Efficacy of nonionic low-osmolar gadodiamide injection in animals with intracranial mass lesions.

Gadodiamide injection is a nonionic, low-osmolar formulation of a paramagnetic metal chelate complex consisting of gadodiamide and caldiamide sodium. The efficacy of gadodiamide injection as a magnetic resonance (MR) imaging enhancement medium was evaluated by imaging intracranial 9L-glioma lesions induced in rats and naturally occurring lesions in dogs. T1- and T2-weighted spin-echo images were obtained before and after administration of gadodiamide injection at doses of 0.1 and 0.2 mmol/kg. On the precontrast T1-weighted images, the intracranial lesions were not well seen, appearing isointense to normal brain parenchyma. Although the presence of disease was shown unequivocally on the T2-weighted images, the margins of the masses could not be delineated. Postcontrast T1-weighted images were characterized by marked enhancement of the tumor, with no change in signal intensity in the surrounding edematous brain tissue. Gadodiamide injection was efficacious in identifying areas of blood-brain barrier breakdown associated with intracranial masses.     

High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.     

Phase III clinical evaluation of Gd-HP-DO3A in head and spine disease.

As part of a phase III clinical trial, 25 patients with suspected intracranial or spinal disease underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg Gd-HP-DO3A (1,4,7-tris[carboxymethyl]-10-[2' hydroxypropyl]-1,4,7,10- tetraazacyclododecane), a neutral (nonionic) gadolinium chelate. Laboratory analysis included a complete blood count; blood chemistry; measurement of electrolyte levels; hepatic function, clotting function, and iron metabolism panels; and urinalysis both before and 24 hours after contrast agent administration. No statistically significant changes related to contrast agent administration were noted in laboratory values after administration of the contrast agent. In this selected group of patients, the contrast agent-enhanced study provided greater diagnostic information than did the precontrast study in 69% of head cases and 67% of spine cases. These initial clinical trials demonstrate that Gd-HP-DO3A is a safe, efficacious agent for head and spine examinations.     

Selective enhancement of experimental rat brain tumors with Gd-TPPS

The synthetic metalloporphyrin gadolinium (III)-tetraphenylporphine sulfonate (TPPS) was successfully used as a contrast agent for in vivo magnetic resonance (MR) imaging of rat brain glioma. After injection of Gd-TPPS, the signal intensity of experimental rat brain glioma distinctly increased on T1-weighted MR images, an effect similar to that produced by the clinically applied MR imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA). In contrast to other contrast agents studied (Gd-DTPA, manganese [III]-TPPS), Gd-TPPS produced hypointensity in glioma on T2-weighted images. The tumor-selective accumulation of paramagnetic Gd-TPPS in glioma shortened T1 by 53%, from 1,315 msec ± 199 to 628 msec ± 106, and T2 by 34%, from 86 msec ± 4 to 57 msec ± 5 (2 days after injection of 0.25 mmol/kg Gd-TPPS). The relaxation times of normal cortex, striaturn, corpus callosum, and temporal muscle were not significantly affected. As a result, gliomas appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Owing to the strong effect of Gd-TPPS on the T2 of glioma, normal brain tissue, tumor, and peritumorous edema could be distinguished on T2-weighted images alone.     

In vivo fluorine-19 MR imaging: Relaxation enhancement with Gd-DTPA

The lack of a naturally occurring background signal from fluorine in magnetic resonance (MR) imaging makes fluorinated compounds potentially attractive candidates for tissue-specific MR contrast agents. Problems associated with the in vivo use of fluorinated compounds are toxicity, which limits the amount of agent that can be used; multiple resonance lines; and an excessively long T1, which leads to long sequence TRs and consequently long imaging times. Many fluorinated agents also possess complex MR spectra that result in chemical shift artifacts if not corrected. The authors demonstrate the use of an extracellular fluorinated agent with a single MR peak for selective imaging of a brain abscess in an animal model and show that the image signal per unit of acquisition time can be enhanced through the use of a T1 relaxation agent, gadolinium diethylenetriamine-pentaacetic acid (DTPA). Trifluoromethylsulfonate was administered at a fluorine-19 dose of 4 mmol/kg, and fluorine images of the induced abscess were acquired before and after the injection of a standard dose of Gd-DTPA (0.1 mmol/kg); non—section-selected projection images were used. Typical imaging times were less than 5 minutes. The signal enhancement factor achieved was approximately four (4.0 ± 0.8) with use of a 500/12 (TR msec/TE msec) spinecho sequence.     

