Contrast media: future aspects.

In spite of the dramatic development in CT, there was no major breakthrough in the iodinated contrast media development. New agents based on hybrid between MRI and CT compounds may be a new innovative alternative. This new approach may also open new indications such as radiotherapy.

Near monochromatic X-rays for digital slot-scan mammography: initial findings.

X-ray spectra are composed of a broad bremsspectrum and anode-characteristic emission lines. In mammography typically molybdenum (Mo), rhodium (Rh) or tungsten (W) anodes are used in combination with Mo, Rh or aluminium filters. Only the photons with energies between 17 and 22 keV of the resulting spectrum are suitable for the soft tissue imaging needed for mammography. The aim of this article is to present first results obtained with a monochromator module mounted at the exit of the X-ray tube of a conventional clinical mammography unit. The experimental setup consists of a Siemens Mammomat 300, an X-ray monochromator module and a linear array detector for image acquisition. The technique is similar to the slot-scan technique known from digital mammography. The experimental machine allows to obtain images both with polychromatic and monochromatic X-rays. Initial evaluation of the system was performed by examination of a contrast-detail phantom (CD-MAM-phantom, Nijmegen, The Netherlands). Images done with the new monochromatic technique were compared to images of the phantom done with polychromatic spectra, with film-screen mammography as well as with digital mammography. The new technique with monochromatic slot-scan mammography resulted in correct identification of 93% of the phantom. Digital slot-scan mammography with polychromatic beam resulted in correct identification of 87%, digital full-field mammography in 83% and conventional film-screen mammography in 70% of the phantom. The results suggest that monochromatization has a potential for improving image quality or decreasing dose in X-ray mammography.

Assessment of nicorandil therapy in ischemic myocardial injury by using contrast-enhanced and functional MR imaging.

PURPOSE: To determine the potential of mesoporphyrin- and gadopentetate dimeglumine-enhanced and functional magnetic resonance (MR) imaging in the assessment of the acute effect of nicorandil on ischemic injury of the myocardium. MATERIALS AND METHODS: Spin-echo MR imaging was used to monitor changes in myocardial contrast and function in reperfused myocardial injury. Inversion-recovery echo-planar MR imaging was used to depict the injured region. Myocardial injury in rats was produced by using 30 minutes of coronary occlusion followed by 24 hours reperfusion. Nicorandil (n = 9) was infused during occlusion and early reperfusion. Control animals (n = 11) received no therapy. At 24 hours, after administration of mesoporphyrin and gadopentetate dimeglumine and histochemical staining, the function and size of the injured region of the left ventricle (LV) were determined. A t test was used to compare data between groups of animals, whereas regression and Bland-Altman analyses were used to determine correlation and agreement between MR imaging and histomorphometry, respectively. RESULTS: Treated animals showed reduced infarction size as compared with the control group from 25.6% +/- 7.9 (SD) to 7.9% +/- 6.8 of LV myocardial area (P < .001), as defined with mesoporphyrin-enhanced MR imaging; while the size of the rim increased from 10.8% +/- 10.0 to 16.1% +/- 14.4 (P < .05). The diastolic-midventricular cavity area was smaller in treated animals (15.2 mm(2) +/- 4.3) compared with the control group (28.5 mm(2) +/- 7.9; P < .001). At functional MR imaging, nicorandil improved systolic reduction in LV cavity area (57.5% +/- 17.3) compared with the control group (38.0% +/- 16.0; P < .05) and preserved regional LV wall thickening at the site of injury (12.2% +/- 11.1 in treated group vs 0.3% +/- 8.6 in the control group; P < .05). CONCLUSION: Contrast material-enhanced MR imaging has the potential to demonstrate reduction in size of ischemically injured myocardium, whereas functional MR imaging demonstrated the recovery of LV function 24 hours after nicorandil therapy.

Producing parallel x rays with a bent-crystal monochromator and an x-ray tube.

