Comparison of MRA Techniques for Calcification Detection M. Mossa-Basha1, H. Liu1, D. Hippe1, N. Balu1, J. Sun1, D. Shibata1, C. Yuan1 1Department of Radiology, University of Washington

Disclosures None relevant to this presentation

Background Intracranial vascular calcifications Associated with Current and future stroke1,2 Cognitive decline and dementia 3,4 Microstructural changes on DTI and increased volume of white matter disease4

Background Intracranial vascular calcification detection Thin-slice CT is the reference standard Development of MRI techniques for detection important to avoid radiation and with CTA, potentiation of radiation-related mutations from iodinated contrast CT CTA

Background 3D TOF MRA has been employed for calcification detection CT

Background Simulataneous Non-Contrast Angiography and intraPlaque Hemorrhage (SNAP)5 Slab selective phase sensitive inversion recovery sequence Produces heavily T1-weighted dark blood (plaque hemorrhage) and bright blood (MRA) images

SNAP: Plaque Hemorrhage Background- SNAP Slab selective phase-sensitive inversion recovery sequence Negative signals creates MRA Positive signals produces iph SNAP: MRA SNAP: Plaque Hemorrhage SNAP: Joint

Dual SNAP Contrast using Phase Sensitive Polarity Maps Balu N et al, ISMRM 2014, Milan SNAP1 IPH Angiogram (Stenosis) SNAP2 Calcification Plaque burden SNAP1 I1 I2 SNAP2 Phase Sensitive Polarity Map

Dual contrast with phase sensitive maps: S1 shows phase corrected T1w image. This is the traditional SNAP image but does not show calcification or outer wall boundaries. S1<0 provides MRA of SNAP for luminal surface evaluation. I2 shows juxtaluminal calcification S2 is generated from I2 using the phase sensitive polarity function map generated from S1 or the original SNAP and reference images. S2 provides a PD weighted black- blood image to show plaque boundaries (lumen and outerwall). High risk plaque identification using four weightings from a single scan. Red arrow: Intraplaque hemorrhage, yellow arrows: Calcification

Purpose To evaluate the ability of SNAP Ref to detect intracranial artery wall calcifications as compared 3D TOF MRA relative to thin slice CT/CTA.

Methods After IRB approval, radiology database was reviewed for consecutive patients who underwent a clinical MRA exam Requirements 3D TOF MRA and SNAP imaging performed Scanned on a 3T Philips Ingenia (Philips Healthcare; Best, Netherlands) MR scanner Thin-slice (0.625 mm) CT or CTA examination within 1 year of the MRA exam

MRI Parameters TOF MRA SNAP TR/TE (ms) 23/3.45 13/7.3   TOF MRA SNAP TR/TE (ms) 23/3.45 13/7.3 In-plane resolution (mm) 0.4 x 0.6 0.6 x 0.6 Slice thickness (mm) 0.6 Flip angle 18 15 FOV (mm) 200 x 200 x 126 180 x 180 x 45 Matrix 500 x 332 300 x 300 NSA 1 SENSE (RL/FH) 2.5/1 - Slices 210 150 Oversample factor 1.25 Scan time 7:45 9:38

Image Analysis A blinded review was performed by a board certified neuroradiologist Consecutive SNAP2 sequences reviewed in random order, followed by 3D TOF MRA and finally thin slice CTA images in consecutive days, all images reviewed in axial plane Intracranial arterial segments evaluated individually: cavernous, ophthalmic, supraclinoid and terminal carotid artery segments, M1 middle cerebral, A1 anterior cerebral, P1 posterior cerebral arterial segments on the right and left and the basilar artery

Statistical Methods Sensitivity and specificity for detecting calcification per vessel was computed for SNAP2 and TOF-MRA using CT as the reference standard. Overall agreement with CT was assessed using unweighted Cohen’s kappa and linearly weighted Cohen’s kappa for both SNAP2 and TOF-MRA.

Statistical Methods Agreement was assessed for presence/absence of calcification per vessel and calcification size category per vessel (none, <50% circumferential involvement and >50% circumferential involvement) based on previously established evaluation. Diagnostic performance and agreement metrics were compared between SNAP2 and TOF-MRA using the non-parametric bootstrap, to account for potential dependence between vessels from the same subject.

Results 11 patients included 143 total arterial segments 129 segments were analyzable on all modalities 7 of the 11 patients had calcification identified in at least 1 arterial segment

Results Modality Arteries Segment No. SNAP N(%) TOF-MRA N(%) CT N(%)   Modality Arteries Segment No. SNAP N(%) TOF-MRA N(%) CT N(%) All arteries Any segment 129 29 (22.5) 17 (13.2) 24 (18.6) Internal carotid artery 79 27 (34.2) 13 (16.5) 24 (30.4) Cavernous 18 5 (27.8) 3 (16.7) 6 (33.3) Supraclinoid 21 14 (66.7) 4 (19.0) 13 (61.9) Ophthalmic 1 (5.6) Terminus 22 3 (13.6) 5 (22.7) 0 (0.0) Anterior arteries 44 1 (2.3) A1 M1 1 (4.5) Posterior arteries Basilar artery 6 2 (33.3) 3 (50.0)

Results Using CT as reference standard SNAP had higher sensitivity (75.0% vs. 29.2%, p=0.01) and similar specificity (89.5% vs. 90.5%, p=0.8) compared to TOF-MRA SNAP: higher agreement with CT for calcification compared to TOF MRA Presence/absence (kappa: 0.60 vs. 0.22, p=0.01) Calcification size categories (weighted kappa: 0.61 vs. 0.20, p=0.008)

Diagnostic performance of SNAP and TOF-MRA and agreement with CT   SNAP TOF-MRA Difference (SNAP - TOF) Metric Estimate (95% CI) P-value Sensitivity, % 75.0% (43.8--99.9%) 29.2% (6.7--57.1%) 45.8% (13.3--72.2%) 0.014 Specificity, % 89.5% (82.9--95.7%) 90.5% (83.9--95.3%) -1.0% (-9.3--8.0%) 0.79 Unweighted kappa (presence/absence) 0.60 (0.32--0.78) 0.22 (0.00--0.39) 0.38 (0.11--0.58) 0.012 Unweighted kappa (size)* 0.51 (0.27--0.64) 0.11 (-0.02--0.22) 0.40 (0.16--0.56) 0.003 Weighted kappa (size)* 0.61 (0.30--0.75) 0.20 (0.00--0.36) 0.41 (0.13--0.61) 0.008

Comparison of Calcification on CT, SNAP I2 and TOF MRA Non-contrast CT SNAP I2 TOF MRA Calcifications (short arrows) are shown on CT, SNAP I2 and TOF MRA. Due to improved contrast resolution between calcifications and background tissues, on SNAP I2 calcifications are more readily appreciated relative to TOF MRA.

Discussion/Conclusion This study shows the feasibility of SNAP I2 for the evaluation of intracranial calcifications. In comparison to 3D TOF MRA, SNAP I2 more accurately depicted calcifications. When combined with the MRA and intraplaque hemorrhage images provided by SNAP, this technique can provide first line luminal and vessel wall imaging information with a single acquisition.

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