1. Contrast-Enhanced Neuro MRA in the NSF Era: Possible Contrast Dose Reduction with a High- Relaxivity Contrast Agent
Matthew J. Kuhn, MD
Department of Radiology
University of Illinois School of Medicine
Peoria, IL, USA

3. Background
Higher doses of gadolinium-based contrast agents (GBCA) are often used for contrast-enhanced MRA (CE-MRA)
Patients with moderate-to-severe (stages 3-5) chronic kidney disease undergoing contrast-enhanced MR imaging are known to be at increased risk for developing nephrogenic systemic fibrosis (NSF)
Risk increases with higher GBCM doses or repeated GBCM exposures (1-2)
Herein we review information on the application of lower doses of the higher-relaxivity gadobenate dimeglumine (MultiHance; Gd-BOPTA) for CE-MRA of the carotid arteries and intracranial vessels

4. r1 and r2 Relaxivities at Different Magnet Strengths*
r1 (mmol-1s-1)
r2 (mmol-1s-1) T
Gd-DTPA
Gd-BOPTA
0.2
5.7 ± 0.3
10.9 ± 0.4
9.2 ± 0.3
18.9 ± 0.6
1.5
3.9 ± 0.2
7.9 ± 0.4
5.3 ± 0.2
18.9 ± 0.5 3
3.3 ± 0.2
5.9 ± 0.4
5.2 ± 0.3
17.5 ± 0.5
*Measured in human plasma at 37°C Pintaske J. Invest Radiol 2006;41: (3)

5. Abdominal Aorta MRA Crossover Comparison
Higher peak/shorter T1 30
Gd-DTPA
Gd-BOPTA
Wider plateau 25
Equivalent 0.1 mmol/kg doses at 2 mL/s
Higher tail
Mean Signal Intensity (a.u.) 20 15 AA
AAAA 40 60 80
100
120
140
Time (s)
Knopp MV. Invest Radiol 2002;37: (4)

6. Methods and Materials 2 intraindividual crossover studies (5-6)
Total of 24 patients underwent CE-MRA with
Higher-relaxivity agent gadobenate dimeglumine (Gd-BOPTA), and
Conventional contrast agent gadopentetate dimeglumine (Gd-DTPA) for CE-MRA
All subjects received both agents in 2 separate but identical imaging studies
Contrast enhancement evaluated in a blinded manner using both qualitative and quantitative metrics

7. Study 1: Comparison of Equal Doses of Gd-BOPTA and Gd-DTPA
12 healthy subjects evaluated with equal 0.1 mmol/kg bodyweight doses of Gd-DTPA and Gd-BOPTA
Significant (p≤0.021) ↑ in CNR with Gd-BOPTA; overall increases of
23.3% - internal carotid
26.7% - middle cerebral
28.5% - basilar arteries
Significant (p≤0.026) reader preference for Gd-BOPTA globally and for assessments of extracranial arteries, Circle of Willis, and vessels distal to Circle of Willis
Bueltmann E. Invest Radiol 2008; 43:695–702

8. CNR in the ICA, MCA, and BA

9. Preferences Following Matched-Pairs Comparison of Image Sets

10. Supra-Aortic MRA Crossover Comparison
0.1 mmol/kg
Gd-BOPTA
0.1 mmol/kg
Gd-DTPA
Bueltmann E. Invest Radiol 2008;43:

11. Study 2: Comparison of Single Dose of Gd-BOPTA and Double Dose of Gd-DTPA
12 patients with known or suspected stenoocclusive disease of the vessels of interest evaluated with
Gd-DTPA at a dose of 0.2 mmol/kg
Gd-BOPTA at a dose of 0.1 mmol/kg
Increase in SI and CNR [p=0.002] with Gd-BOPTA over Gd-DTPA
Qualitatively superior arterial contrast enhancement & vessel conspicuity with Gd-BOPTA, despite lower dose
Pediconi F. Radiol Med 2003; 106:87–93

12. Quantitative Analysis: Contrast-to-Noise Ratios
Mean SD
Max
Min
P value
CNR post Gd-DTPA
8.0
2.33
13.0
3.0
0.0002
CNR post Gd-BOPTA
16.16
20.0
12.0
Pediconi F. Radiol Med 2003;106:87-93

13. Carotid MRA Crossover Comparison
0.2 mmol/kg
Gd-DTPA
0.1 mmol/kg
Gd-BOPTA
Pediconi F. Radiol Med 2003;106:87-93

14. Summary of Results
In a comparison of equal single doses of Gd-BOPTA and Gd-DTPA, use of Gd-BOPTA resulted in statistically significant improvements in signal intensity (SI) and signal to noise ratio (SNR)
In a comparison of a single dose of Gd-BOPTA with a double dose of Gd-DTPA, Gd-BOPTA resulted in significantly greater increases in SI and SNR than comparator, despite the lower administered dose

15. Conclusions
Intraindividual CE-MRA studies in the brain and carotid arteries show that MRA may be performed with a single dose of higher-relaxivity Gd-BOPTA
When Gd-BOPTA is administered at the same dose as the non-protein binding comparator Gd-DTPA, enhancement is consistently better
Results are similar when Gd-BOPTA is given at half the dose (0.1 mmol/kg) of the comparator GBCA Gd-DTPA (0.2 mmol/kg)
These results suggest the potential to limit patient exposure to GBCA
Important in era of NSF

16. References Broome DR. AJR 2007; 188:586–592
Sadowski EA. Radiology 2007; 243:148–157
Pintaske J. Invest Radiol 2006; 41:
Knopp MV. Invest Radiol 2002; 37:706–715
Bueltmann E. Invest Radiol 2008; 43:695–702
Pediconi F. Radiat Med 2003; 106:87–93