兔肝VX2移植瘤模型核磁共振扩散成像研究

目的研究兔肝VX2移植瘤不同时期核磁共振扩散成像特征。方法20只新西兰兔随机分为对照组（8只）和实验组（12只），实验组于CT导引下行兔肝VX2瘤组织植入。分别于移植后14天、19天、24天进行核磁共振平扫及扩散成像检测。结果兔肝VX2移植瘤灶在14天时平扫，T2WI呈稍高信号；19天时T2WI可见病灶内少量的囊变样高信号；24天时信号明显欠均匀，中间可见囊变样T2WI高信号。不同时期实验组与对照组相比，ADC数值存在显著性差异（P〈0．05）。结论在追踪兔肝VX2移植瘤生长过程中，核磁共振扩散成像具有重要价值。     

MRI tumor characterization using Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M™), a protein‐avid contrast agent

The rationale and objectives were to define the MRI tumor‐characterizing potential of a new protein‐avid contrast agent, Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M?; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd kg^?1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N‐ethyl‐N‐nitrosourea (ENU), 45–250 mg kg^?1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two‐compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (K^PS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff–Bloom–Richardson score) and location of necrosis. Eighteen tumor‐bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. K^PS and fEV*, but not fPV obtained from tumors correlated significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56, respectively. Estimates for K^PS and fEV* but not fPV were significantly lower in a group consisting of benign and low‐grade malignant tumors compared with the group of less‐differentiated high‐grade tumors (1.61 ± 0.64 vs 3.37 ± 1.49, p < 0.01; 0.45 ± 0.17 vs 0.78 ± 0.24, p < 0.01; and 0.076 ± 0.048 vs 0.121 ± 0.088, p = 0.24, respectively). It is concluded that the protein‐avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low‐grade malignant lesions from high‐grade cancers. Copyright © 2006 John Wiley & Sons, Ltd.     

Selective X‐ray contrast enhancement of the spleen of living mice mediated by gold nanorods

Gold nanomaterials (AuNPs) represent a promising new class of contrast agents for X‐ray computed tomographic (CT) imaging in both research and clinical settings. These materials exhibit superior X‐ray absorption properties compared with other iodinated agents, and thus require lower injection doses. Gold is nonimmunogenic and therefore contributes to safety profile in living specimens. Unfortunately, most reports on the use of AuNPs as X‐ray CT enhancers only demonstrate marginal enhancement of the intended anatomical structure. In this study, we demonstrate the dramatic properties of gold nanorods (GNR) to serve as robust X‐ray CT contrast‐enhancing agent for selective imaging of the spleen. These organ‐specific uptake properties were delineated by performing longitudinal CT imaging of living mice that were dosed with GNR at 2 day intervals. Rapid uptake in spleen was noted within 12 h of first systemic administration with a change in contrast enhancement of 90 Hounsfield units (ΔHU = 90) and with two subsequent injections a total contrast enhancement of over 200 HU was observed. The resulting images provide excellent contrast that will enable the detailed anatomical visualization and study of a range of pre‐clinical models of spleen disease including infection and cancer. Copyright © 2014 John Wiley & Sons, Ltd.     

A dual CT‐MR dendrimer contrast agent as a surrogate marker for convection‐enhanced delivery of intracerebral macromolecular therapeutic agents

The feasibility of using Gd dendrimer‐based macromolecules (Gd‐G8 dendrimer) as a dual CT and MR contrast agent for monitoring convection‐enhanced delivery of therapy in the brain is evaluated both in vitro and in vivo with optimal dosing established. In vitro CT attenuation values of the Gd‐based agents (～6.0 HU mM ^?1) were ～1.6 times greater than iodine‐based agents and the attenuation of the Gd‐DTPA was comparable to Gd‐G8 dendrimer. Visible enhancement was observed on both CT and MR using Gd‐G8 dendrimer over a range of 23–78 mM ; however, a concentration of at least 47 mM in Gd was required for adequate delineation of the injection site on both CT and MR. MR offers greater sensitivity than CT in estimating the volume of distribution (V_d) and effectively quantified the agent's concentration and diffusion using T₁ mapping at much lower concentrations of Gd (<10 mM in [Gd]). Copyright © 2008 John Wiley & Sons, Ltd.     

