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Kawamura Y, Itou H, Kida A, Sunakawa H, Suzuki M, Kawamura K. Therapeutic response and prognostic factors of 14 dogs undergoing transcatheter arterial embolization for hepatocellular masses: A retrospective study. J Vet Intern Med 2023; 37:1455-1465. [PMID: 37224273 PMCID: PMC10365048 DOI: 10.1111/jvim.16746] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 05/07/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Information regarding the therapeutic effect and outcome of transcatheter arterial embolization (TAE) for hepatic masses is limited in veterinary medicine. HYPOTHESIS/OBJECTIVES To analyze the therapeutic response, outcome (overall survival), and their predictors in dogs that underwent TAE for primary hepatocellular masses. We hypothesized that larger pre-TAE tumors would be associated with worse outcomes. ANIMALS Fourteen client-owned dogs. METHODS Retrospective study. Medical records between 1 September 2016 and 30 April 2022 were reviewed to identify dogs treated with TAE for hepatic masses diagnosed as hepatocellular origin by cytological or histopathological examination. Computed tomography images were compared before and after TAE. The univariate Cox proportional hazards test was performed to assess the associations between variables and survival. Univariate linear regression analysis was performed to assess the associations between variables and the tumor reduction percentage: ([post-TAE volume - pre-TAE volume]/pre-TAE volume) × 100. RESULTS The median survival time was 419 days (95% confidence interval, 82-474). History of intra-abdominal hemorrhage (P = .03) and pre-TAE tumor volume/body weight (P = .009) were significantly associated with overall survival. The mean reduction percentage was -51% ± 40%. Pre-TAE tumor volume/body weight ratio (cm3 /kg; P = .02, correlation coefficient = 0.704) was significantly correlated with the volume reduction percentage. CONCLUSIONS History of intra-abdominal hemorrhage and large pre-TAE tumor volume/body weight ratio could be predictive factors for adverse outcomes after TAE. Pre-TAE tumor volume/body weight ratio could be a predictive factor for therapeutic effect.
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Affiliation(s)
- Yuta Kawamura
- Kawamura Animal HospitalNiigata CityJapan
- Department of Radiology, Division of Diagnostic Radiology, Faculty of MedicineYamagata UniversityIida‐NishiJapan
| | | | | | | | - Moe Suzuki
- Kawamura Animal HospitalNiigata CityJapan
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Can Dynamic Contrast-Enhanced CT Quantify Perfusion in a Stimulated Muscle of Limited Size? A Rat Model. Clin Orthop Relat Res 2020; 478:179-188. [PMID: 31794491 PMCID: PMC7000042 DOI: 10.1097/corr.0000000000001045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Muscle injury may result in damage to the vasculature, rendering it unable to meet the metabolic demands of muscle regeneration and healing. Therefore, therapies frequently aim to maintain, restore, or improve blood supply to the injured muscle. Although there are several options to assess the vascular outcomes of these therapies, few are capable of spatially assessing perfusion in large volumes of tissue. QUESTIONS/PURPOSES Can dynamic contrast-enhanced CT (DCE-CT) imaging acquired with a clinical CT scanner be used in a rat model to quantify perfusion in the anterior tibialis muscle at spatially relevant volumes, as assessed by (1) the blood flow rate and tissue blood volume in the muscle after three levels of muscle stimulation (low, medium, and maximum) relative to baseline as determined by the non-stimulated contralateral leg; and (2) how do these measurements compare with those obtained by the more standard approach of microsphere perfusion? METHODS The right anterior tibialis muscles of adult male Sprague Dawley rats were randomized to low- (n = 10), medium- (n = 6), or maximum- (n = 3) level (duty cycles of 2.5%, 5.0%, and 20%, respectively) nerve electrode coupled muscle stimulation directly followed by DCE-CT imaging. Tissue blood flow and blood volume maps were created using commercial software and volumetrically measured using NIH software. Although differences in blood flow were detectable across the studied levels of muscle stimulation, a review of the evidence suggested the absolute blood flow quantified was underestimated. Therefore, at a later date, a separate set of adult male Sprague Dawley rats were randomized for microsphere perfusion (n = 7) to define blood flow in the animal model with an accepted standard. With this technique, intra-arterial particles sized to freely flow in blood but large enough to lodge in tissue capillaries were injected. Simultaneously, blood sampling at a fixed flow rate was simultaneously performed to provide a fixed blood flow rate sample. The tissues of interest were then explanted and assessed for the total number of particles per tissue volume. Tissue blood flow rate was then calculated based on the particle count ratio within the reference sample. Note that a tissue's blood volume cannot be calculated with this method. Comparison analysis to the non-stimulated baseline leg was performed using two-tailed paired student t-test. An ANOVA was used to compare difference between stimulation groups. RESULTS DCE-CT measured (mean ± SD) increasing tissue blood flow differences in stimulated anterior tibialis muscle at 2.5% duty cycle (32 ± 5 cc/100 cc/min), 5.0% duty cycle (46 ± 13 cc/100 cc/min), and 20% duty cycle (73 ± 3 cc/100 cc/min) compared with the paired contralateral non-stimulated anterior tibialis muscle (10 ± 2 cc/100 cc/min, mean difference 21 cc/100 cc/min [95% CI 17.08 to 25.69]; 9 ± 1 cc/100 cc/min, mean difference 37 cc/100 cc/min [95% CI 23.06 to 50.11]; and 11 ± 2 cc/100 cc/min, mean difference 62 cc/100 cc/min [95% CI 53.67 to 70.03]; all p < 0.001). Similarly, DCE-CT showed increasing differences in tissue blood volumes within the stimulated anterior tibialis muscle at 2.5% duty cycle (23.2 ± 4.2 cc/100 cc), 5.0% duty cycle (39.2 ± 7.2 cc/100 cc), and 20% duty cycle (52.5 ± 13.1 cc/100 cc) compared with the paired contralateral non-stimulated anterior tibialis muscle (3.4 ± 0.7 cc/100 cc, mean difference 19.8 cc/100 cc [95% CI 16.46 to 23.20]; p < 0.001; 3.5 ± 0.4 cc/100 cc, mean difference 35.7 cc/100 cc [95% CI 28.44 to 43.00]; p < 0.001; and 4.2 ± 1.3 cc/100 cc, mean difference 48.3 cc/100 cc [95% CI 17.86 to 78.77]; p = 0.010). Microsphere perfusion measurements also showed an increasing difference in tissue blood flow in the stimulated anterior tibialis muscle at 2.5% duty cycle (62 ± 43 cc/100 cc/min), 5.0% duty cycle (89 ± 52 cc/100 cc/min), and 20% duty cycle (313 ± 269 cc/100 cc/min) compared with the paired contralateral non-stimulated anterior tibialis muscle (8 ± 4 cc/100 cc/min, mean difference 55 cc/100 cc/min [95% CI 15.49 to 94.24]; p = 0.007; 9 ± 9 cc/100 cc/min, mean difference 79 cc/100 cc/min [95% CI 33.83 to 125.09]; p = 0.003; and 18 ± 18 cc/100 cc/min, mean difference 295 cc/100 cc/min [95% CI 8.45 to 580.87]; p = 0.023). Qualitative comparison between the methods suggests that DCE-CT values underestimate tissue blood flow with a post-hoc ANOVA showing DCE-CT blood flow values within the 2.5% duty cycle group (32 ± 5 cc/100 cc/min) to be less than the microsphere perfusion value (62 ± 43 cc/100 cc/min) with a mean difference of 31 cc/100 cc/min (95% CI 2.46 to 60.23; p = 0.035). CONCLUSIONS DCE-CT using a clinical scanner is a feasible modality to measure incremental changes of blood flow and tissue blood volume within a spatially challenged small animal model. Care should be taken in studies where true blood flow values are needed, as this particular small-volume muscle model suggests true blood flow is underestimated using the specific adaptions of DCE-CT acquisition and image processing chosen. CLINICAL RELEVANCE CT perfusion is a clinically available modality allowing for translation of science from bench to bedside. Adapting the modality to fit small animal models that are relevant to muscle healing may hasten time to clinical utility.
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Goode K, Weisse C, Berent A, Lamb K. Evaluation of hepatic tumor portal perfusion using mesenteric angiography: A pilot study in 5 dogs. J Vet Intern Med 2019; 33:776-782. [PMID: 30565353 PMCID: PMC6430931 DOI: 10.1111/jvim.15395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 11/16/2018] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Mesenteric angiography is a sensitive method for visualizing portal perfusion in the dog. OBJECTIVES To evaluate hepatic portal perfusion in dogs with incompletely resectable hepatic tumors using mesenteric angiography. ANIMALS Five client-owned dogs with incompletely resectable hepatic tumors evaluated with mesenteric angiography. METHODS Retrospective case series. Electronic medical records at the Animal Medical Center were analyzed to identify dogs that underwent mesenteric portography to determine blood flow to nonresectable hepatic tumors and subsequently determine ideal routes for transarterial embolization, vascular stent placement, or both. The images obtained from mesenteric angiography were analyzed and compared to those obtained from computed tomography angiography. RESULTS Portography was accomplished using direct mesenteric venography in 3 dogs with hepatocellular carcinoma (HCC), cranial mesenteric arteriography in 1 dog with hepatic adenoma or well-differentiated HCC, and via splenic arteriovenous fistula in 1 dog with diffuse hepatic hemangiosarcoma metastases. Mean pixel densities in areas of hepatic tumor growth identified statistically significant decreases in portal blood flow (P = .02) compared to normal hepatic parenchyma. CONCLUSIONS AND CLINICAL IMPORTANCE Initial findings indicate that the blood supply to large and metastatic hepatic tumors in dogs may correlate with that in humans, such that the majority of the tumor blood supply arises from the hepatic artery and not the portal vein. Differences in blood supply between normal hepatic parenchyma and hepatic tumors might be exploited by developing selective tumor therapies such as arterial embolization or chemoembolization that largely spare normal liver tissue. Further investigation is warranted.
