The post-hepatectomy recurrence rate of hepatocellular carcinoma(HCC)is persistently high,affecting the prognosis of patients.An effective therapeutic option is crucial for achieving long-term survival in patients wit...The post-hepatectomy recurrence rate of hepatocellular carcinoma(HCC)is persistently high,affecting the prognosis of patients.An effective therapeutic option is crucial for achieving long-term survival in patients with postoperative recurrences.Local ablative therapy has been established as a treatment option for resectable and unresectable HCCs,and it is also a feasible approach for recurrent HCC(RHCC)due to less trauma,shorter operation times,fewer complications,and faster recovery.This review focused on ablation techniques,description of potential candidates,and therapeutic and prognostic implications of ablation for guiding its application in treating intrahepatic RHCC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new...BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.展开更多
Hepatocellular carcinoma(HCC)is the most common primary malignant liver tumor in China.Preoperative diagnosis of HCC is challenging because of atypical imaging manifestations and the diversity of focal liver lesions.A...Hepatocellular carcinoma(HCC)is the most common primary malignant liver tumor in China.Preoperative diagnosis of HCC is challenging because of atypical imaging manifestations and the diversity of focal liver lesions.Artificial intelligence(AI),such as machine learning(ML)and deep learning,has recently gained attention for its capability to reveal quantitative information on images.Currently,AI is used throughout the entire radiomics process and plays a critical role in multiple fields of medicine.This review summarizes the applications of AI in various aspects of preoperative imaging of HCC,including segmentation,differential diagnosis,prediction of histo-pathology,early detection of recurrence after curative treatment,and evaluation of treatment response.We also review the limitations of previous studies and discuss future directions for diagnostic imaging of HCC.展开更多
17-4PH stainless steel powders were prepared using a supersonic nozzle in a close-coupled gas atomization system. The characteristics of powder particles were carried out by means of a laser particle size analyzer, sc...17-4PH stainless steel powders were prepared using a supersonic nozzle in a close-coupled gas atomization system. The characteristics of powder particles were carried out by means of a laser particle size analyzer, scanning electron microscopy (SEM), and the X-ray diffraction (XRD) technique. The results show that the mass median particle diameter is about 19.15 μm. Three main types of surface microstructures are observed in the powders: well-developed dendrite, cellular, and cellular dendrite structure. The XRD measurements show that, as the particle size decreases, the amount of fcc phase gradually decreases and that of bcc phase increases. The cooling rate is inversely related to the particle size, i.e., it decreases with an increase in particle size.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinica...BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.展开更多
BACKGROUND Desmoid fibroma is a rare soft tissue tumor originating from the aponeurosis,fascia,and muscle,and it is also known as aponeurotic fibroma,invasive fibroma,or ligamentous fibroma.AIM To investigate the clin...BACKGROUND Desmoid fibroma is a rare soft tissue tumor originating from the aponeurosis,fascia,and muscle,and it is also known as aponeurotic fibroma,invasive fibroma,or ligamentous fibroma.AIM To investigate the clinical and imaging features of desmoid tumors of the extremities.METHODS Thirteen patients with desmoid fibroma of the extremities admitted to our hospital from October 2016 to March 2021 were included.All patients underwent computed tomography(CT),magnetic resonance imaging(MRI),and pathological examination of the lesion.Data on the diameter and distribution of the lesion,the relationship between the lesion morphology and surrounding structures,MRI and CT findings,and pathological features were statistically analyzed.RESULTS The lesion diameter ranged from 1.7 to 8.9 cm,with an average of 5.35±2.39 cm.All lesions were located in the deep muscular space,with the left and right forearm each accounting for 23.08%of cases.Among the 13 patients with desmoid fibroma of the extremities,the lesions were"patchy"in 1 case,irregular in 10,and quasi-round in 2.The boundary between the lesion and surrounding soft tissue was blurred in 10 cases,and the focus infiltrated along the tissue space and invaded the adjacent structures.Furthermore,the edge of the lesion showed"beard-like"infiltration in 2 cases;bone resorption and damage were found in 8,and bending of the bone was present in 2;the boundary of the focus was clear in 1.According to the MRI examination,the lesions were larger than 5 cm(61.54%),round or fusiform in shape(84.62%),had an unclear boundary(76.92%),showed uniform signal(69.23%),inhomogeneous enhancement(84.62%),and"root"or"claw"infiltration(69.23%).Neurovascular tract invasion was present in 30.77%of cases.CT examination showed that the desmoid tumors had slightly a lower density(69.23%),higher enhancement(61.54%),and unclear boundary(84.62%);a CT value<50 Hu was present in 53.85%of lesions,and the enhancement was uneven in 53.85%of cases.Microscopically,fibroblasts and myofibroblasts were arranged in strands and bundles,without obvious atypia but with occasional karyotyping;cells were surrounded by collagen tissue.There were disparities in the proportion of collagen tissue in different regions,with abundant collagen tissue and few tumor cells in some areas,similar to the structure of aponeuroses or ligaments,and tumor cells invading the surrounding tissues.CONCLUSION Desmoid tumors of the extremities have certain imaging features on CT and MRI.The two imaging techniques can be combined to improve the diagnostic accuracy,achieve a comprehensive diagnosis of the disease in the clinical practice,and reduce the risk of missed diagnosis or misdiagnosis.In addition,their use can ensure timely diagnosis and treatment.展开更多
基金Supported by the National Key Research and Development Program of China,No.2020AAA0109503.