In‐vivo high‐resolution X‐ray microtomography for liver and spleen tumor assessment in mice

The present study sought to validate the use of glycery1‐2‐oley‐1,3‐bis‐[7‐(3‐amino‐2,4,6‐triiodophenyl)‐ heptanoate] (DHOG) contrast agent for mouse spleen tumor and liver metastasis imaging by high‐resolution X‐ray microtomography. Three groups of female nude mice were compared: controls (n = 5), and mice injected with 2.5 × 10⁶ STC1 tumor cells in the spleen, imaged at 15 days (group G15, n = 5) and at 30 days (group G30, n = 5, of which one died before imaging). Micro‐CT scans (X‐ray voltage, 50 kVp; anode current, 200 µA; exposure time, 632 ms; 180 rotational steps resulting in 35 µm isotropic spatial resolution) were acquired at 0, 0.75, 2 and 4 h after i.v. injection of DHOG. CT number (Hounsfield units: HU) and contrast‐to‐noise ratios (CNR) were determined in three organs. Statistical analysis was performed by Mann–Whitney U‐test. Contrast enhancement in normal spleen and liver increased, respectively to 1020 ± 159 and 351 ± 27 HU over baseline at 4 h, and 482 ± 3 and 203 ± 14 HU on day 6 after a single contrast injection. Automated three‐dimensional reconstruction and modeling of the spleen provided accurate and quantifiable images. Spleen tumor and liver metastases did not take up DHOG, making them detectable in contrast to the increased signal in normal tissue. The smallest liver metastasis detected measured 0.3 mm in diameter. High‐resolution X‐ray micro‐CT in living mice using DHOG contrast agent allowed visualization and volume quantification of normal spleen and of spleen tumor and its liver metastases. Copyright © 2007 John Wiley & Sons, Ltd.     

Color Doppler ultrasound of liver lesions: Signal enhancement after intravenous injection of the ultrasound contrast agent Levovist®

Patients with focal liver lesions (hemangioma, focal nodular hyperplasia, adenoma, hepatocellular carcinoma, metastatic lesions, focal fatty lesion) received the ultrasound contrast agent Levovist® (300 mg/mL and 400 mg/mL) intravenously. This ultrasound contrast agent (a suspension of micrometer-sized microparticles of galactose and microscopic gaseous bubbles) can pass through the lungs without impairment. After the administration of Levovist®, increased color flow signals were detected in the liver. Five of 6 patients with metastatic liver lesions showed previously undetected blood flow in the rim of the tumor. In 4 patients with hepatocellular carcinoma, enhanced signal intensity was observed in the vessels of the rim and in 3 of those patients in the center of the tumor. One patient with adenoma and one patient with focal nodular hyperplasia showed signal enhancement in the central area of the tumor. No signal enhancement was observed in hemangiomas, a focal fatty lesion, or in a carcinoid metastatic lesion. Levovist® increased the echointensity of normal and tumor vessels in liver lesions. This new ultrasound contrast agent led to the detection of tumor vessels previously not detectable by conventional color flow imaging. © 1996 John Wiley & Sons, Inc.     

兔VX2肝癌模型的影像学表现和栓塞技术的实验研究

目的建立兔VX2肝癌模型,探讨其影像学表现和介入栓塞技术。方法将VX2瘤组织块种植于30只新西兰大白兔肝左叶,建立兔肝癌模型。行DSA前,将种植成功的兔子进行CT、MR检查,不同剂量碘油栓塞术后CT复查并观察各组生存情况。结果经剖腹探查证实肝脏种植成功24只(成功率80%,24/30);肝种植两周后CT平扫肿瘤多呈等或低密度区,增强扫描动脉期表现为边缘环状强化;MRI上肿瘤实质部分T1WI与T2WI分别表现为均匀低信号和稍高信号,DWI上瘤灶呈明显高信号,境界清晰,坏死部分呈长T1长T2信号影。DSA肝实质期可见肿瘤染色,栓塞时可见碘油在肿瘤部位充填、沉积,术后CT均能见瘤区有高密度碘油沉积,大部分为瘤周沉积。根据体重和超选择情况确定栓塞碘油剂量效果较好。结论兔肝VX2肿瘤模型的建立与复制成功率高。CT、MR和DSA有利于荷瘤兔的监测和筛选。暴露股动脉穿刺和用微导管超选择,可对肝脏荷瘤兔进行有效的选择性肝动脉造影和栓塞。     

Dynamic contrast‐enhanced computed tomography for the quantification of tumor response to vasoactive agents in a rat tumor model: preliminary results

Rationale and Objectives

The purpose of this pilot study was to establish the ability of dynamic contrast enhanced computed tomography (DCE‐CT) to detect changes in tumor blood flow (BF) and oxygenation induced by vasoactive substances in rats.

