Superparamagnetic Iron Oxide Hepatic MR Imaging: Efficacy and Safety Using Conventional and Fast Spin-Echo Pulse Sequences

The purpose of this study was to evaluate the technical efficacy and safety of iv ferumozldes (Feridex^a), a superparamagnetic iron oxide contrast agent for detection of hepatic lesions using conventional spin-echo and fast spin-echo MR images. Precontract and postcontrast MR studies were performed on 25 patients with suspected focal hepatic lesions. Conventional Tl-and T2-weighted MR images, as well as fast spin-echo and fat suppressed fast spin-echo MR images, were evaluated. Quantitative assessment of the contrast agent was performed obtaining region of interest measurements of the liver, spleen, and selected hepatic lesions. The pulse sequences were also evaluated subjectively for overall image quality and a subjective assessment of lesion detection. The use of a superparamagnetic iron oxide contrast agent led to a decrease in hepatic signal intensity on all pulse sequences. Lesion-to-liver contrast increased 41.1%, 36.5%, and 32.0% on the conventional T2, fast spin-echo, and fat suppressed fast spin echo pulse sequences, respectively. Lesion-to-liver contrast decreased on the T1-weighted postcontrast pulse sequence by 23.8%. Despite Improvement in lesion-to-liver contrast, radiologists subjectively preferred the precontract sequences because of overall better image quality. At a dose of 10 μmol/kg, fenunoxides favorably impacts lesion-to-liver contrast, and may be useful in hepatic imaging, more with conventional T2-weighted spin-echo pulse sequences than with T2-weighted fast spin-echo pulse sequences.     

SPIO-enhanced 2D-TOF MR angiography of the portal venous system: Results of an intraindividual comparison

The purpose of this study was to investigate whether MR angiography (MRA) of the portal venous system may be improved by means of superparamagnetic iron oxides (SPIOs) during accumulation phase imaging and to study the underlying contrast mechanisms. MRA of the portal venous system was performed on 48 patients before and after intravenous injection of a new SPIO (Resovist, Schering AG, Berlin, Germany). Resovist, as a predominantly liver parenchymal darkening agent on T2-weighted MR images with uptake into the reticuloendothelial cell system, was administered intravenously by bolus injection of 8 to 12 μmol Fe/kg body weight. Patients were scanned with breath-hold coronal and axial two-dimensional (2D) time of flight (TOF) MRA (TR = 31.0 msec, TE = 9.8 msec, flip angle (FA) = 50°, and 6.9-second acquisition time per section) sequences. Signal intensity values of liver parenchyma, the portal venous system, and background were obtained for quantitative analysis. The clinical relevance of additional plain and contrast-enhanced MRA studies for surgical planning was assessed by independent reading of three readers. Liver signal-to-noise ratio (SNR) significantly decreased following iv injection of Resovist; however, SNR values of the portal veins or hepatic veins did not change significantly. Visibility of the portal venous system improved significantly (tertiary branches visible: pre in 15.2% versus post in 87.0% of patients). Resovist-enhanced 2D-TOF MRA may improve planning of liver resections by better demonstrating the relationship of central liver lesions and vessels on source images. The decrease in liver SNR at a constant vessel SNR after iv injection of Resovist improves MRA of the liver. SPIO-enhanced 2D-TOF MRA scans are superior to plain 2D-TOF MRA studies and may be added for the workup of preoperative patients.     

Enhancement effects of a hepatocyte receptor—specific MR contrast agent in an animal model

The enhancement characteristics of the liver and spleen produced by a hepatocyte-specific magnetic resonance imaging agent, an arabinogalactan-coated ultrasmall superparamagnetic iron oxide derivative, BMS 180550, were evaluated. Both heavily T1- and T2-weighted sequences were used. Imaging was performed in the farm pig model, as a function of contrast agent concentration (5, 10, and 20 μmol of iron per kilogram) and delay (immediate, 0.5, 2.5, 5.0, 7.5, and 9.0 hours) after bolus injection of BMS 180550. BMS 180550 provided excellent contrast enhancement characteristics by producing marked positive enhancement with T1-weighted sequences and marked negative enhancement with T2-weighted sequences. The T1-weighted enhancement immediately after contrast agent injection was of greater magnitude in the spleen (329% ± 83) than in the liver (66% ± 16). Postcontrast negative enhancement with T2-weighted sequences was largely hepatocyte specific at 5 and 10 μmol/kg but was also seen within the spleen at 20 μmol/kg. The authors discuss the possible mechanisms that produce these changes and conclude that 10 μmol/kg BMS 180550 is near the optimum dose for maximizing the enhancement properties of this agent with all sequences in the farm pig.     

