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) mm3Res. : 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/: 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

ResultResultss

• 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