A bent Laue monochromator and a conventional x-ray tube were used to produce a fan beam that was parallel in the plane perpendicular to the plane of the fan. The x-ray fan beam was tunable in energy and had about 12% energy bandwidth at a slice height of 5 mm when tuned to 50 keV. The beam's energy was slightly coupled to the vertical position on the beam's height. The slice height could be varied from 1 to 10 mm. The flux at 50 keV was approximately 2x10(6) photons/mm2/s with a rotating anode tungsten x-ray tube operating at 120 kVp and 100 mA. The narrow energy bandwidth of the beam produced is advantageous over a conventional divergent polychromatic beam for all radiography applications, while the parallelism of the beam enhances its intensity by about threefold and offers some advantages for computed tomography.

Occlusive myocardial infarction: investigation of bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging in a cat model.

PURPOSE: To test whether bis-gadolinium mesoporphyrins-enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium mesoporphyrins-enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2'3'5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity-enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time. In one of the two remaining cats, a doughnut pattern of signal intensity enhancement was noted. The other cat showed intensely homogeneous enhancement of infarcted myocardium at MR imaging. The size of the area of signal intensity enhancement at MR imaging in these two cats was accurately mapped to that of the infarction on the TTC-stained specimens. CONCLUSION: Occlusive myocardial infarction cannot be accurately detected at bis-gadolinium mesoporphyrins-enhanced MR imaging.

Viable myocardium in reperfused acute myocardial infarction: rest and stress first-pass mr imaging.

Feasibility of identifying viable myocardium in rest and stress magnetic resonance imaging (MRI) was evaluated using 3 hr occlusion and 30 min reperfusion model of left anterior descending (LAD) coronary artery in 12 felines. At rest MRI, viable myocardium confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC)-staining showed rapid signal intensity (SI) rise followed by gradual decline not significantly different from normal myocardium that the two hyperperfused regions were distinguishable only from the hypoperfused nonviable myocardium. At stress MRI, hyperemia induced perfusion change was most pronounced in normal myocardium with earlier and greater peak enhancement followed by brisk 'washout' phase while minimally augmented enhancement in viable myocardium was still in 'washin' phase. From these findings, it was concluded that viable myocardium is identified in rest and stress MRI as redistributing hypo- perfusion compared to persistent hyper-perfusion of the normal myocardium and the persistent hypo-perfusion of the nonviable myocardium.

Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent.

RATIONALE AND OBJECTIVES: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium. METHODS: The pharmacokinetics of Gadomer-17 were investigated in different species (rat, rabbit, dog, monkey) for up to 7 days after intravenous (i.v.) injection of 25-100 micromol/kg body weight. In addition, elimination and biodistribution were evaluated after single i.v. injection of Gadomer-17 in rats. RESULTS: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space without significant diffusion into the interstitial space. The volume of distribution (Vc) in the initial or alpha-phase ranged from 0.04 l/kg (rats, rabbits) to 0.06 l/kg (monkeys) and 0.07 l/kg (dogs), which reflects mainly the plasma volume. The blood/plasma concentration profile was found to be biphasic. The volume of distribution at a steady state is clearly smaller than that of other contrast media, which distribute to the extracellular space. After single i.v. injection in rats, the dendritic contrast medium was rapidly and completely eliminated from the body, mainly via glomerular filtration. No long-term accumulation or retention of the nonmetabolized agent was detectable in organs or tissues. CONCLUSIONS: Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.

Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging.

