M-finite applications of the M-Series (MRI) Presentation​.pptx

This presentation highlights the applications and capabilities of the M-Series™ compact MRI systems. Anatomical, functional, and molecular imaging can be performed on the M-Series and are often applied in cancer, cardiac, neuroscience, and multimodal imaging studies. It showcases example data from a variety of papers and training sessions in which the focus is on anatomy, neurobiology, and oncology. The presentation shows data from contrast agents which further enhances the capabilities of the M-Series, providing invaluable insights into tissue/tumor perfusion, myocardial infarction size, and molecular targets.

1. Footer 1 1 WWW.SCINTICA.COM M-finite applications of the M-Series Compact, Self-Shielded, High Performance, Small Animal MRI

2. Outline M-Series Magnet Design and User Experience Poll Question Application Areas Anatomy & Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging Footer 2

3. M- Series TM Magnet Design Requires no special infrastructure or cooling Compact and self-shielded with minimal external fringe field Easily installed within an animal facility , or existing laboratory next to other equipment or furnishings Operates very quietly during image acquisition Systems are installed with first images being acquired in less than 1 day 3

4. M-Series (M5) Components Footer 4 Electronics Cabinet and User Workstation Compact Magnet Animal Handling System Animal handling systems for mice and rats

5. Animal Handling System Fully integrated animal handling and coil system includes: Mouse or rat beds to suite a variety of sized animals Anatomy specific coils Animal heating Physiological monitoring Anesthesia delivery and scavenging 5

6. Animal Preparation and Imaging Set-Up 6

7. Software Interface and User Experience The M-Series software is intuitive , and easy to operate; designed to quickly generate reproducible , and quantitative results No need to have a background in MR physics to operate the system – default sequences are available and can be further optimized Experienced MR users have full flexibility to customize options to tailor the performance of the system to meet their needs Software is study based, and optimized protocol sets may be selected by the user 7

8. M-Series Systems The M-Series are designed with the pre-clinical researcher in mind No MRI technician needed Streamlined workflow for animal preparation and positioning User-friendly software interface Wide variety of applications Footer 8

9. Audience Poll

10. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 10

11. Anatomy and Morphology: Normal Mouse 11 T2 weighted FSE on Mouse Abdomen T1 weighted SE on Mouse Abdomen 400 m resolution 4:54m:s, 7 excitations   420 m resolution 6:12m:s, 11 excitations  

12. 12 4:20m:s; 5 excitations 250 m resolution   20:20m:s; 25 excitations 120 m resolution   12:20m:s; 10 excitations 24:20m:s; 20 excitations Anatomy and Morphology Resolution, Signal to Noise Ratio, and Acquisition Time T2 weighted FSE on Mouse Brain T1 weighted SE on Mouse Abdomen 200 m resolution   9:56m:s; 7 excitations 200 m resolution   19:19m:s; 14 excitations 400 m resolution   4:54m:s; 7 excitations

13. Anatomy and Morphology: Spinal Imaging Footer 13 Fixed mouse T1 weighted imaging Live mouse T2 weighted imaging Live mouse T2 weighted imaging

14. Anatomy and Morphology: Hind Limb Inflammation Acute inflammation was induced by topical application of an irritant Lesion volume (red) = 486mm 3 Entire ipsilateral leg volume ( blue+red ) = 1120mm 3 Contralateral leg volume (green) = 824mm 3 14 T2 weighted: SE(TE/TR=50/1500, FOV=60mm, Matrix=256x256, Res. 235um, Acq. Time 6:24m:s)

15. Anatomy and Morphology: Visceral Fat Segmentation Images can be automatically segmented based on grey-scale intensities of connected voxels – in these T1 weighted images adipose tissue appears very bright Volume = 1075mm 3 15

16. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 16

17. Neurology: Normal Mouse 17 T2 weighted: FSE Coronal/Sagittal 120um, 12:20m:s; Axial 160um, 16:00m:s

18. Neurology: Glioblastoma (UIC training) Footer 18 Glioblastoma model with frequent edema Fluid attenuation T2 weighted imaging (FLAIR) T2 weighted imaging T2 weighted imaging Edema in red Edema in red Tumor in blue T2 weighted: FSE Axial 250um, 6:44m:s Images courtesy of Dr. David Largaespada’s group at University of Minnesota

19. Neurology: Orthotopic Glioblastoma Day 4 – normal anatomical structures are visible Day 15 – tumor is visible, spread throughout the brain, enlarged ventricles Tumor volume = 20mm 3 19 T2 weighted: FSE (TE/TR=73.8/3100, FOV=40x20mm, Matrix=256x128, NEX=20, ETL=16, Res. 156um, Acq. Time 10 min) 4 days post injection 15 days post injection

