Functional brain imaging using a long intravenous half-life gadolinium-based contrast agent

PURPOSE: We describe a technique for functional MR imaging (fMRI) with high spatial and temporal resolution using a long intravascular half-life gadolinium-based contrast agent, MS-325. METHODS: All fMRI measurements used a rat model of sensory cortex activation with forepaw electrical stimulation under alpha-chloralose anesthesia. Standard blood oxygen level-dependent (BOLD) fMRI measurement was initially performed. MS-325 was then intravenously administered and a MS-325 fMRI measurement was performed by using a 3D gradient-echo sequence. RESULTS: We found that a dose of 0.1 mmol/kg MS-325 produced adequate signal intensity changes in rat sensory cortex to demonstrate activations. Using a boxcar stimulation pattern with a standard correlation analysis, the locations of the most significantly activated voxels (ie, highest Z score) in the MS-325 and BOLD fMRI measurements were not significantly different. CONCLUSIONS: MS-325 fMRI has the advantage of using a T1-weighted sequence, rather than the highly T2*-weighted sequences used in other common fMRI techniques. This could reduce the susceptibility artifacts associated with fMRI.     

Characterization of focal liver lesions with a new ultrasound contrast agent using continuous low acoustic power imaging: comparison with contrast enhanced spiral CT

PURPOSE: To evaluate the concordance of the enhancement patterns of a new ultrasound contrast agent (SonoVue) with those obtained with dual-phase contrast-enhanced spiral CT (CE-CT) in the characterization of focal liver lesions (FLLs). MATERIALS AND METHODS: Sixty-two patients with focal liver lesions discovered at ultrasound and also studied with CECT underwent contrast-enhanced ultrasound using continuous low acoustic power imaging after receiving a 2.4 ml bolus of the new US contrast agent SonoVue, consisting of a dispersion of sulphur hexafluoride microbubbles. The examinations were made using ATL HDI-5000, Acuson SEQUOIA and Aloka 5500 Prosound ultrasound systems with 5.2 MHz curved-array probes. The concordance between US and CE-CT images was evaluated on site by two radiologists blinded to CT RESULTS: The FLLs were assessed in the arterial (20 s after CM injection), portal (after 45-60 s) and late (after 120 s) phases for: 1) presence/absence of enhancement 2) distribution of enhancement (homogenous or target distribution, centripetal or centrifugal flow, and other), 3) qualitative enhancement pattern (hyperechoic, hypoechoic, or isoechoic) versus normal liver parenchyma. RESULTS: The concordance between SonoVue-enhanced US and CE-CT was 85%. Moreover during portal venous phase with CEUS it was possible to differentiate between malignancy or benignity of 91% of lesions. CONCLUSIONS: The preliminary data obtained in this study suggest that continuous low acoustic power imaging and contrast-enhanced US show similar results to CT in contrast distribution and contrast enhancement patterns.     

In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T

LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin α_νβ₃ receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ～1% in the tumor and controlateral regions, and decreased to ～0.3% after 2 h; while RGD‐lipoCEST signal was ～1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with α_νβ₃ receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Arthrography of the glenohumeral joint: experience with a non-ionic dimeric contrast agent and future perspectives

The role of conventional arthrography versus computed tomography (CT) arthrography of the glenohumeral joint using iotrolan was evaluated in patients with different shoulder problems. In addition, a diagnostic combination of conventional and CT arthrography was compared with magnetic resonance (MR) arthrography of the glenohumeral joint. Two diagnostic protocols were used. Protocol 1: conventional followed after 30 min by CT arthrography of 37 joints using a double contrast technique with iotrolan 300. Protocol 2: conventional followed after 90–180 min by MR arthrography in 20 patients using a single-contrast technique with 10 ml iotrolan 300 and 1 ml gedopentetate dimeglumine 500 mM. Ten patients also underwent CT arthrography. Neither patient group experienced contrast-related complications. Image quality was good for all conventional arthrograms, excellent in 45/47 CT arthrograms and good in 20 MR arthrograms. CT and MR arthrography were diagnostically valuable in many patients. We conclude that glenohumeral joint evaluation should be perfomed first using conventional or CT arthrography. Iotrolan has proven to be highly reliable and safe in these applications. Iotrolan in combination with gadopentetate dimeglumine, permits MR arthrography following completion of the standard examinations if necessary.     