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Affiliation(s)
- Kelsey Goode
- Department of Interventional RadiologyThe Animal Medical CenterNew YorkNew York
| | - Chick Weisse
- Department of Interventional RadiologyThe Animal Medical CenterNew YorkNew York
| | - Allyson Berent
- Department of Interventional RadiologyThe Animal Medical CenterNew YorkNew York
| | - Ken Lamb
- Lamb Statistical ConsultingWest St. PaulMinnesota
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A Combination of UTMD-Mediated HIF-1 α shRNA Transfection and TAE in the Treatment of Hepatic Cancer. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1937460. [PMID: 30911540 PMCID: PMC6399560 DOI: 10.1155/2019/1937460] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Revised: 11/08/2018] [Accepted: 12/31/2018] [Indexed: 01/08/2023]
Abstract
To explore the antitumor effect of hypoxia-inducible factor-1α short hairpin RNA (HIF-1α shRNA) delivered by ultrasound targeted microbubble destruction (UTMD) and transcatheter arterial embolization (TAE) on rats with hepatic cancer. After the models of transplantation hepatoma were established, Wistar rats were randomly divided into 4 groups: Control group, UTMD group, TAE group, and UTMD+TAE group. Contrast-enhanced ultrasound (CEUS) was used to monitor tumor size on day 14 after four different treatments. Western blotting and immunohistochemistry were applied to measure the protein level of HIF-1α and VEGF in the hepatic cancer tissue. In comparison with UTMD+TAE group (21.25±10.68 days), the mean survival time was noticeably shorter in the Control group and TAE group (13.02±4.30 days and 15.03±7.32 days) (p<0.05, respectively). There was no statistical difference between UTMD+TAE group and UTMD group of the mean survival time (p>0.05). In addition, our results proved that the tumor sizes in UTMD+TAE group were obviously smaller than those in other groups (p<0.05, respectively). By CEUS, we clearly found that the tumor size was the smallest on day 14 in the UTMD+TAE group. The western blotting and immunohistochemistry results proved that the protein levels of HIF-1α and VEGF in UTMD+TAE group were obviously lower than those in TAE group and Control group on days 7 and 14 (p<0.05, respectively). However, there was no statistical difference between UTMD+TAE group and UTMD group (p>0.05). In this study we tried to explore the antitumor effect through a combination of UTMD-mediated HIF-1α shRNA transfection and TAE on rats with hepatic cancer. Our results showed that UTMD-mediated HIF-1α shRNA transfection and TAE can obviously silence HIF-1α and VEGF expression, thereby successfully inhibiting the growth of the tumor.
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Fang M, Mei X, Yao H, Zhang T, Zhang T, Lu N, Liu Y, Xu W, Wan C. β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine in vitro and in vivo. Oncol Lett 2018; 15:3957-3964. [PMID: 29467906 DOI: 10.3892/ol.2018.7788] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Accepted: 09/27/2017] [Indexed: 02/05/2023] Open
Abstract
The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine in vitro as well as in in vivo. Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%). Furthermore, β-elemene-ligustrazine combination treatment resulted in the highest downregulation of G protein-coupled receptor 124, vascular endothelial growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein expression levels. In addition, the combined treatment led to an increase in the mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 in OS-732 cells. Additionally, β-elemene-ligustrazine caused a decrease in nuclear factor-κB, interleukin-8, C-X-C motif chemokine receptor 4 and urokinase-type plasminogen activator mRNA expression, as well as an increase in caspase-3, caspase-8, and caspase-9 mRNA expression. In vivo, the β-elemene-ligustrazine combination was able to reduce the weight and the bulk of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the results described above regarding changes to mRNA and protein expression were further confirmed in vivo in the tumor tissue of mice. The results of the present study have suggested that the combination of β-elemene-ligustrazine exhibits greater anticancer effects compared with β-elemene- or ligustrazine-alone treatment.
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Affiliation(s)
- Min Fang
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Xiaolong Mei
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Hui Yao
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Tao Zhang
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Tao Zhang
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Na Lu
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Yanshi Liu
- Department of Clinical Medicine, Tianjin Medical University, Tianjin 300270, P.R. China
| | - Wenyue Xu
- Department of Ultrasonography, Tianjin Liulin Hospital, Tianjin 300222, P.R. China
| | - Chunyou Wan
- Department of Trauma, Tianjin Hospital, Tianjin 300211, P.R. China
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Computed Tomography Perfusion Following Transarterial Chemoembolization of Hepatocellular Carcinoma: A Feasibility Study in the Early Period. J Comput Assist Tomogr 2017; 41:708-712. [PMID: 28296685 DOI: 10.1097/rct.0000000000000592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVES The aim of this study was to assess the feasibility of computed tomography (CT) perfusion in early follow-up after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). METHODS Fifteen patients with a total of 16 HCC who were referred to our institution for TACE were included in the study. Computed tomography perfusion was performed within 1 to 3 days before and 4 to 7 days after TACE. Multiphase contrast-enhanced CT was performed 35 (SD, 20) days after TACE. Hepatic arterial blood flow and portal venous blood flow, as well as the perfusion index (PI), were calculated for each HCC using the dual input maximum slope method. Visual grading of the PI and visual grading of the amount of deposition of embolic material within the HCC were performed using a 6-step scale. Differences in perfusion before and after TACE and correlation of perfusion before TACE with the amount of embolization material depositions 1 week and 1 month after TACE were tested. RESULTS No statistically significant correlation was found between pre-TACE perfusion parameters and the amount of embolization material deposition in the post-TACE studies. There was no statistically significant difference between pre- and post-TACE arterial blood flow and portal venous blood flow, whereas PI was significantly lower after TACE. Congruently, visual grading of PI was statistically significantly lower after TACE. There was no statistically significant difference in quantitative pre-TACE and post-TACE PI between tumors, which showed hypervascularization in the multiphase follow-up CT and tumors that did not show hypervascularization. However, tumors that showed hypervascularization in the multiphase follow-up CT had significantly higher visual grading of PI after TACE than tumors that did not show hypervascularization. CONCLUSIONS Our findings indicate that visual interpretation of the PI of HCC derived from dual-input maximum slope CT perfusion may be an early predictor of response to TACE.
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Kantarci M, Pirimoglu B. Radiological Response to the Locoregional Treatment in Hepatocellular Carcinoma: RECIST, mRECIST, and Others. J Gastrointest Cancer 2017. [PMID: 28624974 DOI: 10.1007/s12029-017-9969-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Mecit Kantarci
- Department of Radiology, Faculty of Medicine, Ataturk University, 25040, Erzurum, Turkey.
| | - Berhan Pirimoglu
- Department of Radiology, Faculty of Medicine, Ataturk University, 25040, Erzurum, Turkey
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Ni JY, Xu LF, Wang WD, Huang QS, Sun HL, Chen YT. Transarterial embolization combined with RNA interference targeting hypoxia-inducible factor-1α for hepatocellular carcinoma: a preliminary study of rat model. J Cancer Res Clin Oncol 2017; 143:199-207. [PMID: 27638772 DOI: 10.1007/s00432-016-2237-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 08/30/2016] [Indexed: 12/19/2022]
Abstract
PURPOSE To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery. The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting assays, respectively. RESULTS In vitro experiment, the specific HIF-1α-siRNA was proved to inhibit expression levels of HIF-1α and vascular endothelial growth factor (VEGF) effectively. In animal study, real-time RT-PCR assay showed the average relative mRNA expressions of HIF-1α were 0.31 ± 0.01, 0.65 ± 0.03, 0.46 ± 0.005, and 1.00 ± 0.00 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Western blotting assay showed the average relative protein expressions of HIF-1α were 0.13 ± 0.02, 0.87 ± 0.02, 0.39 ± 0.02, and 1.02 ± 0.01 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Compared with control, TAE, and siRNA groups, TAE + siRNA can significantly inhibit protein expressions of HIF-1α and VEGF (P HIF-1α < 0.001; P VEGF < 0.001). Overall survival of rats underwent TAE + siRNA was significantly longer than that of rats treated with TAE monotherapy (P = 0.001). CONCLUSION This animal study showed TAE combined with HIF-1α-RNAi could significantly improve efficacy of TAE in treating HCC by inhibiting expressions of HIF-1α and VEGF after TAE treatment.
