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Single Session of MR Coronary Angiography and Myocardial Perfusion Imaging
Using a New Blood Pool Compound B-22956 (Gadocoletic Acid):
Initial Experience in a Porcine Model of Coronary Artery Disease
Jie Zheng, Debiao Li, Fabio Maggioni,
Dana Abendschein, Orlando Simonetti, Gerhard Laub,
J Paul Finn, Robert J Gropler, Friedrich M Cavagna
Zheng J et al, Investigative Radiology 2005;40:604-613
NEGATIVENEGATIVE
NEGATIVENEGATIVE
POSITIVEPOSITIVENON DIAGNOSTICNON DIAGNOSTIC
POSITIVEPOSITIVENON DIAGNOSTICNON DIAGNOSTIC
Diagnostic Decision Tree Diagnostic Decision Tree for Coronary Artery Diseasefor Coronary Artery Disease
~ 4.4 m ~ 4.4 m procedures/yprocedures/y
Stress ECG
Ultrasound
$ 400.-
rule out CADrule out CADmedicationmedication
Stress Perfusion Imaging
Nuclear Medicine rule out CADrule out CADmedicationmedication
~ 2.2 m ~ 2.2 m procedures/yprocedures/y
X-Ray Coronary Angiography or IVUS
$ 300.-
$ 700.-
>$ 3,000.-
~ 13 m ~ 13 m procedures/yprocedures/y
Radiation
Invasive
Advantages of Cardiac MRIAdvantages of Cardiac MRI
No radiation and minimal invasiveness (IV injection)
3-dimensional anatomic images (3D coronary artery and myocardial imaging)
Comprehensive functional imaging - Myocardial mechanical work- Myocardial perfusion- Myocardial oxygenation- Myocardial Viability
Challenges of Cardiac MRIChallenges of Cardiac MRI
Prone to cardiac and respiratory motions Low signal-to-noise ratio Low spatial resolution relative to motionless
organs (brain, kidney, etc)
Intravascular or blood-pool contrast agents can potentially overcome these limitations!
New Experimental Contrast for New Experimental Contrast for MR Coronary Angiography: MR Coronary Angiography: B-22956/1B-22956/1
Low molecular weight Gd chelate with very highLow molecular weight Gd chelate with very high affinity for serum proteins :affinity for serum proteins :
Apparent longitudinal relaxivityApparent longitudinal relaxivity (0.5 mM in Seronorm(0.5 mM in Seronorm®®) :) :
Binding (0.5 mM) to HSA 0.6 mM Binding (0.5 mM) to HSA 0.6 mM 94 % 94 % (80 %)*(80 %)*
Binding (0.5 mM) to PSA 0.6 mMBinding (0.5 mM) to PSA 0.6 mM 90 % 90 % (56 %)*(56 %)*
Binding (0.5 mM) to MSA 0.6 mMBinding (0.5 mM) to MSA 0.6 mM 92 % 92 % (81 (81 %)*%)*
* data in parenthesis are for MS-325, a protein binding contrast agent undergoing Clinical Trials and * data in parenthesis are for MS-325, a protein binding contrast agent undergoing Clinical Trials and FDA approvalFDA approval
rr11 27 27 mM mM-1-1 ·s ·s -1-1 (35 mM(35 mM-1-1 ·s ·s -1-1)*)*
MPR Images (Siemens Symphony 1.5T) after 0.125 mmol/kg MPR Images (Siemens Symphony 1.5T) after 0.125 mmol/kg Injection of Injection of B-22956/1B-22956/1 [[Res. : 0.7 Res. : 0.7 ×× 0.7 0.7 ×× 0.7 mm 0.7 mm33]]
1 min 1 min postcontrastpostcontrast
33 min 33 min postcontrastpostcontrast
17 min 17 min postcontrastpostcontrast
RCA
RCA
LADLCx
Res. : 1.0 × 1.0 × 2.0 (1.0) mm3
Volume RenderingVolume Rendering
3D MR Coronary Angiography in Pigs 3D MR Coronary Angiography in Pigs after after B-22956/1B-22956/1 (0.1 mmol/kg b.w.) (0.1 mmol/kg b.w.)
RCA
B-22956/1B-22956/1 0.02 mmol/kg0.02 mmol/kg
2.7 s 6.4 s 9.1 s 16.4 s 20.0 s 23.6 s
Conventional Gadolinium (FDA approved MRI Conventional Gadolinium (FDA approved MRI contrast agent)contrast agent)®® 0.04 mmol/kg 0.04 mmol/kg
2.4 s 5.6 s 8.0 s 14.4 s 17.6 s 20.8 s
Myocardial Perfusion Imaging in Pig @ 1.5T Myocardial Perfusion Imaging in Pig @ 1.5T (IR-True FISP TR/TE/(IR-True FISP TR/TE/αα: 3.5/1.8/70°): 3.5/1.8/70°)
Materials and Methods
• Six Yucatan mini-swine (mean weight = 18 kg)• Coronary balloon angioplasty injury and atherogenic diet
feeding atherosclerotic plaques in 2 or 3 coronary arteries
• X-ray angiography prior to MR scans• MR precontrast coronary imaging• Injection of 0.1 or 0.15 mmol/kg B-22956/1 (Bracco)• MR postcontrast scans (breath-holds (BH) and navigator-
echo gated imaging (NAV))
X-rayX-ray
Pig 2: LCx, Pig 2: LCx, Mild Stenosis < 50%Mild Stenosis < 50%
50-70%
LCx
Post-BHPost-BHPost-NAVPost-NAV
LAD
Pig 2: RCA, Pig 2: RCA, Moderate Stenosis 50-70%Moderate Stenosis 50-70%
X-rayX-ray
Post-BHPost-BHPost-NAVPost-NAV
50-70%
X-rayX-ray
RCA
Pig 1: RCA, Pig 1: RCA, High Grade Stenosis > 95%High Grade Stenosis > 95%
Post-NAVPost-NAV
RCA
Pig 1: RCA, Pig 1: RCA, PerfusionPerfusion High Grade Stenosis > 95%High Grade Stenosis > 95%
LV
RV LAD
RCA
Low Perfusion in RCALow Perfusion in RCA
Normal Perfusion in LADNormal Perfusion in LAD
ResultsResults
• Breath-hold and high-resolution navigator-echo gated scans could repeat after the contrast injection
• MR Coronary Angiography results qualitatively confirmed x-ray findings in terms of stenosis degree and locations
• Functional assessment of myocardial perfusion simultaneously
ConclusionsConclusions
Availability of Availability of B-22956/1B-22956/1 will greatly facilitate the will greatly facilitate the successful development of Magnetic Resonance successful development of Magnetic Resonance Coronary Angiography and quantification of Coronary Angiography and quantification of myocardial perfusionmyocardial perfusion
Clinical Trials are warranted to further Clinical Trials are warranted to further assess the potential of this contrast agentassess the potential of this contrast agent