Effect of tamoxifen in an experimental model of breast tumor studied by dynamic contrast-enhanced magnetic resonance imaging and different contrast agents

OBJECTIVES: The aim of this study was to compare the efficacy of gadoteridol, B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37-albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor implanted in rats. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10 mammary adenocarcinoma cells (13762 MAT B III). Treatment with tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and, 24 hours later, using (Gd-DTPA)37-albumin. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging data showed that tamoxifen treatment decreased vascular permeability to B22956/1, whereas no difference was detectable in permeability to gadoteridol or to (Gd-DTPA)37-albumin. No effect on fractional plasma volume was detected with either of contrast agents. CONCLUSIONS: B22956/1 is superior to both small Gd chelates and macromolecular contrast agents in the assessment of the effect of tamoxifen treatment on tumor vasculature.     

Hepatic metastases: liposomal Gd-DTPA-enhanced MR imaging

Liposomal gadolinium diethylenetriaminepentaacetic acid (DTPA) encapsulated within 70- and 400-nm vesicles was tested as a contrast agent for magnetic resonance (MR) imaging of the liver in rats with hepatic metastases. Liposomal Gd-DTPA caused significant improvement in contrast between liver and tumor (P less than .005) on T1-weighted MR images. Smaller 70-nm liposomal Gd-DTPA vesicles caused greater contrast enhancement, reflecting the larger surface-area-to-volume ratio of the smaller vesicles. Liposomal Gd-DTPA-enhanced images permitted significant improvement in metastasis detection by five blinded radiologists (P less than .005). By comparison, free Gd-DTPA without liposomes caused a statistically significant reduction in contrast between tumor and liver and reduced lesion detection (P less than .01). Liposomal Gd-DTPA also resulted in sustained vascular enhancement for 1 hour after administration. The results suggest that paramagnetic liposomes may become a useful MR imaging contrast agent.     

Optimization of Gd-DTPA-enhanced balanced turbo field echo sequence in abdominal imaging: a basic study.

PURPOSE: To determine the optimum imaging conditions for the balanced turbo field echo (bTFE) sequence in abdominal imaging, we performed phantom experiments and scanning of a normal volunteer while noting the correlation among signal intensity, k-space ordering, flow velocity and Gd-DTPA concentration. MATERIALS AND METHODS: Initially, the abdomen of a healthy volunteer and some samples (water, blood and bovine albumin solutions with various Gd-DTPA concentrations, and olive oil) were examined with the bTFE sequence under various conditions to define the correlation among signal intensity, k-space ordering and Gd-DTPA concentration. Another experiment was performed to assess the correlation between the flow velocity and Gd-DTPA concentration. With the centric-bTFE sequence, we measured the signal intensity of water samples having various Gd-DTPA concentrations flowing in a long tube with an internal diameter of 4 mm. RESULTS: The experiments revealed the following issues: (i) The contrast of bTFE images was much influenced by k-space ordering; (ii) Gd-DTPA did not exhibit an overt enhancement effect in water and blood under stable conditions; (iii) The signal intensity of moving water decreased in centric-bTFE images, and this signal drop became more significant as the fluid speed increased; and (iv) Gd-DTPA decreased the range of signal loss in the moving fluid; however, this effect had no correlation with Gd-DTPA concentration. CONCLUSION: When the bTFE sequence was employed for abdominal imaging, centric view ordering, fat suppression and Gd-DTPA contrast enhancement were assumed to be necessary.     

Gd-DTPA标记单克隆抗体对荷人肝癌裸鼠的MR成像研究

目的评价特异性MR对比剂Gd-DTPA-单克隆抗体HAb18对肿瘤的强化效果.材料与方法制备Gd-DTPA标记的单克隆抗体,并测定每分子抗体所结合的Gd 3数目及其免疫活性.12只荷人肝癌裸鼠分为两组,分别给予Gd-DTPA-McAb和Gd-DTPA后进行MR扫描,测量SE T1WI平扫及增强后10 min、30 min、1 h、3 h、6 h、12 h、24 h、48 h图像内肿瘤的信号强度,绘制信号强度-时间曲线,并计算肿瘤强化率及对比度噪声比.结果 Gd-DTPA-单克隆抗体组在注射MR对比剂后的早期,肿瘤表现为缓慢轻度的强化,在注射对比剂24 h后,肿瘤强化达25%,与其他各时间点有统计学差异.Gd-DTPA对照组内,肿瘤表现为快进快出的强化特点.结论使用Gd-DTPA-单克隆抗体进行靶向显像具有特异性作用,有助于肿瘤的定性诊断.     

MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation

PURPOSE: To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature. MATERIALS AND METHODS: NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)(30) were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) for each contrast medium. RESULTS: Strongly positive and significant correlations were observed between MR imaging-derived K(PS )estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)(30) (r = 0.88; P <.001) or larger particulate USPIO (r = 0.82; P <.001). A significant correlation (P <.05) was observed with each contrast medium between K(PS) and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging-derived mean permeability values generated with the two contrast media. CONCLUSION: USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K(PS) correlated strongly with histopathologic tumor grade, MVD, and K(PS) values derived by using albumin-(Gd-DTPA)(30) in the same tumors.     

对比剂Gd-DTPA对肝外胆管癌磁共振扩散加权成像的影响

目的:探讨对比剂钆喷替酸葡甲胺(Gd-DTPA)对肝外胆管癌磁共振扩散加权成像(DWI)图像质量及表观扩散系数(ADC)的影响。方法:回顾性分析经病理证实并被DWI检出的57例肝外胆管癌患者的DWI图像资料,比较静脉注射对比剂Gd-DTPA增强前后及不同b值条件下肝外胆管癌病灶信噪比(SNR)、病灶与正常肝脏间对比信噪比(CNR)及ADC值的差异。结果:同一b值条件下,增强前后病灶SNR、CNR、ADC值的差异均无统计学意义(P>0.05);增强前后肝外胆管癌病灶SNR、CNR及ADC值均随着b值的增大而降低,其差异均有统计学意义(P<0.05)。结论:肝外胆管癌病灶的DWI图像质量及ADC值不受Gd-DTPA影响,所以选择合适b值的增强后DWI序列是可行的。     

Improvement of brain lesion detection at 0.1 T by simultaneous use of Gd-DTPA and magnetization transfer imaging

Imaging parameters were optimized at 0.1 T to improve contrast-to-noise ratios (CNR) when combining magnetization transfer (MT) imaging and the use of paramagnetic contrast medium. This was accomplished by imaging a phantom containing serial concentrations of Gd-DTPA in cross-linked bovine serum albumin. With the use of simulations, the dependence of CNR on imaging parameters was studied. Conventional and MT images were obtained from 10 brain tumor patients with single and triple doses of Gd-DTPA. Simulations demonstrated the importance of TR in postcontrast sequences. The CNR in MT images is less sensitive to TR than in conventional images. A significant CNR improvement caused by MT remains at longer TR when there is no contrast enhancement without MT. The clinical results indicate that a single dose of Gd-DTPA combined with MT cannot replace imaging with a triple dose. However, MT significantly improved the CNR after single and triple Gd-DTPA-doses on T₁-weighted and proton-density images.     

Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR imaging and inductively coupled plasma atomic emission spectroscopy in rat brain tumors

BACKGROUND AND PURPOSE: After the advent of extracellular contrast media, hepatobiliary-specific gadolinium chelates were developed to improve the diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is a new paramagnetic contrast agent with partial biliary excretion that produces prolonged enhancement of liver parenchyma on T1-weighted images. However, whether Gd-BOPTA is useful as a contrast agent in central nervous system disease, particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a brain tumor-selective contrast agent was compared with that of gadopentetate dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two contrast agents was performed, and tissue concentrations were measured with inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd-BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at every time course until 2 hours after administration and no enhancement in peritumoral tissue and normal brain. Corresponding results with ICP-AES showed significantly greater uptake of Gd-BOPTA in tumor samples than that in peritumoral tissue and normal brain 5 minutes after administration. Gadolinium was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging in brain tumors and possibly an effective absorption agent for neutron capture therapy.     

