Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.     

Structural effect on degradability and in vivo contrast enhancement of polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast agents

The structural effect of biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents, polydisulfide gadolinium (Gd)(III) chelates, on their in vitro degradability, and cardiovascular and tumor imaging were evaluated in mice. Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA l-cystine copolymers (GDCP), Gd-DTPA d-cystine copolymers (dGDCP) and Gd-DTPA glutathione (oxidized) copolymers (GDGP), with different sizes and narrow molecular weight distribution were prepared and evaluated both in vitro and in vivo in mice bearing MDA-MB-231 tumor xenografts. GDGP with large steric hindrance around the disulfide bonds had greater T(1) and T(2) relaxivities than GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous thiols decreased with increasing steric effects around the disulfide bonds in the order of GDCC>GDCP, dGDCP>GDGP. The size and degradability of the contrast agents had a significant impact on vascular contrast enhancement kinetics. The agents with a large size and low degradability resulted in more prolonged vascular enhancement than the agents with a small size and high degradability. It seems that the size and degradability of the agents did not significantly affect tumor enhancement. All agents resulted in significant contrast enhancement in tumor tissue. This study has demonstrated that the vascular enhancement kinetics of the polydisulfide MRI contrast agents can be controlled by their sizes and structures. The polydisulfide Gd(III) chelates are promising biodegradable macromolecular MRI contrast agents for magnetic resonance angiography and cancer imaging.     

MR imaging of liver abscesses; application of Gd-DTPA

The potential utility of Gd-DTPA contrast enhancement of MR images in the evaluation of liver abscesses was assessed in rodents. Twelve rats with surgically implanted sterile liver abscesses were imaged at various stages of focal hepatic inflammation, 48 hours, 4 days, 7 days, 14 days and 21 days after lesion induction. Spin echo images, acquired before and repeatedly after intravenous injection of 0.2 mmol/kg Gd-DTPA, demonstrated improvement of the lesion-to-background contrast ranging from 2% to 40% depending on the stage of the disease. The enhancement pattern also varied with abscess evolution. Two, four and seven-day-old abscesses typically showed a ring enhancement, whereas two- and three-week-old abscesses presented largely homogeneously enhancing lesions. In the earlier lesions, contrast enhanced rim surrounding the low intensity center corresponded histologically to the formation of a capsule consisting of fibrous tissue and inflammatory cells. The center was necrotic. Data show that abscesses can be detected on images acquired with long repetition and echo times without injection of Gd-DTPA. The administration of Gd-DTPA, however, improved the lesion-to-background contrast and helped to define the abscess capsule evolution.     

Step-down infusions of Gd-DTPA yield greater contrast-enhanced magnetic resonance images of BBB damage in acute stroke than bolus injections

A rat model of transient suture occlusion of one middle cerebral artery (MCA) was used to create a unilateral reperfused cerebral ischemic infarct with blood-brain barrier (BBB) opening. Opening of the BBB was visualized and quantitated by magnetic resonance (MR) contrast enhancement with a Look-Locker T(1)-weighted sequence either following an intravenous bolus injection (n=7) or during a step-down infusion (n=7) of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). Blood levels of Gd-DTPA after either input were monitored via changes in sagittal sinus relaxation rate. Blood-to-brain influx constants (K(i)) were calculated by Patlak plots. On the basis of the MRI parameters and lesion size, the ischemic injury was determined to be similar in the two groups. The bolus injection input produced a sharp rise in blood levels of Gd-DTPA that declined quickly, whereas the step-down infusion led to a sharp rise that was maintained relatively constant for the period of imaging. Visual contrast enhancement and signal-to-noise (S/N) ratios were better with the step-down method (S/N=1.8) than with bolus injection (S/N=1.3). The K(i) values were not significantly different between the two groups (P>.05) and were around 0.005 ml/(g min). The major reason for the better imaging of BBB opening by the step-down infusion was the higher amounts of Gd-DTPA in plasma and tissue during most of the experimental period. These results suggest that step-down MR contrast agent (MRCA) administration schedule may be more advantageous for detection and delineation of acute BBB injury than the usually used bolus injections.     

