Since magnetic resonance imaging (MRI) was first performed with contrast, the emergence of new contrast agents has shifted radiological clinical practice over time. Several factors may be desirable when choosing a contrast agent, excluding differences in agent cost: (1) Higher relaxivity results in more signal for better lesion detection, (2) higher stability of the gadolinium chelate, which is associated with less dechelation to free gadolinium that can deposit in tissues, (3) MRI at 3 T gains more signal over 1.5 T, and (4) half dose may be preferable to a full dose if contrast is comparable, to reduce cost and potentially reduce side effects. A number of articles have been included that look at these factors, with a section on gadolinium brain deposition. Given that nephrogenic systemic sclerosis (NSF) has largely been eliminated since 2009,1 this topic was not included in order to give attention to more current contrast issues. The purpose of this article is to review the literature on MRI contrast agent performance and dose optimization in radiological clinical practice. First, musculoskeletal imaging is reviewed, focusing on how dynamic contrast enhanced (DCE) MR perfusion has affected clinical practice, followed by a discussion of contrast-enhanced MRI in rheumatoid arthritis, and how shoulder MR arthrography can be performed without contrast. Neuroimaging is then reviewed focusing on varying linear versus macrocyclic agent performance in different field strengths, at different doses, followed by a discussion of gadolinium deposition in the brain. Body imaging is then similarly reviewed, focusing on liver and vascular imaging.
MUSCULOSKELETAL IMAGING
In recent years, DCE MR perfusion has been evaluated for multiple uses in musculoskeletal imaging. A few uses in which this technique has been shown to be valuable include differentiating tumor from post-treatment change, assessing vascularity in the proximal fragment of scaphoid fractures, response to treatment with inflammatory conditions, and in guiding targeted biopsy of musculoskeletal soft tissue tumors.
DCE MR perfusion involves rapid imaging of a volume of tissue repeatedly over time after a gadolinium bolus injection, using a gradient-echo based T1-weighted sequence that undersamples k-space in order to maintain fast temporal resolution. The k-space trajectory is chosen to maximize filling of the center of k-space throughout the scan that results in high tissue contrast while relatively sacrificing soft tissue detail as the periphery of k-space is filled to a lesser degree.2 Regarding tumor treatment response, Miyazaki et al evaluated 13 musculoskeletal tumors using multiple DCE MR perfusion maps and correlating them with a 2D graph plotting K1 versus distribution volume (Vd), a 3D graph plotting K1 versus Vd versus permeability-surface area product (PS). They found that good responders to treatment after increasing number of treatments showed improvement in both the 2D and 3D graphs, while nonresponders showed little improvement, suggesting that the perfusion maps could be used to visually assess for tumor response.3 Guo et al4 studied the vascular effects of adding bevacizumabto neoadjuvant chemotherapy in osteosarcoma using DCE MR perfusion. They found that at 24 hours, Ktrans significantly dropped below baseline after the first dose of bevacizumab alone, and although the level returned to baseline at 72 hours, a lower Ktrans at week 10 was significantly associated with greater tumor necrosis and longer event-free survival.4 DCE MR perfusion has also been evaluate to guide biopsy. Specifically, Noebauer-Huhmann et al used DCE perfusion at 3 T to target 42 soft tissue tumors for biopsy. They found that DCE MR perfusion could accurately be performed. Using routine MRI sequences and DCE MR perfusion, using the wash-in rate parameter, they were able to stratify tumors into benign, intermediate, or malignant categories in 100% of cases, predict a tissue-specific entity in 95.2%, and predict tumor grade in 90.5% of cases.