Angiogenesis is a critical step in tumor development and more than 25 angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo imaging of angiogenesis represents a unique opportunity of repeatedly quantitating microvascular parameters prior to and during anti-angiogenic treatments. While several imaging tracers have been proposed for MR and nuclear imaging, there does not exist any consensus of what constitutes an ideal size of an imaging agent. A series of synthetic pegylated DOTA derivatized graft copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested in two breast cancer models differing in vascular endothelial growth factor (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy) and absolute blood and tumor concentrations were determined by ICP-AES measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in low plasma levels. Slow leakage across neovasculature into tumor interstitium was clearly dependent on the molecular mass of all tested agents in MCF-7 tumors. However, a cutoff was observed with minimal extravasation occurring at and above 120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused detectable differences in extravasation of all polymers, including the 120 kDa compound. We conclude that large molecular weight contrast agents with a molecular mass of <120 kDa extravasate from experimental tumor neovasculature and may not be an accurate marker for measuring true blood volume fractions when in vivo imaging is performed in the steady state.

Contrast-enhanced MR imaging of coronary arteries: comparison of intra- and extravascular contrast agents in swine.

PURPOSE: To compare the efficacy of an intravascular contrast agent, gadomer-17, in improving magnetic resonance (MR) imaging of coronary arteries with that of an extravascular agent, gadopentetate dimeglumine, in pigs. MATERIALS AND METHODS: Eight pigs underwent imaging after three injections: 0.20 mmol of gadopentetate dimeglumine per kilogram of body weight and 0.05 and 0.10 mmol/kg gadomer-17. Coronary images were acquired repeatedly after each injection by using an inversion-recovery-prepared segmented three-dimensional sequence with either breath holding (n = 4) or respiratory gating (n = 4). Coronary artery-to-myocardium contrast-to-noise ratios (CNRs) were compared between injections. RESULTS: At breath-hold imaging, substantial CNR improvement over precontrast images was observed in images acquired during the first pass of gadopentetate dimeglumine in coronary arteries and up to 6 and 10 minutes after 0.05 and 0.10 mmol/kg of gadomer-17 injections, respectively. The CNR with 0.10 mmol/kg of gadomer-17 was 20% (P <.05) higher than that with gadopentetate dimeglumine at first-pass imaging. At respiratory-gated imaging, significant CNR improvement (P <.05) over precontrast images was observed in images acquired up to 10, 30, and 50 minutes after gadopentetate dimeglumine and both gadomer-17 injections, respectively. The CNR on the first images obtained after 0.10 mmol/kg gadomer-17 injection was 168% (P <.05) higher than that on the images obtained after gadopentetate dimeglumine injection. CONCLUSION: Gadomer-17 provided greater and more persistent CNR improvements than did gadopentetate dimeglumine; further evaluation of its utility for coronary imaging in humans is warranted.

Passive tracking of catheters and guidewires by contrast-enhanced MR fluoroscopy.

Passive MR tracking of catheters and guidewires is usually done by dynamically imaging a single thick slab, subtracting a baseline image, and combining the result with a previously acquired MR angiogram. In the in vitro and in vivo experiments reported here, it is demonstrated that this approach may be greatly simplified by using a suitable intravascular contrast agent. The proposed method, contrast-enhanced MR fluoroscopy, combines tracking and angiography into a single sequence and allows direct visualization of the magnetically prepared parts of catheters and guidewires with respect to the vasculature at a frame rate of about one image per 1.5 seconds. Contrast-enhanced MR fluoroscopy, although still limited in temporal resolution, thus obviates the need for subtraction and overlay techniques and eliminates the sensitivity of tracking to subject motion between acquisitions. Magn Reson Med 45:17-23, 2001.

Simultaneous MRI measurement of blood flow, blood volume, and capillary permeability in mammary tumors using two different contrast agents.

A technique for the simultaneous measurement of three vascular parameters: blood flow (Frho), blood volume (v(b)), and the capillary permeability-surface area product (PSrho) in breast tumors using dynamic contrast-enhanced magnetic resonance imaging (MRI) is presented. Features of the technique include measurement of precontrast tumor T(1), rapid temporal sampling, measurement of the arterial input function, and use of a distributed parameter tracer kinetic model. Parameter measurements are compared that were determined using two contrast agents of different molecular weights, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA; 0.6 kDa) and Gadomer-17 (17 kDa), in 18 spontaneous canine mammary tumors. Measurements of Frho and v(b) corresponded well with literature values, and the mean PSrho measured using Gd-DTPA was a factor of 15 higher than that measured using Gadomer-17. J. Magn. Reson. Imaging 2000;12:991-1003.