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MESH Headings
- Animals
- Carcinoma, Hepatocellular/secondary
- Carcinoma, Hepatocellular/therapy
- Cell Line, Tumor
- Embolization, Therapeutic
- Gene Expression
- Gene Knockdown Techniques
- Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Liver Neoplasms, Experimental/pathology
- Liver Neoplasms, Experimental/therapy
- Lung Neoplasms/prevention & control
- Lung Neoplasms/secondary
- RNA Interference
- RNA, Small Interfering/genetics
- Rats, Sprague-Dawley
- Vascular Endothelial Growth Factor A/biosynthesis
- Vascular Endothelial Growth Factor A/genetics
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Affiliation(s)
- Jia-Yan Ni
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China
| | - Lin-Feng Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
| | - Wei-Dong Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China
| | - Qiao-Sheng Huang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China
| | - Hong-Liang Sun
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China
| | - Yao-Ting Chen
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China
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Shao GL, Zheng JP, Guo LW, Chen YT, Zeng H, Yao Z. Evaluation of efficacy of transcatheter arterial chemoembolization combined with computed tomography-guided radiofrequency ablation for hepatocellular carcinoma using magnetic resonance diffusion weighted imaging and computed tomography perfusion imaging: A prospective study. Medicine (Baltimore) 2017; 96:e5518. [PMID: 28099329 PMCID: PMC5279074 DOI: 10.1097/md.0000000000005518] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The purpose of this study is to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with computed tomography-guided radiofrequency ablation (CT-RFA) in the treatment of hepatocellular carcinoma (HCC) using magnetic resonance diffusion weighted imaging (MR-DWI) and CT perfusion imaging (CT-PI). METHODS From January 2008 to January 2014, a total of 522 HCC patients receiving TACE combined with CT-RFA were included in this study. All patients underwent TACE followed by CT-RFA, and 1 day before treatment and 1 month after treatment they received MR-DWI and CT-PI. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the concentration of alpha-fetoprotein (AFP). Tumor response was evaluated using the revised RECIST criteria. One-year follow-up was conducted on all patients. Receiver-operating characteristic (ROC) curve was drawn to evaluate the efficacy of TACE combined with CT-RFA for HCC using MR-DWI and CT-PI. RESULTS Total effective rate (complete remission [CR] + partial remission [PR]) of TACE combined with CT-RFA for HCC was 82.95%. HCC patients of CR + PR had lower hepatic blood flow (HBF), hepatic blood volume (HBV), permeability surface (PS), hepatic arterial perfusion (HAP), and hepatic perfusion index (HPI) levels than those of SD + PD, but HCC patients of CR + PR had higher mean transit time (MTT) level than those of SD + PD. The patients of PR + CR had higher apparent diffusion coefficient (ADC) values than those of SD + PD. The patients of PR + CR showed lower AFP concentration than those of SD + PD. ROC curve analysis indicated that the area under the curve (AUC) of AFP, HBV, PS, HAP, HPI, and ADC was more than 0.7, but the AUC of HBF, MTT, and PVP were less than 0.7. After treatment, the AFP, HBF, HBV, PS, HAP, and HPI in the HCC patients with recurrence were higher than those in the HCC patients without, but MTT and ADC in the HCC patients with recurrence were lower than those in the HCC patients without. CONCLUSION These findings indicate that MR-DWI and CT-PI can effectively evaluate the efficacy of TACE combined with CT-RFA and postoperative recurrence of HCC.
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Yang K, Zhang XM, Yang L, Xu H, Peng J. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2016; 22:4835-4847. [PMID: 27239110 PMCID: PMC4873876 DOI: 10.3748/wjg.v22.i20.4835] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 03/29/2016] [Accepted: 04/20/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed.
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Hepatocellular Carcinoma Screening With Computed Tomography Using the Arterial Enhancement Fraction With Radiologic-Pathologic Correlation. Invest Radiol 2016; 51:25-32. [DOI: 10.1097/rli.0000000000000201] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Advanced Hepatocellular Carcinoma: Perfusion Computed Tomography-Based Kinetic Parameter as a Prognostic Biomarker for Prediction of Patient Survival. J Comput Assist Tomogr 2015. [PMID: 26222909 DOI: 10.1097/rct.0000000000000288] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The aim of this study was to find prognostic biomarkers in perfusion computed tomography (PCT)-based kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic chemotherapy. METHODS Twenty-two patients with advanced HCC underwent PCT imaging and subsequently received bevacizumab in combination with gemcitabine and oxaliplatin. Pretreatment PCT data within advanced HCC were analyzed using the Tofts-Kety, 2-compartment exchange, adiabatic approximation to the tissue homogeneity (AATH), and distributed parameter models. Blood flow, blood volume, extraction fraction (E), and other 3 parameters were calculated. Kinetic parameters in each model were evaluated with 1-year survival discrimination using Kaplan-Meier analysis and with overall survival using univariate Cox regression analysis. RESULTS Only the AATH model-derived E was statistically significantly prognostic for 1-year survival. The increased AATH model-derived E was significantly associated with longer overall survival (P = 0.005). CONCLUSIONS The AATH model-derived E was an effective prognostic biomarker for advanced HCC.
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Chen CS, Zhao Q, Qian S, Li HL, Guo CY, Zhang W, Yan ZP, Liu R, Wang JH. Ultrasound-guided RNA interference targeting HIF-1 alpha improves the effects of transarterial chemoembolization in rat liver tumors. Onco Targets Ther 2015; 8:3539-48. [PMID: 26664137 PMCID: PMC4669929 DOI: 10.2147/ott.s94800] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aim To investigate whether ultrasound-guided RNA interference (RNAi) targeting hypoxia-inducible factor-1alpha (HIF-1α) can enhance the efficacy of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma. Materials and methods Rats with orthotopic hepatocellular carcinoma were randomized to four groups and treated as follows: 1) control; 2) siHIF-1α; 3) TACE; 4) siHIF-1α+TACE. Lentivirus (4×108 transfection units) with or without small interfering RNA (siRNA) expression in 0.6 mL transduction reagent was injected into tumors using a standard 1 mL syringe under ultrasonic guidance. In the siHIF-1α+TACE and siHIF-1α groups, rats received siRNA-expressing lentivirus; the rats in the TACE and control groups received lentivirus without siRNA. TACE was performed by placing a microcatheter into the gastroduodenal artery. Results The median survival time, body weight, and tumor volume of the siHIF-1α+TACE group were better than those of the TACE, siHIF-1α, and control groups. A comparative analysis of the different treatment groups demonstrated that HIF-1α RNAi could downregulate the levels of HIF-1α and VEGF, inhibit tumor angiogenesis, and lessen metastases; all of these effects were enhanced by TACE. Conclusion HIF-1α RNAi, which was administered in vivo in liver tumors under ultrasound guidance, improved the efficacy of TACE in treating hepatocellular carcinoma in an animal model.
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Affiliation(s)
- Cheng-Shi Chen
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China ; Department of Radiology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, People's Republic of China
| | - Qing Zhao
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Sheng Qian
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Hai-Liang Li
- Department of Radiology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, People's Republic of China
| | - Chen-Yang Guo
- Department of Radiology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, People's Republic of China
| | - Wei Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Zhi-Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Jian-Hua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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Du F, Jiang R, Gu M, He C, Guan J. The clinical application of 320-detector row CT in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma. Radiol Med 2015; 120:690-4. [DOI: 10.1007/s11547-015-0523-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 02/09/2015] [Indexed: 02/06/2023]
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Kim SH, Kamaya A, Willmann JK. CT perfusion of the liver: principles and applications in oncology. Radiology 2014; 272:322-44. [PMID: 25058132 DOI: 10.1148/radiol.14130091] [Citation(s) in RCA: 127] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging-such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods-remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented.
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Affiliation(s)
- Se Hyung Kim
- From the Department of Radiology, Molecular Imaging Program at Stanford, School of Medicine, Stanford University, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621 (S.H.K., A.K., J.K.W.); and Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea (S.H.K.)
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Computed tomographic perfusion imaging for the prediction of response and survival to transarterial radioembolization of liver metastases. Invest Radiol 2014; 48:787-94. [PMID: 23748229 DOI: 10.1097/rli.0b013e31829810f7] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE The purpose of this study was to evaluate prospectively, in patients with liver metastases, the ability of computed tomographic (CT) perfusion to predict the morphologic response and survival after transarterial radioembolization (TARE). METHODS Thirty-eight patients (22 men; mean [SD] age, 63 [12] years) with otherwise therapy-refractory liver metastases underwent dynamic, contrast-enhanced CT perfusion within 1 hour before treatment planning catheter angiography, for calculation of the arterial perfusion (AP) of liver metastases, 20 days before TARE with Yttrium-90 microspheres. Treatment response was evaluated morphologically on follow-up imaging (mean, 114 days) on the basis of the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). Pretreatment CT perfusion was compared between responders and nonresponders. One-year survival was calculated including all 38 patients using the Kaplan-Meier curves; the Cox proportional hazard model was used for calculating predictors of survival. RESULTS Follow-up imaging was not available in 11 patients because of rapidly deteriorating health or death. From the remaining 27, a total of 9 patients (33%) were classified as responders and 18 patients (67%) were classified as nonresponders. A significant difference in AP was found on pretreatment CT perfusion between the responders and the nonresponders to the TARE (P < 0.001). Change in tumor size on the follow-up imaging correlated significantly and negatively with AP before the TARE (r = -0.60; P = 0.001). Receiver operating characteristics analysis of AP in relation to treatment response revealed an area under the curve of 0.969 (95% confidence interval, 0.911-1.000; P < 0.001). A cutoff AP of 16 mL per 100 mL/min was associated with a sensitivity of 100% (9/9) (95% CI, 70%-100%) and a specificity of 89% (16/18) (95% CI, 62%-96%) for predicting therapy response. A significantly higher 1-year survival after the TARE was found in the patients with a pretreatment AP of 16 mL per 100 mL/min or greater (P = 0.028), being a significant, independent predictor of survival (hazard ratio, 0.101; P = 0.015). CONCLUSIONS Arterial perfusion of liver metastases, as determined by pretreatment CT perfusion imaging, enables prediction of short-term morphologic response and 1-year survival to TARE.