Contrast-enhanced MR imaging of liver and spleen: First experience in humans with a new superparamagnetic iron oxide

The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 μmol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 μmol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P <.05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 μmol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 μmol Fe/kg for the liver and 12.8 μmol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent.     

Hepatocellular carcinoma in cirrhosis: enhancement patterns at dynamic gadolinium- and superparamagnetic iron oxide-enhanced T1-weighted MR imaging

PURPOSE: To prospectively compare intraindividual differences in enhancement patterns between gadolinium- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging in patients with histologically proved hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-two patients (18 men, four women; mean age, 58.9 years) with 36 pathologically proved HCC lesions underwent contrast material-enhanced dynamic T1-weighted gradient-echo MR imaging twice. Gadopentetate dimeglumine was used at the first session. After a mean interval of 5 days, a second session was performed with a bolus-injectable SPIO agent, ferucarbotran. Qualitative analysis of contrast enhancement patterns with each agent during hepatic arterial, portal venous, and equilibrium phases was performed by two readers who classified lesions as isointense, hypointense, or hyperintense compared with surrounding liver parenchyma and searched for presence of hyperintense peritumoral ring enhancement. Results of signal intensity analysis during different vascular phases at both sessions were compared by using the McNemar test, and kappa statistic was used to evaluate agreement between signal intensity and enhancement pattern of lesions during different vascular phases. RESULTS: On gadolinium-enhanced hepatic arterial phase images, HCC lesions (n = 36) were hyperintense in 21 (58%) cases, hypointense in 10 (28%), and isointense in five (14%). On ferucarbotran-enhanced hepatic arterial phase images, HCC lesions were isointense in 18 (50%) cases, hypointense in 11 (31%), and hyperintense in seven (19%). On gadolinium-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 17 (47%) and 21 (58%) cases, hyperintense in 10 (28%) cases and one (3%) case, and isointense in nine (25%) and 14 (39%) cases. On ferucarbotran-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 15 (42%) and 11 (31%) cases, hyperintense in three (8%) and three (8%) cases, and isointense in 18 (50%) and 22 (61%) cases. CONCLUSION: For HCC, contrast enhancement pattern on T1-weighted gradient-echo MR images shows marked variability with gadolinium or SPIO contrast agents.     

Coronary MR angiography using citrate‐coated very small superparamagnetic iron oxide particles as blood‐pool contrast agent: Initial experience in humans

Purpose:

To evaluate very small superparamagnetic iron oxide particles (VSOP‐C184) as blood‐pool contrast agent for coronary MR angiography (CMRA) in humans.

Materials and Methods:

Six healthy volunteers and 14 patients with suspected coronary artery disease underwent CMRA after administration of VSOP‐C184 at the following doses: 20 μmol Fe/kg (4 patients), 40 μmol Fe/kg (5 patients), 45 μmol Fe/kg (6 healthy volunteers), and 60 μmol Fe/kg (5 patients). In healthy volunteers, contrast‐to‐noise ratio (CNR), signal‐to‐noise ratio (SNR), and vessel edge definition (VED) of contrast‐enhanced CMRA were compared with non–contrast‐enhanced CMRA. In patients, a per‐segment intention‐to‐diagnose evaluation of contrast‐enhanced CMRA for detection of significant coronary stenosis (≥50%) was performed.

Results:

Three healthy volunteers (45 μmol Fe/kg VSOP‐C184) and two patients (60 μmol Fe/kg VSOP‐C184) had adverse events of mild or moderate intensity. VSOP‐C184 significantly increased CNR (15.1 ± 4.6 versus 6.9 ± 1.9; P = 0.010), SNR (21.7 ± 5.3 versus 15.4 ± 1.6; P = 0.048), and VED (2.3 ± 0.6 versus 1.2 ± 0.2; P < 0.001) compared with non–contrast‐enhanced CMRA. In patients, contrast‐enhanced CMRA yielded sensitivity, specificity, and diagnostic accuracy for detection of significant coronary stenosis of 86.7%, 71.0%, 73.1%, respectively.