In vivo microscopic evaluation of the microvascular behavior of FITC-labeled macromolecular MR contrast agents in the hamster skinfold chamber.

RATIONALE AND OBJECTIVES: The extravasation properties of two macromolecular MR imaging contrast media (CM) in relation to structural differences of the terminal vascular bed were investigated to determine whether differentiation between normal (physiological) and tumor (pathological) tissue can be achieved by means of extravasation characteristics. METHODS: Gd-DTPA-polylysine (50 kD, CM1) and Gd-DOTA cascade polymer (Gadomer 17; 20 kD, CM2) were labeled with fluorescein isothiocyanate (FITC) to enable in vivo fluorescence microscopy of the microcirculation. After implantation of a dorsal skinfold chamber and 7 days (range, 6-8) after induction of an amelanotic melanoma (A-Mel-3), 14 male hamsters weighing 85 g (range, 70-95 g) received 200 micromol/kg of CM1 by intravenous injection into the jugular vein. CM2 was similarly investigated after an interval of 24 hours. Fluorescence microscopy was performed in areas of subcutaneous tissue, striated muscle, and tumor tissue. Microscopic images were registered by a charge-coupled-device video camera and transferred to a video system. Distribution intensities of CM were evaluated on a digitally based measurement system. A control investigation was performed with FITC-dextran (150 kD). RESULTS: Gd-DTPA-polylysine showed no extravasation into physiological tissue for the first 10 minutes after injection. After this period, however, the first signs of leakage became apparent. Gd-DOTA cascade polymer was extravasated after 5 minutes into the tumor-free tissue. In tumor capillaries, Gd-DTPA-polylysine could be detected in the extravasal space as well as in physiological tissue after 15 minutes. After injection of Gd-DOTA cascade polymer, direct leakage from tumor capillaries was observed, with a contrast maximum between tumor and surrounding tissue occurring 3 to 5 minutes after CM injection. Good delineation of tumor vascularization from striated muscle and subcutaneous tissue was achieved. CONCLUSIONS: The CM studied showed different microvascular permeation properties. Faster leakage of Gd-DOTA cascade polymer was observed in areas with neoplastic tumor vessels, whereas extravasation in physiological tissue was detected after a period of 5 minutes. Gd-DTPA-polylysine demonstrated nonspecific leakage at later time points.

Gadolinium mesoporphyrin as an MR imaging contrast agent in the evaluation of tumors: an experimental model of VX2 carcinoma in rabbits.

OBJECTIVE: We determined the enhancement features of experimentally induced malignant tumors on MR imaging with the use of gadolinium mesoporphyrin, a recently developed MR contrast agent that may be necrosis-specific. MATERIALS AND METHODS: VX2 carcinoma was inoculated into 24 rabbit thighs. T1-weighted contrast-enhanced MR imaging with IV gadopentetate dimeglumine (2-min delay) and gadolinium mesoporphyrin (20-hr delay) was performed 3-4 days (n = 6), 6-7 days (n = 6), 10-11 days (n = 5), and 13-14 days (n = 7) after the implantation of VX2 carcinoma. All tumors were sectioned along the same plane of MR images, and a detailed MR imaging-histopathologic correlation was performed. RESULTS: Pathologically, areas enhanced with gadolinium mesoporphyrin included necrotic tissue, viable tumor, inflammatory granulation tissue, hemorrhage, and fibrosis. On gadopentetate dimeglumine-enhanced MR images, unenhanced areas of the tumor corresponded with intratumoral necrosis and hemorrhage. CONCLUSION: Gadolinium mesoporphyrin enhances tumor necrosis on delayed phase MR imaging; however, it is impossible to specifically depict necrosis with gadolinium mesoporphyrin because it also enhances other parts of lesions, including viable tumor.