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Moserle L, Jiménez-Valerio G, Casanovas O. Antiangiogenic Therapies: Going beyond Their Limits. Cancer Discov 2013; 4:31-41. [DOI: 10.1158/2159-8290.cd-13-0199] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Hao XJ, Li JP, Jiang HJ, Li DQ, Ling ZS, Xue LM, Feng GL. CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation. Hepatobiliary Pancreat Dis Int 2013; 12:617-21. [PMID: 24322747 DOI: 10.1016/s1499-3872(13)60097-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Assessment of tumor response after argon-helium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion. METHODS The control group comprised 40 volunteers without liver disease. The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation. Computed tomography perfusion parameters were measured: hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. RESULTS After treatment, in the tumor foci, permeability of capillary vessel surface was higher, and hepatic blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial perfusion values were lower (P<0.05). In the liver parenchyma surrounding the tumor, hepatic arterial perfusion was significantly lower (P<0.05); however, there was no significant difference in hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, or hepatic portal perfusion (P>0.05). CONCLUSION Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.
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Affiliation(s)
- Xue-Jia Hao
- Department of Radiology, Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China.
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Fang ZT, Wang GZ, Zhang W, Qu XD, Liu R, Qian S, Zhu L, Zhou B, Wang JH. Transcatheter arterial embolization promotes liver tumor metastasis by increasing the population of circulating tumor cells. Onco Targets Ther 2013; 6:1563-72. [PMID: 24235842 PMCID: PMC3821789 DOI: 10.2147/ott.s52973] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Transcatheter arterial embolization (TAE) is widely used as an effective palliative treatment for hepatocellular carcinoma (HCC), and can prolong survival time. However, the high incidence of tumor recurrence and metastasis after TAE is still a major problem. Recent studies demonstrated that circulating tumor cells (CTCs) contribute to tumor metastasis. In this study, we tried to clarify whether the residual HCC after TAE can increase metastasis by increasing the number of CTCs. An orthotopic liver tumor model in the Buffalo rat was established using green fluorescent protein (GFP)-transfected HCC cell line, McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent TAE treatment from the gastroduodenal artery. Iodized oil or saline was injected intra-arterially. Blood samples were taken on day 0, 1, 3, 7, 14, and 21 for detection of CTCs after TAE treatment. We analyzed the number of CTCs and assessed the metastatic potential of surviving tumor cells in rats between TAE and control groups. Our results demonstrated that the metastatic colonies in the lung were significantly increased by TAE treatment. The number of CTCs was also significantly increased by TAE treatment from day 7 to day 21. The expression of hypoxia-inducible factor (HIF)-1α and epithelial–mesenchymal transition (EMT) marker proteins (N-cadherin and vimentin) was upregulated, but E-cadherin was downregulated after TAE treatment. In conclusion, the metastatic potential of residual HCC can be induced by TAE treatment in a rat liver tumor model, which involves the acquisition of EMT features and an increased number of CTCs.
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Affiliation(s)
- Zhu-Ting Fang
- Department of Intervention Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China ; Department of Intervention Radiology, Provincial Hospital of Fujian Province, Teaching Hospital of Fujian Medical University, Fuzhou, People's Republic of China
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Zhao LQ, He W, Yan B, Wang HY, Wang J. The evaluation of haemodynamics in cirrhotic patients with spectral CT. Br J Radiol 2013; 86:20130228. [PMID: 23881800 DOI: 10.1259/bjr.20130228] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To evaluate haemodynamics in cirrhotic patients with portal hypertension using spectral CT imaging. METHODS 118 cirrhotic patients with portal hypertension were included in the study group (further divided into Child-Pugh A, B and C subgroups). The control group consisted of 21 subjects with normal liver functionality. All subjects underwent three-phase spectral CT scans. Material decomposition images with water and iodine as basis material pairs were reconstructed. The iodine concentrations for the hepatic parenchyma in both arterial and portal venous phases were measured. The arterial iodine fraction (AIF) was obtained by dividing the iodine concentration in the hepatic arterial phase by that in the portal venous phase. AIF values from the study and control groups were compared using analysis of variance and between subgroups using a post-hoc test with Bonferroni correction, with a statistical significance of p<0.05. RESULTS The AIF was 0.25±0.05 in the control group, and 0.29±0.10, 0.37±0.12 and 0.43±0.14 in the study group with Child-Pugh Grades A, B and C, respectively. The difference in AIF between the control and study groups was statistically significant. The differences were statistically significant between the subgroups with multiple comparisons except between the control group and the Child-Pugh A group (p=0.685). CONCLUSION AIF measured in spectral CT could be used to evaluate the liver haemodynamics of cirrhotic patients. ADVANCES IN KNOWLEDGE The AIF, provided by spectral CT, could be used as a new parameter to observe liver haemodynamics.
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Affiliation(s)
- L-Q Zhao
- Department of Radiology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China
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Macdonald W, Shefelbine SJ. Characterising neovascularisation in fracture healing with laser Doppler and micro-CT scanning. Med Biol Eng Comput 2013; 51:1157-65. [PMID: 23881721 PMCID: PMC3751219 DOI: 10.1007/s11517-013-1100-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Accepted: 07/09/2013] [Indexed: 11/27/2022]
Abstract
Vascularity of the soft tissues around a bone fracture is critical for successful healing, particularly when the vessels in the medullary canal are ruptured. The objective of this work was to use laser Doppler and micro-computer tomography (micro-CT) scanning to characterise neovascularisation of the soft tissues surrounding the fracture during healing. Thirty-two Sprague–Dawley rats underwent mid-shaft osteotomy of the left femur, stabilised with a custom-designed external fixator. Five animals were killed at each of 2, 4 days, 1, 2, 4 and 6 weeks post-operatively. Femoral blood perfusion in the fractured and intact contralateral limbs was measured using laser Doppler scanning pre- and post-operatively and throughout the healing period. At sacrifice, the common iliac artery was cannulated and infused with silicone contrast agent. Micro-CT scans of the femur and adjacent soft tissues revealed vessel characteristics and distribution in relation to the fracture zone. Blood perfusion dropped immediately after surgery and then recovered to greater than the pre-operative level by proliferation of small vessels around the fracture zone. Multi-modal imaging allowed both longitudinal functional and detailed structural analysis of the neovascularisation process.
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Affiliation(s)
- W Macdonald
- Department of Bioengineering, Imperial College, South Kensington, London, SW7 2AZ, UK.
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Ghanaati H, Alavian SM, Jafarian A, Ebrahimi Daryani N, Nassiri-Toosi M, Jalali AH, Shakiba M. Imaging and Imaging-Guided Interventions in the Diagnosis and Management of Hepatocellular Carcinoma (HCC)-Review of Evidence. IRANIAN JOURNAL OF RADIOLOGY 2012; 9:167-77. [PMID: 23407596 PMCID: PMC3569547 DOI: 10.5812/iranjradiol.8242] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 10/24/2012] [Accepted: 10/27/2012] [Indexed: 12/12/2022]
Abstract
The imaging of hepatocellular carcinoma (HCC) is challenging and plays a crucial role in the diagnosis and staging of the disease. A variety of imaging modalities, such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine are currently used in evaluating patients with HCC. Although the best option for the treatment of these cases is hepatic resection or transplantation, only 20% of HCCs are surgically treatable. In those patients who are not eligible for surgical treatment, interventional therapies such as transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radio-frequency ablation (RFA), percutaneous microwave coagulation therapy (PMC), laser ablation or cryoablation, and acetic acid injection are indicated. In this paper, we aimed to review the evidence regarding imaging modalities and therapeutic interventions of HCC.
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Affiliation(s)
- Hossein Ghanaati
- Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
- Corresponding author: Hossein Ghanaati, Medical Imaging Center, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. Tel.: +98-2166581516, Fax: +98-2166581578, E-mail:
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Jafarian
- Hepatobilliary and Liver Transplantation Division, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Department of Gastroenterology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Nassiri-Toosi
- Department of Gastroenterology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Jalali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
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Treatment Response After Unusual Low Dose Sorafenib: Diagnosis with Perfusion CT and Follow-up in a Patient with Recurrent Hepatocellular Carcinoma. J Gastrointest Cancer 2012; 43 Suppl 1:S234-8. [DOI: 10.1007/s12029-012-9403-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Monitoring response to antiangiogenic treatment and predicting outcomes in advanced hepatocellular carcinoma using image biomarkers, CT perfusion, tumor density, and tumor size (RECIST). Invest Radiol 2012; 47:11-7. [PMID: 21512396 DOI: 10.1097/rli.0b013e3182199bb5] [Citation(s) in RCA: 125] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE Our aim was to investigate the hypothesis that the CT perfusion (CTP) is a more sensitive image biomarker when compared with tumor burden (Response Evaluation Criteria in Solid Tumors [RECIST]) and tumor density (HU) for monitoring treatment changes and for predicting long-term outcome in advanced hepatocellular carcinoma (HCC) treated with a combination of antiangiogenic treatment and chemotherapy. MATERIAL AND METHODS In this phase II clinical trial, 33 patients with advanced HCC were enrolled and 23 were included in the current study. A diagnostic dual-phase contrast-enhanced CT and perfusion CT was performed at baseline and days 10 to 12 after initiation of antiangiogenic treatment (Bevacizumab). The patients subsequently received bevacizumab in combination with gemcitabine and oxaliplatin (GEMOX-B) and contrast-enhanced CT was performed at the end of treatment (after completing 3 cycles of GEMOX-B chemotherapy) and after every 8 week until there was evidence of disease progression or intolerable toxicity. The CTP protocol included a targeted dynamic cine acquisition for 25 to 30 seconds after 50 to 70 mL of iodinated contrast media injection at 5 to 7 mL/s. The CTP parameters were compared with tumor size (according to Response Evaluation Criteria in Solid Tumors, RECIST 1.1) and density measurements (HU) before and after treatment and correlated with patient's outcome in groups with and without tumor thrombus. A one-sided P value was calculated and the Bonferroni correction was used to address the issue of multiple comparisons. RESULTS On days 10 to 12 after initiation of bevacizumab, significant decrease in CTP parameters was noted (P < 0.005). There was a mild reduction in mean tumor density (P = 0.016) without any significant change in mean tumor size. Tumors with higher baseline mean transit time values on CTP correlated with favorable clinical outcome (partial response and stable disease) and had better 6 months progression-free survival (P = 0.002 and P = 0.005, respectively). The baseline transfer constant (Ktrans) of responders (1425.19 ± 609.47 mL/1000 mL/min) was significantly higher than that of nonresponders (935.96 ± 189.47 mL/1000 mL/min). The tumor thrombus in the portal vein demonstrated baseline perfusion values and post-treatment change values similar to the HCC. CONCLUSION In advanced HCC, CTP is a more sensitive image biomarker for monitoring early antiangiogenic treatment effects as well as in predicting outcome at the end of treatment and progression-free survival as compared with RECIST and tumor density.
