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CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients’ CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Precis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts

No studies have reported the isolation of serotype Salmonella Isangi from cases of salmonellosis in mainland China. We investigated an outbreak of foodborne disease with salmonella and collected the samples from the patients and surplus foods. Salmonella strains were isolated and the serotype was identified according to the Kauffmann-White scheme. The relatedness of the isolates was determined using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Antimicrobial susceptibility was conducted by the broth microdilution method. There were 74 diners in the case, 33 of which got ill, with an attack rate of 44.6% (33/74). A total of 24 samples were collected from the outbreak cases, six Salmonella Isangi strains were isolated and susceptible to all tested drugs. PFGE and WGS analysis suggested that the pathogen dissemination through a single or limited vector(s), the steamed fish and mixed food (fry spicy chicken, braised pork ribs, and goose leg), may be the source of infection or be cross-contaminated. We first report the characteristics of an outbreak and molecular strain relatedness of Salmonella Isangi in mainland China.

The performance and diagnostic utility of magnetic resonance imaging (MRI) in pregnancy is fundamentally constrained by fetal motion. Motion of the fetus, which is unpredictable and rapid on the scale of conventional imaging times, limits the set of viable acquisition techniques to single-shot imaging with severe compromises in signal-to-noise ratio and diagnostic contrast, and frequently results in unacceptable image quality. Surprisingly little is known about the characteristics of fetal motion during MRI and here we propose and demonstrate methods that exploit a growing repository of MRI observations of the gravid abdomen that are acquired at low spatial resolution but relatively high temporal resolution and over long durations (10–30 minutes). We estimate fetal pose per frame in MRI volumes of the pregnant abdomen via deep learning algorithms that detect key fetal landmarks. Evaluation of the proposed method shows that our framework achieves quantitatively an average error of 4.47 mm and 96.4% accuracy (with error less than 10 mm). Fetal pose estimation in MRI time series yields novel means of quantifying fetal movements in health and disease, and enables the learning of kinematic models that may enhance prospective mitigation of fetal motion artifacts during MRI acquisition.

