1. Sylwia Heinze-Paluchowska Department of Magnetic Resonance Imaging (NZ56)

2. Introduction  Coronary heart diseases - the single most common cause of death in the EU and US  The animal model of the mouse is gaining increasing popularity in basic cardiovascular research Deaths by cause, latest available year, Europe

3. The purpose of our project was to:  design and construct specialized hardware components  develop MR protocols dedicated to measurements of cardiac function of small animals in vivo  evaluate cardiac dynamics in mice receiving pharmacotherapy (clopidogrel, canrenon, antiplatelet teraphy) Purpose

4. Animal model Mouse heart’s weight 0,1 g; heart dimensions 13 mm (long axis) and 8 mm (short axis). Heart rate: 400-600 bpm (RR 100-150 ms). Left atrium Left ventricle Right atrium Right ventricle 30 mm End-systole and end-diastole MR images of the left ventricle (LV)

5. Subjects and Methods: Cardiac function in TG (Tg  q*44) and wild-type (FVB) mice was analyzed using MRI.  Tg  q* 44 mice mimics many of the phenotypic characteristics of dilated cardiomyopathy in humans.  Cardiac function was measured in TG and wild-type mice at the age of 2-14 months.  Dobutamine induced stress was used to unmask the alterations in cardiac function at early stage of heart failure progression that was not clearly visible by monitoring cardiac function at rest.

6. MRI system  4,7T/310 magnet (Bruker, Germany)  MARAN DRX Console (Resonance Instruments Ltd., GB)  Animal monitoring system (SA Instruments Ltd, USA)  Dedicated, homebuilt probehead :  Unshielded gradient system  RF birdcage coil  Animal handling system  Temperature controller Homebuilt gradient system and RF probehead

7. MRI of the mice heart in vivo Mouse (FVB, Tg  q*44) Animal handling system RF birdcage coil 4,7 T magnet with MARAN DRX console, device to anaesthesia and animal monitoring system ECGAnaesthesia All animal experimental procedures were in accordance with institutional guidelines, given by the Ethic Commission of the Jagiellonian University Medical College.

8. 8 Methodology  MR images acquired through 120% of the cardiac cycle in the short-axis plane at papillary muscles level.

9. Protocol ECG triggered fast gradient echo (cine- like FLASH with flow-compensation) TR = 5 ÷ 6 ms TE = 2,5 ms FOV = 30 x 30 mm Slice thickness1,5 mm (1mm) Matrix 128  128 NS 8 Flip angle  =30  TG mouse Wild-type mouse

10. Image analysis Semiautomatic analysis of the LV images with the use of Aphelion software (prof. L. Wojnar, Cracow University of Technology)

11. 0 20 40 60 80 100 120 0,0050,00100,00150,00200,00250,00 Acquisition time [ms] Slice volume [%] FVB 4 month.TG 4 month. TG 10 month. TG 12 month. TG 14 month. T. Skórka, S. Heinze-Paluchowska, et al., XL Seminar on Nuclear Magnetic Resonance and Its Applications, 2007 Analysis of cardiac function in vivo by MRI

12. Assessment of cardiac parameters using ECG gated MRI  Ejection Rate ER [1/ms],  Filling Rate FR [1/ms],  Fractional Area Change FAC [%]: where: ESA - End Systolic Area EDA - End Diastolic Area. Ejection rate (ER) and Filling rate (FR) are equal to absolute value of regression line slopes. Fractional Contraction is equal to normalized difference between end-diastolic and end-systolic LV slice areas.

13. Results 9 The mean values of the Fractional Area Change for both TG and FVB mice at various ages  Application of homebuilt hardware components and advanced image analysis allowed for rapid image acquisition  Good quality MR images of mouse heart in vivo enabled quantification of cardiac systolic and diastolic dynamics in mice.  Our methodology enabled us to demonstrate that the progression of systolic and diastolic cardiac dysfunction in Tgaq*44 mice displays a different pattern. Four chamber view of the mouse heart

14. Acknowledgements IFJ PAN dr T. Skórka mgr U. Tyrankiewicz mgr inż. P. Skóra inż. P. Borowiec R. Wiertek prof. dr hab. A. Jasiński dr W. Węglarz CM UJ dr Ł. Drelicharz prof. dr hab. S. Chłopicki Politechnika Krakowska prof. dr hab. L. Wojnar

15. THANK YOU FOR YOUR ATTENTION

16. Model zwierzęcy– myszy TGαq*44