脑转移瘤钆造影增强与磁化传递成像双对比研究

本文搜集经组织学证实的１５例颅内转移瘤病例，采用Ｇｄ－ＤＴＰＡ增强和增强后磁化传递对比技术（ＭＴＣ）相结合的方法，初步探讨了ＭＴＣ在检测脑转移瘤中的价值，发现：（１）ＭＴＣ在低磁场强度下对Ｇｄ－ＤＴＰＡ增强有协同作用；（２）两者结合可进一步发现和明确常规ＳＥ序列成像上没有或可疑的病灶，从而可提高检出率，防止漏检。     

Regional comparison of tumor vascularity and permeability parameters measured by albumin-GD-DTPA and GD-DTPA

Sequential albumin-Gd-DTPA and Gd-DTPA dynamic enhancement studies were performed in an animal tumor model for the comparison of regional vascularity and permeability parameters measured by these two different sizes of contrast agents. The early albumin-Gd-DTPA enhancement arises from the vascular compartment, and the averaged signal enhancement derived from the first 3 to first 6 images postinjection can be reliably used to assess vascularity. The signal intensity in the images during the period of 5-10 min post-albumin-Gd-DTPA injection shows a steady linear variation. The intercept of the linear relationship is another indicator of the vascularity and the slope represents the tumor permeability to albumin-Gd-DTPA. The Gd-DTPA enhancement study was analyzed by a two-compartmental pharmacokinetic model to calculate the regional vascularity and permeability. The permeability parameters measured from albumin-Gd-DTPA and Gd-DTPA show an excellent correlation. The vascularity parameters measured from albumin-Gd-DTPA show good linear correlation with the low vascularity groups measured by Gd-DTPA, but show saturation for the high vascularity groups. The enhancement mechanisms for both contrast agents are discussed to relate the imaging parameters to the physiological variables.     

Brain tumors: MR imaging with gadolinium-DTPA

Magnetic resonance (MR) imaging was performed on 40 patients with intracranial tumors, before and after intravenous administration of gadolinium-DTPA (Gd-DTPA). Precontrast studies included a comprehensive protocol of spin-echo sequences. Tumors were visualized on precontrast images either directly or indirectly by anatomic distortion caused by the mass. However, differentiation of the tumor from adjacent tissues was possible in only 17 of 40 cases. Delineation of the tumor was best on precontrast, T2-weighted images. After administration of Gd-DTPA (0.1 mmol/kg), increased signal intensity from the tumor was observed in all patients. The localized increase in signal intensity in the tumor considerably improved the tumor delineation in 36 of 40 patients. Whereas most of the meningiomas, neuromas, and adenomas could be delineated prior to administration of contrast material if appropriate pulse sequences were applied, glioblastomas and intracranial metastases required Gd-DTPA administration for diagnostically sufficient tumor display.     

Fluctuations in tumor blood perfusion assessed by dynamic contrast-enhanced MRI.

Temporal heterogeneity in blood perfusion is a common phenomenon in tumors, but data characterizing the nature of the blood flow fluctuations are sparse. This study investigated the occurrence of blood flow fluctuations in A-07 melanoma xenografts by using gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced MRI (DCE-MRI). Each tumor was subjected to two DCE-MRI acquisitions separated by 1 hour. The data were processed by Kety analysis and resulted in two E.F images (E is the initial extraction fraction of Gd-DTPA and F is the perfusion) and two lambda images (lambda is the partition coefficient of Gd-DTPA) for each tumor. The E . F images were used to determine the changes in blood perfusion arising in the time between the two imaging sequences. The lambda images were used to control the reproducibility of the experimental procedure. The study showed that DCE-MRI with subsequent Kety analysis is a useful method for detection of blood flow fluctuations in A-07 tumors, and strongly suggested that the peripheral regions of A-07 tumors are more exposed to temporal changes in blood perfusion than are the central regions.     

Initial experiences with gadolinium DTPA in magnetic resonance tomography of bone and soft tissue tumors

MR was performed in 41 patients suffering from benign and malignant bone and soft-tissue tumor before and after intravenous injection of the paramagnetic agent gadolinium-DTPA (Gd-DTPA). Using T1-weighted parameters, the contrast of tumor tissue versus muscle could be increased by Gd-DTPA. Thus, extraosseous extension as well as infiltration of the spinal canal was depicted to better advantage. Inhomogeneities were visualized with higher frequency and improved contrast. In several instances, there was no differentiation between tumor and adjacent edema without application of Gd-DTPA. T2-weighted images without Gd-DTPA exhibited higher contrast as compared to T1-weighted images after Gd-DTPA. The contrast to tumor tissue versus fat and bone marrow respectively was reduced after applying Gd-DTPA. Thus, for the evaluation of bone marrow infiltration, T1-weighted images without Gd-DTPA proved to be indispensable.     

