Minimizing 4DCBCT imaging dose and scan time with Respiratory Motion Guided 4DCBCT: a pre-clinical investigation.

Current conventional 4D Cone Beam Computed Tomography (4DCBCT) imaging is hampered by inconsistent patient breathing that leads to long scan times, reduced image quality and high imaging dose. To address these limitations, Respiratory Motion Guided 4D cone beam computed tomography (RMG-4DCBCT) uses mathematical optimization to adapt the gantry rotation speed and projection acquisition rate in real-time in response to changes in the patient's breathing rate. Here, RMG-4DCBCT is implemented on an Elekta Synergy linear accelerator to determine the minimum achievable imaging dose. 8 patient-measured breathing traces were programmed into a 1D motion stage supporting a 3D-printed anthropomorphic thorax phantom. The respiratory phase and current gantry position were calculated in real-time with the RMG-4DCBCT software, which in turn modulated the gantry rotation speed and suppressed projection acquisition. Specifically, the effect of acquiring 20, 25, 30, 35 and 40 projections/respiratory phase bin RMG scans on scan time and image quality was assessed. Reconstructed image quality was assessed via the contrast-to-noise ratio (CNR) and the Edge Response Width (ERW) metrics. The performance of the system in terms of gantry control accuracy was also assessed via an analysis of the angular separation between adjacent projections. The median CNR increased linearly from 5.90 (20 projections/bin) to 8.39 (40 projections/bin). The ERW did not significantly change from 1.08 mm (20 projections/bin) to 1.07 mm (40 projections/bin), indicating the sharpness is not dependent on the total number of projections acquired. Scan times increased with increasing total projections and slower breathing rates. Across all 40 RMG-4DCBCT scans performed, the average difference in the acquired and desired angular separation between projections was 0.64°. RMG-4DCBCT provides the opportunity to enable fast low-dose 4DCBCT (∼70 s, 200 projections), without compromising on current clinical image quality.

Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways.

INTRODUCTION: Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction. METHODS: Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (∼13-21 µm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach. RESULTS: Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat. CONCLUSIONS: We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm.

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

AIMS: The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. METHODS AND RESULTS: Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. CONCLUSIONS: Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles.