Mn[III] uroporphyrin I: a novel metalloporphyrin contrast agent for magnetic resonance imaging.

We have used an intracranial 9L rat brain tumor model to determine whether a novel metalloporphyrin, Mn[III] uroporphyrin I (MnUROP-I), could function as an intravenous MRI contrast agent for brain tumors. In several experiments, 24 male Fischer 344 rats were inoculated intracranially with 9L brain tumor cells. On day 15 postinoculation, animals were anesthetized and the femoral vein exposed. Prior to the intravenous injection of the contrast agent, a precontrast scan (1 Tesla in a standard head coil) was performed. Thirty min after injection of the contrast agent, a postcontrast scan was performed. Although there was only a suggestion of abnormality on the precontrast scans, the presence of tumor was visibility enhanced in the postcontrast scans. In 3 animals scanned at 24 hr postinjection, persistent tumor enhancement was demonstrated. Measured tumor sizes on the MRI scans were consistent with sizes measured at autopsy and histologically. These results demonstrate that MnUROP-I is an effective MRI contrast agent for the detection of an intracranial brain tumor in the rat model.     

Gd-DTPA adrenal gland enhancement at 1.5 T

The change in relative signal intensity of normal adrenal glands in 31 patients was evaluated following bolus administration of 0.1 mmol/kg of gadolinium diethylenetriamine pentacetic acid (Gd-DTPA). A marked increase in relative intensity of greater than 300% was observed within 2.5 min following contrast administration upon comparison of pre- and postcontrast T1-weighted gradient-echo images (TR = 47 msec, TE = 13 msec, pulse angle 80 degrees). Significantly elevated relative intensities of 55% and 44% persisted on postcontrast T1-weighted spin-echo images obtained at further delay times averaging 8 and 20 min, respectively, when compared to the identical precontrast sequence.     

MRI of blood volume with MS 325 in experimental choroidal melanoma

Functional magnetic resonance imaging (MRI) allows quantitative blood volume imaging in vivo at high tissue resolution. The purpose is to apply this technique for untreated and hyperthermia-treated experimental choroidal melanoma. MS 325 was used as new intravascular albumin-bound gadolinium-based contrast agent. Pigmented choroidal melanomas were established in albino rabbits. MRI was performed in 7 untreated eyes and 7 eyes treated with a Neodymium:Yttrium-Lanthanum-Fluoride-laser at 1047 nm. 3D-spoiled gradient echo pulse sequences were used to acquire T' weighted axial images. First, a set of images was collected without contrast agent. MS 325 was then injected i.v. and images were obtained within 12 min after injection. Signal intensities were measured within tumor, ciliary body, choroid, and iris and relative signal intensities were determined for these tissues in relation to vitreous. In untreated tumors, the relative signal intensity was higher after injection of MS 325 (5.61+0.70) than without MS 325 (2.90+0.33; p = 0.0002). In contrast, the relative signal intensity of treated tumors did not differ significantly before and after MS 325 (6.19+1.59 and 6.13+1.64). Histopathological sections indicated vascular occlusion in treated tumors. All other studied tissues of untreated and treated eyes showed a significant increase of relative signal intensities in the presence of MS 325. An animal model for the research on contrast agents in MRI is presented. Blood volume measurement with MS 325 was adapted for experimental choroidal melanomas. Reduced change of relative signal intensity indicates compromised blood volume after vascular occlusion in hyperthermia-treated melanoma. Further studies are needed to investigate whether this technique allows the evaluation of tumor viability following treatments.     

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.     

Value of Gd-DTPA-enhanced MR imaging of the labyrinth in patients with sudden hearing loss

Recent reports describe labyrinthine enhancement on MRI as a highly specific sign of labyrinthine disease. This paper reports 44 patients with unilateral sensorineural hearing loss (SNHL) and laboratory evidence of cochlear damage investigated with Gd-enhanced MR imaging. Enhancement of the cochlea was observed in only one patient with a lesion at the fundus of the internal auditory canal (IAC) that extended into the cochlea after Gd-DTPA administration. In one more patient, MR imaging demonstrated large vestibular aqueducts as underlying cause for his hearing loss, but no enhancement of the labyrinth was observed. No abnormal signal intensity on precontrast MR scans nor pathologic enhancement of the membranous labyrinth were identified in the other 42 patients. Gd-enhanced MR imaging appears to be insensitive in demonstrating labyrinthine disease and normal examination findings in a patient with sudden SNHL cannot exclude damage at the cochlear level.     

Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered (23)Na MRI, (1)H diffusion-weighted MRI and PET imaging

The effects of 5-fluorouracil (5FU, 150 mg/kg, ip) on subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) tumors were monitored by in vivo (1)H MRI to evaluate the water apparent diffusion coefficient (ADC), by single-quantum (SQ) and triple-quantum-filtered (TQF) (23)Na MRI to evaluate compartmental Na(+) content and by positron emission tomography (PET) to evaluate 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) uptake in the tumor. The MRI experiments were performed on untreated control and treated mice once before and then daily for 3 days after treatment. The PET experiments were performed on separate groups of age- and tumor-volume-matched animals once before and then 3 days after treatment. Tumor volumes significantly decreased in treated animals 2 and 3 days posttreatment. At the same time points, in vivo MRI measurements showed an increase in both total tissue SQ (23)Na signal intensity (SI) and water ADC in treated tumors while control tumors showed no change in these parameters. TQF (23)Na SI and FDG uptake were significantly lower in treated tumors compared with control tumors 3 days after 5FU treatment. The correlated increases in total tissue (23)Na SI and water ADC following chemotherapy reflect an increase in extracellular space, while the lower TQF (23)Na SI and FDG uptake in treated tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density.     