Conclusion:

CMRA using VSOP‐C184 was feasible and yielded moderate diagnostic accuracy for detection of significant coronary stenosis within this proof‐of‐concept setting. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

MR assessment of iodinated contrast-medium-induced nephropathy in rats using ultrasmall particles of iron oxide

The purpose of this study was to determine the diagnostic value of ultrasmall particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations to evaluate experimental nephropathy. This study was conducted in 23 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Eleven rats received selective intra-arterial renal administration of diatrizoate (370 mg I/m1) and were compared to two control groups, including five animals injected with isotonic saline and seven noninjected animals. MR imaging was performed 28 hours after the procedure, including T1- and T2-weighted images before and after intravenous administration of successively 5 μmol Fe/kg and 60 μmol/kg of USPIO. Results were interpreted qualitatively and quantitatively with respect to pathologic data, and differences were studied statistically. The maximal signal intensity decrease was noted in normal kidneys in cortex (?65 ± 4%) and medulla (?84 ± 5%) on T2-weighted images after injection of 60 μmol/kg of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative analysis showed that the highest sensitivity and specificity to diagnose kidney involvement were obtained with T2-weighted MR images (75% and 91%, respectively) when 60 μmol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo evaluation of the severity of experimentally induced iodinated contrast media renal impairment in animals.     

多层螺旋CT双通路注射法行肝门静脉系统成像的研究

目的:确定多层螺旋CT肝门静脉系统检查的合理延迟时间及双通路注射对比剂法的可行性。方法:分为2个步骤研究:①随机选择无腹部及心血管疾患的患者53例,以3 ml/s速率注射造影剂20 ml,行同层动态扫描,计算腹主动脉、肝门静脉、下腔静脉、肝实质的对比剂时间密度曲线,及它们的相关性。②47例需门静脉检查的患者,行MDCT肝区移床式、动态扫描,在右肘部静脉及下肢静脉同时注入对比剂,对比剂总量1.5~2 ml/kg。扫描时使用对比剂自动示踪软件,设动脉血管阈值为120 HU启动扫描,动脉期扫描完成后延时20.1±5.54 s行门静脉扫描,分别评价肝门静脉、肝静脉、下腔静脉的显示率及程度。结果:①20 ml对比剂注射同层动态扫描肝门层面腹主动脉达峰时间为18.5±4.81 s,肝门静脉达峰时间是38.61±6.59 s,下腔静脉达峰时间是55.44±12.16 s,肝实质的达峰时间是56±5.7 s。②肝门静脉显示率达100%,肝门静脉主干等显示程度平均评分2.50~2.93;相关小分支静脉显示率为87%~98%,显示平均评分2.25~2.63。结论:MDCT右肘部静脉及下肢静脉同时注入对比剂,在动脉期扫描完成后,延时20.1±5.54 s行肝门静脉检查,肝门静脉系统成像效果良好。     

Early radiation effects on the liver demonstrated on superparamegnetic iron oxide-enhanced T1-weighted MRI

Early radiation-induced liver injury during radiotherapy detected by a particulate reticuloendothelial MR contrast agent (superparamagnetic iron oxide; SPIO) is described in a patient with cholangiocarcinoma. The irradiated hepatic parenchyma appeared as a heterogeneous, less decreased signal intensity area than the nonirradiated area on MR images after SPIO administration. Resultant differences in signal intensity were better visualized on SPIO-enhanced T1-weighted images than SPIO-enhanced T2-weighted images, although SPIO-enhanced T2*-weighted fast field echo imaging was the most sensitive.     

The diagnosis of splenic lymphoma by MR imaging: value of superparamagnetic iron oxide

This study was designed to evaluate superparamagnetic iron oxide (AMI-25) as a contrast agent for MR to distinguish normal spleens from those diffusely infiltrated by lymphoma. As diffuse splenic involvement lacks visible tumor-tissue boundaries, signal-intensity measurements of spleens were used as a diagnostic criterion in 33 patients (lymphoma, n = 8; benign splenomegaly, n = 5; normal subjects, n = 20). Unenhanced MR images were insensitive (four of eight patients) and nonspecific (20 of 25 patients) in the diagnosis of lymphoma. After injection of superparamagnetic iron oxide (40 mumol Fe/kg), lymphomatous spleens showed a significantly higher signal intensity (p less than .05) than did normal spleens or spleens enlarged by benign disease (hepatic cirrhosis, n = 4; spherocytosis, n = 1). Changes in splenic MR signal intensity unambiguously identified eight of eight lymphomatous spleens and 25 of 25 normal or enlarged spleens that did not contain lymphoma. Phagocytosis of superparamagnetic iron oxide in lymphomatous spleens is reduced because of diffuse displacement of splenic macrophages by lymphoma cells and/or by immunologic suppression of macrophage activity. Our results suggest that superparamagnetic iron oxide (AMI-25) can improve the accuracy of MR imaging in the diagnosis of splenic lymphoma. With further development, this noninvasive technique may reduce the need for diagnostic splenectomy in lymphoma patients.     