Materials and Methods

Under ultrasound guidance, a fiber‐optic probe was guided into thigh tumors in eight rats and attached to an oxygenation/blood flow‐sensing device. A DCE‐CT sequence was acquired at the oxygen‐sensing probe tip during injection of iodinated contrast media. Group 1 rats (n = 6) were administered a vasodilator (hydralazine, 5 mg/kg i.v.) and group 2 rats (n = 2) were given physiologic saline in a similar volume. DCE‐CT was repeated at the probe tip after 30 min. BF in the whole tumor and at the probe tip were estimated pre‐ and post‐drug administration and the percentage change was calculated.

Results

DCE‐CT defined significant differences between pre‐ and post‐drug BF in the whole tumor (p = 0.007) and at the probe tip (p = 0.03). Estimates of percentage change in BF in the whole tumor agreed with fiber‐optic measure of percentage change perfusion (r² = 0.60; p = 0.02) and pO₂ (r² = 0.65; p = 0.02). Estimates of percentage change in BF at the probe tip agreed with fiber‐optic measures of percentage change in perfusion (r² = 0.83; p = 0.001) and pO₂ (r² = 0.62; p = 0.02).

Conclusions

Preliminary results indicate that DCE‐CT is capable of identifying alterations in tumor BF in rats. The percentage change in BF agrees with a validated estimate of tumor perfusion and oxygenation. This research technique may prove useful for assessment of tumor BF during combined chemotherapeutic and radiation therapy to improve outcome. Copyright © 2010 John Wiley & Sons, Ltd.     

Prospective evaluation of selected clinical criteria for cranial computed tomography in non‐trauma adult patients

Objective: To evaluate the usefulness of previously published criteria by Rothrock et al. and Harris et al. for urgent, cranial CT in non‐trauma presentations. Methods: A prospective, observational study of consecutive adult patients with non‐trauma presentations to Westmead Emergency Department, undergoing urgent cranial CT over a period of 2 years and 10 months. Clinical data were assessed to determine the presence of the proposed Rothrock and Harris criteria. Clinically significant findings defined by CT were intracerebral haemorrhage, acute infarction, intracranial infection, acute hydrocephalus, cerebral oedema and malignancy. Results: A total of 1911 patients were studied. Among them, 21.7% (414/1911) of patients had clinically significant findings on CT. Application of the Harris criteria demonstrated a sensitivity of 93.5% (387/414, 95% CI 90.7–95.7) and a false negative rate of 6.5% (27/414, 95% CI 4.3–9.3) with a potential reduction in number of scans by 27.8%. With application of the Rothrock criteria, the possible scan reduction rate was 15% with a sensitivity of 98.8% (409/414, 95% CI 97.2–99.6) and a false negative rate of 1.2% (5/414, 95% CI 0.4–2.8). Conclusion: The Harris criteria were not validated by our study. The Rothrock criteria are also not confidently validated, but can be a useful guide for emergency physicians to help prioritize high‐risk patients who might have clinically significant cranial CT findings. We have not replicated their very high sensitivity and very low false negative rates.     

兔VX2肝癌模型建立方法的比较及股动脉插管方法的应用

目的比较不同的兔VX2肝癌模型的建立方法,探讨股动脉插管技术的应用。方法将60只实验兔随机分成3组,每组20只,分别用瘤细胞悬液直视下注射法、直视下瘤块注入后用明胶海绵封堵穿刺通道法及直视下瘤块注入后局部压迫法建立兔VX2肝癌模型。结果60只实验兔中死亡2只,存活兔经剖腹探查证实肝脏种植成功54只(成功率93.1%,54/58);三组成瘤率分别为79%(15/19)、100%(19/19)、100%(20/20),前者成瘤多为多结节、分叶状,腹腔及全身转移多见,与后两者均有统计学差异,后两者成瘤状况无统计学差异,多为孤立病灶且成瘤速度快,腹腔及远处转移少见。成瘤后的影像学及组织病理学亦证实前述结果。所有实验兔处死前均经股动脉直视下Seldinger法置入4F导管鞘后引入导管行血管造影及其他介入操作,成功56例(成功率96.6%,56/58)。结论直视下注入瘤块后局部压迫法操作简便、成瘤率高,且多为孤立病灶,转移少见,更适合建立兔VX2肝癌模型的实验要求。经股动脉置鞘后行介入操作方法可行,尤其适用于复杂的介入操作。     