Biodistribution of GdCl3 and Gd-DTPA and their influence on proton magnetic relaxation in rat tissues

The biodistribution and relative molar effectiveness of the ionic (GdCl3) and chelated (Gd-DTPA) forms of gadolinium (Gd) to enhance proton relaxation rates in rat kidney, liver and spleen were evaluated. Rats were given intravenous injections of either GdCl3 (100 mumol/kg) or Gd-DTPA (178 mumol/kg). Gd-DTPA was primarily contained in the vascular compartment and was quickly accumulated in the kidney after injection with a relaxivity of 4.3 sec-1 (mumol/g kidney)-1. It was eliminated quickly from the body with only 2% of the injected dose remaining after 120 min. After GdCl3 injection, Gd was found primarily in liver and spleen. It accumulated continuously reaching 72% of the injected does in these two tissues after 120 min. Despite this continuous increase in tissue Gd concentration, the relaxation rates showed saturation in liver and spleen. The results suggest that after GdCl3 was injected it distributed either in a protein bound form that was effective at causing relaxation or in a colloid form that was not effective. The biodistribution of GdCl3 was such that it was determined by the phagocytic action of the recticuloendothelial system on a colloid. The biodistribution and tissue relaxivity of Gd-DTPA suggest it will be a useful vascular MRI contrast agent. However, the usefulness of GdCl3 as an MRI contrast agent is limited not only by its acute toxicity but also by its saturable effect on tissue relaxation rates. Consequently, GdCl3 has only a modest influence on tissue relaxivity.     

In vivo MR evaluation of Gd-DTPA conjugated to dextran in normal rabbits.

A dextran-Gd-DTPA compound has been recently synthesized utilizing 70,800 Da molecular weight dextran. This polymeric contrast agent for magnetic resonance imaging has been found chemically to be very stable and to demonstrate in vitro improved relaxivities of 1.5 to 2.3 times that of monomeric Gd-DTPA at 100 MHz. This MR experiment examines the in vivo distribution and relaxivity of the 70,800 Da molecular weight dextran-Gd-DTPA compound in a rabbit model by measuring the change in signal-to-noise ratio of a variety of organs (renal cortex, renal medulla, liver, brain, and torcula herophile) compared to the preinjection state. Results demonstrate prolonged (beyond 60 min) enhancement of the renal cortex, renal medulla, liver and torcula, and no enhancement of brain parenchyma.     

A comparative evaluation of CH3-DTPA-Gd (NMS60) for contrast-enhanced magnetic resonance angiography

In a canine model the signal dynamics of a new oligomer-based MR contrast agent (NMS60, 2158 Da) were compared to Gd-DTPA to investigate the agents' potential for magnetic resonance angiography (MRA). Twelve male mongrel dogs were imaged sequentially under anesthesia with two different MRA sequences (Tlw 3DSPGR). Initial enhancement was measured every 9 s for eight points in time. Thereafter, spatial highly resolved MRAs were obtained at 5, 10, 15, 20, 30, 45, and 60 min post-injection of two different dosages. Over the first 20 s following bolus administration the average arterial enhancement of 0.1 mmol(Gd)kg NMS60 was 44% greater than Gd-DTPA. Twenty minutes post-injection the relative signal intensity of NMS60 was as high as the peak signal intensity with Gd-DTPA at the same dosage level (0.1 mmol(Gd)/kg). In the animals that received NMS60 injections the vascular conspicuity was overly superior to those who received Gd-DTPA. No significant toxicity effects were noted for either dosage level. The intermediate weight contrast agent NMS60 offers greater vascular enhancement and retention time than Gd-DTPA. For a given set of optimized imaging parameters this offers improved spatial details, less arterial/venous overlap, and better vascular contrast.     