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.     

Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.     

Magnetic resonance imaging of soft-tissue tumors: Comparison with computed tomography

Twenty-seven patients with soft-tissue tumors were examined with a Picker 0.15-tesla resistive magnet and by computed tomography (CT). In all but one patient, MRI was better than or equal to CT in defining the anatomic extent of the tumor. We could determine whether major vascular structures were engulfed by the tumor in 80% of the MRI examinations but only in 62% of the CT scans. MRI and CT were equally effective in determining the presence or absence of bony invasion. The MRI images of all the tumors showed increased signal intensity relative to normal muscle when spin-echo (SE) sulse sequences with long repeat times were used (SE: echo time [TE], 60 ms; repetition time [TR], 2,000 ms). When T1 weighted pulse sequences were used (SE: TE, 30 ms; TR, 500 ms or inversion recovery: inversion time, 500 ms; TE, 40 ms; TR, 2,000 ms) the malignant tumors showed decreased signal intensity compared to normal muscle. Only lipomas showed high signal intensity on both T1 and T2 weighted pulse sequences.     

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.     

Exophytic benign tumors of the liver: appearance on MRI.

The purpose of our study was to determine the MR imaging appearance of exophytic benign liver tumors on precontrast and postgadolinium images. We reviewed our 9.5 year experience with MRI of the liver with dynamic gadolinium enhanced imaging to identify four patients with five histologically proven exophytic benign liver tumors. The histological diagnoses were cavernous hemangioma (2), focal nodular hyperplasia (FNH) (1), and hepatocellular adenoma (HCA) (2 exophytic adenomas in a patient with adenomatosis of the liver). All MRI studies were performed at 1.5 T and included: in-phase and out-of-phase T1-weighted spoiled gradient echo (SGE), T2-weighted fat-suppressed echo train spin echo, single shot T2-weighted sequences, and serial postgadolinium T1-weighted SGE sequences without and with fat-suppression. Prospective interpretations were reviewed and retrospective consensus readings of all MR images were performed assessing location, size, origin, morphology, visibility of the connection to the liver, signal characteristics on precontrast T1-weighted and T2-weighted images, and enhancement patterns on serial postgadolinium images. Three of the five tumors were pedunculated and connected to the liver by a thin stalk, which was prospectively identified in one patient. On precontrast and serial postgadolinium images, all exophytic tumors showed signal characteristics comparable to imaging features of standard intraparenchymal benign liver tumors. Our findings illustrate that the characteristic T1, T2, and postgadolinium imaging findings of these tumors permit correct identification of their liver origin despite their exophytic location, even if their connection with liver is not visualized.     

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.     

Comparison of quantitative imaging of cartilage for osteoarthritis: T2, T1ρ, dGEMRIC and contrast-enhanced computed tomography

Evaluation of glycosaminoglycan (GAG) concentration in articular cartilage is of particular interest to the study of degenerative joint diseases such as osteoarthritis (OA). Noninvasive imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) have demonstrated the potential to assess biochemical markers of cartilage integrity such as GAG content; however, many imaging techniques are available and the optimization of particular techniques in the diagnosis of joint disease remains an active area of research. In order to highlight the differences between these various approaches, this work compares MRI (T1, T2 and T1ρ) and contrast-enhanced CT in human articular cartilage, in both the presence and absence of gadolinium-based contrast agent. Pre- and postcontrast T2 values were found to be similar on a regional level and correlated with each other. As expected, T1 values were shortened significantly on both a global and a spatial basis in the presence of gadolinium (Gd); similar results were found for T1ρ. T2 values were found to correlate mildly with postcontrast T1, T1(Gd) and with precontrast T1ρ values. In addition, contrast-enhanced CT values correlated with both precontrast T1ρ and T1(Gd) more strongly than with precontrast T2. Finally, T1(Gd) and precontrast T1ρ were found to be moderately correlated with CT data. However, T1(Gd) and precontrast T1ρ were found to be almost completely uncorrelated. Together, these results indicate that T1ρ, T2 and contrast-enhanced techniques may provide complementary information about the molecular environment in cartilage during the evolution of OA.     

Paradoxical high signal intensity of hepatocellular carcinoma in the hepatobiliary phase of Gd-EOB-DTPA enhanced MRI: initial experience

Purpose

To describe the paradoxical high signal intensity of hepatocellular carcinoma (HCC) in the hepatobiliary phase on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).

