitatively obtain the phase information before the tomographic reconstructions, while typical phase retrieval methods in PB-PCCT, such as homogenous transport of intensity equation (TIE-Hom), are essentially low-pass filters and thus improve the signal to noise ratio at the expense of the reduced spatial resolution of the reconstructed image. To improve the reconstructed spatial resolution, measured phase contrast projections with high edge enhancement and the phase projections retrieved by TIE-Hom were weighted summed and fed into an iterative tomographic algorithm within the framework of the adaptive steepest descent projections onto convex sets (ASD-POCS), which was employed for suppressing the image noise in low dose reconstructions because of the sparse-view scanning strategy or low exposure time for single phase contrast projection. The merging strategy decreases the accuracy of the linear model of PB-PCCT and would finally lead to the reconstruction failure in iterative reconstructions. Therefore, the additive median root prior is also introduced in the algorithm to partly increase the model accuracy. The reconstructed spatial resolution and noise performance can be flexibly balanced by a pair of antagonistic hyper-parameters. Validations were performed by the established phase-contrast Feldkamp-Davis-Kress, phase-retrieved Feldkamp-Davis-Kress, conventional ASD-POCS and the proposed enhanced ASD-POCS with a numerical phantom dataset and experimental biomaterial dataset. Simulation results show that the proposed algorithm outperforms the conventional ASD-POCS in spatial evaluation assessments such as root mean square error (a ratio of 9.78%), contrast to noise ratio (CNR) (a ratio of 7.46%), and also frequency evaluation assessments such as modulation transfer function (a ratio of 66.48% of MTF50% (50% MTF value)), noise power spectrum (a ratio of 35.25% of f50% (50% value of the Nyquist frequency)) and noise equivalent quanta (1-2 orders of magnitude at high frequencies). Experimental results again confirm the superiority of proposed strategy relative to the conventional one in terms of edge sharpness and CNR (an average increase of 67.35%).

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Preventive effect of prophylactic intravenous antibiotics against cholangitis in biliary atresia: a randomized controlled trial.

OBJECTIVE: Biliary atresia (BA) is a neonatal liver disease and requires Kasai portoenterostomy. Many patients develop postoperative cholangitis, resulting in a poor prognosis. The preventive strategy of antibiotics is empirical and lacks a standard regimen. We aimed to analyze the effect of different durations of prophylactic intravenous antibiotics against post-Kasai cholangitis. STUDY DESIGN: A single-center, open-labeled, randomized clinical trial was performed from June 2016 to August 2017. One hundred and eighty BA patients were recruited and randomized into a short-term (n = 90) and a long-term (n = 90) treatment group, and prophylactic intravenous antibiotics were used for 7 versus 14 days, respectively. The primary outcome was the overall cholangitis incidence within 6-months post-Kasai portoenterostomy. The secondary outcomes included cholangitis incidence within 1 and 3 months post-Kasai portoenterostomy, the onset and average episodes of cholangitis, jaundice clearance rate, native liver survival rate, and adverse events within 6-months post-Kasai portoenterostomy. RESULTS: The cholangitis incidence within 6-months post-Kasai in the short-term group was similar to the long-term group (62% vs. 70%, p = 0.27) with intention-to-treat and pre-protocol analysis. There was no significant difference in jaundice clearance rate or native liver survival rate between the two groups. However, the percentage of early onset (61% vs. 38%, p = 0.02) and average episodes (2.4 ± 0.2 vs. 1.8 ± 0.1 episodes, p = 0.01) of cholangitis were lower in the long-term group. CONCLUSION: Long-term intravenous antibiotics can be replaced by the short-term regimen in the general protection against post-Kasai cholangitis.

Gut microbial profile in biliary atresia: a case-control study.

BACKGROUND AND AIM: Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case-control study to investigate the gut microbiota in BA. METHODS: A cross-sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2 weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra-high performance liquid chromatography. RESULTS: Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate-producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. CONCLUSIONS: Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

A Kalman-based tomographic scheme for directly reconstructing activation levels of brain function.