兔VX2肝癌改良模型的建立及螺旋CT评价

目的探讨超声引导下经皮穿刺组织块注射法制作兔VX2肝癌模型,并与开腹组织块种植法进行比较.方法新西兰白兔24只,随机分成2组,12只/组,分别采用超声引导下经皮穿刺注射瘤组织块及开腹瘤组织块接种的方式种植于肝脏.肿瘤种植后14天,CT平扫及增强扫描与病理组织学结合评价肿瘤接种成功率及生长情况.结果肿瘤接种成功率两组均为91.7%.肿瘤最大直径穿刺组和开腹组分别为(1.04±0.12)cm和(1.09士0.14)cm,两种方法无统计学差异.肿瘤种植后发生感染率及肿瘤坏死率,开腹种植组(感染率:45.5%;坏死率:72.7%)明显高于经皮穿刺组(感染率:0;坏死率:27.3%),并有统计学意义(P＜0.05).结论超声引导下经皮穿刺注射瘤组织块建立兔VX2肝癌模型具有方法简单、成功率高、动物损伤小、肿瘤坏死率低等特点,为肝癌临床治疗和相关基础研究提供成熟的大型实验动物模型.     

兔VX2肝癌模型动态磁共振扩散张量成像的量化研究

目的探讨对兔VX2种植型肝癌模型的成瘤过程进行动态磁共振扩散张量成像(DTI)量化研究的可行性及价值。方法在肿瘤植入后第14、18、22、26天分别对4组共16只新西兰大白兔VX2种植型肝癌模型和4组共4只正常新西兰大白兔进行磁共振成像及DTI;动态量化分析平均扩散系数(DCavg)、部分各向异性值(FA)的变化规律并与病理结果对照。结果兔VX2种植型肝癌模型的DCavg呈先递增后递减趋势;FA呈先递减后递增趋势;与对照组间差异有显著性;病理结果的多项分析中,瘤内凝固性坏死和纤维增生呈明显递增趋势。结论DTI的量化指标能够动态观测兔VX2种植型肝癌模型的部分生长特性;为DTI对肝脏病变的临床应用提供一定的理论指导。     

Assessment of therapeutic response in hepatocellular carcinoma treated with percutaneous radio frequency ablation: comparison of multiphase helical computed tomography and power Doppler ultrasonography with a microbubble contrast agent.

OBJECTIVE: To compare the results of multiphase helical computed tomography and power Doppler ultrasonography with a microbubble contrast agent in the assessment of the therapeutic response to radio frequency ablation in hepatocellular carcinoma. METHODS: In 66 patients with 73 nodular hepatocellular carcinomas ranging from 1.0 to 4.0 cm (mean, 2.6 cm) in diameter, contrast-enhanced power Doppler ultrasonography was performed after intravenous bolus injection of a galactose-based microbubble contrast agent before and after radio frequency ablation. The results of the studies were compared with the findings of follow-up 3-phase helical computed tomography. All patients were regularly followed up with computed tomography for more than 1 year (range, 13-19 months). RESULTS: In 8 (11%) of 73 hepatocellular carcinomas, immediate follow-up computed tomography obtained within 2 hours after radio frequency ablation showed focal enhancing portions within the treated lesions, suggesting residual non-necrotic tumors. All 8 of these tumors had intratumoral flow signals on contrast-enhanced power Doppler ultrasonography. The diagnostic agreement between computed tomography and contrast-enhanced power Doppler ultrasonography was achieved in 100%. Among the remaining 65 hepatocellular carcinomas with the absence of residual tumors at both immediate follow-up computed tomography and contrast-enhanced power Doppler ultrasonography, subsequent follow-up computed tomography showed local regrowth at the margins of 10 lesions (15%). CONCLUSIONS: The results of contrast-enhanced power Doppler ultrasonography closely correlated with those of immediate follow-up computed tomography for detecting residual tumors in hepatocellular carcinomas treated with radio frequency ablation. Both techniques, however, showed a limitation in detecting small or microscopic residual tumors and in predicting local regrowth in the treated lesions.     