Multicenter study of gadodiamide injection as a contrast agent in MR imaging of the brain and spine

To evaluate the safety and efficacy of gadodiamide injection, a nonionic gadolinium chelate complex, in magnetic resonance (MR) imaging of the head and spine, a phase II-III trial was conducted in 439 patients with known or suspected lesions in the central nervous system. All patients received gadodiamide injection in a dosage of 0.1 mmol/kg and were monitored; MR images were evaluated for contrast material enhancement. No serious adverse events or clinically important trends in vital signs, laboratory values, or neurologic status were observed. Gadodiamide injection enhanced or facilitated the visualization of lesions in 266 or 353 patients (75.4%) in whom lesions were shown on unenhanced images, enhanced images, or both; in these 266 patients, the diagnosis was changed in 76 patients (28.6%) and facilitated in 190 patients (71.4%). It is concluded that gadodiamide injection is safe and effective for MR imaging of the head and spine in patients with suspected abnormalities of the central nervous system.     

MR Imaging detection of cerebral metastases with a single injection of high-dose gadoteridol

The utility of a single high-dose (0.3 mmol/kg) injection of gadoteridol, a gadolinium chelate, in the detection of brain metastases on magnetic resonance images was studied. Patients (n = 29) with a high suspicion for brain metastases at clinical examination and by history were imaged on two occasions–separated by more than 24 hours and less than 7 days–with a 0.1 mmol/kg contrast agent dose used for the first study and a 0.3 mmol/kg dose for the second. In patients (n = 15) with confirmed brain metastases by clinical, radiologic, and/or histologic criteria, 40 lesions were detected at the 0.3 mmol/kg dose by a single reader blinded to contrast agent dose, compared with 33 lesions at 0.1 mmol/kg, a 21% increase. Three of 15 patients (20%) demonstrated an increase in the number of lesions detected at the higher dose. Region-of-interest analysis of signal intensity measurements showed that lesion contrast (relative to normal brain) improved from 54% at 0.1 mmol/kg to 92% at 0.3 mmol/kg. A 0.3 mmol/kg dose of gadoteridol, administered in a single injection, permits identification of brain metastases not detected at 0.1 mmol/kg. Such information can influence the choice of therapy.     

Detection and quantification of breast tumor necrosis with MR imaging: value of the necrosis-avid contrast agent Gadophrin-3

RATIONALE AND OBJECTIVES: The authors evaluated the use of T1-weighted magnetic resonance (MR) imaging with Gadophrin-3 enhancement and of plain T2-weighted MR imaging to detect and quantify breast tumor necrosis. MATERIALS AND METHODS: Twenty EMT-6 tumors (mouse mammary sarcoma), implanted into the mammary fat pad of BALB/c-AnNCrl mice, underwent MR imaging with plain T2-weighted and T1-weighted fast field echo sequences before and 24 hours after injection of Gadophrin-3, a new necrosis-avid contrast agent. Tumor necrosis on MR images was quantified by means of a dedicated segmentation program and was correlated with histologic findings. RESULTS: In all tumors a central necrosis was revealed by histopathologic analysis, and central enhancement was seen with Gadophrin-3 on T1-weighted images. Small tumors (diameter, < 1 cm) showed an inhomogeneous central enhancement, whereas larger tumors (diameter, > 1 cm) enhanced mainly in the periphery of necrotic tissue. Plain T2-weighted images showed a hyperintense central area in only three of 20 cases with a large central necrosis. CONCLUSION: Gadophrin-3-enhanced T1-weighted images are superior to plain T2-weighted images for the detection of necrosis in a murine tumor xenograft model.     

MR image contrast at high field strength.

The T1 of soft tissues increases with magnetic field strength. Some tissue contrast may be diminished on high-field-strength magnetic resonance (MR) images when conventional TRs are used, because of altered T1 effects on the MR signals. This necessitates longer TRs in techniques that use long TRs, which prolongs the examination excessively. Behavior of macroscopic magnetization is governed by the Bloch equations. Therefore, T1 contributions to the MR signal can be modulated by means of both timing intervals and radio-frequency pulses. The analytic solution to the Block equations allowed calculation of white matter/gray matter and gray matter/cerebrospinal fluid contrast in both spin-echo and inversion-recovery (IR) imaging. Rabbit brains (normal and tumor-containing) were then imaged in vivo at 1.5 and 4.7 T. In addition, MR images of a human head were obtained at 4.0 T. Experimental results supported the theoretical predictions that brain contrast on long TR spin-echo or IR images increases with field strength. However, varying the excitation flip angle allowed optimization of the T1 contribution to the MR signals, improving image contrast and/or reducing examination time. Thus, the dependence of T1 on field strength determines the optimum choice of imaging techniques and parameters in a predictable fashion.     