Application of a superparamagnetic iron oxide (Resovis®) for MR imaging of human cerebral blood volume

The authors describe the feasibility of dynamic MRI using a novel superparamagnetic iron oxide contrast agent. Resovist® was injected as a bolus at doses of 4, 8, and 16 μmol Fe/kg bodyweight in three consented patients participating in a Phase 2 clinical multicenter trial for hepatic MRI. Dynamic images of the brain were obtained with a conventional FLASH sequence. Results were analyzed by evaluation of dynamic images, cerebral blood volume maps, and normalized signal intensity time curves. Resovist® enabled rapid injections and a dose-dependent strong reduction in gray and white matter signal intensity. The small injection volume and good tolerability may enable Resovist® to serve as a perfusion agent. Dedicated clinical trials are warranted to assess the potentials of Resovist® for perfusion MRI and fMRI.     

Contrast enhancement with GD-EOB-DTPA in MR imaging of hepatocellular carcinoma in mice: A comparison with superparamagnetic iron oxide

The purpose of this study was to evaluate the ability of the new liver-specific magnetic resonance contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) to detect hepatocellular carcinoma (HCC). Seventeen mice with 66 chemically induced HCCs underwent magnetic resonance imaging with both Gd-EOB-DTPA (30 μmol/kg) and superparamagnetic iron oxide (SPIO; 10 μmol/kg). After enhancement, lesion-to-liver contrast-to-noise ratios (CNRs) of 47 detected HCCs increased negatively from 3.7 ± 10.7 (mean ± SD) to –55.1 ± 25.8 with Gd-EOB-DTPA (P < .001) and increased positively from 10.4 ± 10.4 to 26.1 ± 16.3 with SPIO (P < .001). The improvement of CNR after administration of SPIO was less in smaller lesions (< 4 mm), whereas that after administration of Gd-EOB-DTPA was independent of lesion size. However, Gd-EOB-DTPA positively enhanced four HCCs (8.5%), both highly differentiated (grade 1) and moderately differentiated (grade 2). Gd-EOB-DTPA allows the conspicuous detection of small HCCs; however, moderately differentiated HCCs occasionally may be positively enhanced.     

肝脏MR动态增强扫描：Gd-EOB-DTPA与Gd-DTPA的个体内对照研究

目的：比较钆塞酸二钠（Gd-EOB-DTPA）及钆喷酸葡胺（Gd-DTPA）肝脏 MR动态增强扫描腹腔脏器及血管的强化特点,重点比较Gd-EOB-DTPA移行期与Gd-DTPA平衡期的图像特点。方法：本研究为前瞻性、个体内随机对照研究。25例病理证实为原发直肠癌或结肠癌、怀疑肝转移的患者,3天内行2次肝脏 MR 动态增强检查,分别使用 Gd-EOB-DTPA及Gd-DTPA两种对比剂。动态增强扫描的序列相同,包括平扫、动脉期、门静脉期、平衡期（Gd-DTPA）／移行期（Gd-EOB-DTPA）。图像客观评估中,测量各期相图像上血管及肝脾实质的信号强度。以椎旁肌肉的信号为参考,计算相对信号强度（RS）并比较两组间的差异,以及不同期相时肝实质RS的差异。主观评估：读片者主观评价增强扫描各期相图像上,主动脉、门静脉及肝静脉与肝实质的相对信号强度。结果：肝实质的RS：在动脉期Gd-DTPA 组明显高于Gd-EOB-DTPA组（t＝3．006,P＝0．005）;在门静脉期及平衡期／移行期,两组检查的差异无统计学意义（t＝1．788,P＝0．086;t＝0．781,P＝0．442）。Gd-EOB-DTPA检查时,门静脉期肝实质RS明显高于动脉期（t＝－3．014,P＝0．006）,移行期RS与门静脉期的差异无统计学意义。Gd-DTPA检查时,平衡期肝实质RS明显低于门静脉期（t＝5．827,P＝0．000）。主观评估：Gd-DTPA增强扫描平衡期图像上所有患者的主动脉、门静脉、肝静脉均为高信号（100％）;Gd-EOB-DTPA 增强扫描移行期图像上主动脉、门静脉、肝静脉均以低或等信号为主（84％,92％,92％）。结论：Gd-EOB-DTPA动态增强 MR 检查,肝脏实质在门静脉期及移行期呈持续强化,其移行期的图像特征与Gd-DTPA平衡期的图像特征有明显不同,在影像诊断时应予以关注。     

