Diffusion Tensor Imaging (DTI) has received increasing attention in the neuroimaging community. However, the complex Diffusion Weighted Images (DWI) acquisition protocol are prone to artifacts induced by motion and low signal-to-noise rations(SNRs). A rigorous quality control (QC) and error correction procedure is absolutely necessary for DTI data analysis. Most existing QC procedures are conducted in the DWI domain and/or on a voxel level, but our own experiments show that these methods often do not fully detect and eliminate certain types of artifacts. We propose a new regional, alignment-independent DTI-QC measure that is based in the DTI domain employing the entropy of the regional distribution of the principal directions. This new QC measurement is intended to complement the existing set of QC procedures by detecting and correcting residual artifacts. Experiments show that our automatic method can reliably detect and potentially correct such residual artifacts. The results indicate its usefulness for general quality assessment in DTI studies.
Abstract Background It is very difficult to predict the early response to NAC only on the basis of change in tumor size. ADC value derived from DWI promises to be a valuable parameter for evaluating the early response to treatment. This study aims to establish the optimal time window of predicting the early response to neoadjuvant chemotherapy (NAC) for different subtypes of locally advanced breast carcinoma using diffusion-weighted imaging (DWI). Methods We conducted an institutional review board-approved prospective clinical study of 142 patients with locally advanced breast carcinoma. All patients underwent conventional MR and DW examinations prior to treatment and after first, second, third, fourth, sixth and eighth cycle of NAC. The response to NAC was classified into a pathologic complete response (pCR) and a non-pCR group. DWI parameters were compared between two groups, and the optimal time window for predicting tumor response was established for each chemotherapy regimen. Results For all the genomic subtypes, there were significant differences in baseline ADC value between pCR and non-pCR group ( p < 0.05). The time point prior to treatment could be considered as the ideal time point regardless of genomic subtype. In the group that started with taxanes or anthracyclines, for Luminal A or Luminal B subtype, postT1 could be used as the ideal time point during chemotherapy; for Basal-like or HER2-enriched subtype, postT2 as the ideal time point during chemotherapy. In the group that started with taxanes and anthracyclines, for HER2-enriched, Luminal B or Basal-like subtype, postT1 could be used as the ideal time point during chemotherapy; for Luminal A subtype, postT2 as the ideal time point during chemotherapy. Conclusions The time point prior to treatment can be considered as the optimal time point regardless of genomic subtype. For each chemotherapy regimen, the optimal time point during chemotherapy varies across different genomic subtypes.
To evaluate cyclic changes of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of normal uterus in different age groups during the menstrual cycle, and the correlation with serum female hormone levels.29 normal volunteers accepted diffusion tensor imaging of the uterus on menstrual phase (MP), follicular phase (FP), ovulatory phase (OP) and luteal phase. FA and ADC values of different uterine layers on midsagittal images were measured. Differences between two age groups during the menstrual cycle were evaluated using liner mixed models and one-way analysis of variance. Pearson correlation analysis compared variation of FA and ADC values with serum female hormone levels measured in MP.During menstrual cycle, endometrial FA values declined, whereas ADC values increased with significant differences (p < 0.05). Serum oestradiol (E) levels correlated moderately with variations of FA values between MP-FP (p = 0.045; r = 0.389) and MP-OP (p = 0.008; r = 0.511). FA and ADC values of junctional zones showed no significant difference (p > 0.05) as well as FA values of myometrium (p = 0.0961), while ADC values of myometrium showed significant increase from menstrual phase to luteal phase (p < 0.05). FA and ADC values of uterine three zonal structures showed significant differences (p < 0.05) at each phase during the menstrual cycle. No significant difference of FA and ADC values was found between age groups (p > 0.05).Dynamic changes of uterine FA and ADC values were observed during menstrual cycle. Variation of FA values between MP-FP, MP-OP correlated moderately with serum E levels.No publications on the relationship between FA and ADC values and the female hormone levels were found; our study prospectively investigated the cyclic changes of FA and ADC values of the normal uterus and the correlation with the basic serum female hormone levels in MP.