Rectal carcinoma: Prospective comparison of conventional and gadopentetate dimeglumine enhanced fat-suppressed MR imaging

The purpose of this study is to compare the usefulness of conventional MR imaging and gadopentetate dimeglumine enhanced fat-suppressed MR imaging for the depiction and staging of rectal carcinoma. Thirty-two patients were prospectively evaluated by MR imaging using a 1.5-T unit. Based on the results of a barium study and/or digital examination, a balloon catheter was inserted to the level of the lesion before examination. Both conventional T1- and T2-weighted images and gadopentetate dimeglumine enhanced fat-suppressed T1-weighted images were obtained for all patients. The kappa statistics were performed for the evaluation of interobserver agreement and the McNemar test was performed for the analysis of staging accuracy. When only T1- and T2-weighted images were used, 5 of 32 tumors were not detected and the extent of 18 of 32 tumors were unclear. However, when gadopentetate dimeglumine enhanced fat-suppressed imaging was added, 24 of 32 tumors were well defined and only one tumor was not detected. In determining the depth of invasion, the staging accuracy was 72% for conventional imaging and 68% for all images combined. There was no significant difference between with gadopentetate dimeglumine fat-suppressed imaging and conventional imaging (P > .05). Use of gadopentetate dimeglumine (fat-suppressed imaging) resulted in overestimation of muscular invasion, peri-rectal fat invasion, and adjacent organ invasion in 12 patients, whereas nine patients were overestimated without the use of gadopentetate dimeglumine. In the detection of metastatic lymph nodes, gadopentetate dimeglumine enhanced fat-suppressed imaging also was not useful. Tumor detection was excellent using gadopentetate dimeglumine enhanced fat-suppressed images. However, the accuracy of staging was not improved by obtaining such images.     

Gadolinium-enhanced T1-weighted renal and abdominal MR imaging: quantitative discrepancy between clinical and in vitro findings

RATIONALE AND OBJECTIVES: This study was conducted to compare the magnetic resonance (MR) contrast medium enhancement of abdominal organs in vivo with the signal intensity (SI) values of known in vitro gadolinium solutions. MATERIALS AND METHODS: A phantom was imaged with the MR contrast medium gadodiamide (Omniscan; Nycomed, Princeton, NJ) of solutions at full-strength (0.5 mmol/mL), one-third, 1/10, and 1/100 concentrations. A fat-suppressed fast spoiled gradient-echo pulse sequence with flip angles ranging from 10 degrees to 170 degrees (at 20 degrees increments) was performed with a 1.5-T magnet. In 12 subjects, the SIs of abdominal organs were determined with identical imaging parameters, before and after administration of gadodiamide injection at 0.1 mmol/kg. RESULTS: As anticipated, the plot of SI in relation to gadodiamide concentration is nonlinear, with a decrease in SI due to T2 effects at concentrations above 0.05 mmol/mL. The kidney showed the highest SI after gadodiamide enhancement (125.2 +/- 11.6 [standard error] at 2.5 minutes), followed by the liver (76.5 +/- 11.5 at 1 minute) and spleen (57.26 +/- 9.35 at 30 seconds). The SI of the renal medulla (114.2 +/- 9.8 at 4.5 minutes) was approximately one-third that in phantom observations. CONCLUSION: The authors observed a marked discrepancy between empirical contrast medium performance in abdominal organs and SI values for comparable gadodiamide concentrations in vitro. One possible reason is the intracellular compartmentalization of water molecules in vivo. These results suggest a need for a better understanding of MR contrast medium performance in vivo.     

MR imaging of myositis ossificans: Variable patterns at different stages

Five patients with a palpable mass at presentation underwent magnetic resonance (MR) imaging. The final diagnosis was myositis ossificans (MO). MR imaging features, particularly after injection of gadopentetate dimeglumine, mimicked those of an inflammatory mass or neoplasm. The lesions were excised in three patients, and the Images were correlated with histologic findings. Three different appearances were noted on MR images, corresponding to the stages of maturation of MO. Two cases Involved early-stage lesions, and Tl-weighted MR images showed a mass with homogeneous intermediate signal intensity. Both lesions showed rim enhancement after contrast agent injection and high signal intensity on T2-weighted images. Pathologic specimens demonstrated stroma with masses of spindle cells in which osteoid production was interspersed. The enhanced rim of the lesion mimicked the expected MR appearance of an abscess or necrotic tumor. Areas of enhancement in adjacent muscle were also seen on postcontrast T1-weighted images. Intermediate-stage MO was present in one case; there was evidence of a thin rim of calcification on plain radiographs and fatty changes in the lesion on T1-weighted Images, corresponding with histologic findings. One case of a mature lesion showed a considerable degree of peripheral calcification both on MR images and at histology. MR imaging is nonspecific in the diagnosis of early-stage MO.     

