In-vivo Cerebral Aneurysm Wall Imaging

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1 In-vivo Cerebral Aneurysm Wall Imaging David M. Hasan, MD Associate Professor Chief of Vascular Neurosurgery University of Iowa Hospitals and Clinics

2 Disclosures NIH funding Founder and CEO of Advanced Endovascular Therapeutics, INC

3 Agenda for the Presentation Introduction Enzyme/ Cytokine imaging Myeloperoxidase (MPO) Macrophage Imaging Nanoparticles (Ferumoxytol) [ 11 C]-PK11195 PET 18-FDG PET/CT Ferric iron imaging Non-specific Inflammation imaging Conclusion

4 Learning Objectives Inflammation play a critical role in aneurysm formation, growth, and rupture It is possible to image in-vivo inflammatory cytokines/enzymes and/or cells in aneurysm wall Imaging inflammation in the aneurysm wall could stratify aneurysms to stable and unstable These techinques are in their infancy (case reports) and to be extrapolated into clinical practice, larger prospective observational studies or clinical trial are needed.

5 Inflammation and Cerebral Aneurysm Formation, growth, and Rupture Chalouhi N, Hoh BL, Hasan D: Review of cerebral aneurysm formation, growth, and rupture. Stroke. 2013;44:

6 Enzyme/Cytokine Imaging

14 MPO activity-specific paramagnetic imaging agent (DTPA(Gd) bishydroxyindolamide [bis-5ht-dtpagd] Using 8-element SENSE receive-only and RF transmit coils we applied the following sequences: black blood double inversion recovery (DIR)19, small field-of-view quadrature inversion recovery (SF-QIR)20, and motion-sensitized driven equilibrium (MSDE).21 All images were acquired with 2 mm slices along the longaxis of the aneurysm in a 50 mm field-of-view giving a measured and reconstructed in-plane resolution of 0.3 and 0.2 mm, respectively. The DIR, SF-QIR, and MSDE scan parameters included TR/TE of 456/10, 750/11 and 698/9 ms; flip angle of 90, 90, and 70, respectively. The number of signal averages for all sequences was 2. The flow velocity encoded gradient echo imaging parameter (VENC) had values between 1 to 8 cm/s.

17 Macrophage-Imaging

20 Iron oxide nanoparticles

21 Nanoparticle-Enhanced MRI

25 Control Aspirin

44 Ferric Iron Imaging

45 We hypothesize that QSM will act as an imaging marker for aneurysm micro-bleed Insight on anatomical and functional parameters of the aneurysm Delineation of the aneurysm wall and hemosiderin accumulation around the aneurysm Compare multiple methods of detection: QSM Susceptibility weighted imaging (SWAN) Cushing Uiowa 2015

47 Anatomy SWAN QSM Cushing Uiowa 2015

55 Non-Specific Inflammation Imaging

Contrast-Enhanced MRI Vessel wall magnetic resonance imaging identifies the site of rupture in patients with multiple intracranial aneurysms: proof of principle. Matouk CC, et al.

56 Contrast-Enhanced MRI Vessel wall magnetic resonance imaging identifies the site of rupture in patients with multiple intracranial aneurysms: proof of principle. Matouk CC, et al. Neurosurgery 2013 Vascular Wall Imaging of Unruptured Cerebral Aneurysms with a Hybrid of Opposite-Contrast MR Angiography. Matsushige T, et al. AJNR 2015 No in-vivo visualization of wall microstructure with current methods.

studies in unstable ANs revealed thickened wall with inflammatory process Matouk CC,

57 Contrast-Enhanced MRI 87% of unstable ANs showed CE (+) 28% of stable ANs showed CE (+) Mural contrast uptake is a function of the density of vasa vasorum Histopathologic studies in unstable ANs revealed thickened wall with inflammatory process Matouk CC, et al. Neurosurg 2013 Edjlali M, et al. Stroke 2014 Nagahata S, et al. Clin Neuroradiol 2014

66 Dynamic-Enhanced MRI Vakil P, et al. AJNR 2015 Increased contrast agent permeability across the aneurysm wall correlated significantly with both aneurysm size and size-independent anatomic risk factors, predicting high-risk aneurysms.

67 Atherosclerosis detected by HOP-MRA IC Ach An. AcoA An. The hybrid of opposite-contrast MRA can detect atherosclerotic plaques in the unruptured aneurysm wall Matsushige T et al. AJNR 2015

68 Summary Inflammation play a critical part in aneurysm formation, growth, and rupture It is possible to image in-vivo inflammatory cytokines/enzymes and/or cells in aneurysm wall Imaging inflammation in the aneurysm wall could stratify aneurysms to stable and unstable These techinques are in its infancy (case reports) and to be extrapolated into clinical practice, larger prospective observational studies or clinical trial are needed.

69 Questions??? Unruptured Aneurysm Ruptured Aneurysm

70 A B

71 B A

73 A B

74 A B C D A B

75 Video

Intracranial aneurysms are common vascular lesions, often consisting

Intracranial aneurysms are common vascular lesions, often consisting ORIGINAL RESEARCH INTERVENTIONAL Vascular Wall Imaging of Unruptured Cerebral Aneurysms with a Hybrid of Opposite-Contrast MR Angiography T. Matsushige, Y. Akiyama, T. Okazaki, K. Shinagawa, N. Ichinose,