It is a clinical problem to identify histological component in enlarged cervical lymph nodes, particularly in differentiation between lymph node metastasis and lymphoma involvement.To construct two kinds of deep learning (DL)-based computer-aided diagnosis (CAD) systems including DL-convolutional neural networks (DL-CNN) and DL-machine learning for pathological diagnosis of cervical lymph nodes by positron emission tomography (PET)/computed tomography (CT) images.We collected CT, PET, and PET/CT images series from 165 patients with enlarged cervical lymph nodes receiving examinations from January 2014 to June 2018. Six CNNs pretrained on ImageNet as DL architectures were used for two kinds of DL-based CAD models, including DL-CNN and DL-machine learning models. The DL-CNN models were constructed via transfer learning for classification of lymphomatous and metastatic lymph nodes. The DL-machine learning models were developed by DL-based features extractors and support vector machine (SVM) classifier. As for DL-SVM models, we also evaluate the effect of handcrafted radiomics features in combination of DL-based features.The DL-CNN model with ResNet50 architecture on PET/CT images had the best diagnostic performance among all six algorithms with an area under the receiver operating characteristic curve (AUC) of 0.845 and accuracy of 78.13% in the testing cohort. The DL-SVM model on ResNet50 extractor showed great performance for the testing cohort with an AUC of 0.901, accuracy of 86.96%, sensitivity of 76.09%, and specificity of 94.20%. The combination of DL-based and handcrafted features yielded the improvement of diagnostic performance.Our DL-based CAD systems on PET/CT images were developed for classifying metastatic and lymphomatous involvement with favorable diagnostic performance in enlarged cervical lymph nodes. Further clinical practice of our systems may improve quality of the following therapeutic interventions and optimize patients' outcomes.
Objective: To explore the preparation and preliminary research on the characteristics of modified nano-bioglass hydrogel. Methods: (1) The nano-bioglass suspension was prepared by adding 67 mL nano-silica suspension into 400 mL saturated calcium hydroxide solution, and its suspension stability was observed. (2) The hydrogel with final mass fraction of 10% gelatin and 1% sodium alginate was prepared and set as control group. On the basis of the hydrogel in control group, the nano-bioglass suspension prepared in experiment (1) was added to prepare the hydrogel with the final mass fraction of 0.5% bioglass, 10% gelatin, and 1% sodium alginate, and the hydrogel was set as the experimental group. The gelling time at 4 and 25 ℃and the dissolution time at 37 ℃ of hydrogel in 2 groups were recorded, and the gelation at 4 and 25 ℃and dissolution condition at 37 ℃of the hydrogel in 2 groups were observed. The hydrogel in 2 groups were collected and cross-linked with 25 g/L calcium chloride solution after cold bath at 4 ℃, and the compression modulus was measured by Young's modulus tester. In addition, the hydrogel in 2 groups were collected and cross-linked as before, and freeze-drying hydrogel was made at -20 ℃. The relative volumes were measured and the porosity of hydrogel in 2 groups was calculated. The number of sample in the experiment was 3. (3) Fibroblasts (Fbs) were isolated and cultured from 12 C57BL/6J mice of 24 hours old and the morphology was observed by inverted microscope, and the third passage of Fbs were cultured for the following experiment. Fbs were collected to make single cell suspension with the cell concentration of 1×10(5)/mL. The single cell suspension was divided into experimental group and control group according the random number table (the same grouping method below), which were added with hydrogel in experimental group and control group prepared in experiment (2), respectively. At culture hour 12, 24, and 48, cells of 3 wells in each group were collected to detect the survival rate by cell counting kit 8 method. (4) The third passage Fbs were collected to prepare the single cell suspension with the cell concentration of (3.0~4.5)×10(7)/mL, which was divided into experimental group and control group, with 1 tube in each group. The single cell suspension in 2 groups were added with green fluorescent probe DIO for staining and then added with 9 mL hydrogel in experimental group and control group prepared in experiment (2), respectively. The mixed solution of Fbs and hydrogel in 2 groups was cross-linked as before to make cell-loaded hydrogel. On culture day 3, the survival of cells in the hydrogel was observed by laser confocal microscope. The cell-loaded hydrogel was prepared as before and without added with green fluorescent probe DIO. On culture day 7, the adhesion and extension of cells in the hydrogel were observed by scanning electron microscope. (5) Twelve 6-week-old female BALB/c-nu nude mice were collected and divided into experimental group and control group, with 6 mice in each group. A round full-thickness skin defect wound with diameter of 1 cm was made on the back of each mouse. Immediately after injury, one cell-loaded hydrogel block in the experimental group and the control group prepared in experiment (4) was placed in the wound of each mouse in the experimental group and the control group, respectively. On post injury day (PID) 7 and 14, 3 nude mice in