ORIGINAL RESEARCH Quantification of Liver Perfusion Using Multidelay Pseudocontinuous Arterial Spin Labeling Xinlei Pan, BS, 1 Tianyi Qian, PhD, 2 Maria A. Fernandez-Seara, PhD, 3 Robert X. Smith, PhD, 4 Kuncheng Li, MD, PhD, 5 Kui Ying, PhD, 6 Kyunghyun Sung, PhD, 7 and Danny J.J. Wang, PhD, MSCE 4,7 * Purpose: To develop a free-breathing multidelay pseudocontinuous arterial spin labeling (pCASL) technique for quanti- tative measurement of liver perfusion of the hepatic artery and portal vein, respectively. Materials and Methods: A navigator-gated pCASL sequence with balanced steady-state free precession (bSSFP) read- out was developed and applied on five healthy young volunteers at 3T. Two labeling schemes were performed with the labeling plane applied on the descending aorta above the liver, and perpendicular to the portal vein before its entry to liver to label the hepatic artery and portal vein, respectively. For each labeling scheme, pCASL scans were performed at five or six postlabeling delays between 200 and 2000 msec or 2500 msec with an interval of 400 or 500 msec. Multide- lay pCASL images were processed offline with nonrigid motion correction, outlier removal, and fitted for estimation of liver perfusion and transit time. Results: Estimated liver perfusion of the hepatic artery and hepatic portal vein were 21.8 6 1.9 and 95.1 6 8.9 mL/100g/ min, with the corresponding transit time of 1227.3 6 355.5 and 667.2 6 85.0 msec, respectively. The estimated liver per- fusion and transit time without motion correction were less reliable with greater residual variance compared to those processed with motion correction (P < 0.05). Conclusion: The liver perfusion measurement using multidelay pCASL showed good correspondence with values noted in the literature. The capability to noninvasively and selectively label the hepatic artery and portal vein is a unique strength of pCASL as compared to other liver perfusion imaging techniques, such as computed tomography perfusion and dynamic contrast-enhanced MRI. J. MAGN. RESON. IMAGING 2015;00:000–000. L iver diseases afflict more than 30 million people in the US, or 1 in 10 Americans. 1 The number of people diag- nosed with liver diseases such as hepatitis C, nonalcoholic fatty liver disease, and liver cancer are on the rise both in the US and worldwide. 2 Liver ultrasonography and magnetic res- onance imaging (MRI) are the two main imaging modalities for detecting, characterizing, and monitoring treatment responses of focal and diffuse liver diseases. 3–5 Ultrasonogra- phy remains the first-line imaging modality for examining liver morphology and blood flow; these are accentuated through the recent development of elastography. MRI offers multiparametric examinations of the morphology, perfusion, and diffusion of the liver. Dynamic contrast-enhanced (DCE) MRI and MR elastography (MRE) are two emerging tech- nologies capable of quantitative assessments of liver perfu- sion/permeability and viscoelasticity, respectively. Liver perfusion imaging is useful in detecting regional and global alterations in liver blood flow caused by a range View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.25070 Received Jul 4, 2015, Accepted for publication Sep 24, 2015. *Address reprint requests to: D.J.J.W., Laboratory of Functional MRI Technology (LOFT), Department of Neurology, UCLA, 660 Charles E Young Dr. South, Los Angeles, CA 90095. E-mail: jwang71@gmail.com From the 1 Department of Biomedical Engineering, Tsinghua University, Beijing, China; 2 Siemens Healthcare, MR Collaboration NE Asia, Beijing, China; Neuroimaging Laboratory, Division of Neuroscience, Center for Applied Medical Research, University of Navarra, Spain; 4 Laboratory of Functional MRI Technology (LOFT), Department of Neurology, University of California Los Angeles, Los Angeles, California, USA; 5 Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China; 6 Department of Engineering Physics, Tsinghua University, Beijing, China; and 7 Department of Radiology, University of California Los Angeles, Los Angeles, California, USA. Additional Supporting Information may be found in the online version of this article. C 2015 Wiley Periodicals, Inc. V

Backgrounds Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has demonstrated 80-90% complete remission (CR) rate in R/R B-ALL; however, 10% to 20% of patients have no response and the potential etiology and risk factors remain unclear. Patients and Methods From Apr. 2017 to Mar. 2019, 254 patients with R/R B-ALL received treatment at our single center with a second-generation CD 19 CAR-T from 5 companies (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460). The targeted median infused CAR-T cell dose was 3x105/kg. For all patients, screening was undertaken for 58 types of B-ALL related gene mutations and 49 congenital immune deficiency gene mutations using next generation sequencing (NGS) method. The patient and CAR-T product characteristics were analyzed to see if any factors affected the initial CR rate. Univariate analysis comparing CR rates between subgroups were carried out using chi-squared tests. Logistic regression model was adopted for multivariate analysis. Results On D30, 90.6% (230/254) patients achieved CR, and minimal residual disease (MRD)-negative CR was 89.4% (227/254). Univariate analysis (Table 1&2) showed a statistical difference in CR rate between females and males (84.54% vs. 94.27%, p=0.011). The CR rate of patients who received prior either CAR-T or blinatumomab treatment was lower than those who had not (50% vs. 91.53%, p=0.01). For the characteristic fusion genes, the CR rate in patients with MLL-AF4 was 80%, which was inferior to those with other or no fusion genes (P=0.041). For gene mutations, a lower CR rate was observed in patients with TP53 mutation compared to those with other or no mutations (72.73% vs. 92.11% vs. 94.39%, P=0.004). Presence of congenital immune deficiency gene mutations did not affect CR rate. Patients with >20% bone marrow (BM) blasts had a worse outcome than those with BM blasts≤20% (79.17% vs. 97.47%, p14 yr, patients with or without extramedullary disease (EMD), or patients receiving different chemotherapies between enrollment and CAR-T cells infusion on top of fludarabine and cyclophosphamide (FC) conditioning regimen. Cytokine release syndrome (CRS) and neurotoxicity had no effect on CR rate.There was a trend towards a lower CR rate in patients who received donor-derived CAR-T versus patient-derived CAR-T products (61.54% vs. 92.12%, p = 0.081). A lower CR rate was observed in patients who received CD28 costimulatory domain versus 4-1BB CAR-T products (77.27% vs. 91.70%, p=0.053). There was no difference in CR rate between patients infused with cell dose ≥3x105/kg vs. cell dose 2x104/kg. No CR difference was observed from different manufacturing companies. Moreover, 125/254 cases had available data for analysis on subsets of CAR-T cells including central memory T cells (Tcm), naive T cells and T memory stem cells (Tscm). Each group was divided into high- or low-level groups based on the median level. The CR rate was 92.19% vs. 88.52% in high and low Tcm groups, 92.31% vs. 88.33% in high or low naive group, and 89.80% vs.90.24% in high and low Tscm groups, respectively. No difference in CR between the groups were observed. Multivariate analysis was performed to investigate factors affecting achievement of CR (Table 3). Female group had lower odds of achieving CR after CAR-T therapy compared to male group [OR=0.232(95%CI 0.082-0.652)]. Compared to patients without TP53 mutation or only with other gene mutations, patients with TP53 mutation were more likely to have a low CR rate after CAR-T treatment [OR=4.511(95%CI 1.295-16.895)]. Patients with BM blast >20% had lower odds of achieving CR compared to those with BM blast ≤20% [OR=0.095 (95%CI 0.022-0.260)]. Treatment with CAR-T with CD28 as a costimulatory domain resulted lower odds of CR compared to treatment with CAR-T with 4-1BB [OR=7.141 (95%CI 1.722-29.612)]. Patients who developed severe neurotoxicity (grade 2-4) post CAR-T had higher odds of achieving CR compared to patients with grade 0-1 neurotoxicity [OR=34.796(95%CI 3.232-374.659)]. Conclusions In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity. Disclosures No relevant conflicts of interest to declare.