文摘The post-hepatectomy recurrence rate of hepatocellular carcinoma(HCC)is persistently high,affecting the prognosis of patients.An effective therapeutic option is crucial for achieving long-term survival in patients with postoperative recurrences.Local ablative therapy has been established as a treatment option for resectable and unresectable HCCs,and it is also a feasible approach for recurrent HCC(RHCC)due to less trauma,shorter operation times,fewer complications,and faster recovery.This review focused on ablation techniques,description of potential candidates,and therapeutic and prognostic implications of ablation for guiding its application in treating intrahepatic RHCC.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2016-I2M-1-001PUMC Youth Fund,No.2017320010+1 种基金Chinese Academy of Medical Sciences Research Fund,No.ZZ2016B01Beijing HopeRun Special Fund of Cancer Foundation of China,No.LC2016B15
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.
基金CAMS Innovation Fund for Medical Sciences(CIFMS),No.2016-I2M-1-001PUMC Youth Fund,No.2017320010+2 种基金Chinese Academy of Medical Sciences(CAMS)Research Fund,No.ZZ2016B01Beijing HopeRun Special Fund of Cancer Foundation of China,No.LC2016B15PUMC Postgraduate Education and Teaching Reform Fund,No.10023201900303.
文摘Hepatocellular carcinoma(HCC)is the most common primary malignant liver tumor in China.Preoperative diagnosis of HCC is challenging because of atypical imaging manifestations and the diversity of focal liver lesions.Artificial intelligence(AI),such as machine learning(ML)and deep learning,has recently gained attention for its capability to reveal quantitative information on images.Currently,AI is used throughout the entire radiomics process and plays a critical role in multiple fields of medicine.This review summarizes the applications of AI in various aspects of preoperative imaging of HCC,including segmentation,differential diagnosis,prediction of histo-pathology,early detection of recurrence after curative treatment,and evaluation of treatment response.We also review the limitations of previous studies and discuss future directions for diagnostic imaging of HCC.
基金financially supported by the National High-Tech Research and Development Program of China (No. 2009AA033901)the National Natural Science Foundation of China (No. 51004019)
文摘17-4PH stainless steel powders were prepared using a supersonic nozzle in a close-coupled gas atomization system. The characteristics of powder particles were carried out by means of a laser particle size analyzer, scanning electron microscopy (SEM), and the X-ray diffraction (XRD) technique. The results show that the mass median particle diameter is about 19.15 μm. Three main types of surface microstructures are observed in the powders: well-developed dendrite, cellular, and cellular dendrite structure. The XRD measurements show that, as the particle size decreases, the amount of fcc phase gradually decreases and that of bcc phase increases. The cooling rate is inversely related to the particle size, i.e., it decreases with an increase in particle size.
基金Supported by PUMC Youth Fund,No. 2017320010Chinese Academy of Medical Sciences (CAMS) Research Fund,No. ZZ2016B01Beijing Hope Run Special Fund of Cancer Foundation of China,No. LC2016B15
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality.HCC-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide nanoparticles.However,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast.Ultra-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast agents.We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro.AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODS The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model.Following intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h post-injection.At the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor samples.RESULTS T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection levels.Additionally,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,respectively.Comparison of U-,UA-,UG-,and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG-or UA-treated mice.CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe(UAG)for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.
基金the Cancer Hospital of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences Institutional Review Board(Approval No.20/120-2316).
文摘BACKGROUND Desmoid fibroma is a rare soft tissue tumor originating from the aponeurosis,fascia,and muscle,and it is also known as aponeurotic fibroma,invasive fibroma,or ligamentous fibroma.AIM To investigate the clinical and imaging features of desmoid tumors of the extremities.METHODS Thirteen patients with desmoid fibroma of the extremities admitted to our hospital from October 2016 to March 2021 were included.All patients underwent computed tomography(CT),magnetic resonance imaging(MRI),and pathological examination of the lesion.Data on the diameter and distribution of the lesion,the relationship between the lesion morphology and surrounding structures,MRI and CT findings,and pathological features were statistically analyzed.RESULTS The lesion diameter ranged from 1.7 to 8.9 cm,with an average of 5.35±2.39 cm.All lesions were located in the deep muscular space,with the left and right forearm each accounting for 23.08%of cases.Among the 13 patients with desmoid fibroma of the extremities,the lesions were"patchy"in 1 case,irregular in 10,and quasi-round in 2.The boundary between the lesion and surrounding soft tissue was blurred in 10 cases,and the focus infiltrated along the tissue space and invaded the adjacent structures.Furthermore,the edge of the lesion showed"beard-like"infiltration in 2 cases;bone resorption and damage were found in 8,and bending of the bone was present in 2;the boundary of the focus was clear in 1.According to the MRI examination,the lesions were larger than 5 cm(61.54%),round or fusiform in shape(84.62%),had an unclear boundary(76.92%),showed uniform signal(69.23%),inhomogeneous enhancement(84.62%),and"root"or"claw"infiltration(69.23%).Neurovascular tract invasion was present in 30.77%of cases.CT examination showed that the desmoid tumors had slightly a lower density(69.23%),higher enhancement(61.54%),and unclear boundary(84.62%);a CT value<50 Hu was present in 53.85%of lesions,and the enhancement was uneven in 53.85%of cases.Microscopically,fibroblasts and myofibroblasts were arranged in strands and bundles,without obvious atypia but with occasional karyotyping;cells were surrounded by collagen tissue.There were disparities in the proportion of collagen tissue in different regions,with abundant collagen tissue and few tumor cells in some areas,similar to the structure of aponeuroses or ligaments,and tumor cells invading the surrounding tissues.CONCLUSION Desmoid tumors of the extremities have certain imaging features on CT and MRI.The two imaging techniques can be combined to improve the diagnostic accuracy,achieve a comprehensive diagnosis of the disease in the clinical practice,and reduce the risk of missed diagnosis or misdiagnosis.In addition,their use can ensure timely diagnosis and treatment.