Gadolinium-DTPA as a contrast agent in magnetic resonance imaging of the brain

Summary One hundred patients with CT-proven intracranial disease have been studied by magnetic resonance imaging (MRI) before and after intravenous injection with Gadolinium-DTPA (Gd-DTPA), in order to assess the role and clinical efficacy of Gd-DTPA. T₂-weighted spin echo sequences, although sensitive to the detection of intracranial disease, in general fail to differentiate macroscopic tumour from oedema. Following Gd-DTPA, T₁-weighted spin echo sequences in primary tumours demonstrated a variable degree of contrast enhancement unrelated to histological type. Small tumours, especially acoustic neuromas and meningiomas in the posterior fossa, were rendered more conspicuous. Optimum time for scanning was between five and 25 min following injection for all lesions except those adjacent to normal enhancing structures such as nasal/sinus mucosa and pituitary gland when delayed scans up to 45 min were necessary. No differences were observed between the 0.1 and 0.2 mmol/kg Gd-DTPA concentrations used and no complications attributable to Gd-DTPA were detected. Clinical advantages of Gd-DTPA include shorter scan times, macroscopic tumour/oedema separation and improved detection of certain tumours, particularly acoustic neuromas.     

Arthrography of the glenohumeral joint: experience with a non-ionic dimeric contrast agent and future perspectives

The role of conventional arthrography versus computed tomography (CT) arthrography of the glenohumeral joint using iotrolan was evaluated in patients with different shoulder problems. In addition, a diagnostic combination of conventional and CT arthrography was compared with magnetic resonance (MR) arthrography of the glenohumeral joint. Two diagnostic protocols were used. Protocol 1: conventional followed after 30 min by CT arthrography of 37 joints using a double contrast technique with iotrolan 300. Protocol 2: conventional followed after 90–180 min by MR arthrography in 20 patients using a single-contrast technique with 10 ml iotrolan 300 and 1 ml gedopentetate dimeglumine 500 mM. Ten patients also underwent CT arthrography. Neither patient group experienced contrast-related complications. Image quality was good for all conventional arthrograms, excellent in 45/47 CT arthrograms and good in 20 MR arthrograms. CT and MR arthrography were diagnostically valuable in many patients. We conclude that glenohumeral joint evaluation should be perfomed first using conventional or CT arthrography. Iotrolan has proven to be highly reliable and safe in these applications. Iotrolan in combination with gadopentetate dimeglumine, permits MR arthrography following completion of the standard examinations if necessary.     

MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent

The purpose of this study was to determine whether intravenous injection of a magnetic resonance (MR) contrast agent, ultrasmall superparamagnetic iron oxide (ferumoxtran-10), can be useful in characterizing lymph nodes in patients with lung cancer. Twelve patients with known or suspected lung cancer were studied. Pre- and postcontrast injection of ferumoxtran-10 MR scans of the chest were obtained. Analysis of the signal intensities and bronchoscopic fine needle aspiration of a single node were performed in each patient. Six of 12 patients had a final diagnosis of lung cancer. T1-weighted images were best for localizing mediastinal lymph nodes. Signal intensity changes before and after contrast were best visualized on T2-weighted and gradient-echo images. All four patients with lung cancer who had nodes positive for malignancy at biopsy had no change in signal intensity of the nodes on T2 images. The signal intensity decreased in the remaining two patients, and the nodes were benign. Of the eight patients with benign disease, five had no change in signal intensity of the nodes. Therefore the sensitivity for tumor involvement of the nodes is 100%, but the specificity is only 37.5%. Ferumoxtran-10 is a contrast agent that can alter the signal intensity of lymph nodes. Lack of signal change may be due to malignant or inflammatory change. Studies in a larger population of lung cancer patients may help to characterize the utility of this agent further. J. Magn. Reson. Imaging 2000;12:899-904.     

