Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA

AIM: To investigate the performance of Gadofluorine P-enhanced magnetic resonance imaging(MRI) on the diagnosis of diabetes in a streptozotocin(STZ)-induced diabetic rat model.METHODS: Fischer 344 rats were treated with STZ.Rats not treated with STZ served as controls. T1-weighted MRI was performed using a 3T scanner before and after the injection of Gd-DOTA or Gadofluorine P(6 diabetic rats, 5 controls). The normalized signal intensity(SI) and the enhancement ratio(ER) of the pancreas were measured at each time point, and the values were compared between the normal and diabetic rats using the Mann-Whitney test. In addition,the values were correlated with the mean islet number.Optimal cut-off values were calculated using a positive test based on receiver operating characteristics.Intrapancreatic Gd concentration after the injection of each contrast media was measured using laser ablation-inductively coupled plasma-mass spectrometry in a separate set of rats(4 diabetic rats, 4 controls for Gadofluorine P; 2, 2 for Gd-DOTA).RESULTS: The normalized SI and ER of the pancreas using Gd-DOTA were not significantly different between diabetic rats and controls. With Gadofluorine P, the values were significantly higher in the diabetic rats than in the control rats 30 min after injection(P < 0.05). The area under the receiver operating characteristic curve that differentiated diabetic rats from the control group was greater for Gadofluorine P than for Gd-DOTA(0.967 vs 0.667, P = 0.085). An increase in normalized SI 30 min after Gadofluorine P was correlated with a decrease in the mean number of islets(r 2 = 0.510, P = 0.014). Intra-pancreatic Gd was higher in rats with Gadofluorine P injection than Gd-DOTA injection(Gadofluorine P vs Gd-DOTA, 7.37 vs 0.00, P < 0.01). A significant difference in the concentration of intrapancreatic Gd was observed between the control and diabetic animals that were sacrificed 30 min after Gadofluorine P injection(control vs diabetic, 3.25 ng/g vs 10.55 ng/g, P < 0.05)CONCLUSION: In this STZ-induced diabetes rat model,Gadofluorine P-enhanced MRI of the pancreas showed high accuracy in the diagnosis of diabetes.

In vivo analysis of post-joint-preserving surgery fracture of 3D-printed Ti-6Al-4V implant to treat bone cancer

Cancer growth in the bone due to its random shape disables bone strength and thus changes its capacity to support body weight or muscles,which can crucially affect the quality of human life in terms of normal walking or daily activities.For successful patient recovery,it is necessary to remove the cancer-affected minimal bone area and quickly replace it with a biocompatible metal implant within less than 2 weeks.An electron beam-melted Ti-6Al-4V implant was designed and applied in a patient to preserve the natural knee joint close to the bone tumor.The developed implant fits the bone defect well,and the independent ambulatory function of the natural knee joint was restored in the patient within six weeks after surgery.A delayed fracture occurred six months after the successful replacement of cancer-affected bone with Ti-6Al-4V implant at the proximal meshed junction of the implant because of a minor downward slip.Microstructural,mechanical,and computational analyses were conducted for the fractured area to find the main reason for the delayed fracture.Our findings pertaining to the mechanical and material investigation can help realize the safe implantation of the three-dimensionally printed titanium implant to preserve the natural joints of patients with massive bone defects of the extremities.

Quantitative volumetric analysis of the optic radiation in the normal human brain using diffusion tensor magnetic resonance imaging-based tractography

To attain the volumetric information of the optic radiation in normal human brains, we per- formed diffusion tensor imaging examination in 13 healthy volunteers. Simultaneously, we used a brain normalization method to reduce individual brain variation and increase the accuracy of volumetric information analysis. In addition, tractography-based group mapping method was also used to investigate the probability and distribution of the optic radiation pathways. Our results showed that the measured optic radiation fiber tract volume was a range of about 0.16% and that the fractional anisotropy value was about 0.53. Moreover, the optic radiation probability fiber pathway that was determined with diffusion tensor tractography-based group mapping was able to detect the location relatively accurately. We believe that our methods and results are help- ful in the study of optic radiation fiber tract information.

Development of Three Dimensional Automatic Body Fat Measurement Software from CT, and Its Validation and Evaluation

Abdominal obesity describes the accumulation of excessive fat in the abdomen. It is known that depending on its distribution, visceral obesity presents a greater danger to health than subcutaneous obesity. To properly prevent and treat visceral obesity, accurate evaluation methods are necessary, and hence quantitative VAT estimation is extremely important. CT scans are the most accurate method for estimating VAT, but it requires a great deal of time and effort, limiting its use in studying or evaluating obesity in patients. This paper proposed automatic measurement software that could quickly differentiate between and measure VAT and SAT. The method was verified using a total of 100 abdominal CT data values;this paper measured the SAT and VAT in the entire abdomen using the automatic measurement software. Additionally, through a comparative evaluation between the automated measurements and manual measurements such as BMI and waist circumference, clinical reliability and viability were validated and evaluated. Between automated measurements and manual measurements, the TAT (r = 0.995, p = 0.01), SAT (r = 0.987, p = 0.01) and VAT (r = 0.993, p = 0.01) showed high correlation. Using BMI as the main metric, the TAT for automated measurements (r = 0.674, p = 0.01) and the TAT for manual measurements (r = 0.703, p = 0.01) showed the strongest correlation. When using waist circumference, the VAT for automated measurements (r = 0.826, p = 0.01) and the VAT for manual measurements (r = 0.822, p = 0.01) showed the strongest correlation. With these results, the reliability and viability of the automatic measurement software were confirmed. The software is expected to help greatly in reducing the time and in providing objective data of VAT measurements from CT scans for clinical research.

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8^(+)T cell responses

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy.However,the adverse side effects associated with agonist antibodies have hindered their clinical development.Here,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs.We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction.However,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γaxis.This was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T cells.Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.