Materials and Methods

A database search was performed to identify cases of HCC that showed unusual prolonged enhancement in the hepatobiliary phase of Gd-EOB-DTPA MRI. All patients received 3.0-T liver MRI including precontrast T1-weighted images, T2-weighted images and a post Gd-EOB-DTPA-enhanced dynamic study. The signal intensity of HCC was measured at pre-enhanced, arterial, portal, delayed and hepatobiliary phase using regions of interest. Radiologic and pathologic correlation was performed for the paradoxically prolonged enhancing portion of HCC in the hepatobiliary phase.

Results

Four patients (all male, age range 44-70; mean 57.5 years) were included in this study. All patients showed HCC lesions that were low signal intensity (SI) on T1-WI, high SI on T2-WI, enhanced in arterial phase, and washed-out in delayed phase. All cases showed paradoxically high SI in hepatobiliary phase, which was unusual for HCC. Pathologically, they were all diagnosed as well-differentiated HCC with prominent cytoplasm and a bile secreting appearance.

Conclusion

HCC may demonstrate the prolonged high signal intensity at the hepatobiliary phase on Gd-EOB-DTPA enhanced MRI. These HCCs tended to be highly differentiated and to have prominent bile secretion.     

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.     

BOLD MRI response to hypercapnic hyperoxia in patients with meningiomas: correlation with Gadolinium-DTPA uptake rate

Because meningiomas tend to recur after (partial) surgical resection, radiotherapy is increasingly being applied for the treatment of these tumors. Radiation dose levels are limited, however, to avoid radiation damage to the surrounding normal tissue. The radiosensitivity of tumors can be improved by increasing tumor oxygen levels. The aim of this study was to investigate if breathing a hyperoxic hypercapnic gas mixture could improve the oxygenation of meningiomas. Blood oxygen level-dependent magnetic resonance imaging and dynamic Gadolinium (Gd)-DTPA contrast-enhanced MRI were used to assess changes in tumor blood oxygenation and vascularity, respectively. Ten meningioma patients were each studied twice; without and with breathing a gas mixture consisting of 2% CO(2) and 98% O(2). Values of T(2)* and the Gd-DTPA uptake rate k(ep) were calculated under both conditions. In six tumors a significant increase in the value of T(2)* in the tumor was found, suggesting an improved tumor blood oxygenation, which exceeded the effect in normal brain tissue. Contrarily, two tumors showed a significant T(2)* decrease. The change in T(2)* was found to correlate with both k(ep) and with the change in k(ep). The presence of both vascular effects and oxygenation effects and the heterogeneous response to hypercapnic hyperoxia necessitates individual assessment of the effects of breathing a hyperoxic hypercapnic gas mixture on meningiomas. Thus, the current MRI protocol may assist in radiation treatment selection for patients with meningiomas.     

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.     

Optimizing brain MRI protocols in the follow-up of patients with multiple sclerosis T2-weighted MRI of the brain after the administration of gadopentetate dimeglumine

The aim of our study was to determine whether T2-weighted (T2w) MRI of the brain could be performed immediately after the administration of gadopentetate dimeglumine (gadolinium DTPA) in patients with multiple sclerosis (MS) without a loss in image quality or diagnostic reliability. Sixteen patients with clinically diagnosed MS were included in the study. Twenty-four patients with various cerebral pathologies (14 patients with multiple lacunar lesions) were examined in order to exclude masking of T2 hyperintense lesions other than MS lesions. Images of 10 patients without pathological changes served as a control condition for the qualitative analysis. In these 50 patients, T1w and T2w MRI was performed before and after the administration of gadolinium DTPA. Signal intensities were measured within T2 hyperintense cerebral lesions, in T1-enhancing lesions and in normal appearing brain tissue on T2w turbo spin-echo (TSE) sequences. Both quantitative and qualitative analysis did not show significant differences between T2w pre- and postcontrast series. T2w MRI performed prior to and after the administration of gadolinium DTPA provides similar information in patients with MS. With a TR of 3.2 s, not a single lesion was obscured on T2w postcontrast series. Acquisition of T2w MR images immediately after the administration of gadolinium DTPA allows for shorter examination time and assures sufficient time for contrast enhancement in cerebral lesions with a disrupted blood-brain barrier.     

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.     

Magnetic resonance imaging of bone after radiation

Magnetic resonance imaging (MRI) was performed in 22 patients at various times (0-3) years) following radiation therapy to the spine. T1 and T2 weighted images were obtained at 0.5 Tesla. Increased signal was seen after 800-6000 rads (8-60 Gy). Marrow effects corresponded to radiation ports. Recurrent tumor was clearly separated from fatty replacement. This was much better seen on T1 weighted images. Five patients that had MRI during their course of radiotherapy (XRT) did not have increased signal on T1 images of the bone marrow. The earliest fatty marrow change was seen nine days following completion of 3000 rads (30 Gy) XRT over one month's duration. One patient who received 800 rads (8 Gy) to the upper thoracic spine for eosinophilic granuloma had no radiation effects on MRI when imaged 16 days following completion of XRT given over five days. Fatty marrow change was seen in this patient on MRI six months later. MRI was particularly useful in defining the extent of prior radiation effects when repeat therapy was needed.