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Ippolito D, Capraro C, Casiraghi A, Cestari C, Sironi S. Quantitative assessment of tumour associated neovascularisation in patients with liver cirrhosis and hepatocellular carcinoma: role of dynamic-CT perfusion imaging. Eur Radiol 2012; 22:803-11. [PMID: 22086560 DOI: 10.1007/s00330-011-2307-z] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Revised: 09/27/2011] [Accepted: 09/28/2011] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To determine the value of perfusion computed tomography (CT-p) in the quantitative assessment of tumour-related neoangiogenesis processes in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Fifty-two biopsy proven HCC lesions were examined with dynamic CT investigations during injection of 50 mL of contrast agent (350 mgI/mL). A dedicated perfusion software which generated a quantitative map of arterial and portal perfusion by means of a colour scale was employed. The following parameters related to the blood microcirculation and tissue perfusion were calculated: hepatic perfusion (Perf), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were statistically analysed, comparing neoplastic lesions with cirrhotic parenchyma. RESULTS Perf, BV, HPI and AP values were higher (P < 0.001), whereas PP and TTP were lower (P < 0.001) in HCC relative to the surrounding liver. No significant correlation was found between perfusion parameters and HCC grade. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different. CONCLUSIONS Our results suggest that CT-p can help in non-invasive quantification of tumour blood supply, related to the formation of new arterial structures (neoangiogenesis), which are essential for tumour growth. KEY POINTS Perfusion computed tomography (CT) enables depiction of tumour vascular physiology. Perfusion CT is non-invasive and is now quick to perform and analyse. Quantitative measurements of hepatic perfusion provide important information about hepatocellular carcinoma (HCC). Such perfusion CT data may help in the determination of the outcome of HCC. Perfusion CT can act as an in-vivo biomarker of tumour-related angiogenesis.
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Affiliation(s)
- Davide Ippolito
- School of Medicine, University of Milano-Bicocca, Milan, Italy.
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RNA interference of hypoxia-inducible factor-1 alpha improves the effects of transcatheter arterial embolization in rat liver tumors. Tumour Biol 2012; 33:1095-103. [DOI: 10.1007/s13277-012-0349-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2011] [Accepted: 02/03/2012] [Indexed: 01/02/2023] Open
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Computed tomographic perfusion imaging for the therapeutic response of chemoembolization for hepatocellular carcinoma. J Comput Assist Tomogr 2012; 36:226-30. [PMID: 22446364 DOI: 10.1097/rct.0b013e318245c23c] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Computed tomographic (CT) perfusion imaging has been applied in many clinical areas, but few studies have addressed the values of CT perfusion imaging in evaluating the therapeutic response of chemoembolization for hepatocellular carcinoma (HCC). OBJECTIVE To assess the perfusion changes of HCC after transarterial chemoembolization, and to investigate the values of CT perfusion imaging in chemoembolization procedure. METHODS Multidetector computed tomographic perfusion imaging was performed in 24 patients with HCC 1 week before and 4 weeks after chemoembolization. The CT perfusion parameters, including hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP), total liver perfusion (TLP), and hepatic arterial perfusion index (HAPI), were calculated by using the slope method. The t statistic was used to analysis the difference of CT perfusion parameter values before and after chemoembolization therapy. RESULTS The values of HAP, TLP, and HAPI in tumors 4 weeks after chemoembolization were significantly decreased than those before chemoembolization (P < 0.05), but the value of HPP in tumors was not (P > 0.05). CONCLUSION Computed tomographic perfusion imaging has the ability to evaluate the perfusion changes in HCC after chemoembolization, which can be used to evaluate the therapeutic response of chemoembolization for hepatocellular carcinoma.
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Eisa F, Brauweiler R, Hupfer M, Nowak T, Lotz L, Hoffmann I, Wachter D, Dittrich R, Beckmann MW, Jost G, Pietsch H, Kalender WA. Dynamic contrast-enhanced micro-CT on mice with mammary carcinoma for the assessment of antiangiogenic therapy response. Eur Radiol 2011; 22:900-7. [PMID: 22071777 DOI: 10.1007/s00330-011-2318-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 09/29/2011] [Accepted: 10/15/2011] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To evaluate the potential of in vivo dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. METHODS 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. RESULTS The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P(per)(K) = 0.032, P(per) (rBV) = 0.029), but not for the total and central tumour VOIs (P(total)(K) = 0.108, P(central)(K) = 0.246, P(total) (rBV) = 0.093, P(central) (rBV) = 0.136). Mean tumour volume was significantly smaller in therapy (P (in vivo) = 0.001, P (ex vivo) = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. CONCLUSIONS This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. KEY POINTS Dynamic contrast enhanced micro-CT (computed tomography) is a new experimental laboratory technique. DCE micro-CT allows early in vivo assessment of antiangiogenic drug therapy response. Pharmaceutical drugs can be tested before translation to clinical practice. Both morphological and functional parameters can be obtained using DCE micro-CT. Antiangiogenic effects can be visualised with DCE micro-CT.
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Affiliation(s)
- Fabian Eisa
- Institute of Medical Physics, University of Erlangen-Nuremberg, Henkest. 91, 91052, Erlangen, Germany.
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Deng G, Zhao DL, Li GC, Yu H, Teng GJ. Combination therapy of transcatheter arterial chemoembolization and arterial administration of antiangiogenesis on VX2 liver tumor. Cardiovasc Intervent Radiol 2011; 34:824-32. [PMID: 21671151 DOI: 10.1007/s00270-011-0179-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2009] [Accepted: 12/03/2010] [Indexed: 12/29/2022]
Abstract
PURPOSE This study was designed to evaluate the antitumorigenic efficiency of Endostar (an antiangiogenic agent) arterially administrated combined with transcatheter arterial chemoembolization (TACE) on liver tumor, and validation of perfusion CT for quantitative measurements of the results. EXPERIMENTAL DESIGN Thirty rabbits bearing VX2 liver tumors were randomly and equally distributed into three groups. One of the following treatment protocols was performed in each group: 1) group 1 was treated with TACE and simultaneously arterially administrated Endostar; 2) group 2 with TACE alone, and 3) a control group that had saline injected through hepatic artery. Routine CT scan was performed before treatment, and perfusion CT imaging was performed 2 weeks after treatment. Immunohistochemical biomarkers of microvascular density (MVD) and the expression of vascular endothelial growth factor (VEGF) were measured for assessments of angiogenesis. RESULTS We observed a statistically significant reduction from the control in the volume, growth rate, and size of the tumor 2 weeks after treatment with both TACE plus Endostar and with TACE alone (P < 0.01). Although there was no statistically significant difference in tumor size between the group with TACE plus Endostar and the group with TACE alone (P > 0.05), MVD and VEGF were significantly less expressed in the TACE plus Endostar group than both groups with TACE alone and the control group (P < 0.01). Blood flow (BF), blood volume (BV), and permeability-surface area products (PS) in the group with TACE plus Endostar on perfusion CT were significantly higher than other two groups (P < 0.05), which were positively correlated with the MVD and VEGF values (P < 0.05). CONCLUSIONS TACE with arterial administration of Endostar simultaneously significantly inhibited the angiogenesis biomarkers associated with TACE in a rabbit model bearing VX2 liver tumor, which indicates that the combined treatment protocol may have potential synergistic effects on liver cancer. It also is suggested that perfusion CT may be useful for monitoring antiangiogenic/antivascular treatment in the liver tumors.
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Affiliation(s)
- Gang Deng
- Jiangsu Key Laboratory of Molecular Imaging and Function Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87# Dingjiaqiao Road, Nanjing 210009, China
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Wright KC, Ravoori MK, Dixon KA, Han L, Singh SP, Liu P, Gupta S, Johnson VE, Kan Z, Kundra V. Perfusion CT assessment of tissue hemodynamics following hepatic arterial infusion of increasing doses of angiotensin II in a rabbit liver tumor model. Radiology 2011; 260:718-26. [PMID: 21633050 DOI: 10.1148/radiol.11101868] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT). MATERIALS AND METHODS This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures. RESULTS Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01). CONCLUSION Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.
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Affiliation(s)
- Kenneth C Wright
- Department of Diagnostic Radiology, Section of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA.