Ng et al5 evaluated vascularity in the proximal fracture fragment in 35 patients with scaphoid delayed-union and nonunion using noncontrast MRI, contrast-enhanced MRI, and DCE MR perfusion. They found DCE MR perfusion to be more accurate than either noncontrast or contrast-enhanced MRI, noting that one must consider the time frame between injury and MRI.5
Regarding inflammatory conditions, Jans et al6 examined 3T DCE MR perfusion in 6 patients with erosive osteoarthritis in the interphalangeal joints of the second and fifth fingers before and after 12 months of antitumor necrosis factor treatment. They found significant decreasing maximum upslope and absolute and relative enhancement compared with baseline scans, suggesting that this is a promising way to monitor therapy response.6
The importance of MRI has also been evaluated in rheumatoid arthritis as has the appropriate dose. Early diagnosis of rheumatoid arthritis is important as highly effective treatment is available, disease-modifying antirheumatic (DMRAD) medications, and synovitis and bone marrow edema may precede osseous erosions. Fox et al7 retrospectively evaluated 48 patients to see whether contrast-enhanced MRI may positively impact patient management. Significant management changes occurred in 79% of the positive MRI studies and in 11% of the negative MRI studies. Eighty percent of the patients with DMARDs added had an improvement of symptoms and none of the patients whose medications were stopped had symptom recurrence. They concluded that contrast-enhanced MRI may help to guide treatment and should be considered in patients with known or suspected rheumatoid arthritis when the clinical picture is unclear.7 Also regarding early rheumatoid arthritis, Schueller-Weidekamm et al8 studied such 57 patients at 3-T MRI. Each patient received a half dose (0.05 mmol/kg) of gadobenatedimeglumine and was scanned after a 6-minute delay with a T1-weighted coronal series (5-minute, 40-second acquisition time). The patient then had a second half dose injected where after a repeat coronal T1-weighted series was obtained. Effectively, the second series was scanned after a full dose of contrast, although the first half of this full dose was administered no less than 12 minutes before the second scan. Overall, they showed a high correlation between half-dose and full-dose gadobenate in synovial signal intensities, concluding that half dose at 3 T may be adequate in evaluating synovitis or tenosynovitis in rheumatoid arthritis.8
Helms et al9 raised the question whether contrast is even needed for shoulder arthrography. They studied 100 shoulder MR arthrogram patients, whereby gadoteridol diluted with saline (1 : 200) was injected into the shoulder joint. At first, T2 images were solely evaluated for rotator cuff or labral pathology and after a delay the full study was evaluated. Fifteen discordant cases were resolved by consensus. Overall, they concluded that MR arthrography using saline alone for joint distention would be equivalent to gadolinium MR arthrogram that could shorten examination time by eliminating the T1-weighted images and decrease cost by avoiding gadolinium.9
NEUROIMAGING
Multiple studies have been performed to evaluate conspicuity of brain metastases and primary brain tumors. As brain metastases can be millimeters in size, lesion conspicuity is very important for diagnosis. Thus, higher signal to noise (SNR) and contrast to noise ratios (CNR) are quite desirable. A number of neuroimaging studies have looked at contrast agent performance considering the type of contrast (linear vs macrocyclic), differences in relaxivity, the effects of magnet strength, and at different doses.
As gadobenate has about twice the relaxivity of gadopentetate at both 1.5 and 3 T, Morelli et al10 performed a study to see whether half-dose gadobenate (0.05 mmol/kg) may be equivalent to full-dose gadopentetate (0.1 mmol/kg). They implanted gliomas in 13 rat brains scanned them on either 1.5 or 3 T, in a random order, on consecutive days. SNR, CNR, and contrast enhancement parameters that they evaluated were all significantly lower on both 1.5 and 3 T with half-dose gadobenate than with full-dose gadopentetate. They therefore concluded that despite the increased relaxivity of gadobenate, half-dose contrast enhancement is not adequate compared with full-dose gadopentetate.10
Of the gadolinium agents approved for neuroimaging, gadobutrol has the highest relaxivity of the macrocyclic agents and gadobenate has the highest relaxivity of the nonmacrocyclics.11
In the MERIT study, Seidl et al12 evaluated gadobenate dimeglumine versus gadobutrol in 114 patients for a variety of lesions including primary intra-axial and extra-axial brain tumors, metastases, other tumors, and nontumors. Each study patient had 2 identical MRI scans at 1.5 T except for the type of gadolinium. One scan was done with gadobenate and the other with gadobutrol, each with a dose of 0.1 mmol/kg. They found a significant overall reader preference for gadobenate over gadobutrol, as well as for several additional diagnostic endpoints. Contrast to noise and lesion to background ratios were also significantly better for gadobenate.12
