Prostatic Arterial Embolization With Polyvinyl Alcohol(PVA) Electrospun Nanofibers In A Canine Model Of Benign Prostatic Hyperplasia(BPH)

Part ? Establishment of a beagle canine model and feasibility of functional MR imaging of benign prostatic hyperplasiaObjective:To establish a beagle canine model of testosterone propionate(TP)-induced benign prostatic hyperplasia(BPH)and to assess the feasibility of functional MR imaging.Materials and Methods:The study was approved by the institutional ethics committee for animal research.Sixteen beagle dogs were randomly assigned to the model group(n=8)or control group(n=8).The beagle dogs in the model group were castrated by an urologist.Intramuscular Benzylpenicillin(1,600,000 IU)was injected daily for three days to prevent infection.After one month,2.5 mg/kg of TP were injected intramuscularly daily for 3 months.All beagle dogs underwent 3T MRI(Magnetom Skyra,Siemens Medical Solutions,Erlangen.Germany).The dogs were positioned lower limbs first,prone position with a 20-channel transmit/receive(TX/RX)head coil around the prostate for image acquisition under general anesthesia.The prostatic volume(PV)of all dogs was measured on MRI before and at 3 months after initiation of hormone administration.For each dog,an MRI examination protocol consisted of sagittal,coronal,and axial T1-weighted imaging(T1 WI),T2-weighted imaging(T2WI),3D sampling perfection with application of optimized contrasts using different flip angle evolutions(3D-SPACE),diffusion weighted imaging(DWI).diffusion tensor imaging(DTI),susceptibility-weighted imaging(SWI).and T2-mapping.The image quality was assessed by two observers independently.Samples paired t test was used to compare the PV between the baseline 1 month after surgical castration and the data collected 3 months after hormonal therapy.The t test was applied in the intergroup comparison.P<0.05 was used to indicate a significant difference.Inter-reader agreement for the image quality was assessed with Cohen's Kappa test.Results:The canine BPH model was successfully established in model group.The mean PV was(3.99 ± 1.74)cm3 in model group and(4.12± 0.92)cm3 in control group before hormone administration.The mean PV increased significantly after 3 months of hormone administration,which was(17.60 ± 1.42)cm3 in model group and(4.29 ± 0.88)cm3 in control group.The PV has no great change in control group(P?0.05).The signal-to-noise ratio and spatial resolution of each MR sequence was good.Conclusion:A beagle canine model of TP-induce BPH is successfully established.3.0 T MRI may facilitate noninvasive assessment of morphological and functional changes of BPH model.Part ? Prostatic arterial embolization with polyvinyl alcohol electrospun nanofibers in a canine model of benign prostatic hyperplasia(BPH):preliminary studyObjective:To explore the safety,feasibility and efficacy of embolization with polyvinyl alcohol(PVA)electrospun nanofibers in a canine model of benign prostatic hyperplasia(BPH).Materials and Methods:Five adult male beagle dogs(Beagle A,Beagle B,Beagle C,Beagle D,Beagle E)were included in this study.All beagle dogs were randomly numbered.The beagle dogs were castrated by an urologist.Intramuscular Benzylpenicillin(1,600,000 IU)was injected daily for three days to prevent infection.After one month,2.5 mg/kg of TP were injected intramuscularly daily for 3 months.All beagle dogs underwent 3T MRI.The prostatic volume(PV)of all dogs was measured on MRI before and at 3 months after initiation of hormone administration.All beagle dogs underwent prostatic arterial embolization(PAE)after 3 months of hormone administration.PAE was performed with superselective catheterization of the prostatic artery on each side through a femoral artery puncture after 3 months of TP therapy.Embolization was performed with the use of homemade 150-200 ?m polyvinyl alcohol(PVA)electrospun nanofibers.Beagle A,Beagle B,Beagle C was sacrificed by rapid