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 mkuhn6@gmail.com

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

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;41:213-221 (3)

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;37:706-715 (4)

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

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

CNR in the ICA, MCA, and BA

Preferences Following Matched-Pairs Comparison of Image Sets

Supra-Aortic MRA Crossover Comparison 0.1 mmol/kg Gd-BOPTA 0.1 mmol/kg Gd-DTPA Bueltmann E. Invest Radiol 2008;43:695-702

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

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

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

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

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

References Broome DR. AJR 2007; 188:586–592 Sadowski EA. Radiology 2007; 243:148–157 Pintaske J. Invest Radiol 2006; 41:213-221 Knopp MV. Invest Radiol 2002; 37:706–715 Bueltmann E. Invest Radiol 2008; 43:695–702 Pediconi F. Radiat Med 2003; 106:87–93