In functional near-infrared spectroscopy (fNIRS), the conventional indirect approaches first separately recover the spatial distribution of the changes in the optical properties at every time point, and then extract the activation levels by a time-course analysis process at every site. In the tomographic implementation of fNIRS, i.e., diffuse optical tomography (DOT), these approaches not only suffer from the ill-posedness of the optical inversions and error propagation between the two successive steps, but also fail to achieve satisfactory temporal resolution due to the requirement for a complete data set. To cope with the above adversities of the indirect approaches, we propose herein a direct approach to tomographically reconstructing the activation levels by incorporating a Kalman scheme. Dynamic simulative and phantom experiments were conducted for the performance validation of the proposed approach, demonstrating its potentials to improve the calculated images and to relax the speed limitation of the instruments.

Gold-nanorod-enhanced Raman spectroscopy encoded micro-quartz pieces for the multiplex detection of biomolecules.

The rapid analysis and detection of biomolecules has become increasingly important in biological research. Hence, here we propose a novel suspension array method that is based on gold nanorod (AuNR)-enhanced Raman spectroscopy and uses micro-quartz pieces (MQPs) as microcarriers. AuNRs and Raman reporter molecules are coupled together by Au-S bonds to obtain surface-enhanced Raman scattering labels (SERS labels). The SERS labels are then assembled on the surfaces of the MQPs via electrostatic interactions, yielding encoded MQPs. Experimental results showed that the encoded MQPs could be decoded using a Raman spectrometer. A multiplex immunoassay experiment demonstrated the validity and specificity of these encoded MQPs when they were used for bioanalysis. In concentration gradient experiments, the proposed method was found to give a linear concentration response to the target biomolecule at target concentrations of 0.46875-30 nM, and the detection limit was calculated to be 1.78 nM. The proposed method utilizes MQPs as carriers rather than conventional microbeads, which allows the interference caused by the background fluorescence of microbeads to be eliminated. The fluorescence of the encoded MQPs can be simply, rapidly, and inexpensively quantified using fluorescence microscopy. By dividing the quantitative and qualitative detection of biomolecules into two independent channels, crosstalk between the encoded signal and the labeled signal is averted and high decoding accuracy and detection sensitivity are guaranteed. Graphical abstract.

Investigation on the Dependency of Phase Retrieval Accuracy Versus Edge Enhancement to the Noise Ratio of X-ray Propagation-Based Phase-Contrast Imaging.

Phase retrieval is necessary for propagation-based phase-contrast imaging (PB-PCI). Arhatari established a model for predicting the impact of the sample-to-detector distance and the system noise on the phase retrieval performance. We have extended Arhatari's model to account for the parameters of excessive source size, finite detector resolution, and geometrical magnification for more practical cases. However, there exist interaction effects among these parameters resulting in difficulty of predicting the phase retrieval performance. In this study, we found that optimizing the trade-off among these parameters for phase retrieval is consistent with the improvement of edge enhancement to noise ratio (EE/N) in the "forward problem" of the PB-PCI. Hence, we engaged in establishing a relationship between EE/N and phase retrieval performance in terms of the "forward problem" and "inverse problem" of the PB-PCI, respectively. Our results showed that, at fixed detector resolution, phase retrieval from the phase-contrast projections at the same EE/N level resulted in the consistent phase retrieval performance. Therefore, the performance of phase retrieval can be predicted based on the EE/N level and be quantitatively optimized by increasing EE/N.

Determination of optical properties of turbid medium from relative interstitial CW radiance measurements using the incomplete P3 approximation.

Interstitial determination of the tissue optical properties is important in biomedicine, especially for interstitial laser therapies. Continuous wave (CW) radiance techniques which examine light from multiple directions have been proposed as minimally invasive methods for determining the optical properties under an interstitial probe arrangement. However, both the fitting algorithm based on the P3 approximation and the analytical method based on the diffusion approximation (DA), which are currently used recovery algorithms, cannot extract the optical properties of tissue with low transport albedos accurately from radiance measurements. In this paper, we proposed an incomplete P3 approximation for the radiance, the P3in for short, which is the asymptotic part of the solution for the P3 approximation. The relative differences between the P3in and the P3 were within 0.48% over a wide range of clinically relevant optical properties for measurements at source detector separations (SDS) from 5 mm to 10 mm and angles from 0° to 160°. Based on the P3in, we developed an analytical method for extracting the optical properties directly using simple expressions constructed from the radiance measurements at only two SDSs and four angles. The developed recovery algorithm was verified by simulated and experimental radiance data. The results show that both the absorption and reduced scattering coefficients were recovered accurately with relative errors within 5.28% and 3.86%, respectively, from the simulated data and with relative errors within 10.82% and 10.67%, respectively, from the experimental data over a wide range of albedos from 0.5 to 0.99. Since the developed P3in-based radiance technique can obtain the optical properties rapidly from the measurements at only two SDSs and four angles, it is expected to be used for in vivo and in situ determination of the optical properties in online treatment planning during laser therapies.