Attenberger et al13 compared gadobutrol with both the macrocyclic agent gadoterate meglumine and the linear agent gadopentetate dimeglumine at 1.5 and 3 T in rat brains implanted with glioma tissue. A total of 24 rats were evaluated, split into 3 groups, the first 2 groups evaluating gadobutrol versus either gadoterate or gadopentetate, all at 1.5 T. The last group evaluated only gadobutrol, at both 1.5 and 3 T. A full contrast dose (0.1 mm/kg) was used for all doses. They found gadobutrol to have higher tumor SNR and CNR than gadopentetate and gadoterate at all time points. Specifically, there was a significant difference in CNR or gadobutrol over gadopentetate at 7 minutes postcontrast, while gadobutrol had a significantly higher CNR than gadoterate at 5 and 9 minutes postcontrast. All time points postcontrast showed a significantly higher SNR and CNR at 3 T than at 1.5 T when evaluating gadobutrol alone.13
Morelli et al14 also evaluated the linear agent gadodiamide versus gadobutrol at 1.5 and 3 T in 54 rat brains implanted with glioma tissue. Three groups were studied; in the first group, full-dose (0.1 mmol/kg) gadodiamide and gadobutrol were evaluated at 3 T, with injections separated by 24 hours, with the second group studied similarly but at 1.5 T. In the third group, full-dose or half-dose (0.05 mmol/kg) gadobutrol alone was given and scanned at both 1.5 and 3 T. They found that gadobutrol was significantly better than gadodiamide regarding SNR, CNR, and contrast enhancement at both 1.5 and 3 T for all time points assessed postcontrast. Regarding gadobutrol alone, CNR and contrast enhancement were not significantly different between half dose at 3 T and full dose at 1.5 T, although SNR was significantly better at 3 T.14
Maravilla et al compared 2 macrocyclic agents, gadobutrol and gadoteridol, to see whether the 2-fold higher concentration of gadobutrol (1 vs 0.5 mol/L) would cause any significant differences in contrast enhancement. One hundred ninety-eight known or suspected brain tumor patients were randomized to either contrast agent at full dose (0.1 mmol/kg) at 1.5 T, with the 2 scans separated by at least 48 hours. A total of 246 histologically confirmed tumor lesions and 62 nontumor lesions were identified and analyzed for the detection rate, while only the tumor lesions were analyzed for accuracy of tumor characterization and for confidence in brain tumor characterization. Overall, they found that gadoteridol and gadobutrol provided similar information for diagnosing brain lesions.15
T1 SHORTENING IN THE CNS
Recent literature has been written describing the deposition of gadolinium contrast in the brain in patients with intact blood-brain barriers. Studies have been performed proving gadolinium deposition, some even quantifying the amounts. Evidence is pointing to the low-stability agents as the ones most associated with brain deposition, and Ramalho et al1 recently wrote a review article summarizing the literature on this topic. A few studies have been included for review.
Kanda et al16 also studied neuronal tissue in 10 patients postmortem (5 with prior exposure to gadolinium and 5 without gadolinium exposure) without a diagnosis of severely compromised renal function (estimated glomerular filtration rate [eGFR] < 45 mL/min/1.73 m2) or acute renal failure. They used inductively coupled plasma mass spectrometry (ICP-MS) to examine tissue from the dentate nucleus, globus pallidus, and frontal lobe gray and white matter. Gadolinium was deposited in each of the areas assessed, in amounts significantly greater than in the control group, noting significantly higher concentrations in the dentate nucleus and the globus pallidus.16 McDonald et al17 examined T1 signal intensity (S.I.) in 13 patients who each had at least 4 gadolinium contrast-enhanced brain MRI examinations with postmortem neuronal tissue sampling, compared with 10 control patients who did not receive gadolinium-based contrast. Neural tissue from the dentate nuclei, pons, globus pallidus, and thalamus were analyzed with ICP-MS, transmission electron microscopy, and light microscopy. All patients had relatively normal renal function at the time of MRI. The found that the control group had no detectable levels of gadolinium, while in the group receiving gadolinium, neuronal tissue contained 0.1 to 58.8 μg of gadolinium per gram of tissue. This gadolinium deposition showed a significant dose dependence that correlated with S.I. changes on unenhanced T1-weighted MR images.17
