MR Coronary Angiography with the New Intravascular Contrast Agent B-22956/1: First Human Experience

We assessed the potential of the new intravascular contrast agent B-2295611 for application in MRCA. TI of blood and nzyocardium was measured for 24 volunteers receiving various doses on a Siemens Symphony scanner using a segmented IR TrueFlSP sequence Blood TI amounted to 35 and 55 ms at 5 and 30 min after 0 1 mmol/kg of B-22956/1, respectively Free-breathing IR 3 0 segmented GRE MR Coronary Angiographies were performed on 12 volunteers on a Philips Gyroscan scanner afier 0.075 mmollkg of B-2295M. SNR and CNR increased by 37 and 92%, respectively, over previously recorded baseline scans with T2 preparation. Introduction: The protein-binding gadolinium chelate B-22956i1 has shown strong promise for application as an intravascular contrast agent for Magnetic Resonance Coronary Angiography (MRCA) in animal imaging experiments [I]. This paper aims at determining the clinical potential of this agent by assessing extent and duration of TI-shortening in blood and myocardium as well as the visualization of the coronary artery tree in freebreathing MR Coronary Angiography of normal volunteers. Materials and Methods Contrast Agent: B-2295611 was administered as a 0.25 M solution in saline at a rate of 20mLimin. TI nzeasurements : Longitudinal relaxation times were measured for six dose groups of four volunteers each. Dose levels of 0.01, 0.02, 0.05, 0.1, 0.125 and 0.15 mmolikg were tested. Relaxation rate measurements were performed on a 1.5T Siemens scanner equipped with a gradient set of 40mTim strength and 200 T i d s slew rate using a 2D Inversion-Recovery segmented TrueFISP sequence with TR of 3.0ms and flip angle: 40" which had been previously validated on phantoms [2]. Blood TI values were measured in the descending aorta by twelve breath-hold acquisitions of 40 successive segments each with an echo train length=8 following the inversion pulse. Myocardium TI values were measured by acquiring three breath-hold acquisitions of 13 segments each having an echo train length=32. MR Coronary Angiography: Free breathing MR Coronary Angiography using a specially adapted [3] Inversion Recovery 3D navigator echo gated and corrected, segmented gradient recalled echo sequence was performed on twelve healthy male volunteers on a 1.5 T Philips Gyroscan ACS NT scanner between 5 and 45 min after administration of 0.075 mmolikg of B-2295611 at a rate of 20mLimin. Ten adjacent slices of 3mm each were acquired for a Field of View of 360mm and a 512 matrix. Acquisition volumes were targeted to cover either the territory of the RCA or the territory of the LAD including the proximal and median part of the LCX. Other acquisition parameters included TRITE: 7.512. lms; flip angle: 40'; inversion time: 180ms; imaging window: 70ms; and gating window : 5mm. Postcontrast scans were compared with precontrast scans taken with the same parameters but substituting the inversion pulse with a T2 preparation scheme [4] (TE: 50ms) for native contrast enhancement. Image analysis included determination of intraluminal SNR of coronaly arteries, vessel-muscle CNR, and visible length (VL) of coronary arteries. Results and Discussion TI nzeasurements: The T I values measured for blood and myocardium prior to as well as at 5, 15-20, and 25-30 min after administration of Qarious doses of B-22956/1 are shown in Table 1. The average value for blood amounted to 35ms at 5 min after a dose of 0.1 mmolikg, while TI of myocardium was more than fourfold at the same time point. Blood T, was as low as 55ms at 30 min after administration. Thus, B-2295611 shows unprecedented efficacy for blood T, shortening, both in terms of magnitude and duration of the effect. Up to 0.1 mmolikg the relaxation rate enhancement of blood scales almost linearly with the dose, reinforcing the notion that there are more than one binding site for this chelate on the HSA molecule. Thus, a positive dose-effect correlation will hold also at doses which are higher than that resulting in an equimolar concentration of 0-2295611 and HSA in plasma (roughly 0.05 mmol/kg). MR Coronaiy Angiography: Free-breathing MR Coronary Angiographies taken after administration of 0.075 mmolikg of B-2295611 showed strong improvement over native scans with T2 preparation over the whole observation period (up to 45 min after administration) both in terms of visually perceived image qualities (Fig.1) and of objective image quality parameters (Table 2). Images of MRCA taken at 30 min after administration clearly visualized the first branching point, the second branch (a. marginalis) and the full extent of the bifurcation after the crux. Table 1 In-vivo longitudinal relaxation times (ms) for blood (native Ti' 1450 ms) and myocardium (native T, 950 ms) after administration of various doses of B2295UI Dose of Blood TI Blood TI Blood TI 0.010 mmolikg 303 ms 375 ms 385 ms 0 020 mmolikg 168 ms 210 ms 235 ms 0.050 mmol1kg 75 ms 105 ms 113ms 0.100 mmolikg 35 ms 55 ms 55 ms 0.125 mmol1kg 30 ms 38 ms 45 ms 0 1 S O mmol1kg 30 ms 30 ins 30 ms B-2295611 5 min post 15-20 min post 25-30 rnin post Dose of Myocard. TI Myocard. TI Myocard.T1 B-22956/1 5 min post 15-20 min post 25-30 min post 0.010 mmolikg 515 ms 480 ms 480 ms 0.020 mmolikg 350 ms 350 ms 350 ms 0.050 mmolikg 233 ms 260 ms 268 ms 0.100 mmolikg 148 ms I60 ms 165 ms 0.125 mmolikg 120 ms 140 ms 190 ms Table 2 Obiective imaEe aualitv parameters for postcontrast and native scans, . values are average for 12 subjects i S E M Ta preparation B-22956i1 (5-15 min post) lntraluminal SNR 34.5 + 5.6 47.4 f 4 1 Vessel-muscle CNR 21.6 + 5.5 42.1 i-8 1 VL of coronary arteries (mm) 46 f 13 60 f 9 Fig 1 Reformatted multi-planar precontrast T2-prep images ofthe RCA (a) and the LAD/LCX (c); postcontrast rmages of the RCA at 30 min (b) and of the LAD/LCXat 5 nun (4 afler confrasf Conclusion: The high intravascular containment of B-2295611 resulting from its strong binding (hound fraction 94%) to HSA and its slow elimination from plasma (elimination half life 7h) allow for a prolonged imaging window with high intraluminal signal intensity and efficient suppression of myocardial muscle. Our results bode well for successful clinical application of contrast enhanced, free breathing high resolution MR Coronary Angiography.