The prospective evaluation of Gd-DTPA in 225 consecutive cranial cases: adverse reactions and diagnostic value

This prospective study evaluates two facets of gadopentetate dimeglumine (Gd-DTPA) enhanced MR imaging in 225 consecutive cranial cases in patients greater than 18 years of age: (i) patient and physician perception of adverse reactions, (ii) diagnostic value of the Gd-DTPA enhanced exam. The 225 cases included 173 head cases, 27 IAC cases, and 25 sella cases. Forty-six percent of the cases were abnormal excluding cases of mild atrophy and ischemic white matter disease judged to be related to aging and not pertinent to the patient's presenting complaint. Concerning adverse reactions, 83% of patients had no complaints. Five percent of the patients had reactions that were judged by the physician to be related to Gd-DTPA. All reactions were minor and required no therapy. In a subset of exams (115) that were blindly and independently interpreted by two board-certified, fellowship-trained radiologists, the Gd-DTPA-enhanced exam resulted in a change in diagnosis in 5%-8% of cases. Additionally, a major benefit of Gd-DTPA administration was the increased diagnostic confidence afforded by the addition of a contrast enhanced exam due to improved lesion characterization and exclusion of additional significant intracranial pathology. In 52%-69% of the abnormal cases, Gd-DTPA provided additional diagnostic information and in 26%-39% the absence of enhancement aided in interpretation. The Gd-DTPA-enhanced exam aids in the diagnosis and characterization of neoplastic disease, acoustic neuroma, subacute infarction, inflammatory disease (meningeal and parenchymal), and certain vascular abnormalities.     

Contrast-enhanced MR angiography in rats with hepatobiliary contrast agents

The aim of this animal study was to evaluate the feasibility of contrast-enhanced magnetic resonance (MR) angiography with two hepatobiliary contrast agents, Gd-DTPA-DeA and Gd-EOB-DTPA. Coronal images of the rat abdomen were acquired using a three-dimensional spoiled gradient recalled sequence before and after the administration of Gd-DTPA-DeA, Gd-EOB-DTPA, or Gd-DTPA. Four sets of postcontrast images were collected every 90 s. Contrast ratios were calculated for the abdominal aorta on the source images, and the retention index was defined as the ratio of the contrast ratio on the last imaging to that on the first postcontrast imaging. Partial minimum intensity projection (MIP) images covering the abdominal aorta were generated from the first and second postcontrast imagings, and the image quality was visually evaluated. The contrast ratio on the first postcontrast imaging was the highest for Gd-DTPA-DeA, followed by Gd-EOB-DTPA and Gd-DTPA. Retention indices were higher with Gd-DTPA-DeA than with Gd-EOB-DTPA and Gd-DTPA, implying a prolonged contrast effect with Gd-DTPA-DeA. On the MIP image from the first postcontrast imaging, delineation of the abdominal aorta tended to be better with Gd-DTPA-DeA and Gd-EOB-DTPA than with Gd-DTPA, and the difference was evident at low injection doses. Image quality for the second postcontrast imaging was higher with Gd-DTPA-DeA than with the other two agents, suggesting a longer imaging window for Gd-DTPA-DeA. In conclusion, Gd-DTPA-DeA and Gd-EOB-DTPA showed stronger contrast enhancement for the rat abdominal aorta and provided MR angiograms of higher image quality when compared with Gd-DTPA at the same injection dose. These hepatobiliary agents may make it possible to perform contrast-enhanced MR angiography even at a low injection dose.     

An MRA study of vascular stenosis in a pig model using CH3-DTPA-Gd (NMS60) and Gd-DTPA

PURPOSE: This study used an experimental arterial stenosis model in pigs to evaluate the utility of a new medium-weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd complex containing three Gd(3+) atoms, molecular weight of 2158 Da) compared to Gd-DTPA for contrast-enhanced MRA. MATERIALS AND METHODS: We used six male white hybrid pigs. Under anesthesia, one femoral artery was exposed and an inflatable cuff placed around it. The cuff was tightened around the vessel until 80-90% stenosis was achieved using digital subtraction angiography as a guide. Animals were then immediately transferred to the MRI scanner and images acquired pre- and postcontrast injection (0.1 or 0.2 mmol Gd/kg Gd-DTPA or NMS60, as a rapid bolus) using high-resolution and dynamic MRA. RESULTS: The dynamic MRA scans acquired during contrast bolus injection clearly showed the stenosed femoral artery as a segment of close to zero enhancement during the arterial phase of the bolus transit, while on the high-resolution scans the stenosis was difficult to detect due to venous signal contamination. The signal-to-noise at peak enhancement on the dynamic scans was significantly greater with 0.1 mmol Gd/kg NMS60 compared to 0.1 mmol Gd/kg Gd-DTPA (14.6 vs. 9.9, P < .05) and not significantly greater than 0.2 mmol Gd/kg (14.6 vs. 12.8). DISCUSSION AND CONCLUSION: This new medium-weight contrast agent demonstrated significantly greater enhancement than Gd-DTPA and may be valuable to aid detection of vascular stenosis in humans.     

Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.     

Gadolinium-DTPA-enhanced MRI of intraocular tumors

The value of gadolinium-enhanced MRI in 30 patients with intraocular lesions has been evaluated. Seventeen patients had a uveal melanoma, two a ciliary body melanoma, three had uveal metastases, one lymphoma, four had senile macula degenerations, and three uveal nevi. Twelve of 17 patients with melanoma were followed up by MRI after ruthenium plaque therapy on 2–4 occasions. Melanomas showed high precontrast signal intensities and only a slight enhancement after intravenous Gd-DTPA was given. After ruthenium plaque therapy precontrast signal intensities (SI) decreased while a moderate signal increase on postcontrast scans was noted. Scars or tumor residues were better delineated on enhanced images. All other tumors than melanotic melanomas showed low SI on precontrast scans and a high signal increase after Gd-DTPA administration. Small amelanotic tumors were better delineated on postcontrast scans. In addition Gd-DTPA-enhanced MRI allowed differentiation between tumor and hemorrhage. No signal increase after Gd-DTPA application was seen in subretinal or vitreous hemorrhages of varying ages.     

An evaluation of gadolinium polyoxometalates as possible MRI contrast agent

Two gadolinium polyoxometalates, K(9)GdW(10)O(36) and K(11)[Gd(PW(11)O(39))(2)], have been evaluated both in vivo and in vitro as candidates for tissue-specific MRI contrast agents. T(1)-relaxivities of 6.89 mM(-1). s(-1) for K(9)GdW(10)O(36) and 5.27 mM(-1). s(-1) for K(11)[Gd(PW(11)O(39))(2)] are slightly higher than that of the commercial MRI contrast agent (Gd-DTPA). Both compounds bind with bovine serum albumin and human serum transferrin and favorable liver-specific contrast enhancement in in vivo MRI with Sprague-Dawley rats after i.v. administration has been demonstrated. Imaging studies demonstrate that the two agents have a long residence time, showing MR signal enhancement in the liver for more than 40 min, longer than commercially available contrast agents. In vivo and in vitro assays showed that GdW(10) and Gd(PW(11))(2) are promising liver-specific MRI contrast agents and GdW(10) may be used in the diagnosis of the pathological state. However, with the higher acute toxicity, the two gadolinium polyoxometalates need to be modified and studied further before clinical use.     

3D spin-lock imaging of human gliomas

We investigated whether the simultaneous use of paramagnetic contrast medium and 3D on-resonance spin lock (SL) imaging could improve the contrast of enhancing brain tumors at 0.1 T. A phantom containing serial concentrations of gadopentetate dimeglumine (Gd-DTPA) in cross-linked bovine serum albumin (BSA) was imaged. Eleven patients with histologically verified glioma were also studied. T₁-weighted 3D gradient echo images with and without SL pulse were acquired before and after a Gd-DTPA injection. SL effect, contrast, and contrast-to-noise ratio (CNR) were calculated for each patient. In the glioma patients, the SL effect was significantly smaller in the tumor than in the white and gray matter both before (p = 0.001, p = 0.025, respectively), and after contrast medium injection (p < 0.001, p < 0.001, respectively). On post-contrast images, SL imaging significantly improved tumor contrast (p = 0.001) whereas tumor CNR decreased slightly (p = 0.024). The combined use of SL imaging and paramagnetic Gd-DTPA contrast agent offers a modality for improving tumor contrast in magnetic resonance imaging (MRI) of enhancing brain tumors. 3D gradient echo SL imaging has also shown potential to increase tissue characterization properties of MR imaging of human gliomas.     

