Effect of convection enhanced delivery on the microstructure of brain extracellular space in aged rats / 北京大学学报(医学版)

OBJECTIVE@#To compare the changes of extracellular space (ECS) structure and local drug distribution in adult brain and aged brain at different drug delivery rates in minimally invasive treatment of encephalopathy by convection enhanced delivery (CED) via ECS pathway.@*METHODS@#Thirty-six SD male rats were divided into adult rats group (2-8 months, n=18) and aged rats group (18-24 months, n=18) according to the age of the month. According to the drug rates (0.1 μL/min, 0.2 μL/min, and 0.3 μL/min), they were randomly divided into 3 subgroups, 6 in each subgroup. Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) with a concentration of 10 mmol/L were introduced into the caudate nucleus of each group of rats by stereotactic injection. Tracer-based magnetic resonance imaging (MRI) was used to dynamically monitor the diffusion and distribution images of the Gd-DTPA in the brain interstitial system (ISS). Using the self-developed MRI image measurement and analysis system software to process and analyze the obtained images, the diffusion coefficient, clearance rate, volume fraction, and half-life of each group of rats in the caudate nucleus ECS could be acquired. The effects and differences of drug clearance and ECS structural function in the brain of aged rats and adult rats were compared and analyzed at different drug delivery rates. Magnetic tracer DECS-mapping technique was used to observe the distribution and drainage of tracer in caudate nucleus.@*RESULTS@#At the injection rate of 0.1 μL/min, the volume fraction in the aged rats was increased compared with that in the adult rats (18.20%±0.04% vs. 17.20%±0.03%, t=3.752, P=0.004), and the degree of tortuosity was decreased (1.63±0.04 vs. 1.78±0.09, t=-3.680, P=0.004), the drug clearance rate was decreased [(1.94±0.68) mm2/s vs. (3.25±0.43) mm2/s, t=-3.971, P=0.003], and the molecular diffusion in ECS was increased [(3.99±0.21)×10-4 mm2/s vs. (3.36±0.37)×10-4 mm2/s, t=3.663, P=0.004]. When the rate of injection increased to 0.2 μL/min, the drug clearance in ECS of the aged rats was slowed down [(2.53±0.45) mmol/L vs. (3.37±0.72) mmol/L, t=-1.828, P=0.021]. However, there were no significant differences in volume fraction, molecular diffusion in ECS and macroscopic drug metabolism parameters. When the rate of injection increased to 0.3 μL/min, the volume fraction in the aged rats was decreased (17.20%±0.03% vs. 18.20%±0.05%, t=-0.869, P=0.045), and the drug clearance rate in ECS was significantly accelerated [(4.04±0.76) mmol/L vs. (3.26±0.55) mmol/L, t=1.786, P=0.014], and there was no significant difference in tortuosity and the rate of molecular diffusion in the ECS.@*CONCLUSION@#The drug clearance and ECS structural parameters of brain ECS in aged brain with CED administration were changed at different rates, and it has the least effect on ECS in the aged brain at the injection rate of 0.2 μL/min. For the application of CED for the treatment of encephalopathy, we should consider the influence of factors such as age and injection rate, and provide reference for the development of individualized clinical treatment plan for minimally invasive treatment of encephalopathy via ECS pathway.

Application of computed tomography virtual noncontrast spectral imaging in evaluation of hepatic metastases: a preliminary study / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography (CT) virtual noncontrast (VNC) spectral imaging in a retrospective analysis.</p><p><b>METHODS</b>Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast (TNC) and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial, portal venous, and equilibrium phases. The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial (VNCa), venous (VNCv), and equilibrium (VNCe) phase by the material decomposition process using water and iodine as a base material pair. The image quality and the contrast-to-noise ratio (CNR) of metastasis of the four groups were compared with ANOVA analysis. The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chi-square test.</p><p><b>RESULTS</b>There were no significant differences in image quality among TNC, VNCa and VNCv images (P > 0.05). The quality of VNCe images was significantly worse than that of other three groups (P < 0.05). The mean CNR of metastasis in the TNC and VNCs images was 1.86, 2.42, 1.92, and 1.94, respectively; the mean CNR of metastasis in VNCa images was significantly higher than that in other three groups (P < 0.05), while no statistically significant difference was observed among VNCv, VNCe and TNC images (P > 0.05). The metastasis detection rate of the four nonenhanced groups with no statistically significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>The quality of VNCa and VNCv images is identical to that of TNC images, and the metastasis detection rate in VNC images is similar to that in TNC images. VNC images obtained from arterial phase show metastases more clearly. Thus, VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.</p>

AGM region and hematopoiesis during ontogeny--review / 中国实验血液学杂志

During mammalian ontogeny, hematopoietic activity can be found in distinct anatomical sites, which con-tribute to primitive or definite hematopoiesis. The origin of the hematopoietic stem cell (HSC) has been a controversial issue in the field of hematopoiesis. It has long been believed that the origin derives from the extra-embryonic yolk sac. However, there is now considerable evidence that the first adult repopulating HSC is autonomously generated from a distinct region within the embryonic mesoderm, the aorta-gonad-mesonephros (AGM) region. This review describes the origin and precise location of HSC in the embryo and in AGM region, the hematopoietic microenvironment and the hematopoietic regulatory mechanisms in AGM region.