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Rengo M, Bellini D, De Cecco CN, Osimani M, Vecchietti F, Caruso D, Maceroni MM, Lucchesi P, Iafrate F, Palombo E, Paolantonio P, Ferrari R, Laghi A. The optimal contrast media policy in CT of the liver. Part II: Clinical protocols. Acta Radiol 2011; 52:473-80. [PMID: 21498280 DOI: 10.1258/ar.2011.100500] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The advent of multidetector computed tomography (MDCT) revolutionized abdominal imaging. In particular, the definitive assessment of CT injection protocols, for the evaluation of the liver parenchyma, is still a critical issue for radiologists. Over the last years, this feature encouraged several authors to address their efforts to find the most accurate delay between the contrast medium injection and the effective scan-start, for the identification and characterization of liver lesions. Technological developments of the present century such as number of slices, submillimetric collimation, and the use of multiple dynamic post-contrast phases per single examination, may all contribute to increase the radiation exposure of single patients. The aim of this review is to propose liver imaging protocols, taking into consideration different clinical needs such as patients with chronic liver disease, healthy patients with focal liver lesion, and oncological patients to minimize radiation exposure. Finally, two recent innovations in MDCT which illustrate the potential application of multi-energy computed tomography (MECT) and perfusion computed tomography (CTp) when evaluating liver parenchyma will be discussed in a short closing paragraph.
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Affiliation(s)
- Marco Rengo
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Davide Bellini
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Carlo N De Cecco
- Department of Radiological Sciences, University of Rome ‘Sapienza’, St Andrea Hospital, Rome
| | - Marcello Osimani
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Fabrizio Vecchietti
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Damiano Caruso
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Marco M Maceroni
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Paola Lucchesi
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Franco Iafrate
- Department of Radiological Sciences, Sapienza - Università di Roma, Rome
| | - Erica Palombo
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
| | - Pasquale Paolantonio
- Department of Radiological Sciences, Azienda Ospedaliera San Giovanni – Addolorata, Rome, Italy
| | - Riccardo Ferrari
- Department of Radiological Sciences, Azienda Ospedaliera San Giovanni – Addolorata, Rome, Italy
| | - Andrea Laghi
- Department of Radiological, Oncological and Pathological Sciences, University of Rome Sapienza, Polo Pontino, Latina
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Li JP, Zhao DL, Jiang HJ, Huang YH, Li DQ, Wan Y, Liu XD, Wang JE. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease. Hepatobiliary Pancreat Dis Int 2011; 10:43-9. [PMID: 21269934 DOI: 10.1016/s1499-3872(11)60006-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. METHODS CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CONCLUSIONS CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.
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Affiliation(s)
- Jin-Ping Li
- Department of Radiology, Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China
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CT color mapping of the arterial enhancement fraction of VX2 carcinoma implanted in rabbit liver: comparison with perfusion CT. AJR Am J Roentgenol 2011; 196:102-8. [PMID: 21178053 DOI: 10.2214/ajr.09.3971] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE The purpose of this study was to compare the arterial enhancement fraction (AEF) calculated at multiphasic liver CT with the hepatic perfusion index (HPI) measured with cine mode perfusion CT. MATERIALS AND METHODS Cine mode perfusion CT was performed after VX2 tumor implantation in the livers of 10 rabbits. HPI and its color map were obtained with a computer application. With raw data from cine mode perfusion CT, images were extracted in the unenhanced, arterial, and portal venous phases to simulate multiphasic liver CT. On the basis of simulated multiphasic CT images, the AEF color map was obtained with prototype software. HPI and AEF were compared for the same regions of interest in the liver parenchyma, whole liver tumor, and viable tumor portion. RESULTS In the liver parenchyma, the mean HPI was 23.3% ± 2.6% (SD) and the AEF 24.4% ± 2.8%; in whole liver tumor, 73.4% ± 9.5% and 78.4% ± 10.5%; and in the viable tumor portion, 78.0% ± 7.7% and 78.3% ± 7.5%. The differences were not statistically significant (p > 0.05, Wilcoxon's signed rank test). Measurement agreement between the two parameters was moderate (Bland-Altman 95% limits of agreement, -14.9% and 19.2%), but there was a strong positive correlation between AEF and HPI (within-subject r = 0.91, p < 0.001). Functional maps of HPI and AEF correlated with the histologic findings. CONCLUSION AEF calculated from simulated multiphasic liver CT images correlates strongly with HPI obtained at cine mode perfusion CT. Further study of the AEF is warranted to explore its value in providing hepatic perfusion information without additional radiation exposure.
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Ippolito D, Bonaffini PA, Ratti L, Antolini L, Corso R, Fazio F, Sironi S. Hepatocellular carcinoma treated with transarterial chemoembolization: Dynamic perfusion-CT in the assessment of residual tumor. World J Gastroenterol 2010; 16:5993-6000. [PMID: 21157976 PMCID: PMC3007114 DOI: 10.3748/wjg.v16.i47.5993] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To asses the value of computed tomography (CT)-perfusion in the detection of residual hepatocellular carcinoma (HCC) vascularization after transarterial chemoembolization (TACE).
METHODS: Thirty-two consecutive patients were prospectively included in this study. All patients had liver cirrhosis and a confirmed HCC lesion which was treated with TACE. One month after treatment, perfusion measurements of treated lesions were carried out. The CT-perfusion (CT-p) protocol was performed with 16 slice multidetector computed tomography which included the following parameters: 8 dynamic slices/scan per 40 scans after iv injection of 50 mL of iodinated contrast (350 mg/mL) at a flow rate of 6 mL/s. Treated lesions were evaluated using dedicated perfusion software, which generated a quantitative colour map of perfusion. The following parameters were considered: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), hepatic perfusion index (HPI), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution and statistically analyzed.
RESULTS: Perfusion parameters of the treated lesions could be quantitatively assessed using CT-p analysis. The presence of residual tumor tissue was observed in 13 of the 32 patients. The values of the perfusion parameters measured within the relapse tissue were: HP (mL/100 g per minute): median = 44.4 (1stqt = 31.3, 3rdqt = 55.8); BV (mL/100 g): median = 18.7 (1stqt = 11.5, 3rdqt = 22.5); AP (mL/min): median = 39.0 (1stqt = 36.5, 3rdqt = 61.3); HPI (%): median = 34.0 (1stqt = 30.4, 3rdqt = 38.9); TTP (s): median = 17.3 (1stqt = 15.8, 3rdqt = 26.5). With the use of the univariate paired Wilcoxon signed rank test, HP, AP and HPI were shown to be significantly higher (P < 0.001) in the relapse site than in the primary lesion. The BV and TTP parameters showed a tendency to be greater and lower, respectively, in the relapse site than in the primary lesion.
CONCLUSION: In patients with HCC treated with TACE, CT-p provides measurement of flow parameters related to residual arterial structures in viable tumor, thus helping in the assessment of therapeutic response.
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The role of perfusion CT as a follow-up modality after transcatheter arterial chemoembolization: an experimental study in a rabbit model. Invest Radiol 2010; 45:427-36. [PMID: 20440211 DOI: 10.1097/rli.0b013e3181e07516] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To prospectively evaluate the feasibility of perfusion CT as a follow-up modality after transcatheter arterial chemoembolization (TACE) and to compare these findings with those of histopathology as the reference standard in a VX2 tumor rabbit model. MATERIALS AND METHODS VX2 carcinoma tumors were implanted into the liver of 20 rabbits 3 weeks prior to TACE. Perfusion CT was performed prior to TACE and 1- and 4-week after TACE. After obtaining perfusion index maps on perfusion CT, 2 radiologists measured the parametric perfusion indices of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability of the capillary vessel surface (PS), and hepatic arterial fraction (HAF) of primary tumors on pre-TACE perfusion CT, chemoembolized primary tumors on 1-week perfusion CT, and recurred tumors on 4-week perfusion CT. The normal liver parenchyma indices were also recorded. In addition, the radiologists investigated the presence of a recurred tumor adjacent to the chemoembolized area on perfusion index maps of 4-week CT images. The areas of higher hepatic blood flow (HBF), hepatic blood volume (HBV), PS, and HAF, and lower MTT on 4-week perfusion CT than the normal liver parenchyma and the identical area on 1-week perfusion CT were considered as recurred tumors. Histopathology revealed the presence of a recurred tumor, and mean vessel density (MVD) was determined by immunochemical staining for CD31. CT perfusion indices were compared by use of the t test. Comparisons were made for the primary tumor versus normal liver parenchyma on pre-TACE CT, the primary tumor on pre-TACE CT versus the chemoembolized tumor on 1-week CT, the recurred tumor on 4-week CT versus the identical area on 1-week CT, and the primary tumor on pre-TACE CT versus the recurred tumor on 4-week CT. For the detection of recurred tumors, the sensitivity and specificity for 4-week perfusion CT were calculated. Correlation analysis between the recurred tumor perfusion indices and the MVD of the corresponding tumor region was performed. Among 20 rabbits, 6 were excluded from the analysis, and results were based on 14 rabbits. RESULTS Recurred tumors were histologically proven in 8 of 14 rabbits (57.1%). The BF, BV, PS, and HAF indices of primary tumors were significantly higher, whereas the MTT was significantly lower than that of the normal liver parenchyma on pre-TACE perfusion CT and that of chemoembolized areas on 1-week perfusion CT (P < 0.05). In addition, recurred tumors also showed significantly higher BF, BV, PS, and HAF, and lower MTT indices than the identical areas on 1-week perfusion CT (P < 0.05). The perfusion indices of recurred tumors were not significantly different from the indices of primary tumors (P > 0.05). Both sensitivity and specificity were 100% for 4-week perfusion CT. There were significant positive correlations between BF (r = 0.947), BV (r = 0.758), PS (r = 0.759), HAF (r = 0.955), and MVD in recurred tumors, and a significant inverse correlation between MTT (r = -0.782) and MVD was observed (P < 0.05). CONCLUSIONS We believe that perfusion CT is a feasible alternative modality for the successful early response assessment and early detection of a marginally recurred tumor after TACE. However, perfusion CT has limitations for the prediction of tumor recurrence after TACE.