Irreversibly damaged myocardium at MR imaging with a necrotic tissue-specific contrast agent in a cat model.

PURPOSE: To investigate the capability of a necrosis-avid magnetic resonance (MR) contrast agent, bis-gadolinium mesoporphyrins, for assessment of irreversibly damaged myocardium and to evaluate the time course of signal enhancement in the reperfused myocardium. MATERIALS AND METHODS: Nine cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery followed by 90 minutes of reperfusion. Contrast material-enhanced T1-weighted spin-echo images were obtained for 12 hours in five cats and 6 hours in four cats. Pathologic examinations of the resected specimens were performed with 2'3'5-triphenyl tetrazolium chloride (TTC) histochemical staining and electron microscopy. The size of enhanced area on MR images was compared with that of irreversibly damaged myocardium with TTC staining. The time course of signal enhancement was evaluated. RESULTS: The size of enhanced area on MR images was well correlated with that of irreversibly damaged myocardium with TTC staining. Maximum enhancement occurred 1-3 hours after administration of the contrast material, with mean enhancement of 171% that of normal myocardium. Electron microscopic examinations showed severe myocardial damage in the irreversibly damaged myocardium but only mild edematous changes in the reversibly damaged myocardium. CONCLUSION: MR images enhanced with bis-gadolinium mesoporphyrins provide accurate sizing of irreversibly damaged myocardium with a strong and persistent signal enhancement in the reperfused myocardium.

Dynamic contrast-enhanced MR imaging of bacterial abscess and VX2 carcinoma in rabbits: comparison of gadopentetate dimeglumine and a macromolecular contrast agent.

OBJECTIVE: The objective of this study was to compare enhancement patterns of a blood-pool contrast agent, Gadomer-17, with those of gadopentetate dimeglumine in bacterial abscesses and VX2 carcinoma in rabbits. MATERIALS AND METHODS: Fourteen rabbits with experimentally induced bacterial abscesses and VX2 carcinoma in both thighs underwent dynamic contrast-enhanced MR imaging with Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval. The enhancement ratios (postcontrast to precontrast signal intensities) of lesions in the same animal were assessed and correlated with microvessel density. RESULTS: For Gadomer-17, the enhancement ratio of the abscesses (1.66 +/- 0.39) peaked 15 min after the injection, while that of the carcinoma (2.05 +/- 0.16) peaked at 10 min. The enhancement ratios of the carcinoma were consistently higher than those of the abscesses up to 30 min. For gadopentetate dimeglumine, peak enhancement ratio of the abscesses (2.30 +/- 0.75) was seen 5 min after the injection, while that of the carcinoma (2.32 +/- 0.51) was seen at 3 min. The enhancement ratios of the carcinomas were significantly higher at 1 min, but significantly lower at 20-30 min, compared with those of the abscesses, as a result of rapid decrease of enhancement ratios in the carcinomas. The microvessel density was 9.8 +/- 5.2 vessels per field of view for the abscesses and 36.3 +/- 9.5 vessels per field of view for the carcinoma (p < 0.001). CONCLUSION: Delayed peak enhancement and slow decay were found in both bacterial abscess and VX2 carcinoma with Gadomer-17, whereas early peak enhancement and rapid decay were found especially in VX2 carcinoma with gadopentetate dimeglumine. Enhancement ratios on MR imaging with a blood-pool contrast agent correlated well with the microvessel density in bacterial abscess and VX2 carcinoma.

Comparison of two blood pool contrast agents for 0.5-T MR angiography: experimental study in rabbits.