[The Research on Measurement System and Method of Tissue Optical Parameters with Wide Spectra Based on Double-Integrating-Spheres].

The measurement of tissue optical parameters is the focusing research content of Biomedical Photonics. The optical properties of human tissue are closely related to the physiological and pathological state. In recent years, the tissue imaging diagnosis and non-invasive detection of componentsbecome the hot research topics, applying the tissue optical properties especially the absorption and scattering properties. These provide the basis for the study of optical imaging and the spectrum detection of body composition etc. The Double-Integrating-Spheres (DIS) method can measure the absorption coefficient, scattering coefficient and so on in vitro tissuesimultaneously. It has the advantages of accurate, rapid, large applicable scope. The method applya standard method for measuring the optical parameters. This paper build the wide spectrum measurement system of optical parameters based on DIS and super continuum lasers. Then we analyze the transfer function, error sources and the best measuring conditions of the system. Finally we establish the correction forward model based on BP-MCML and the inverse algorithm of the optical parameters based on L-M algorithm. The optical parameters of intralipid solution in the wavelength range of 1,100~1,400 nm are measured. The experiment results show that the improved inverse algorithm is accurate. The multiple measurements standard deviation is within 3%. Compared the results of scattering coefficient and absorption coefficient at different wavelengths to the results of other research groups, the deviation is less than 3.4%.

Quantitative assessment of the effect of cholesterol on blood glucose measurement using near infrared spectroscopy and a method for error reduction.

BACKGROUND AND OBJECTIVE: There is a growing body of evidence suggesting that the accurate measurement of blood glucose concentration can be perturbed by many factors. Current literature is limited in describing the influence of cholesterol on non-invasive blood glucose measurements by near-infrared spectroscopy (NIRS). This study aims to investigate the influence of cholesterol on blood glucose measurement through clinical oral glucose tolerance test (OGTT) and NIRS. Further, a method to reduce the prediction errors induced by cholesterol is proposed, facilitating the clinical application of non-invasive blood glucose sensing by NIRS. STUDY DESIGN/MATERIAL AND METHODS: We obtained clinical data of glucose and cholesterol concentrations at specific time points (0, 0.5, 1, 2, and 3 h) during OGTTs from 115 subjects. The subjects were grouped into: Norm for normal control, IGT for Impaired Glucose Tolerance, and Diabetes. In addition, spectral data between 1200 and 1800 nm were collected from 130 phantom samples, which are separated into seven groups depending on glucose and cholesterol levels. Statistical methods including One Sample T-test (OSTT), Pearson Correlation Analysis(PCA), and Unary Linear Regression (ULR) were used to analyze clinical data and spectral data to determine the relationship between glucose and cholesterol concentrations with the time course of OGTT. Reference wavelength-based method (RWM) was introduced to diminish the influence of cholesterol on glucose measurement and further the prediction error induced by cholesterol was reduced when using partial least square (PLS) model. RESULTS: Clinical results statistically show that there is a strong negative correlation between the changes of glucose and cholesterol concentrations in the diabetes group. The spectra of cholesterol exhibit similar absorbance peaks to those of glucose within NIR range. PLS modelling results demonstrate that glucose prediction is influenced by cholesterol concentrations in a calibration model. Furthermore, a model expression (ΔCg=0.0356Cc+1.0129 R(2) = 0.993) is fitted to quantitatively describe the glucose prediction increment (ΔCg) due to cholesterol concentration (Cc). The results show that glucose prediction accuracy can be improved up to 38.36% by using RWM when using NIRS. CONCLUSIONS: The cholesterol has an effect on blood glucose sensing. RWM is useful to help realize non-invasive blood glucose sensing by NIRS.

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung.

Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.

Clinical Characteristics and Prognosis of Biliary Atresia with Low Serum Matrix Metalloproteinase-7 Levels.