Effect of contrast dose and field strength in the magnetic resonance detection of brain metastases

PURPOSE: To compare the diagnostic efficacy of a standard and cumulative triple dose of magnetic resonance (MR) imaging contrast agent in the evaluation of brain metastases using a high-field 3.0 T MR unit versus a standard field 1.5 T MR unit. METHODS: Twenty-two patients with suspected brain metastases were examined at both field strengths using identical postcontrast coronal 3D gradient echo with magnetization preparation, which was adjusted separately for each field strength. In both groups initially, iv injection of 0.1 mmol/kg body weight gadolinium chelate (gadodiamide) and thereafter, 0.2 mmol/kg body weight gadodiamide were administered. Subjective assessment of the images was performed independently by 3 neuroradiologists. Objective measurement of signal-to-noise and contrast-to-noise ratios was obtained. RESULTS: The subjective assessment of cumulative triple-dose 3.0 T images obtained the best results compared with other sequences, detecting 84 metastases, followed by 1.5 T cumulative triple-dose enhanced images with 81 brain metastases. The objective assessment confirmed those results, showing significantly higher signal-to-noise and contrast-to-noise ratios with 3.0 T than with 1.5 T. CONCLUSIONS: Cumulative triple-dose images of both field strengths were superior to standard field strengths. However, administration of gadodiamide contrast agent produces higher contrast between tumor and normal brain on 3.0 T than on 1.5 T, resulting in better detection of brain metastases and leptomeningeal involvement.     

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.     

Ampullary carcinoma: Demonstration by current MR techniques

The objective of this study was to demonstrate the appearance of ampullary carcinoma using current MR techniques, including fat suppression, gadolinium enhancement, and MR cholangiography. Nine patients with ampullary carcinoma were examined by MRI at 1.5 T. MR examinations included T1-weighted spoiled gradient echo, T1-weighted fat-suppressed, and immediate postgadolinium spoiled gradient echo images for all patients and MR cholangiography for three patients. The imaging features of ampullary carcinomas, including tumor size and morphology, signal intensity, and enhancement characteristics, were determined. Ampullary carcinomas shown on MR images ranged in size from 1.5 to 5.5 cm. Tumors were low in signal intensity on precontrast T1-weighted spoiled gradient echo and T1-weighted fat-suppressed images relative to normal pancreatic tissue and enhanced less than normal pancreas on immediate postgadolinium spoiled gradient echo images. Tumor conspicuity was greatest on immediate postgadolinium spoiled gradient echo images. MR cholangiography demonstrated high grade obstruction of the common bile duct and mild dilatation of the pancreatic duct at the level of the ampulla with abrupt termination of the ducts in two untreated patients and moderate dilatation of the common bile duct in one patient who had a biliary stent. Ampullary carcinomas can be demonstrated on MR images as small masses arising at the ampulla. Tumors are well defined on immediate postgadolinium spoiled gradient echo images.     

Nodular sarcoidosis of the liver and spleen: Appearance on MR images

Small nodular lesions in the liver and spleen have been reported as an infrequent manifestation of sarcoidosis. Five patients with this appearance on either dynamic contrast material—enhanced computed tomographic (CT) or ultrasound scans underwent magnetic resonance (MR) imaging with and without dynamic gadolinium enhancement. The lesions were relatively uniform in size, ranging from 0.5 to 1.5 cm. On CT scans, they were hypoattenuating relative to surrounding parenchyma. On MR images, the lesions were hypointense relative to background parenchyma with all sequences. No substantial enhancement was observed in the lesions, although lesion conspicuity decreased over time on serial postcontrast images. Lesion conspicuity was greatest on either T2-weighted fat-suppressed (T2FS) images or early-phase dynamic contrast-enhanced images. Abdominal adenopathy was seen in three of the five patients and was hyperintense relative to liver on T2FS images in two and intermediate in intensity in one patient.     

MR imaging of Hippel-Lindau disease: value of gadopentetate dimeglumine.