Intermediate band solar cells (IBSCs) are conceptual and promising for next generation high efficiency photovoltaic devices, whereas, IB impact on the cell performance is still marginal due to the weak absorption of IB states. Here a rational design of a hybrid structure composed of ZnTe:O/ZnO core-shell nanowires (NWs) with Al bowtie nanoantennas is demonstrated to exhibit strong ability in tuning and enhancing broadband light response. The optimized nanowire dimensions enable absorption enhancement by engineering leaky-mode dielectric resonances. It maximizes the overlap of the absorption spectrum and the optical transitions in ZnTe:O intermediate-band (IB) photovoltaic materials, as verified by the enhanced photoresponse especially for IB states in an individual nanowire device. Furthermore, by integrating Al bowtie antennas, the enhanced exciton-plasmon coupling enables the notable improvement in the absorption of ZnTe:O/ZnO core-shell single NW, which was demonstrated by the profound enhancement of photoluminescence and resonant Raman scattering. The marriage of dielectric and metallic resonance effects in subwavelength-scale nanowires opens up new avenues for overcoming the poor absorption of sub-gap photons by IB states in ZnTe:O to achieve high-efficiency IBSCs.

The aim of this study was to investigate if there were differences in the two-point discrimination (2-PD) of fingers among students at different stages of a chiropractic program.This study measured 2-PD thresholds for the dominant and nondominant index finger and dominant and nondominant forearm in groups of students in a 4-year chiropractic program at the International Medical University in Kuala Lumpur, Malaysia. Measurements were made using digital calipers mounted on a modified weighing scale. Group comparisons were made among students for each year of the program (years 1, 2, 3, and 4). Analysis of the 2-PD threshold for differences among the year groups was performed with analysis of variance.The mean 2-PD threshold of the index finger was higher in the students who were in the higher year groups. Dominant-hand mean values for year 1 were 2.93 ± 0.04 mm and 1.69 ± 0.02 mm in year 4. There were significant differences at finger sites (P.05) among all year groups compared with year 1. There were no significant differences measured at the dominant forearm between any year groups (P = .08). The nondominant fingers of the year groups 1, 2, and 4 showed better 2-PD compared with the dominant finger. There was a significant difference (P = .005) between the nondominant (1.93 ± 1.15) and dominant (2.27 ± 1.14) fingers when all groups were combined (n = 104).The results of this study demonstrated that the finger 2-PD of the chiropractic students later in the program was more precise than that of students in the earlier program.