The value of paramagnetic contrast agent gadolinium-DTPA in the diagnosis of pituitary adenomas

Summary The purpose of this study was to assess the role of MR imaging and the paramagnetic contrast agent Gadolinium-DTPA(Gd-DTPA) in the diagnosis of pituitary macroadenomas. 44 macroadenomas were examined with MRI before and after intravenous application of Gd-DTPA. Gd-DTPA produced excellent enhancement of solid adenoma. The best contrast between adenoma and surrounding structures could be gained on post-Gd T1-weighted images. Post-Gd images were equivalent to pre-Gd images in the evaluation of supra-and infrasellar extensions of macroadenomas. Post-Gd images had advantages in the evaluation of cavernous sinus invasion by adenoma. The difference in degree of contrast enhancement between adenoma and cavernous sinus facilitated the exact evaluation of lateral extension by adenoma in 18 cases. Almost equal degree of enhancement of both structures impaired tumor-sinus contrast in 2 cases. In the other 24 cases the tumor filled the cavernous sinus completely. It is our opinion that Gd-DTPA can be used on a widespread basis because of its excellent capability to highlight and delineate pituitary adenomas.     

New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.     

High-resolution vascular imaging of the rat spine using liposomal blood pool MR agent

BACKGROUND AND PURPOSE: High-resolution, vascular MR imaging of the spine region in small animals poses several challenges. The small anatomic features, extravascular diffusion, and low signal-to-noise ratio limit the use of conventional contrast agents. We hypothesize that a long-circulating, intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would facilitate visualization of small anatomic features of the perispinal vasculature not visible with conventional contrast agent (gadolinium-diethylene-triaminepentaacetic acid [Gd-DTPA]). METHODS: In this study, high-resolution MR angiography of the spine region was performed in a rat model using a liposomal-Gd, which is known to remain within the blood pool for an extended period. The imaging characteristics of this agent were compared with those of a conventional contrast agent, Gd-DTPA. RESULTS: The liposomal-Gd enabled acquisition of high quality angiograms with high signal-to-noise ratio. Several important vascular features, such as radicular arteries, posterior spinal vein, and epidural venous plexus were visualized in the angiograms obtained with the liposomal agent. The MR angiograms obtained with conventional Gd-DTPA did not demonstrate these vessels clearly because of marked extravascular soft-tissue enhancement that obscured the vasculature. CONCLUSIONS: This study demonstrates the potential benefit of long-circulating liposomal-Gd as a MR contrast agent for high-resolution vascular imaging applications.     

Dynamics of tumor imaging with Gd-DTPA—polyethylene glycol polymers: Dependence on molecular weight

Macromolecular contrast media offer potential advantages over freely diffusible agents in magnetic resonance (MR) imaging outside the central nervous system. To identify an optimum molecular weight for macromolecular contrast media, the authors studied a novel macromolecular contrast agent, gadolinium diethylenetriaminepentaacetic acid polyethylene glycol (DTPA-PEG), synthesized in seven polymer (average) molecular weights ranging from 10 to 83 kd. Twenty-eight rabbits bearing V2 carcinoma in thighs underwent T1-weighted spin-echo imaging before injection and 5–60 minutes and 24 hours after injection of the Gd-DTPA-PEG polymers or Gd-DTPA at a gadolinium dose of 0.1 mmol/kg. Tumor region-of-interest measurements were obtained at each time point to determine contrast enhancement dynamics. Blood-pool enhancement dynamics were observed for the Gd-DTPA-PEG polymers larger than 20 kd. Polymers smaller than 20 kd displayed dynamics similar to those of the freely diffusible agent Gd-DTPA. Above the 20 kd threshold, tumor enhancement was more rapid for smaller polymers. The authors conclude that the 21.9-kd Gd-DTPA-PEG polymer is best suited for clinical MR imaging.     