PURPOSE: To evaluate two experimental blood pool agents for potential use in equilibrium phase abdominal magnetic resonance (MR) angiography. MATERIALS AND METHODS: MR imaging at 0.5 T was performed in 37 rabbits before and after intravenous injection of a gadolinium-based blood pool contrast agent (SH L 643 A), superparamagnetic iron oxide blood pool agent (SH U 555 C), or gadopentetate dimeglumine. T1-weighted fast spoiled gradient-echo images from the renal arteries to below the iliac bifurcation were obtained. The aorta-to-tissue signal difference-to-noise ratio (SDNR) was measured over time. RESULTS: Both blood pool agents yielded excellent demonstration of the rabbit abdominal aorta. At a dose of 0.1 mmol/kg, both provided a statistically significant increase in aorta-to-tissue SDNR in comparison with that achieved with gadopentetate dimeglumine (200% increase for SH L 643 A, 95% increase for SH U 555 C; P < .05). A 0.1 mmol/kg dose of SH L 643 A provided a 24% increase in SDNR relative to the increase with a 0.37 mmol/kg dose of gadopentetate dimeglumine. Time-dependent enhancement properties of the blood pool agents differed due to differences in elimination method. CONCLUSION: Both blood pool agents were found to be promising contrast agents for 0.5-T MR angiography; however, their clinical applicability warrants further investigation. The gadolinium-based agent had several advantages over the iron oxide compound, including less T2* dephasing, lack of susceptibility artifacts, and fast renal elimination.

Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats.

PURPOSE: To measure the difference in size of reperfused myocardial infarction with necrosis-specific (bis-gadolinium-mesoporphyrin [hereafter, mesoporphyrin]) and standard extracellular (gadopentetate dimeglumine) magnetic resonance (MR) contrast media. MATERIALS AND METHODS: Echo-planar (for T1 measurement) and spin-echo (for infarction size) MR imaging were conducted in 32 rats subjected to reperfused reversible (n = 16) and irreversible (n = 16) myocardial injuries. All animals received gadopentetate dimeglumine 1 hour after reperfusion and underwent imaging. Sixteen rats received mesoporphyrin at 2 hours, the other 16 rats received gadopentetate dimeglumine at 24 hours, and all animals underwent imaging at 24 hours. RESULTS: Mesoporphyrin produced prolonged (22 hours) reduction in T1 in irreversibly, but not in reversibly, injured myocardium. The size of the mesoporphyrin-enhanced region (37% +/- 4 [SEM] of left ventricular surface area) closely correlated with the true infarction size as measured by means of histomorphometry (36% +/- 3, r = 0.90). The size of the gadolinium-enhanced region overestimated (48% +/- 2 and 43% +/- 1 at 1 and 24 hours of reperfusion, respectively) the size of true infarction (36% +/- 3, P < .05, r = 0.02), but it was close to the size of the area at risk (r = 0.93). CONCLUSION: The sizes of hyperenhanced regions displayed by using mesoporphyrin and gadopentetate dimeglumine differed from each other. The difference in size of the hyperenhanced region demarcated by mesoporphyrin and gadopentetate dimeglumine may provide an estimation of potentially salvageable myocardium.

Comparison of Gadomer-17 and Gd-DTPA in image quality of contrast-enhanced MR angiographies using flow phantom model.

The purpose of this study was to compare the image quality of 3D-TOF MR angiography (MRA) using Gadomer-17 with that using Gd-DTPA in a flow phantom model, and to present preliminary data about the proper dose concentration of Gadomer-17. In the visual analysis of vessel conspicuity, we compared the quality of pre- and post-contrast MIP images. For quantitative analysis, the signal intensities were measured in the axial base 3D-TOF images, and then the relative contrast enhancement was calculated. The results of our studies were that: 1. Maximal signal intensities were obtained at 1 mmol/L of Gadomer-17 and 4 mmol/L of Gd-DTPA. 2. Flow-related signal loss was decreased by Gd-DTPA proportional to the concentration, but Gadomer-17 did not show such a dose accumulative effect. In conclusion, after comparing the results of Gd-DTPA, it was clear that improved MRA images and higher signal intensities of vessels were obtained when lower concentrations of Gadomer-17 were used.