Dynamic signal intensity changes in liver with superparamagnetic MR contrast agents.

The dynamic effects of three different superparamagnetic magnetic resonance (MR) contrast agents on liver signal were evaluated with an echo-planar imaging technique. The contrast agents were (a) USPIO (ultrasmall superparamagnetic iron oxide), which has a long blood half-life and was developed for MR imaging of lymph nodes and bone marrow; (b) AG (arabinogalactan)-USPIO, an asialoglycoprotein receptor--directed iron oxide with hepatocyte uptake; and (c) AMI-25, a conventional reticuloendothelial iron oxide agent. Dynamic liver signal intensity (SI) curves reflect different uptake mechanisms for the different agents. Receptor blocking experiments indicate that intracellular redistribution or clustering of the AG-USPIO (known to occur from electron microscopy studies) does not contribute to the decrease in liver SI. Monitoring liver SI over time with echo-planar imaging may provide a better understanding of the kinetics of the growing number of MR contrast agents and allow optimization of imaging protocols to exploit peak enhancement.     

MR imaging of the liver: Effect of portal hypertension on hepatic parenchymal enhancement using a gadolinium chelate

The purpose of this study was to prospectively investigate the extent to which reduced portal blood flow in patients with hepatic cirrhosis and portal hypertension affects hepatic parenchymal enhancement during gadolinium-chelate-enhanced dynamic MR imaging. Breath-hold three-dimensional (3D) spoiled gradientrecalled echo (GRE) MR imaging technique obtained after intravenous administration of a gadolinium chelate was used to measure hepatic parenchymal enhancement and time to peak enhancement in 20 patients with hepatic cirrhosis and clinical evidence of portal hypertension (group 1) and in 20 control subjects without portal hypertension (group 2) who were matched for age, sex, and body weight. Mean peak hepatic enhancement values ± SD and times to peak enhancement ± SD were determined for both groups of patients. Mean peak enhancement value (±SD) was 78.7% ± 36.2 in group 1 and 91.6% ± 46.2 in group 2 (not significant). However, in the nine patients in group 1 with splenomegaly, mean peak enhancement value was 61.3% ± 14.4, whereas it was 93.0% ± 42.7 in the 11 patients without splenomegaly (P < .05). Mean time to peak enhancement was 84 seconds ± 23 in group 1 and 54.0 sec ± 25.0 in group 2 (P < .01). Our results show that mean peak enhancement value of hepatic parenchyma after intravenous administration of a gadolinium chelate is significantly altered for patients with portal hypertension and splenomegaly. In addition, the time to peak enhancement is delayed significantly when portal hypertension is present. Thus, it is possible that the optimal time for imaging the liver during the portal phase must be tailored to the status of the portal system of the patient.     

Enhancement efficacy of magnetic starch microspheres (MSM) in conventional spin-echo and turbo spin-echo sequences at 0.5 T and 1.5 T

The efficacy of the superparamagnetic contrast agent magnetic starch microspheres (MSM) was evaluated in vitro by NMR relaxometry and in vivo by MR imaging using T2-weighted spin-echo (SE) and turbo spin-echo (TSE) sequences at 0.5 T and 1.5 T in 60 normal rats who received MSM in doses of 10–50 μmol/kg. MR imaging was performed using T2-weighted SE and TSE sequences. The relaxation rates 1/T1 and 1/T2 for liver and spleen increased linearly with MSM concentrations up to 30 μmol/kg body weight, and approached almost constant levels for higher doses. The slopes in the linear part of the 1/T2 diagram were 0.62 Hz ± 0.03 for the liver and 0.51 Hz ± 0.06 × kg/μmol for the spleen. On all T2-weighted sequences at 0.5 T and 1.5 T, liver signal-to-noise ratio (SNR) decreased by a factor of 2-3 already at the lowest dose of 10 μmol/kg. SNR values of TSE sequences exceeded values for SE sequences by 50–80%. The SNR decrease was not significantly different between SE and TSE sequences. Our results show that MSM is well suited as a T2 contrast agent at both magnetic field strengths when using conventional SE and fast TSE sequences.     