A retrospective observational study by Errante et al18 examined progressive T1 S.I. increase on unenhanced T1 images in the dentate nucleus compared with the pons in 2 patient cohorts, 38 with multiple sclerosis, and 37 with brain metastases, with normal renal function who had prior administrations of gadodiamide. Patients with 6 of more MRI scans had a significantly higher dentate to pons S.I. ratio in their last scan than their first scan. They also showed a linear relationship between the increase in T1 S.I. and the prior number of enhanced MRI scans in these 2 cohorts, suggesting substantial dechelation of this agent.18 Kanda et al19 retrospectively compared 19 patients who had undergone at least 6 contrast-enhanced MRI studies with 16 patients who had undergone at least 6 unenhanced MRI studies. They evaluated dentate nucleus to pons and globuspallidus to thalamus S.I. ratios. Both S.I. ratios had a significant correlation with the number of prior gadolinium administrations, noting that the globus pallidus to thalamus ratio also had a significant correlation with radiation therapy and liver function. The S.I. ratios were also significantly greater for those undergoing contrast-enhanced studies than those undergoing unenhanced studies.19
Radbruch et al20 performed a retrospective study on 2 groups of 50 patients who had at least 6 administrations of gadolinium contrast. One group exclusively had the linear agent, gadopentetate dimeglumine, and the second group had exclusively the macrocyclic agent gadoterate meglumine. S.I. ratios of the dentate to pons and globus pallidus to thalamus on unenhanced T1-weighted images were compared between from the patients first and last T1-weighted images. They concluded that the linear agent gadopentetate dimeglumine is associated with a significant increase in dentate nucleus S.I., while the macrocyclic agent gadoterate meglumine is not.20 Kanda et al21 also performed a retrospective study evaluation of 127 patients who underwent prior contrast-enhanced MRI of the brain with different types of gadolinium chelates, measuring the dentate nucleus to cerebellum S.I. ratio while evaluating the number of prior gadolinium administrations. Nine patients had hyperintensity in the dentate nuclei. They found a significant association between dentate nucleus S.I. and linear gadolinium chelate agents but no such association with macrocyclic agents.21
BODY IMAGING
A few issues with gadolinium use in body imaging include evaluating the macrocyclic agent gadobutrol against other contrast agents particularly given its higher molarity, examining agents at half dose or double dose, studying gadoxetic acid, a high relaxivity agent approved only for hepatobiliary imaging, and examining vascular contrast agents at standard or different doses including the blood pool agent gadofosveset trisodium.
A multicenter randomized clinical phase 3 trial by Hammerstingl et al22 compared the efficacy of the macrocyclic agent gadobutrol with the linear agentg adopentetate in 497 patients with known or suspected liver lesions. Contrast dose was 0.1 mmol/kg and the imaging protocol included dynamic 3D imaging, static conventional, and fat-saturated T1-weighted imaging. They ultimately concluded that gadobutrol is not inferior to gadopentetate, that either could be used for the assessment of liver lesions, and that both agents had a similar excellent safety profile.22 A smaller study by Kim et al23 of 23 patients with 37 small hepatocellular carcinomas also compared gadobutrol with gadopentetate. They found a superior degree of enhancement with gadobutrol, but accuracy, sensitivity, and positive predictive value for diagnosing hepatocellular carcinoma were all equivalent between the 2 agents.23
Homayoon et al24 studied dynamic MRI in noncirrhotic livers using half-dose gadobenate versus full-dose gadodiamide. Eighteen patients were studied for quality of lesions, with 12 hemangiomas and 7 focal nodular hyperplasias (FNHs), while liver vessel enhancement and global diagnostic imaging quality were also evaluated. They found no significant differences in any qualitative metrics and the only quantitative metric of statistical significance was that of higher CNR at 20 seconds in FNHs with gadodiamide. They therefore concluded that contrast enhancement of half-dose gadobenate is similar to full-dose gadodiamide for the lesions studied, and that gadobenate is a reasonable alternative to standard dose extracellular agents in dynamic liver MRI.24 Becker-Weidman et al25 examined hepatocellular carcinomas in 35 patients after MRI systems improvements that included both 3D gradient recalled echo (GRE) and T2-weighted single-shot fast spin-echo sequence optimization, switching from 0.1 mmol/kg gadodiamide or gadopentetate to 0.05 mmol/kg of gadobenate, and uniformly using semi-automated real-time bolus tracking for timing purposes. After such changes, they discovered a significant increase in detection of small (<2 cm) hepatocellular carcinomas with a sensitivity of 87.5%, previously 55.6%.25