The effect of Gd-DTPA on T(1)-weighted choline signal in human brain tumours

The influence of Gd-DTPA on T(1)-weighted (T(1)W) proton MR spectra has been investigated in 19 patients with histologically verified low (n = 13) or high-grade (n = 6) gliomas. Repeat measurements were performed on 9 patients (7 low-grade and 2 high-grade), with 28 examinations performed in total. Comparison of spectra obtained before and after 0.2 mmol/kg Gd-DTPA showed contrast agent induced broadening of the choline signal without significant signal area change. Lack of enhancement of the choline signal with the T(1)-weighted acquisitions implies that the contrast agent and the trimethylamine-containing species do not undergo significant direct interaction. Contrast agent induced changes in the choline signal observed in this and previous studies may, therefore, be attributable to T2*/susceptibility-based effects.     

NMR imaging study of the pharmacodynamics of polylysine-gadolinium-DTPA in the rabbit and the rat

The pharmacodynamics of polylysine-(Gd-DTPA) (Schering, Berlin, Germany), a new blood pooling contrast agent for MRI, were studied in the rabbit and the rat. Polylysine-(Gd-DTPA) is a compound with high LD50. Due to its high molecular weight (50.000) and physico-chemical properties, it remains in the vascular system; during the first hour, the plasma level is three times higher than for Gd-DTPA. MRI was performed at 1.5 T using a SE sequence with TR/TE = 300/15 or 20 msec. Signal intensities of muscle, liver and kidney were measured before and after intravenous injection of the contrast agent (0.1 mmol/kg) during 8 hours in the rat (n = 3) and up to 2 wk in the rabbit (n = 3). A dose response study in three additional rabbits confirmed that the 0.1 mmol/kg dose was optimal. The pharmacodynamics results show that the effects of polylysine-(Gd-DTPA) are similar in both the rabbit and the rat. The liver signal is enhanced by about 60% immediately after injection in both species. This enhanced signal decays to half its maximal value in about one hour, which makes the contrast agent useful for clinical applications at a dose of 0.1 mmol/kg. In the kidney medulla and cortex the signals are enhanced by much larger factors (about 3 to 4); it takes at least one day for the kidney to clear the contrast agent in both species.     

pH-sensitive paramagnetic liposomes for MRI: assessment of stability in blood

The pH-dependent stability of dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomal GdDTPA-BMA was investigated in human blood and after exposure to selected blood components. Relaxometry, visual observations and cryo-transmission electron microscopy (cryo-TEM) were employed for the assessment of stability. The liposomes were stable in buffer at physiological pH and the T(1)-relaxivity (r(1)) of the system was significantly lowered compared to that of non-liposomal GdDTPA-BMA, which could be explained by an exchange limited relaxation process. Lowering the pH, however, gave a marked increase in r(1), due to liposome aggregation and subsequent leakage of GdDTPA-BMA. After a few minutes incubation in human blood the liposomes were destabilised and leaky at both high and low pH, and blood components likely to cause the instability were studied. Physiological level of Na(+) (150 mM) did not affect the relaxometric behavior of the liposomes at pH 7.4, but shifted the pH-r(1) profile laterally to higher pH-values compared to a level of 50 mM Na(+). Increased screening of the surface charges and, concomitantly, a lowering of the energy-barrier against aggregation is a plausible explanation for this phenomenon. In contrast, both Ca(2+) and Mg(2+) (physiological level, both 2 mM) caused massive aggregation of the liposomes and leakage of contents, and were therefore much more detrimental to the stability of the liposomes than a physiological level of Na(+). This could be due to the higher screening ability of divalent cations, but aggregation could also be induced through an inter-liposomal "bridging" effect. Physiological level of both Na(+) and Ca(2+) caused less leakage than for lower Na(+) concentration (50 mM Na(+) and 2 mM Ca(2+)), probably due to competition for the negative surface charges. Albumin also destabilised the liposomes, and it was shown to be due to an interaction between albumin and PA in the liposomal membrane.     