Hippel-Lindau disease is an autosomal dominant disorder characterized by tumors of the central nervous system and abdominal viscera. Frequent multisystem radiologic evaluation of persons at risk is desirable. Twenty-seven patients with Hippel-Lindau disease or a family history of the disease were examined with both unenhanced and gadopentetate dimeglumine-enhanced magnetic resonance (MR) imaging to study the usefulness of the contrast medium in the evaluation of these patients. The MR studies were correlated with computed tomographic (CT) scans in seven patients and cerebral angiograms in five. Twelve patients had hemangioblastomas in the brain, and eight of these patients also had spinal cord lesions (most were multiple), well demonstrated with gadopentetate dimeglumine. Contrast-enhanced MR imaging enabled detection of more central nervous system lesions and provided better delineation than unenhanced MR imaging, CT, or angiography. In addition, four patients with multiple renal cysts seen on CT scans and unenhanced MR images had enhancing lesions that were later proved to be renal cell carcinoma at angiography and/or surgery. Four patients had cystic lesions in the pancreas that did not enhance and were later proved to be pancreatic cysts. The authors conclude that gadopentetate dimeglumine-enhanced MR imaging appears to be a useful method for evaluating and following up patients with Hippel-Lindau disease.     

Bowel disease: prospective comparison of CT and 1.5-T pre- and postcontrast MR imaging with T1-weighted fat-suppressed and breath-hold FLASH sequences.

The potential of new high-field-strength magnetic resonance (MR) imaging sequences to evaluate bowel disease was investigated and compared with computed tomographic (CT) studies. Thirty-two patients were studied, 14 with known or suspected gastrointestinal tumors and 18 with known or suspected bowel inflammatory conditions. T1-weighted fat-suppressed spin-echo and breath-hold FLASH (fast low-angle shot) images were obtained before and after intravenous injection of 0.1 mmol/kg gadopentetate dimeglumine. Pathologic confirmation was obtained by biopsy (n = 18), surgical excision (n = 8), or endoscopy (n = 6). CT and MR images were analyzed separately in a prospective fashion and reviewed by consensus. Information from CT and MR images was comparable in cases of confirmed bowel neoplasia. CT scans had better spatial resolution, while fat-suppressed gadolinium-enhanced MR images had better contrast resolution. In the 18 cases of bowel inflammation, CT scans showed concentric wall thickening in 16, while MR images showed concentric wall thickening in 14 and increased contrast enhancement in 17. Contrast enhancement was better appreciated on fat-suppressed images than on FLASH images. The results suggest that MR imaging may play a role in the evaluation of bowel disease.     

Contrast-enhanced MR imaging of diffuse and focal splenic disease with use of magnetic starch microspheres

The diagnostic value of magnetic starch microspheres (MSM), a new superparamagnetic contrast agent, was studied in experimental models of diffuse and focal splenic disease in rats by means of ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Owing to small differences in unenhanced T1 and T2 values between diffuse lymphoma and normal spleen, MR imaging failed to distinguish tumor-bearing animals from control animals by signal-to-noise ratios (SNRs) obtained with T1- and T2-weighted spin-echo sequences. One hour after injection of 20 μmol/kg MSM, lymphomatous spleen showed significantly (P <.001) reduced enhancement relative to normal splenic tissue. As a result, animals with diffuse lymphoma (SNR: 10.3 ± 1.7) could be easily differentiated from control animals (SNR: 5.5 ± 0.6) on T2-weighted (TR msec/TE msec = 2,000/45) images. In focal splenic disease, MSM produced normal enhancement of nontumorous splenic tissue, whereas relaxation times of tumors were not different before and after contrast agent injection. On T2-weighted images (2,000/45), the tumor-spleen contrast-to-noise ratio increased from (4.8 ± 1.6 to 21.8 ± 1.9 +354%), improving conspicuity of splenic tumors. The results show that MSM-enhanced MR imaging improves the detection of diffuse and focal splenic disease.     

Assessing response to therapy of spinal metastases with gadolinium-enhanced MR imaging.

The utility of gadolinium-enhanced magnetic resonance (MR) imaging in assessing the response of spinal metastases to therapy was evaluated. Fifteen patients (62 affected vertebral bodies) with spinal metastases were evaluated with gadopentetate dimeglumine-enhanced imaging before and after irradiation or chemotherapy. Signal intensities of the lesions and of adjacent normal vertebral bodies were compared. Before therapy, metastatic foci enhanced significantly more than did normal vertebral bodies. After therapy, the lesions were divided into 37 responding lesions (group 1) and 25 nonresponding lesions (group 2). In group 1, lesion enhancement diminished considerably and the patients with these lesions remained clinically asymptomatic for 2-6 months. In group 2, lesion enhancement did not diminish much, and the difference between the groups was significant. Gadolinium-enhanced MR imaging may thus be a useful method for assessing the effectiveness of therapy for spinal metastases.