Improved sensitivity of proton MR to oxygen-17 as a contrast agent using fast imaging: detection in brain

The potential utility of H2(17)O as a contrast agent has been demonstrated in biological solutions and isolated tissues but its use has been impaired by the need to run heavily T2-weighted spin-echo images. By choosing an appropriate steady-state free precession experiment sensitive to T1/T2, we have improved the available contrast-to-noise per unit time by more than a factor of 5. This allows easy measurement of the proton effects for concentrations as low as 0.4% H2(17)O in less than 1 min. Injection into small animals produces a marked reduction in the overall image intensity. Consecutive imaging at the rate of one every 52 s has been used to follow the rate of change in brain image intensity immediately after injection.     

Functional imaging with MR T1 contrast: a feasibility study with blood-pool contrast agent

The aim of this study was to prove the concept of using a long intravenous half-life blood-pool T1 contrast agent as a new functional imaging method. For each of ten healthy subjects, two dynamic magnetic resonance (MR) protocols were carried out: (1) a reference run with a typical T2* echo-planar imaging (EPI) sequence based on the blood oxygenation level-dependent (BOLD) effect and (2) a run with a T1-sensitive three-dimensional (3D) gradient-echo (GRE) sequence using cerebral blood volume (CBV) contrast after intravenous administration of a contrast agent containing a chelate of gadolinium diethylene-triamine-pentaacetate with a phosphono-oxymethyl substituent. All sequences were performed during the execution of a block-type finger-tapping paradigm. SPM5 software was used for statistical analysis. For both runs maximum activations (peak Z-score = 5.5, cluster size 3,449 voxels) were localized in the left postcentral gyrus. Visual inspection of respective signal amplitudes suggests the T1 contrast to be substantially smaller than EPI (0.5% vs 1%). A new functional imaging method with potentially smaller image artefacts due to the nature of CBV contrast and characteristics of the T1 sequence was proposed and verified.     

Fixed drug eruption induced by an iodinated non-ionic X-ray contrast medium: a practical approach to identify the causative agent and to prevent its recurrence

We describe the case of a 61-year-old physician who developed a fixed drug eruption (FDE) after i.v. administration of a non-ionic monomeric iodinated X-ray contrast medium (CM) (iopromide). During CM injection, a sensation of heat occurred, which was most intense in the right inguinal region. Four hours later, the FDE arose with a red macule of approximately 2 cm in diameter covering a dermal infiltration in the right inguinal region, and enlarged up to a final size of 15×8 cm, accompanied by a burning sensation. The patient's history revealed a similar reaction in the same localization and of the same clinical appearance after CM injection 1 year before. Patch testing 4 months later revealed positive reactions to iomeprol and iohexol. Iopamidol injection for another CT examination 23 months later was well tolerated. Based on these results, we suggest patch testing after CM-induced FDE, which could help to select a CM for future CT examinations. Late onset of adverse CM reactions may manifest as FDE. Patch testing within the previous skin reaction area is the diagnostic tool that should be used to confirm the suspected agent, possible cross-reacting agents and well-tolerated agents.     