Gadoxetic acid is a liver-specific combined hepatobiliary and renally cleared agent for which the recommended dose is 0.025 mmol/kg, one-fourth that of standard dosing (0.1 mmol/kg) for the majority of gadolinium contrast agents. As dynamic liver MRI evolved from 2D to 3D sequences, which have different signal behaviors, Zech et al26 studied standard dose (0.025 mmol/kg) and double-dose (0.50 mmol/kg) gadoxetic acid versus standard dose gadopentetate (0.1 mmol/kg) in pigs, also studying different injection rates of 1 and 2 mL/s for each dose. A minimum of 48 hours passed between contrast dose injections in each individual pig. They found that arterial enhancement in gadoxetic acid enhanced dynamic liver MRI was comparable to that of gadopentetate despite the lower standard dose of gadoxetic acid, likely due to its increased relaxivity. The lower injection rate of 1 mL/s was found to have better arterial enhancement than the 2 mL/s rate.26 Double-dose gadoxetic acid was also studied by Motosugi et al27 in 28 patients with chronic liver disease who had a total of 54 hepatocellular carcinomas. Each patient was injected with gadoxetic acid on separate occasions, once with standard dose (0.025 mmol/kg) and the second time with double dose (0.05 mmol/kg). They found a significant improvement in arterial enhancement of hepatocellular carcinomas with the double dose, and found significantly better lesion–to-liver contrast in the hepatocellular phase in those patients with Child-Pugh class B disease.27
Feuerlein et al28 studied the relative enhancement of the hepatic parenchyma and portal vein using a weight-independent dose of 10 mL of gadoxetic acid for enhanced abdominal MRI in 102 patients. The patients were stratified into 3 dose groups: recommended dose (0.02 to 0.03 mmol/kg), intermediate dose (0.03 to 0.045 mmol/kg), or high dose (0.045 to 0.06 mmol/kg). They found no statistically significant difference between the 3 groups regarding port vein-to-liver contrast and concluded that such contrast cannot be improved with gadoxetic acid over the examined dose spectrum of 0.025 to 0.06 mmol/kg.28
Standard dose gadobenate (0.1 mmol/kg) was compared with double-dose gadoxetic acid (0.05 mmol/kg) for dynamic and hepatobiliary phase MRI in healthy volunteers at 3 T by Frydrychowicz et al.29 The interval between the 2 scans for each volunteer was an average of 21.8 hours. They found statistically significant better SNR in the portal vein and hepatic vein in the portal venous and venous phases, and a statistically significant better SNR performance during the hepatobiliary phase. Thus, they suggested that gadobenate may be preferred over gadoxetic acid only for dynamic phase imaging.29
Camren et al30 examined thoracic vasculature for SNR and vessel edge sharpness (ES) at 1.5 T comparing gadobenate dimeglumine and the blood pool agent gadofosveset trisodium. Twenty patients had ECG-gated 3D steady state magnetic resonance angiogram (MRA) 3 to 4 minutes after injection of gadobenate and twenty different patients had the MRA after gadofosveset injection. They found no significant difference in SNR or ES between the 2 contrast agents concluding that high-quality thoracic SS-MRA can be obtained with gadobenate comparable to gadofosveset provided that imaging is done shortly after contrast injection.30 Also regarding gadofosveset, Kim et al31 studied the feasibility of and possible does for MRA of the thoracic vasculature in 30 volunteers. Ten volunteers received a dose of 0.03 mmol/kg, 10 of 0.02 mmol/kg, and 10 of 0.01 mmol/kg, each having their MRA scan at 5 minutes postinjection in the equilibrium phase. After both qualitative and quantitative analysis, they found adequate visualization of the vasculature for all assessed vessels at both 0.03 and 0.02 mmol/kg. Over 90% of assessed vessels were adequately seen at 0.01 mmol/kg, although SNR and CNR were significantly lower than the higher doses.31
Heverhagen et al32 investigate different contrast doses to see how it would affect S.I. and image contrast in abdominal vessels compared with each other and with the liver and spleen. Sixty patients were assigned to 1 of 3 groups of different contrast concentration, 0.1, 0.2, or 0.3 mmol/kg of gadopentetate. 3D FLASH MRA was performed on a 1.0-T MR scanner. They did not find a significant difference in maximum S.I. nor in vessel conspicuity with increasing contrast dose and although they found that an increase in contrast dose increases vessel contrast, it did not significantly do so. Overall, they concluded that a single dose (0.1 mmol/kg) is sufficient for high-quality MRA of the abdomen.32 The higher concentration 1.0 M gadobutrol was compared with 0.5 M gadopentetate, by Hadizadeh et al, using equimolar doses (0.1 mmol/kg) at 1.5 T, to evaluate 3D MRA of the abdominal vasculature in 15 patients. They determined that small abdominal vessels could be better visualized and that vessel-to-tissue contrast was significantly higher with gadobutrol than with gadopentetate at equimolar dosing.33
CONCLUSION
After this review article, the reader should be more familiar with recent advances in the clinical practice of gadolinium use in contrast-enhanced MRI studies, and have a better appreciation for dose optimization. Continued studies will be needed to further optimize agent selection and dosing in routine clinical practice, particularly in light of gadolinium deposition in the brain.