20. Neurology: Traumatic Brain Injury TBI caused by percussion injury to the skull Injury appears clearly on a T2 weighted image due to the inflammatory lesion Effect of preventative measures or therapeutic response can be evaluated 20 T2 weighted: FSE (TE/TR=74/2840, FOV=50, Matrix=256x256, Res. 195µm, Acq . Time 13:46 min:sec ) Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev

21. Neurology: Epilepsy Epilepsy was induced by intoxication with paraoxone causing severe cholinergic symptoms Significant changes are visible in the cortex 48 hours post exposure 21 T2 weighted: FSE (TE/TR=74/3400, FOV=50, Matrix=256x256, Res. 195µm, Acq . Time 16:30 min:sec ) Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev 3 hours post PO exposure 48 hours post PO exposure

22. Neurology: Stroke Stroke was induced by photothrombosis in the rat brain The stroke lesion is clearly visible on T2 weighted images due to the inflammation in the area 22 T2 weighted: FSE (TE/TR=74/3030, FOV=50, Matrix=256x256, Res. 195µm, Acq . Time 14:41 min:sec ) Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev

23. Neurology: Stroke Stroke volume was calculated in VivoQuant , and found to be 19.0mm 3 23 Images courtesy of L. Lacovitti’s lab at Thomas Jefferson University, Hospital for Neuroscience Stroke was induced by photothrombosis in the mouse brain The stroke lesion is clearly visible on T2 weighted images due to the inflammation in the area

24. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 24

25. Cancer Biology: Tumor Detection Fat-suppressed T2-weighed MRI can be used to monitored tumour burden over time using the same animal as its own control 25 Fat-suppressed T2 weighted: FSE (TE/TR=10-60/4000ms, Inversion time = 100ms) Th- MYCN GEMM 2min scan 8min scan TRAMP GEMM 8min scan O.t. medulloblastoma 3min scan KPC GEMM O.t. Prostate bone marrow metastasis 12min scan RH-41 xenograft 4min scan

26. Cancer Biology: Tumour Response Assessment in GEM model of neuroblastoma 26 Fat-suppressed T2 weighted: FSE (TE/TR=10/4500ms, FOV=60x30mm, slice thickness 1 mm, Matrix=144x72, NEX=2, Inversion time = 100ms, total scan time <2min) Rapid screening: Mouse is back in its cage within 5mins Reduced bias: Compared to physical palpation Reduction in animal used: enhanced statistical power Enhanced data curation Nijhuis A et al., Nat Commun . 2022 Poon E et al., J Clin Investig . 2020 Dubiella C et al., Nat Chem Bio. 2021 Roeschert C et al., Nat Cancer. 2021 183 mm 3 426 mm 3 593 mm 3 29 mm 3 277 mm 3 867 mm 3 143 mm 3 0 mm 3

27. Cancer Biology: Flank tumor (UIC training) 27 T1 weighted imaging T2 weighted imaging Images courtesy of Dr. David Largaespada’s group at University of Minnesota

28. Cancer Biology: Xenograft Tumor Model Subcutaneous head and neck tumor located on the hind limb Tumor can be identified with clear borders on the T2 weighted image – images taken 3 weeks post implantation Internal structures, such as cysts and lobes, can easily be seen Tumor volume is easily quantified = 730mm 3 28 T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq . Time 4:40 min) Model Courtesy of Dr. J. Mahmood, PhD., Radiation Medicine Program, Princess Margaret Cancer Center, UHN

29. Cancer Biology: Nerve Sheath (UIC training) 29 Images courtesy of Dr. David Largaespada’s group at University of Minnesota

30. Cancer Biology: Orthotopic Cervical Tumor Model Therapeutic effect can be monitored over time using the same animal as it’s own control 30 T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq Time 4:40 min) T1 weighted: SE (TE/TR=9.8/500, FOV=80x30mm, Matrix=256x96, NEX=3, Res. 312um, Acq Time 2:42min:sec) Model Courtesy of Drs. Naz Chaudary , Richard Hill & Shawn Stapleton, Princess Margaret Cancer Center Control (n=4) Treated (n=30) 5.5 weeks 179±46 mm 3 93±8.5 mm 3 7 weeks 227±64 mm 3 134±11 mm 3 Control Treated