多层面螺旋CT肝脏双期增强技术的研究—造影剂量及团注造影剂跟踪技术的影响

目的：评价造影剂量及团注造影剂跟踪技术对多层面螺旋CT肝脏双期增强效果的影响。材料与方法：40名观察对象随机分为三组,分别从周围静脉注入Omnipaque 300 100ml、100ml和75ml。第一组以固定时间间隔扫描,第二组及第三组以团注造影剂跟踪技术启动扫描。以腹主动脉增强值超过150Hu为动脉期开始,肝实质增强值大于20Hu为动脉期结束。结果：①第一组中5例（45％）动脉期扫描序列未处于其最佳扫描间期,第二组为2例（13％）,第三组为1例（8％）;②第一组中2例（18％）肝实质强化峰值未包括在其门静脉期扫描序列中,2例（18％）强化峰值位于扫描序列的末期,而第二组和第三组的强化峰值均位于其扫描序列的中心层面;③各组间主动脉及肝实质增强值的差异无统计学意义。结论：①团注造影剂跟踪技术能更准确确定动脉期的起点;②75ml 的造影剂量能够满足多层面螺旋CT肝脏双期增强的要求。     

Detection and differential diagnosis of hepatic masses using pulse inversion harmonic imaging during the liver-specific late phase of contrast enhancement with Levovist

PURPOSE: The purpose of this study was to investigate whether late-phase pulse inversion harmonic imaging (PIHI) increases conspicuity in hepatic masses, helps to differentiate benign from malignant lesions, and demonstrates a greater number of and smaller metastatic lesions than do conventional (fundamental) sonography and helical CT. METHODS: Thirty patients (17 women and 13 men; age range, 35-77 years; mean age, 54 years) with known or suspected liver masses were evaluated using both fundamental sonography and contrast-enhanced PIHI during the liver-specific late phase of Levovist. The patients also underwent contrast-enhanced triphasic helical CT examinations within 1 week after sonography. In 4 of the patients, gadolinium-enhanced MRI was also performed as a part of their clinical work-up. RESULTS: The increase in the lesions' conspicuity on PIHI compared with fundamental sonography was significantly greater in malignant lesions than in benign lesions (p< 0.001). An echogenic rim was observed on PIHI in 8 (53%) of 15 malignant lesions. The mean number of metastatic lesions visualized on PIHI (5.5 +/- 5.3) was significantly higher than the mean number visualized on fundamental sonography (2.5 +/- 2.1, p < 0.05). Although lesions as small as 3 mm were observed on PIHI, the mean sizes of the smallest lesions demonstrated using fundamental sonography, PIHI, and helical CT were not significantly different. CONCLUSIONS: Late-phase PIHI is a useful technique for characterizing hepatic lesions and demonstrating both a greater number of and smaller metastases. It may help to differentiate benign from malignant liver masses and may obviate unnecessary and expensive further imaging.     

Skeletal muscle analyses: agreement between non‐contrast and contrast CT scan measurements of skeletal muscle area and mean muscle attenuation

Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been associated with poor prognosis in various patient populations. Both non‐contrast and contrast CT scans are used to determine SMA and MRA. The effect of the use of a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement between these two scan options. SMA and MRA of 41 healthy individuals were analysed on a paired non‐contrast and contrast single CT scan, and agreement between paired scan results was assessed with use of Bland–Altman plots, intraclass correlation coefficients (ICCs), standard error of measurements (SEM) and smallest detectable differences at a 95% confidence level (SDD₉₅). Analyses were stratified by tube voltage. Difference in SMA between non‐contrast and contrast scans made with a different tube voltage was 7·0 ± 7·5 cm²; for scans made with the same tube voltage this was 2·3 ± 1·7 cm². Agreement was excellent for both methods: ICC: 0·952, SEM: 7·2 cm², SDD₉₅: 19·9 cm² and ICC: 0·997, SEM: 2·0 cm², SDD₉₅: 5·6 cm², respectively. MRA of scans made with a different tube voltage differed 1·3 ± 11·3 HU, and agreement was poor (ICC: 0·207, SEM: 7·9 HU, SDD₉₅: 21·8 HU). For scans made with the same tube voltage the difference was 6·7 ± 3·2 HU, and agreement was good (ICC: 0·682, SEM: 5·3 HU, SDD₉₅: 14·6 HU). In conclusion, SMA and MRA can be slightly influenced by the use of contrast agent. To minimise measurement error, image acquisition parameters of the scans should be similar.     

Assessment of tumor angiogenesis: dynamic contrast‐enhanced MRI with paramagnetic nanoparticles compared with Gd‐DTPA in a rabbit Vx‐2 tumor model

The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd‐DTPA) using dynamic contrast‐enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12–14 days after Vx‐2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd‐DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K_i) maps were calculated using a two‐compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K_i values estimated using PNs were significantly lower than those obtained for Gd‐DTPA (p = 0.018). When PNs and Gd‐DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd‐DTPA data (p = 0.34). The mean K_i for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd‐DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd‐DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis. Copyright © 2010 John Wiley & Sons, Ltd.