PURPOSE: Serum matrix metalloproteinase-7 (MMP-7) levels can precisely differentiate biliary atresia (BA) from non-BA cholestasis. However, serum MMP-7 levels of some BA patients were within normal range or slightly elevated. This study aimed to investigate the clinical characteristics and prognosis of biliary atresia with low serum MMP-7 levels. METHOD: This is a retrospective cohort study. Cases of BA from July 2020 to December 2022 were consecutively enrolled. They were divided into low-MMP-7 group (MMP-7 ≤ 25 ng/ml) and high-MMP-7 group (MMP-7 > 25 ng/ml) according to serum MMP-7 levels preoperatively. The perioperative clinical characteristics, the 3-month and 6-month jaundice clearance rate post-Kasai procedure, and the native liver survival were compared between the two groups. RESULTS: A total of 329 cases were included in this study, 40 of which were divided into the low-MMP-7 group. Preoperative GGT and direct bilirubin levels in the low-MMP-7 group were significantly lower than those in the high-MMP-7 group (258.6 U/L, interquartile range [IQR]: 160.4411.6 vs. 406.8 IU/L, IQR: 215,655.0, P = 0.0076; 103.8 µmol/L, IQR: 79.0,121.4 vs. 115.3 µmol/L, IQR: 94,138.8, P = 0.0071), while the gender, the day at surgery and preoperative ALT, AST, TBA, total bilirubin levels showed no significant differences (P > 0.05). The 3-month and 6-month jaundice clearance rate post-Kasai procedure in the low-MMP-7 group were lower than those in the high-MMP-7 group (29.73% vs. 53.09%, P = 0.049; 32.14% vs. 54.73%, P = 0.023). The 1-year native liver survival rate was 29.63% for the low-MMP-7 group and 53.02% for the high-MMP-7 group (P = 0.022). CONCLUSION: Preoperative clinical characteristics were similar between low-MMP-7 group and high-MMP-7 group, while patients with low serum MMP-7 levels showed worse prognosis, indicating that this might be listed as a new clinical subtype of BA which could contribute to designing new treatment strategies for BA in the future. STUDY TYPE: Cohort Study. LEVEL OF EVIDENCE: Level II.

Progress in Biomarkers Related to Biliary Atresia.

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

PGNet: Projection generative network for sparse-view reconstruction of projection-based magnetic particle imaging.

BACKGROUND: Magnetic particle imaging (MPI) is a novel tomographic imaging modality that scans the distribution of superparamagnetic iron oxide nanoparticles. However, it is time-consuming to scan multiview two-dimensional (2D) projections for three-dimensional (3D) reconstruction in projection MPI, such as computed tomography (CT). An intuitive idea is to use the sparse-view projections for reconstruction to improve the temporal resolution. Tremendous progress has been made toward addressing the sparse-view problem in CT, because of the availability of large data sets. For the novel tomography of MPI, to the best of our knowledge, studies on the sparse-view problem have not yet been reported. PURPOSE: The acquisition of multiview projections for 3D MPI imaging is time-consuming. Our goal is to only acquire sparse-view projections for reconstruction to improve the 3D imaging temporal resolution of projection MPI. METHODS: We propose to address the sparse-view problem in projection MPI by generating novel projections. The data set we constructed consists of three parts: simulation data set (including 3000 3D data), four phantoms data, and an in vivo mouse data. The simulation data set is used to train and validate the network, and the phantoms and in vivo mouse data are used to test the network. When the number of novel generated projections meets the requirements of filtered back projection, the streaking artifacts will be absent from MPI tomographic imaging. Specifically, we propose a projection generative network (PGNet), that combines an attention mechanism, adversarial training strategy, and a fusion loss function and can generate novel projections based on sparse-view real projections. To the best of our knowledge, we are the first to propose a deep learning method to attempt to overcome the sparse-view problem in projection MPI. RESULTS: We compare our method with several sparse-view methods on phantoms and in vivo mouse data and validate the advantages and effectiveness of our proposed PGNet. Our proposed PGNet enables the 3D imaging temporal resolution of projection MPI to be improved by 6.6 times, while significantly suppressing the streaking artifacts. CONCLUSION: We proposed a deep learning method operated in projection domain to address the sparse-view reconstruction of MPI, and the data scarcity problem in projection MPI reconstruction is alleviated by constructing a sparse-dense simulated projection data set. By our proposed method, the number of acquisitions of real projections can be reduced. The advantage of our method is that it prevents the generation of streaking artifacts at the source. Our proposed sparse-view reconstruction method has great potential for application to time-sensitive in vivo 3D MPI imaging.