intravenous injection of 20mL potassium chloride solution under anesthesia 1 week,1 month,3 months after PAE,respectively.Beagle D and Beagle E were sacrificed in the same manner as described above 6 months after PAE.The prostates and surrounding tissues were harvested for histopathology study.Histopathologic study was performed by the urologic pathologist.In order to simulate the effect of androgen levels on the dogs and distinguish the effect of PAE,2.5 mg/kg of TP was injected intramuscularly daily after PAE until the end of the experiment.Results:The canine BPH model was successfully established in all five dogs.The mean PV increased significantly after 3 months of hormone administration.Digital subtraction angiography(DSA)clearly depicted of the prostatic arteries after 3 months of hormone administration.PAE was successfully performed using Roberts uterine cather in all five dogs.No serious PAE-related complication was observed during and after the procedure.In all five dogs,no significant abnormalities were found in the bladder,the ureters,vas deferens,urethra,sigmoid,or rectum.Under the microscope,the PVA electrospun nanofibers in blood vessels with no spillover,mild inflammation in the prostate,and neutrophils and mononuclear cell infiltration around blood vessel were found in Beagle A 1 week after PAE.The prostate of Beagle B 1 month after PAE showed cystic changes,atrophied gland,decreased inflammatory cells,more fibroblasts,focal hemosiderin deposition,and no evidence of neocapillarization.The prostate gland sections were gray,which revealed cystic portions of various sizes in the prostates of Beagle C,Beagle D and Beagle E.The parenchyma around the cavity showed atrophy under the microscope.In addition,focal hemosiderin deposition,scattered inflammatory cell infiltration,and fibrosis were found.Remnants of the glandular hyperplasia and embolic particles in blood vessels of the gland were present.Tunica intima and tunica media of the vessel walls was thickened with hyaline degeneration.The blood vessels lumen was reduced markedly.Conclusion:PAE with PVA electrospun nanofibers in a canine model of BPH is feasible,effective and safe.Part III Prostatic arterial embolization in a canine model of benign prostatic hyperplasia:a 3T multi-parametric MR imaging and whole-mount step-section pathology correlated longitudinal studyPurpose:To explore the morphological and functional characteristics of prostatic arterial embolization(PAE)in a canine model of benign prostatic hyperplasia(BPH)with 3T multi-parametric MR imaging(mp-MRI)and whole-mount step-section pathology correlation.Materials and Methods:Eight adult male beagle dogs with hormone-induced BPH underwent 3T mp-MRI before and 1,3 and 6 months after PAE,with subsequent whole-mount step-section pathologic assessment.Images were acquired using the following sequences:T1WI.T2WI.3D-SPACE,DWI.SWI,T2-mapping.DCE.Variance analysis was performed to assess statistical differences in prostatic volume(PV),apparent diffusion coefficient(ADC)value,and T2 value.Pearson correlation analysis was performed to correlate ADC value,T2 value and PV,respectively.Results:The PV decreased from baseline to 1,3 and 6 months after PAE from(25.88 ± 7.09)cm3 to(6.48 ± 2.08)cm3(6.48 ± 3.39)cm3,(6.20 ±2.88)cm3.The ADC values sequentially decreased from baseline to 1,3 and 6 months after PAE from(1497.06 ± 222.72)× 10-6 mmM2/s,(1056.00 ± 189.46)× 10-6 mm2/s,(950.48 ±77.85)× 10-6 mm2/s to(980.98± 107.78)×10-6mm2/s,respectively.The T2 values decreased from baseline to 1,3 and 6 months after PAE were(83.74 ± 5.29)ms.(68.72 ± 5.66)ms,(53.9 ± 15.04)ms,(49.81 ± 13.34)ms,respectively.ADC and T2 values were positively correlated with PV(r=0.823 and 0.744,respectively).Micro-hemorrhages and hemosiderin were found in all beagle dogs on SWI after PAE.Conclusion:3T mp-MRI may facilitate noninvasive assessment of longitudinal morphological and functional changes of BPH after PAE.