31. Cancer Biology: Multi modal detection of orthotopic model of prostate bone marrow metastasis 31 Fat-suppressed T2 weighted: FSE (TE/TR=36/7300ms, FOV=60x30mm, slice thickness 0.8 mm, Matrix=240x120, NEX=8, Inversion time = 100ms, total scan time 12min) Control Injected (right leg) Bioluminescence imaging Maximum intensity projection (MIP) (3 slices) Control Injected

32. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 32

33. Cardiovascular Biology: CINE Imaging 33 Images courtesy of Erik Blackwood at the Translation Cardiac Research Center The University of Arizona

34. 34 Data from short axis For the Left Ventricle: End Diastole and End Systole LV mass (ED/ED LVM), in g End Diastolic Volume (EDV), in ml End Systolic Volume (ESV), in ml Stroke Volume (SV), in ml Ejection Fraction (EF), as % Cardiac Output, in l/min, when the user inputs the heart rate Heart Rate, in bpm, as input by the user For the Right Ventricle: End Diastole and End Systole LV mass (ED/ED LVM), in g End Diastolic Volume (RVEDV), in ml End Systolic Volume (RVESV), in ml Stroke Volume (RVSV), in ml Ejection Fraction (EF), as %

35. Strain Analysis-Long Axis (CINE) 35

36. Strain Analysis-Exported data 36

37. Angiography – TOF 2D Footer 37 Mouse: Brain Mouse: Cardiovascular system Mapping of blood vessels in the body without the use of contrast agents

38. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 38

39. Contrast Agent Imaging 50µL Primovist (Gd-EOB-DTPA), was injected i.v. through the tail vein T1 weighted imaging was performed pre and post contrast injection 39

40. Contrast Agent Imaging VivoQuant was used to subtract the pre and post contrast injection images, the results were colored green 40

41. Contrast Agent Imaging: Normal Mouse Dynamic Contrast Enhanced imaging was performed during the injection – 1 frame/sec 41

42. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 42

43. Multi-Modal Imaging: PET/MRI The SimPET insert expands the capabilities of the M7 system to allow for simultaneous PET/MR imaging MR images compliment the highly sensitive PET images in detecting functional information, abnormalities, and early disease, providing anatomical context 43

44. Multi-Modal Imaging: PET/MRI Reconstructed images of a hot rod phantom with rod diameters of 0.75, 1.00, 1.35, 1.70, 2.00, 2.40mm Reconstructed using 3D OSEM algorithm with incorporation of point spread function (a) or without point spread function (b) Example image: effects of tumor associated macrophages on tumor hypoxia and aerobic glycolysis (Cancer Research, 2019) 44

45. Multi-Modal Imaging: PET/MRI – Tumor Imaging Tumor showed increase metabolism on FDG-PET compared to contralateral muscle (ratio = 2.7) Central region of tumor showed decreased PET signal, T2 weighted MR image indicates increased fluid content – possibly a necrotic core CT images may provide additional anatomical context 45 Model courtesy of Dr. R. DeSouza , STTARR (UHN) PET PET + CT + MRI MRI – T1w CT MRI – T2w Necrotic Core Tumor Tumor volume is best measured on MRI = 410 mm 3

46. Complimentary Nature of Imaging Modalities Bioluminescence helps to confirm viability of the tumor cells, as they express luciferase, approximate volumes may be possible from the BLI signal; anatomical images help to confirm tumor volume - ultrasound (263mm 3 ) or MRI (273mm 3 ) 46 Orthotopic Mammary Fat Pad Tumor (MDA-MB-231) Optical Imaging - BLI Ultrasound MRI

47. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 47

48. Ex Vivo Imaging: MR-Based Histology High resolution images of an ex vivo fixed rat brain sample Exquisite details of the structures within the brain can be visualized, identified, and quantified 48 Sample Courtesy of Prof. Alan Johnson- Duke University, NC Image Resolution: 83x83x300 µm

49. Ex Vivo Imaging: MR-Based Histology Toxicology studies rely on a few histological samples taken throughout an organ to look for lesions, i.e. liver toxicity MR-based histology is performed on intact fixed samples, providing a full 3D image of an organ Lesions are identified, counted, and volume calculated MR images may be used to guide tissue sectioning to confirm lesion characteristics using conventional histology 49

50. Key Research Applications Anatomy and Morphology Neurology Cancer Biology Cardiovascular Biology Contrast Agents Multi-Modal Imaging Ex Vivo Imaging 50

51. M-Series Systems The M-Series are designed for pre-clinical researchers No MRI technician needed Streamlined workflow for animal preparation and positioning User-friendly software interface Wide variety of applications that can contribute to your research Footer 51 WWW.SCINTICA.COM