each group were sacrificed to collect the wound and wound margin tissue, which was stained with hematoxylin-eosin to observe the wound healing. Data were statistically analyzed with independent sample t test. Results: (1) The nano-bioglass particles could be uniformly dispersed in water and had good suspension stability. (2) The hydrogels of the 2 groups were molten at 37 ℃, and no precipitation of particle was observed. The dissolving time of the hydrogel in the experimental group and the control group at 37 ℃ was 5 and 10 min, respectively. The gelation time of the hydrogel in the experimental group and the control group at 25 ℃ was 30 and 180 min, respectively, and the gelation time of the 2 groups at 4 ℃ was 5 and 10 min, respectively. The compression modulus of hydrogel in the experimental group was (53±6) kPa, which was significantly higher than (23±6) kPa in the control group (t=6.364, P 0.05). (3) The cells were in long fusiform, and the proportion of nuclei was high, which was accorded with the morphological characteristics of Fbs. At culture hour 12, 24, and 48, the survival rate of cells in the experimental group was (84±4)%, (89±4)%, and (130±10)%, which was similar to (89±5)%, (90±4)%, and (130±11)% in the control group, respectively (t=1. 534, 0.611, 0.148, P>0.05). (4) On culture day 3, the cells in the two groups had complete morphology in the hydrogel, no nuclear lysis or disappearance were observed, the cytoplasm remained intact, and the fluorescence intensity of the cells in the experimental group was significantly stronger than that in the control group. On culture day 7, the cells in the experimental group and the control group adhered and stretched in the hydrogel, and the number of cells in the experimental group adhered to the hydrogel was significantly more than that in the control group. On PID 7, the wound area of the nude mice in the control group and the experimental group were reduced, the reduction area of mice in the experimental group was more obvious, and a large amount of inflammatory cells were seen in and around the wound in the 2 groups. On PID 14, the wound area of the nude mice in the control group was larger than that of the experimental group, and the number of inflammatory cells in and around the wound was significantly more than that in the experimental group. Conclusions: Nano-bioglass hydrogel possesses good physical, chemical, and biological properties, cell loading potential, and the ability to promote wound healing, which means it has a good potential in clinical application.
Abstract Background Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. Methods A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical‐radiological semantic features; (2) The radiomics models (radiomics+ and radiomics−) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite−) incorporated both above. Results In the testing set, the radiomics+/− models and the composite+/− models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/− models and the composite+/− models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/− and composite+/− models were significantly superior to that of the clinical model ( p < 0.05). Whether the ROI segmentation included or excluded the cavity had no significant effect on these models (radiomics+ vs. radiomics−, composite+ model vs. composite−) ( p > 0.05). Conclusions The present study established a machine learning‐based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability.
It is very difficult to predict the early response to NAC only on the basis of change in tumor size. ADC value derived from DWI promises to be a valuable parameter for evaluating the early response to treatment. This study aims to establish the optimal time window of predicting the early response to neoadjuvant chemotherapy (NAC) for different subtypes of locally advanced breast carcinoma using diffusion-weighted imaging (DWI). We conducted an institutional review board-approved prospective clinical study of 142 patients with locally advanced breast carcinoma. All patients underwent conventional MR and DW examinations prior to treatment and after first, second, third, fourth, sixth and eighth cycle of NAC. The response to NAC was classified into a pathologic complete response (pCR) and a non-pCR group. DWI parameters were compared between two groups, and the optimal time window for predicting tumor response was established for each chemotherapy regimen. For all the genomic subtypes, there were significant differences in baseline ADC value between pCR and non-pCR group (p < 0.05). The time point prior to treatment could be considered as the ideal time point regardless of genomic subtype. In the group that started with taxanes or anthracyclines, for Luminal A or Luminal B subtype, postT1 could be used as the ideal time point during chemotherapy; for Basal-like or HER2-enriched subtype, postT2 as the ideal time point during chemotherapy. In the group that started with taxanes and anthracyclines, for HER2-enriched, Luminal B or Basal-like subtype, postT1 could be used as the ideal time point during chemotherapy; for Luminal A subtype, postT2 as the ideal time point during chemotherapy. The time point prior to treatment can be considered as the optimal time point regardless of genomic subtype. For each chemotherapy regimen, the optimal time point during chemotherapy varies across different genomic subtypes.