REFERENCES
1. Ramalho J, Semelka RC, Ramalho M, et al. Gadolinium-based contrast agent accumulation and toxicity: an update.
AJNR Am J Neuroradiol 2015; [Epub ahead of print].
2. Ahlawat S, Fayad LM. De novo assessment of pediatric musculoskeletal soft tissue tumors: beyond anatomic imaging.
Pediatrics 2015; 136:e194–e202.
3. Miyazaki S, Murase K, Sugawara Y, et al. Visualization of treatment response in tumors by use of dynamic contrast-enhanced magnetic resonance imaging.
Radiol Phys Technol 2008; 1:129–136.
4. Guo J, Glass JO, McCarville MB, et al. Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.
Br J Cancer 2015; 113:1282–1288.
5. Ng AWH, Griffith JF, Taljanovic MS, et al. Is dynamic contrast-enhanced MRI useful for assessing proximal fragment vascularity in scaphoid fracture delayed and non-union?
Skeletal Radiol 2013; 42:983–992.
6. Jans L, De Coninck T, Wittoek R, et al. 3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring.
Skeletal Radiol 2013; 42:255–260.
7. Fox MG, Stephens T, Jarjour WN, et al. Contrast-enhanced magnetic resonance imaging positively impacts the management of some patients with rheumatoid arthritis or suspected RA.
J Clin Rheumatol 2012; 18:15–22.
8. Schueller-Weidekamm C, Lodemann K-P, Grisar J, et al. Contrast-enhanced MR imaging of hand and finger joints in patients with early rheumatoid arthritis: do we really need a full dose of gadobenate dimeglumine for assessing synovial enhancement at 3 T?
Radiology 2013; 268:161–169.
9. Helms CA, McGonegle SJ, Vinson EN, Whiteside MB. Magnetic resonance arthrography of the shoulder: accuracy of gadolinium versus saline for rotator cuff and labral pathology.
Skeletal Radiol 2011; 40:197–203.
10. Morelli JN, Gerdes CM, Zhang W, et al. Enhancement in a brain glioma model: a comparison of half-dose gadobenate dimeglumine versus full-dose gadopentetate dimeglumine at 1.5 and 3 T.
J Magn Reson Imaging 2013; 38:306–311.
11. Bellin MF, Van Der Molen AJ. Extracellular gadolinium-based contrast media: an overview.
Eur J Radiol 2008; 66:160–167.
12. Seidl Z, Vymazal J, Mechl M, et al. Does higher gadolinium concentration play a role in the morphologic assessment of brain tumors? Results of a multicenter intraindividual crossover comparison of gadobutrol versus gadobenate dimeglumine (the MERIT study).
Am J Neuroradiol 2012; 33:1050–1058.
13. Attenberger UI, Runge VM, Morelli JN, et al. Evaluation of gadobutrol, a macrocyclic, nonionic gadolinium chelate in a brain glioma model: comparison with gadoterate meglumine and gadopentetate dimeglumine at 1.5 T, combined with an assessment of field strength dependence, specifically 1.5 versus 3.
J Magn Reson Imaging 2010; 31:549–555.