Measurement of the extracellular volume of human melanoma xenografts by contrast enhanced magnetic resonance imaging

The magnitude of the extracellular volume fraction (ECV) of tumors is of importance for the transport of macromolecular therapeutic agents from the vessel wall to the tumor cells. The aim of this study was to develop a method for measurement of tumor ECV by contrast enhanced MRI. Tumors of two human amelanotic melanoma xenograft lines (A-07 and R-18) grown intradermally in Balb/c nu/nu mice were used as model system, and muscle tissue was used as control. The renal arteries of the mice were ligated prior to i.v. administration of Gd-DTPA, and an MRI protocol for calculating Gd-DTPA concentration in tissue was followed. ECV was calculated from the Gd-DTPA concentrations in the tissue and in a plasma sample. In muscle tissue, the concentration reached a constant level after 1 min and the ECV was calculated to be 0.12 (+/- 0.01), consistent with values reported in the literature. Individual tumors showed large differences in the uptake of Gd-DTPA. The Gd-DTPA concentration in the tissue at 40 min after the Gd-DTPA administration was used to calculate tumor ECV. The ECV was found to differ significantly among regions of individual tumors and among individual tumors. The ECV ranged from 0.075 to 0.33 for A-07 tumors and from 0.016 to 0.097 for R-18 tumors. The intra- and intertumor heterogeneity in ECV was confirmed by histologic findings, showing that contrast enhanced MRI is suitable for non-invasive studies of the ECV in experimental tumors without necrosis.     

Gd HP-DO3A--experimental evaluation in brain and renal MR

GD HP-DO3A, a neutral (nonionic) IV MR contrast agent presently in clinical trials, was evaluated with respect to imaging characteristics in rats. Following administration of 0.25 mmol/kg I.V., 58 +/- 19%, i.e. (n = 6) enhancement was noted in a brain gliosarcoma model. Meningeal spread of neoplasia could be identified due to its enhancement (69 +/- 26%) in nine animals. The time course of renal enhancement was quantitated at two dosages, 0.05 (n = 4) and 0.25 mmol/kg (n = 8). At the higher dose, enhancement of both cortex and medulla plateaued between 9 and 23 min postinjection. At the lower dose, enhancement of renal medulla was maximum at 2 min postinjection. These enhancement characteristics (both brain and kidney), at equivalent contrast dosages, are comparable to that previously published for Gd-DTPA. However, Gd HP-DO3A has the potential to be utilized clinically at higher doses than Gd-DTPA, with no reported adverse effects in initial trials employing up to 0.3 mmol/kg.     

MR imaging of pulmonary parenchyma and emboli by paramagnetic and superparamagnetic contrast agents

Using experimentally induced pulmonary emboli in an animal model, three intravenously administered contrast agents, Gd-DTPA-albumin microspheres (8-15 microns, 0.2 M particles/mg protein, 39-106 micrograms Gd/mg, 50 mg/ml), Gd-DTPA-liposomes (15-30 microns, 130 micrograms/mg lipid, 6 mg Gd/ml) and superparamagnetic ferrosome, (60 nm, 100 mM iron and 20 mg lipid/ml) were examined for MR imaging. Gd-DTPA entrapped in lung capillaries did not enhance the signal intensity of lung parenchyma, but liposomes (5 ml) served as better Gd-DTPA carriers and increased the parenchymal signal intensity by up to a factor of 2.3. However, neither agent improved delineation of pulmonary emboli. Ferrosome decreased the intensity of lung parenchyma, improving detectability of pulmonary emboli by several factors.