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Wang L. Morphological and functional MDCT: problem-solving tool and surrogate biomarker for hepatic disease clinical care and drug discovery in the era of personalized medicine. Hepat Med 2010; 2:111-24. [PMID: 24367211 PMCID: PMC3846718 DOI: 10.2147/hmer.s9052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
This article explains the significant role of morphological and functional multidetector computer tomography (MDCT) in combination with imaging postprocessing algorithms served as a problem-solving tool and noninvasive surrogate biomarker to effectively improve hepatic diseases characterization, detection, tumor staging and prognosis, therapy response assessment, and novel drug discovery programs, partial liver resection and transplantation, and MDCT-guided interventions in the era of personalized medicine. State-of-the-art MDCT depicts and quantifies hepatic disease over conventional CT for not only depicting lesion location, size, and extent but also detecting changes in tumor biologic behavior caused by therapy or tumor progression before morphologic changes. Color-encoded parameter display provides important functional information on blood flow, permeability, leakage space, and blood volume. Together with other relevant biomarkers and genomics, the imaging modality is being developed and validated as a biomarker to early response to novel, targeted anti-VEGF(R)/PDGFR or antivascular/angiogenesis agents as its parameters correlate with immunohistochemical surrogates of tumor angiogenesis and molecular features of malignancies. MDCT holds incremental value to World Health Organization response criteria and Response Evaluation Criteria in Solid Tumors in liver disease management. MDCT volumetric measurement of future remnant liver is the most important factor influencing the outcome of patients who underwent partial liver resection and transplantation. MDCT-guided interventional methods deliver personalized therapies locally in the human body. MDCT will hold more scientific impact when it is fused with other imaging probes to yield comprehensive information regarding changes in liver disease at different levels (anatomic, metabolic, molecular, histologic, and other levels).
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Affiliation(s)
- Liang Wang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
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Nett BE, Brauweiler R, Kalender W, Rowley H, Chen GH. Perfusion measurements by micro-CT using prior image constrained compressed sensing (PICCS): initial phantom results. Phys Med Biol 2010; 55:2333-50. [PMID: 20360635 DOI: 10.1088/0031-9155/55/8/014] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Micro-CT scanning has become an accepted standard for anatomical imaging in small animal disease and genome mutation models. Concurrently, perfusion imaging via tracking contrast dynamics after injection of an iodinated contrast agent is a well-established tool for clinical CT scanners. However, perfusion imaging is not yet commercially available on the micro-CT platform due to limitations in both radiation dose and temporal resolution. Recent hardware developments in micro-CT scanners enable continuous imaging of a given volume through the use of a slip-ring gantry. Now that dynamic CT imaging is feasible, data may be acquired to measure tissue perfusion using a micro-CT scanner (CT Imaging, Erlangen, Germany). However, rapid imaging using micro-CT scanners leads to high image noise in individual time frames. Using the standard filtered backprojection (FBP) image reconstruction, images are prohibitively noisy for calculation of voxel-by-voxel perfusion maps. In this study, we apply prior image constrained compressed sensing (PICCS) to reconstruct images with significantly lower noise variance. In perfusion phantom experiments performed on a micro-CT scanner, the PICCS reconstruction enabled a reduction to 1/16 of the noise variance of standard FBP reconstruction, without compromising the spatial or temporal resolution. This enables a significant increase in dose efficiency, and thus, significantly less exposure time is needed to acquire images amenable to perfusion processing. This reduction in required irradiation time enables voxel-by-voxel perfusion maps to be generated on micro-CT scanners. Sample perfusion maps using a deconvolution-based perfusion analysis are included to demonstrate the improvement in image quality using the PICCS algorithm.
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Affiliation(s)
- Brian E Nett
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
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Fei J, Jia F, Peyrin F, Françoise P, Malaval L, Vico L, Laurence V, Lafage-Proust MH, Marie-Hélène LP. Imaging and quantitative assessment of long bone vascularization in the adult rat using microcomputed tomography. Anat Rec (Hoboken) 2010; 293:215-24. [PMID: 19957340 DOI: 10.1002/ar.21054] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The objective of this study was to develop and validate a technique for both 3D imaging and quantification of the vascular network of bone tissue in the rat. Five month-old male Wistar rats were divided into tail-suspension (21 days) and control groups. Sixty percent barium sulfate solution was infused into the vena cava. The tibiae were evaluated in 2D and 3D before and after decalcification, using conventional microcomputerized tomography (muCT) at 10 and 5 mum resolution and synchrotron radiation (SR) muCT. The perfusion technique and tomography exhibited excellent bone vasculature imaging. Significant positive correlations were observed between 2D histomorphometric and 3D muCT vascular parameters (P < 0.05). 3DmuCT discriminated significant changes of vessel structures in unloading condition: vessel number decreased by 25%, (P < 0.005), vessel separation increased by 27%, P < 0.01. SRmuCT could image sinusoid clusters in bone. muCT is an accurate and reproducible technique for 3D quantitative evaluation of long bone vascularisation in the rat.
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Tumor Blood Flow Measured by Perfusion Computed Tomography and 15O-Labeled Water Positron Emission Tomography. J Comput Assist Tomogr 2009; 33:460-5. [DOI: 10.1097/rct.0b013e318182d2e0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Kambadakone AR, Sahani DV. Body perfusion CT: technique, clinical applications, and advances. Radiol Clin North Am 2009; 47:161-78. [PMID: 19195541 DOI: 10.1016/j.rcl.2008.11.003] [Citation(s) in RCA: 179] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Perfusion CT has made tremendous progress since its inception and is gradually broadening its applications from the research realm into routine clinical care. This has been particularly noteworthy in the oncological setting, where perfusion CT is emerging as a valuable tool in tissue characterization, risk stratification and monitoring treatment effects especially assessing early response to novel targeted therapies. Recent technological advancements in CT have paved ways to overcome the initial limitations of restricted tissue coverage and radiation dose concerns. In this article, the authors review the basic principles and technique of perfusion CT and discuss its various oncologic and non-oncological clinical applications in body imaging.
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Affiliation(s)
- Avinash R Kambadakone
- Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA 02114, USA
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Abstract
Complicated changes occur in hemodynamics of hepatic artery and vein, and portal vein under various kinds of pathologic status because of distinct double hepatic blood supply. This article reviews the clinical application of hepatic computed tomography perfusion in some liver diseases.
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Vasomodulation of tumor blood flow: effect on perfusion and thermal ablation size. Ann Biomed Eng 2008; 37:552-64. [PMID: 19085107 DOI: 10.1007/s10439-008-9605-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2008] [Accepted: 11/12/2008] [Indexed: 01/08/2023]
Abstract
Blood flow is a key factor in the efficacy of radiofrequency (RF) ablation treatment of solid tumors. We hypothesized that vasoactive drugs can modulate tumor blood flow and thereby improve the outcome of this thermal ablation approach. To verify this hypothesis, we measured the tumor perfusion changes in response to phenylephrine (PE) and hydralazine (HYZ) using a CT perfusion method in a rat subcutaneous tumor model. The coagulation sizes induced by RF ablation alone, RF ablation with PE and RF ablation with HYZ were compared. Results demonstrated that HYZ produced a marked decrease in entire tumor and tumor rim blood flow of 31.1 and 29.1%; while PE insignificantly change tumor blood flow (5.1% decrease in whole tumor and 6.0% decrease in tumor rim). A markedly greater coagulation area (0.59 cm2 +/- 0.24) was observed when HYZ was administered before RF ablation. No difference was noted in the coagulation area induced by RF ablation alone or the combination of PE injection followed by RF ablation (0.29 cm2 +/- 0.13 vs. 0.30 cm2 +/- 0.18). Results suggest that HYZ decreases subcutaneous tumor blood flow and enhances the coagulation size induced by RF ablation. PE has little influence on tumor blood flow and does not improve ablation.
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Ippolito D, Sironi S, Pozzi M, Antolini L, Ratti L, Meloni F, Invernizzi F, Valsecchi MG, Fazio F. Perfusion computed tomographic assessment of early hepatocellular carcinoma in cirrhotic liver disease: initial observations. J Comput Assist Tomogr 2008; 32:855-8. [PMID: 19204443 DOI: 10.1097/rct.0b013e318161dc58] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To prospectively assess perfusion computed tomography (CT) for evaluation of tumor vascularity of early hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS The study cohort included 30 patients who had Child-Pugh class A or B liver cirrhosis and a single histopathologically confirmed HCC not exceeding 3 cm in diameter. All patients underwent perfusion CT study using a multidetector 16-slice CT. Four perfusion parameters were measured for the HCCs and cirrhotic liver parenchyma: hepatic perfusion (HP), blood volume (BV), arterial perfusion (AP), and time to peak (TTP). Perfusion parameters were described with quartile (qt) values of their distribution; univariate paired Wilcoxon signed rank test was used for statistical analysis. RESULTS The values of perfusion parameters measured within tumor tissue were the following: HP (milliliters per 100 g per minute): median = 45.7 (first qt = 35.3; third qt = 61.3); BV (milliliters per 100 mg): median = 20.6 (first qt = 13.0; third qt = 27.6); AP (milliliters per minute): median = 44.2 (first qt = 36.7; third qt = 57.0); TTP (seconds): median = 18.7 (first q = 15.9; third qt = 24.0). Our data showed that HP, BV, and AP values were higher (P < 0.001), whereas TTP was lower (P < 0.001), in HCCs relative to the cirrhotic liver parenchyma. For all the CT perfusion parameters calculated, there was a significant difference between HCC and background cirrhotic liver. CONCLUSIONS Preliminary results suggest that in patients with cirrhosis and early HCC, perfusion CT is a feasible technique for noninvasive assessment of tumor vascularity.