Single-dose contrast agent for intraoperative MR imaging of intrinsic brain tumors by using ferumoxtran-10

BACKGROUND AND PURPOSE: Intraoperative MR imaging (IMRI) has advantages over conventional framed and frameless techniques. IMRI, however, also has some drawbacks, especially related to interpretation of gadolinium-enhanced intraoperative imaging resulting from surgically induced blood brain barrier injury, vascular changes, and hemorrhage. Ultra-small superparamagnetic iron particles like ferumoxtran-10 have a long plasma half-life and are trapped by reactive cells within the tumor. These trapped particles provide a method to demonstrate enhancing lesions without the artifact of repeat gadolinium administration in the face of blood brain barrier and vascular injury. METHODS: We present a review of the literature and the cases of two patients who underwent surgery in which IMRI with ferumoxtran-10 was used. RESULTS: Ultra-small superparamagnetic iron particles represent a method to demonstrate enhancing intrinsic brain tumors without the drawbacks of intraoperative gadolinium enhancement. These lesions appear even on low-field strength IMRI. Ferumoxtran-10, administered preoperatively, provides a stable imaging marker, even after surgical manipulation of the brain. CONCLUSION: Fermumoxtran-10 provides a way to lessen artifactual enhancement during IMRI related to the administration of gadolinium.     

Perfusion imaging with a freely diffusible hyperpolarized contrast agent

Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized ¹³C labeled 2‐methylpropan‐2‐ol (also known as dimethylethanol, tertiary butyl alcohol and tert‐butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic ¹³C images acquired in rat brain with a balanced steady‐state free precession sequence following administration of hyperpolarized 2‐methylpropan‐2‐ol show that this agent can be imaged with 2–4s temporal resolution, 2 mm slice thickness, and 700 μm in‐plane resolution while retaining adequate signal‐to‐noise ratio. ¹³C relaxation measurements on 2‐methylpropan‐2‐ol in blood at 9.4T yield T₁ = 46 ± 4s and T₂ = 0.55 ± 0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the balanced steady‐state free precession image intensity in tissue and venous blood indicate that 2‐methylpropan‐2‐ol has a T₂ of roughly 2–4s and a T₁ of 43 ± 24s. In addition, the images indicate that 2‐methylpropan‐2‐ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2‐methylpropan‐2‐ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Efficacy of the iodine-free computed tomography liver contrast agent, Dy-EOB-DTPA, in comparison with a conventional iodinated agent in normal and in tumor-bearing rabbits

RATIONALE AND OBJECTIVES: To investigate the efficacy of the new liver-specific x-ray contrast agent, Dy-EOB-DTPA, in rabbits with VX2 liver tumors by spiral computed tomography (CT) in comparison to iopromide. MATERIALS AND METHODS: The time course of liver enhancement was determined in five groups of two normal anesthetized rabbits, which received intravenous injections of Dy-EOB-DTPA before anesthesia at a dose of 0.5 mmol/kg. Fifteen, 30, 45, 60, and 90 minutes after administration spiral CT images were obtained and the attenuation in the livers were determined. A second group of ten rabbits with implanted VX2 tumors received in a random crossover design either Dy-EOB-DTPA at a dose of 0.5 mmol/kg or, 1 day later, iopromide at a dose of 600 mg iodine/kg. CT images were obtained 60 minutes after Dy-EOB-DTPA administration and both in the arterial and portal-venous phases after iopromide injection. Three radiologists evaluated the images. The rabbits were killed, and their livers were investigated histologically for liver tumors. RESULTS: In normal animals, 0.5 mmol/kg Dy-EOB-DTPA resulted in a liver enhancement of 30 HU during the whole observation period of 90 minutes. In tumor-bearing animals, histology revealed 14 implanted tumors of 3-20 mm diameter. Sixty-five percent of the tumors were below 10 mm. Dy-EOB-DTPA was able to detect 13 tumors (93%), iopromide 11 (79%) both in the arterial and in the portal-venous phase. The difference was statistically not significant. In plain CT, seven tumors (50%) were found (P < 0.01 vs iopromide and Dy-EOB-DTPA). One scar and two sites of necrosis were detected by each of the methods. CONCLUSION: Dy-EOB-DTPA injection at a dose of 0.5 mmol/kg resulted in a long-lasting detectability of 93% of all implanted tumors versus 79% found with iopromide.