A 2-D cyclic variation of integrated backscatter (CVIB) imaging method was established for detecting myocardial ischemia. To demonstrate the feasibility and validity of this method, animal experiments were conducted. Acute myocardial ischemia was induced by occluding left anterior descending coronary artery in 10 anesthetized open-chest dogs. While scanning the normal hearts and the ischemic hearts with a B scanner, digital radiofrequency data were acquired by a real-time acquisition system in synchronism. The offline analysis to the radio-frequency signal with the 2-D CVIB imaging method was performed to verify the consistency between the imaging result and the design of the experiment. In addition, 4 dogs in experiment were treated with the heart pacemaker in order to investigate the influence of changing in heart rate on the detection of ischemic myocardium with the proposed method. The experimental result showed that the 2-D CVIB imaging method succeeded in detecting the ischemic myocardium a...

In ultrasound elastography, tissue axial strains are calculated from the gradient of the estimated axial displacements. However, the common differentiation operation amplifies the noises in the displacement estimation, especially at high frequencies. In this paper, a low-pass digital differentiator (LPDD) is proposed to calculate the axial strain from the estimated tissue displacement. Several LPDDs that have been well developed in the field of digital signal processing are presented. The corresponding performances are compared qualitatively and quantitatively in computer simulations and in preliminary phantom and in vitro experiments. The results are consistent with the theoretical analysis of the LPDDs.

Functional Magnetic Resonance Imaging (fMRI) of inhibitory control has only been investigated in patients with attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). The objective of this study was to investigate the differences of functional areas associated with inhibitory control between boys with pure oppositional defiant disorder (ODD) and controls during a response inhibition task using functional magnetic resonance imaging (fMRI). Eleven boys with pure ODD and ten control boys, aged 10 to 12, performed a GoStop response inhibition task in this study. The task has a series of “go” trials to establish a pre-potent response tendency and a number of “stop” trials to test subjects’ ability to withhold their responses. During the GoStop task, greater activation in the dorsolateral parts of the bilateral inferior frontal gyrus, left middle frontal gyrus (lMFG) and right superior frontal gyrus (rSFG) activation was seen in the ODD boys. Additionally, reduced activation in regions of the right inferior frontal gyrus (rIFG) was seen in the ODD boys in comparison with the control group. The results may suggest that the higher activation in areas adjacent to the rIFG could be the cause of reduced activation in the rIFG; although this is speculative and requires additional supporting evidence. The findings further suggest that ODD is a less pronounced functional disorder compared to ADHD and CD.

We present a study of least mean square (LMS) based adaptive filters for high resolution magnetic resonance (MR) images to improve signal-to-noise ratio (SNR) while maintaining sharp edges. Five variations of a new technique that senses the type of noise or the presence of an edge in the filtering window, called adaptive filtering with noise estimation (AFEN) are presented and compared with the basic two-dimensional LMS (TDLMS) algorithm, adaptive filtering with a mean estimator (AFLME), a two-dimensional averaged LMS (TDALMS) algorithm, and a two-dimensional median weighted LMS (TDMLMS) algorithm. Although TDLMS, TDALMS, and TDMLMS filters give better SNR improvement when applied uniformly to an image, they significantly blur edges. The AFLME and AFEN filters both show approximately a factor of 2 SNR improvement with much better retention of edges, with AFEN showing slightly better performance for both SNR and edge sharpness in phantom and in vivo inner ear images.