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Affiliation(s)
- Davide Ippolito
- Department of Diagnostic Radiology, School of Medicine, University of Milano-Bicocca, Milan, Italy.
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Chen G, Ma DQ, He W, Zhang BF, Zhao LQ. Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2008; 14:5738-43. [PMID: 18837093 PMCID: PMC2748211 DOI: 10.3748/wjg.14.5738] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To prospectively assess the changes in parameters of computed tomography (CT) perfusion pre- and post-transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) in different treatment response groups, and to correlate the changes with various responses of HCC to TACE.
METHODS: Thirty-nine HCC patients underwent CT perfusion examinations pre-(1 d before TACE) and post-treatment (4 wk after TACE). The response evaluation criteria for solid tumors (RECIST) were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post-TACE for different response groups.
RESULTS: Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion (HAP), hepatic arterial fracture (HAF) and hepatic blood volume (HBV) of viable tumors post-TACE were reduced compared with pre-TACE (P = 0.001, 0.030 and 0.001, respectively). In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAF, portal vein perfusion (PVP) and hepatic blood flow (HBF) of viable tumors post-TACE were significantly increased compared with pre-TACE (P = 0.005, 0.012, 0.035 and 0.005, respectively).
CONCLUSION: Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.
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Sun C, Liu C, Wang XM, Chen J, Wang D, Merges R. Functional CT in a rabbit model: Evaluation of the perfusion characteristics before and after Ar-He cryoablation therapy. J Med Imaging Radiat Oncol 2008; 52:351-7. [DOI: 10.1111/j.1440-1673.2008.01967.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ippolito D, Sironi S, Pozzi M, Antolini L, Ratti L, Alberzoni C, Leone EB, Meloni F, Valsecchi MG, Fazio F. Hepatocellular carcinoma in cirrhotic liver disease: functional computed tomography with perfusion imaging in the assessment of tumor vascularization. Acad Radiol 2008; 15:919-27. [PMID: 18572129 DOI: 10.1016/j.acra.2008.02.005] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2007] [Revised: 02/08/2008] [Accepted: 02/09/2008] [Indexed: 02/08/2023]
Abstract
RATIONALE AND OBJECTIVES Our goal was to prospectively determine the value of perfusion computed tomography (CT) in the quantitative assessment of tumor-related angiogenesis in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Forty-seven patients met all the following inclusion criteria: 1) Child-Pugh class A or B liver cirrhosis; 2) presence of a single lesion suspected as HCC at screening ultrasound examination; and 3) lesion diameter between 1 and 3 cm. All patients underwent contrast-enhanced ultrasound, pre- and post-contrast triple-phase CT, and perfusion computed tomographic study using multidetector 16-slice CT. Six parameters related to the blood microcirculation and tissue perfusion were measured for the focal liver lesion and cirrhotic parenchyma: perfusion (P), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution; univariate paired and unpaired Wilcoxon signed rank tests were used for statistical analysis. RESULTS HCC was diagnosed in 21 of the 47 patients; in the remaining 26, HCC was not found at contrast-enhanced ultrasound and multidetector 16-slice computed tomographic study. The values of perfusion parameters measured within tumor tissue were: P (ml/s/100 g): median = 47.0 (first quartile = 36.0, third quartile = 61.4); BV (ml/100 mg): median = 24.0 (first quartile = 18.7, third quartile = 29.3); HPI (%): median = 78.4 (first quartile = 62.9, third quartile = 100); AP (ml/min): median = 45.9 (first quartile = 39.0, third quartile = 60.1); PP (ml/min): median = 9.0 (first quartile = 0.0, third quartile = 24.5); and TTP (seconds): median = 18.7 (first quartile = 16.3, third quartile = 26.5). The corresponding values calculated in cirrhotic surrounding parenchyma were P (ml/s/100 g): median = 11.5 (first quartile = 9.4, third quartile = 13.9); BV (ml/100 mg): median = 10.7 (first quartile = 7.1, third quartile = 14.2); HPI (%): median = 10.6 (first quartile = 8.7, third quartile = 11.9); AP (ml/min): median = 13.2 (first quartile = 10.1, third quartile = 15.5); PP (ml/min) median = 55.2 (first quartile = 40.1, third quartile = 79.5); and TTP (seconds): median = 41.7 (first quartile = 38.9, third quartile = 44.6). P, BV, HPI, and AP values were higher (P < .001), whereas PP and TTP were lower (P < .001) in HCC relative to the surrounding liver. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different (P > .001). CONCLUSION In cirrhotic patients with HCC, perfusion computed tomographic technique can provide quantitative information about tumor-related angiogenesis.
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Affiliation(s)
- Davide Ippolito
- School of Medicine, University of Milano-Bicocca, Milan, Italy.
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Perfusion MDCT Enables Early Detection of Therapeutic Response to Antiangiogenic Therapy. AJR Am J Roentgenol 2008; 191:133-9. [DOI: 10.2214/ajr.07.2848] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Pulido JS, Campeau NG, Klotz E, Primak AN, Saba O, Gunduz K, Cantrill H, Salomão D, McCollough CH. Correlation of histological findings from a large ciliochoroidal melanoma with CT perfusion and 3T MRI dynamic enhancement studies. Clin Ophthalmol 2008; 2:275-81. [PMID: 19668716 PMCID: PMC2693997 DOI: 10.2147/opth.s2071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The initial use of a 64-slice computed tomography (CT) scanner for obtaining quantitative perfusion data from a large ciliochoroidal melanoma, and correlation with 3T magnetic resonance imaging (MRI) dynamic enhancement and tumor histology. METHODS The CT perfusion scan was performed using 80 kVp, 250 mA and 1-sec rotation time for 40 sec. The analysis was performed using commercial perfusion analysis software with a prototype 3-dimensional motion correction tool. Dynamic contrast-enhanced 3-Tesla MRI measured the kinetics of enhancement to estimate the vascular permeability. The time-dependent enhancement patterns were obtained using the average signal intensity using Functool analysis software. The involved globe was enucleated and microscopic evaluation of the tumor was performed. RESULTS The perfusion parameters blood flow, blood volume and permeability surface area product in the affected eye determined by CT perfusion analysis were 118 ml/100 ml/min, 11.3 ml/100 ml and 48 ml/100 ml/min. Dynamic MRI enhancement showed maximal intensity increase of 111%. The neoplasm was a ciliochoroidal spindle cell melanoma which was mitotically active (13 mitoses/40 hpf). Vascular loops and arcades were present throughout the tumor. The patient developed metastases within 9 months of presentation. CONCLUSION Quantitative CT perfusion analysis of ocular tumors is feasible with motion correction software.
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Kan Z, Phongkitkarun S, Kobayashi S, Tang Y, Ellis LM, Lee TY, Charnsangavej C. Functional CT for Quantifying Tumor Perfusion in Antiangiogenic Therapy in a Rat Model. Radiology 2005; 237:151-8. [PMID: 16183931 DOI: 10.1148/radiol.2363041293] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
PURPOSE To determine the histologic basis of perfusion parameters measured at functional computed tomography (CT) and to examine the relationship between changes in perfusion and changes in histologic parameters after antiangiogenic therapy in a rat model. MATERIALS AND METHODS This study had institutional animal care and use committee approval. Among 20 Fischer rats with implanted FN13762 tumors in the liver, 10 were treated with SU5416, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, and 10 were treated with the diluent only as control rats. Six rats chosen at random from each group underwent functional CT for the measurement of tumor blood flow, blood volume, mean transit time, and permeability-surface area product. Tumor tissue slides corresponding to functional CT sections were examined to measure tumor microvascular density, number of luminal vessels, vascular perimeter, and vascular area. Two-tailed Student t testing was used to determine differences in growth, numbers of metastases to major organs, vascularity, and perfusion between SU5416-treated and control tumors. Pearson correlation coefficients were used to investigate relationships between vascular parameters. RESULTS Mean tumor volume and number of metastases, respectively, were lower in SU5416-treated rats than in control rats (1580 mm3 +/- 830 [standard deviation] vs 2330 mm3 +/- 960 and 22.4 +/- 11.0 vs 35.2 +/- 17.3); however, these differences were not significant (P = .084 and P = .079). Mean tumor microvascular density was significantly lower in SU5416-treated rats than in control rats (6.4 vessels per field +/- 4.6 vs 17.2 vessels per field +/- 7.5, P < .001); however, vessel perimeter and vessel area, respectively, were significantly larger in treated rats than in control rats (470 microm per field +/- 320 vs 360 microm per field +/- 270, P = .02; and 4010 microm2 per field +/- 2990 vs 2230 microm2 per field +/- 1750, P = .001). Significant correlations were observed between microvascular density and vessel perimeter and area (r = 0.59 and r = 0.25, respectively; P < .01 for both) in SU5416-treated tumors but not control tumors. Blood flow, blood volume, and permeability-surface area product at functional CT were significantly higher in SU5416-treated tumors than in control tumors (P < .001 for all). CONCLUSION These results validate the idea that functional CT can help quantify the perfusion function of mature vessels but not changes in microvessel density in antiangiogenic therapy.
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Affiliation(s)
- Zuxing Kan
- Department of Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
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