Abstract T-cell exhaustion is defined as T-cell dysfunction leading to loss of effector T-cells function. Restoring exhausted T-cells with agonistic anti-4-1BB monoclonal antibody is a promising strategy for cancer treatment. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a classical target with specific expression profiles in tumors. It has limited expression in normal adult tissues, but is overexpressed in multiple types of cancer, especially in colorectal carcinoma and non-small cell lung cancer. Here, we reported a novel bispecific antibody, LM-24C5 that specifically activates 4-1BB in a CEACAM5-dependent manner with localized T cell activation and reduced systemic toxicity. LM-24C5 was developed by introducing qualified 4-1BB heavy-chain variable into a human IgG1 CEACAM5 monoclonal antibody with disabled FcgR-mediated function. LM-24C5 was evaluated for its binding activity to human CEACAM5 and 4-1BB through protein and cell-based assays. The binding activity of LM-24C5 to tumor cells endogenously expressing CEACAM5 and activated primary T cells was confirmed. LM-24C5 was further evaluated in 4-1BB signalling reporter and co-culture assay with human peripheral blood mononuclear cells (PBMC). In vivo anti-tumor activity of LM-24C5 was assessed in hu4-1BB knock-in mice implanted with colon cancer cell line MC38 overexpressing huCEACAM5. Percentage of tumor infiltrating T cells and central memory CD8+ T cells were evaluated by FACS analysis. In addition, 2-week repeated dose toxicity study of LM-24C5 was conducted in hu4-1BB/4-1BBL double-transgenic mice. LM-24C5 efficiently bound to huCEACAM5-postitive cells (EC50: 3.78 nM) and activated human primary T cells. It induced superior 4-1BB activity (EC50: 1.07 nM) than benchmark antibody Urelumab (EC50: 3.38 nM) in the presence of cells expressing CEACAM5. The strength of 4-1BB activation induced by LM-24C5 was correlated with CEACAM5 expression levels. LM-24C5 was also found to stimulate T-cell activation (CD4+ EC50: 0.471, CD8+: 0.482) in PBMCs in a CEACAM5-dependent manner leading to significant IFN-γ production. Injection of LM-24C5 led to complete tumor regression around one month post treatment. Moreover, the tumor-free mice were resistant to tumor rechallenge, suggesting that LM-24C5 can induce long-term protective immunological memory. We have also observed that LM-24C5 increased tumor infiltrating lymphocytes and percentage of central memory CD8+ T cells in spleens. LM-24C5 was well tolerated in hu4-1BB/4-1BBL double-transgenic mice at a dose of 100mg/kg given once weekly for 2 weeks. In summary, LM-24C5 is a novel CEACAM5 dependent 4-1BB bispecific agonist antibody that could redirect and activate T cells to CEACAM5 positive tumor cells by engaging 4-1BB antigen, thus positioned as a potential novel therapy for colorectal carcinoma and other CEACAM5 positive tumors. Citation Format: Wei Cao, Jianjian Liu, Wentao Huang, Junwei Yang, Lei Shi, Yuan Li, Te Du, Xia Qin, Da Fei, Runsheng Li. Pre-clinical efficacy and toxicity profile of LM-24C5: A novel CEACAM5 x 4-1BB bispecific antibody in cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2650.
Background Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and believed to influence its phenotype. Purpose To explore the effects of obesity on left ventricular (LV) remodeling and long‐term clinical course in Chinese patients with HCM. Study Type Longitudinal. Population A total of 247 patients with HCM classified according to body mass index (BMI) (normal weight: BMI = 18.0–22.9 kg/m 2 [ N = 90]; overweight: BMI = 23.0–24.9 kg/m 2 [ N = 58]; and obese: BMI ≥ 25 kg/m 2 [ N = 99]). Field Strength/Sequence 3.0 T/Balanced steady‐state free precession sequence and phase‐sensitive inversion recovery late gadolinium enhancement (LGE) sequence. Assessment LV function and geometry were measured. LV peak strain analysis was performed. The presence and percentage of LGE in the LV were recorded. The endpoints including heart failure, sudden cardiac death, and overall composite outcome were assessed during a median follow‐up of 4.1 years (interquartile range, 3.0–6.2 years). Statistical Tests One‐way analysis of variance, Kruskal–Wallis test, or chi‐square test; Pearson correlation coefficient ( r ); multivariable linear regression analysis; Kaplan–Meier survival analysis; and Cox proportional hazards model analysis were conducted. A two‐tailed P ‐value < 0.05 was considered statistically significant. Results Obese patients exhibited a significant progressive increase in LV mass compared with normal‐weight patients. The magnitude of all LV strain indices gradually and significantly decreased as BMI increased, whereas LV ejection fraction was not significantly different among BMI groups ( P = 0.364). Multivariable linear regression analysis showed that obesity had a significant association with impaired strain indices as well as with indexed LV mass. Multivariable Cox model analysis retained obesity as an independent marker for future endpoints, and conveyed a > 3‐fold increase in risk compared with patients with normal weight (hazard ratio, 3.04; 95% confidence interval, 1.07–6.57). Data Conclusion Obesity is an important environmental modifier that is associated with adverse LV remodeling and is independently associated with future clinical outcomes in Chinese patients with HCM. Level of Evidence 3 Technical Efficacy Stage 2
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