Iron oxide-enhanced MR lymphography: The evaluation of cervical lymph node metastases in head and neck cancer

Accurate diagnosis of cervical lymph node metastasis is challenging, even with the latest computed tomography or MR equipment and technique. The lack of definitive criteria for distinguishing metastatic from benign nodes is a serious shortcoming of current imaging options. Dextran-coated, ultrasmall superparamagnetic iron oxide is a new MR contrast agent, which accumulates in the reticuloendothelial system of lymph nodes. Small iron oxide particles are taken up by macrophages within normal functioning nodes, reducing their signal on postcontrast MR because of the magnetic susceptibility effects of iron oxide. Metastatic nodes, on the other hand, remain high in signal on postcontrast T2*-weighted gradient echo images. Early clinical experience in cancer patients suggests that iron oxide-enhanced MR lymphography is a valuable imaging technique that may improve diagnostic accuracy for nodal metastases. This article reviews development of superparamagnetic iron oxide compounds, their imaging characteristics, and clinical experience for evaluating head and neck cancer metastases.     

Pulmonary hemorrhage: Imaging with a new magnetic resonance blood pool agent in conjunction with breathheld three-dimensional magnetic resonance angiography

Purpose: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. Methods: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30°) were acquired breathheld over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. Results: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. Conclusion: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.     

Preliminary evaluation of a polyethyleneglycol-stabilized manganese-substituted hydroxylapatite as an intravascular contrast agent for MR angiography

A blood-persistent particulate paramagnetic contrast agent has been formulated via size stabilization of manganese-substituted hydroxylapatite by a polyethylene glycol (PEG) bearing a terminal diphosphonate. At high PEG surface densities (35–40 mol %), particles with mean diameter 8 ± 2 nm were obtained. Relaxivities of autoclaved samples (at 20 MHz proton Lamor frequency) were R1 = 18.7 ± .8 mM^?1 sec^?1 and R2 = 22.3 ± .7 mM^?1 sec^?1. The formulation persisted in rabbit blood with a biphasic clearance profile. Halflives (with amplitudes in parenthesis) were 4 ± 1 minutes (55%), and 49 ± 3 minutes (45%), respectively, for the two phases. A dose of 40 μmol Mn/kg body weight enhanced the signal from rabbit vasculature for more than 45 minutes on MR angiograms. Thus, PEG-modified MnHA particles may find use as T1 agents for MR angiography.     

Contrast-enhanced three-dimensional MR portography.

Three-dimensional (3D) magnetic resonance (MR) portography with contrast material enhancement is a fast means of evaluating the portal venous system that has some advantages over currently used modalities, such as digital subtraction angiography, helical computed tomography, ultrasonography, and nonenhanced MR angiography with time-of-flight and phase-contrast techniques. With contrast-enhanced 3D MR portography, a first-pass study of the mesenteric vasculature is performed after rapid bolus injection of gadopentetate dimeglumine; a 3D fast field echo sequence is used, which can demonstrate the intrahepatic and extrahepatic portal venous system clearly. Repeated sequences after administration of gadopentetate dimeglumine allow separate demonstration of the splanchnic arteries and portomesenteric veins. The images are reconstructed by means of maximum-intensity projection postprocessing, and a subtraction technique can be used to eliminate arterial enhancement and demonstrate portosystemic shunts. The coronal source images simultaneously demonstrate parenchymal lesions of the liver, pancreas, biliary tract, and spleen. This technique is clinically indicated in portosystemic shunt, portal vein thrombosis, hepatocellular carcinoma, pancreatobiliary tumor, hepatic vein obstruction, differentiation of splanchnic arterial from portal venous disease, and gastrointestinal hemorrhage. Its limitations include allergic reactions to contrast media, inappropriate positioning of the 3D acquisition slab, respiratory motion artifacts, and pseudodissection.