14. Morelli JN, Runge VM, Vu L, et al. Evaluation of gadodiamide versus gadobutrol for contrast-enhanced MR imaging in a rat brain glioma model at 1.5 and 3 T.
Invest Radiol 2010; 45:810–818.
15. Maravilla K, Smith M, Vymazal J, et al. Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study).
AJNR Am J Neuroradiol 2015; 36:14–23.
16. Kanda T, Fukusato T, Matsuda M, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy.
Radiology 2015; 276:228–232.
17. McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging.
Radiology 2015; 275:772–782.
18. Errante Y, Cirimele V, Mallio CA, et al. Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation.
Invest Radiol 2014; 49:685–690.
19. Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.
Radiology 2014; 270:834–841.
20. Radbruch A, Weberling LD, Kieslich PJ, et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent.
Radiology 2015; 275:150337.
21. Kanda T, Osawa M, Oba H, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration.
Radiology 2015; 275:803–809.
22. Hammerstingl R, Adam G, Ayuso J-R, et al. Comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine-enhanced magnetic resonance imaging in five hundred seventy-two patients with known or suspected liver lesions: results of a multicenter, double-blind, interindividual, randomized clinical.
Invest Radiol 2009; 44:168–176.
23. Kim YK, Lee YH, Kim CS, et al. Double-dose 1.0-M gadobutrol versus standard-dose 0.5-M gadopentetate dimeglumine in revealing small hypervascular hepatocellular carcinomas.
Eur Radiol 2008; 18:70–77.
24. Homayoon B, Diwakar H, Strovski E, et al. Half-dose gadobenate dimeglumine versus standard-dose gadodiamide in dynamic magnetic resonance imaging of non-cirrhotic livers: a retrospective intra-individual crossover comparison.
Abdom Imaging 2014; 39:955–962.
25. Becker-Weidman DJS, Kalb B, Sharma P, et al. Hepatocellular carcinoma lesion characterization: single-institution clinical performance review of multiphase gadolinium-enhanced MR imaging–comparison to prior same-center results after MR systems improvements.
Radiology 2011; 261:824–833.
26. Zech CJ, Vos B, Nordell A, et al. Vascular enhancement in early dynamic liver MR imaging in an animal model: comparison of two injection regimen and two different doses Gd-EOB-DTPA (gadoxetic acid) with standard Gd-DTPA.
Invest Radiol 2009; 44:305–310.
27. Motosugi U, Ichikawa T, Sano K, et al. Double-dose gadoxetic acid-enhanced magnetic resonance imaging in patients with chronic liver disease.
Invest Radiol 2011; 46:141–145.
28. Feuerlein S, Boll DT, Gupta RT, et al. Gadoxetate disodium-enhanced hepatic MRI: dose-dependent contrast dynamics of hepatic parenchyma and portal vein.
Am J Roentgenol 2011; 196:18–24.
29. Frydrychowicz A, Nagle SK, apos D, et al. Optimized high-resolution contrast-enhanced hepatobiliary imaging at 3 Tesla: a cross-over comparison of gadobenate dimeglumine and gadoxetic acid.
J Magn Reson Imaging 2011; 34:585–594.
30. Camren GP, Wilson GJ, Bamra VR, et al. A comparison between gadofosveset trisodium and gadobenate dimeglumine for steady state MRA of the thoracic vasculature.
Biomed Res Int 2014; 2014:625614.
31. Kim CY, Heye T, Bashir MR, et al. Gadofosveset-enhanced magnetic resonance angiography of the thoracic vasculature in the equilibrium phase: feasibility and impact of dose.
J Comput Assist Tomogr 2013; 37:732–736.
32. Heverhagen JT, Reitz I, Pavlicova M, et al. The impact of the dosage of intravenous gadolinium-chelates on the vascular signal intensity in MR angiography.
Eur Radiol 2007; 17:626–637.
33. Hadizadeh DR, Von Falkenhausen M, Kukuk GM, et al. Contrast material for abdominal dynamic contrast-enhanced 3D MR angiography with parallel imaging: intraindividual equimolar comparison of a macrocyclic 1.0 M gadolinium chelate and a linear ionic 0.5 M gadolinium chelate.
Am J Roentgenol 2010; 194:821–829.