Submillimeter-resolution magnetic resonance (MR) imaging of the inner ear is valuable for diagnosis and treatment planning. Its main advantage for investigations of underlying disease is that it can directly depict the fluid spaces of the membranous labyrinth rather than define only the bony canal, as does computed tomography. A systematic evaluation of factors influencing high-resolution three-dimensional (3D) gradient-echo imaging of the inner ear with a standard clinical MR system is presented. This includes the evaluation of various radio-frequency coils, the design of steady-state pulse sequences, and the optimization of acquisition parameters. A quantitative analysis was facilitated by computer simulations and image processing. The highest signal-to-noise ratio for the membranous labyrinth was obtained with a single 3-inch (7.6-cm) receiver coil and a 3D GRASS (gradient-recalled acquisition in the steady state) sequence with the minimal achievable TR msec/TE msec of 25/7 and a 40 degrees--60 degrees flip angle, which yielded acceptable images with minimal voxel volumes of 0.1 mm3 in 14 minutes.

The parallel magnetic resonance imaging (parallel imaging) technique reduces the MR data acquisition time by using multiple receiver coils. Because of its ill-conditioned system matrix, the reconstruction suffers from noise amplification at high reduction factors, such as in the standard SENSE reconstruction. Total variation (TV) regularization is a popular technique for solving this problem. However, TV regularized images are vulnerable to staircase artifacts and texture loss. In this paper, we proposed a similarity-based regularization technique which enforces the consistence and similarity of pixel values within the image. The phantom simulation and in vivo experimental results demonstrate that this method can effectively suppress noise amplification in SENSE reconstruction while preserving image details. Compared with TV regularized images, images reconstructed by the new method are free of staircase artifacts and suffer less from structure loss.

To reduce the inherent mechanical artifacts in the strain images, many groups have investigated solutions to the inverse problem in elastography. However, in prostate elastography or intravascular elastography where the compression direction is radial, the inverse problem has not been studied thoroughly. In this paper, an iterative approach is proposed to reconstruct tissue elasticity for ultrasound elastography using a radial compression. The method is based upon the stress–strain relations in the polar coordinates. Computer simulations in an intravascular model are performed to illustrate the feasibility of this method in reducing the mechanical artifacts of the strain images. The reconstructed elasticity error and the contrast-transfer efficiency (CTE) as a function of the iteration number show that the inverse approach converges with a few iterations.

Early detection of the breast cancer is one of the keys to decrease the mortality of this disease. Now more and more attention is paid on development of non-invasive mammography. To study the feasibility of breast imaging with near infrared light, a frequency-domain optical scanner of breast cancer was designed and developed in our lab, based on the theory of interaction of Near Infrared (NIR) light and soft tissues. In this paper, the imaging prototype as well as the imaging processing system based on Matlab is described. The results of phantom experiments using the prototype of this scanner show a resolution in millimeter scale. The initial clinical trials show the feasibility of our prototype in clinical study. The prototype can scan a breast in 4 minutes. Images of the same breast obtained both with the prototype and with x-ray mammography are presented.

Background Our previous reports demonstrated that abdominal paracentesis drainage (APD) exerts a beneficial effect on severe acute pancreatitis (SAP) patients. However, the underlying mechanisms for this effectiveness are not well understood. Methods A retrospective cohort of 132 consecutive non-hypertriglyceridemia (HTG)-induced SAP patients with triglyceride (TG) elevation and pancreatitis-associated ascitic fluid (PAAF) was recruited from May 2010 to May 2015 and included in this study. The patients were divided into two groups: the APD group (n = 68) and the non-APD group (n = 64). The monitored parameters mainly included mortality, hospital stay, the incidence of further intervention, levels of serum lipid metabolites and inflammatory factors, parameters related to organ failure and infections, and severity scores. Results The demographic data and severity scores were comparable between the two groups. Compared with the non-APD group, the primary outcomes (including mortality, hospital stay and the incidence of percutaneous catheter drainage) in the APD group were improved. The serum levels of lipid metabolites were significantly lower in the APD group after 2 weeks of treatment than in the non-APD group. Logistic regression analysis indicated that the decreased extent of free fatty acid (FFA)(odds ratio, 1.435; P = 0.015) was a predictor of clinical improvement after 2 weeks of treatment. Conclusion Treatment with APD benefits non-HTG-induced SAP patients with serum TG elevation by decreasing serum levels of FFA.