Biodistribution and clearance of liposomal gadolinium-DTPA

Gadolinium-DTPA (Gd-DTPA) liposomes have been studied previously as liver contrast agents and have been shown to improve the detection of hepatic metastases in rats. We synthesized 100-nm and 50-nm liposomes that encapsulated Gd-DTPA and did biodistribution and clearance studies in rats. Parallel magnetic resonance imaging (MRI) studies were also done. Biodistribution showed a prolonged blood pool phase for Gd-DTPA liposomes with a blood pool half-life of approximately 4 hours for the 100-nm liposomes. The highest uptake per gram of tissue was achieved by the spleen. Clearance of gadolinium from the liver and spleen showed a half-life of 3 to 4 days. The smaller 50-nm Gd-DTPA liposomes resulted in a longer blood pool phase and a higher delivery of gadolinium to the liver, bone marrow, and spleen. Imaging studies after intravenous (IV) administration of liposomal Gd-DTPA showed organ enhancement that paralleled the data on biodistribution studies, with appreciable hepatic enhancement at doses as low as 0.025 mm/kg of liposomal Gd-DTPA.     

二步法预定位技术对荷人肝癌裸鼠模型的MR免疫成像研究

目的利用生物素亲和素系统(biotin avidinsystem,BAS)的靶向定位效应和生物放大作用,提高MR分子免疫成像的敏感性。方法制备生物素化抗人肝癌细胞单克隆抗体HAb18并测定其生物素化程度及抗原结合活性。20只荷人肝细胞癌裸鼠分为3组,二步法预定位组8只,先静脉注射生物素化单克隆抗体600μg,24h后再给予钆喷替酸葡甲胺链霉亲和素(Gd DTPA streptavidin,Gd DTPA SA);HAb18单克隆抗体Gd DTPA组6只,经尾静脉注射Gd DTPA HAb18;Gd DTPA对照组6只,静脉注射Gd DTPA。对实验动物行MR扫描,测量SET1WI平扫及增强后10、30、60min及3、6、12、24、48h图像内肿瘤的信号强度,绘制信号强度时间曲线,并计算肿瘤强化率及对比度噪声比(contrast to noiseratio,CNR)。结果HAb18单克隆抗体经生物素化后,每个抗体分子平均可结合20个分子生物素,其抗原结合活性约为91%。二步法预定位组内,肿瘤信号强度缓慢升高,增强后第6小时,肿瘤的强化率、CNR达到最大值,与其他两组相比较差异有统计学意义。48h后,肿瘤的强化仍肉眼可辨。单克隆抗体组内,肿瘤表现为缓慢轻度强化,增强后24h的强化率达13.5%,肿瘤信号强度、CNR与平扫比较差异均有统计学意义(P值均<0.05)。Gd DTPA对照组内,肿瘤表现为快进快出特点的强化特点。结论二步法预定位技     

Arterial visualization by contrast-enhanced moving-table MR angiography: crossover comparison of 0.1 and 0.2 mmol/kg doses of meglumine gadopentetate in normal volunteers

PURPOSE: To determine the appropriate dose of contrast medium for moving-table MR angiography (MT-MRA) from the abdominal aorta to the ankle by comparing visualization with different doses of meglumine gadopentetate (Gd-DTPA) administered in crossover fashion to normal volunteers. MATERIALS AND METHODS: Twelve healthy adults underwent imaging after crossover administration of 0.1 and 0.2 mmol/kg of Gd-DTPA in random order. Continuous MT-MRA was performed with a fast 3D spoiled gradient echo sequence without parallel imaging technique. Visualization was evaluated in a total of 252 arteries by three blinded readers who independently rated arterial visualization using a 5-grade scale. Signal intensity was determined and the blood concentration of Gd-DTPA was estimated. RESULTS: Arterial visualization in the lower leg region was significantly better with a dose of 0.2 mmol/kg than with 0.1 mmol/kg (P<0.001). For all regions assessed the estimated blood Gd-DTPA level was significantly higher with 0.2 mmol/kg than with 0.1 mmol/kg (abdominal aorta, P=0.030; superficial femoral artery, P<0.001; posterior tibial artery, P=0.039). The vascular signal enhancement ratio and artery-to-muscle signal ratio were significantly higher in the upper leg and lower leg regions at 0.2 mmol/kg. CONCLUSION: With continuous MT-MRA imaging from the abdomen to the ankle in normal volunteers, better arterial visualization and superior contrast were achieved with 0.2 mmol/kg of Gd-DTPA.