Novel Super-Resolution Approach to Time-Resolved Volumetric 4-Dimensional Magnetic Resonance Imaging With High Spatiotemporal Resolution for Multi-Breathing Cycle Motion Assessment.

To develop and evaluate a super-resolution approach to reconstruct time-resolved 4-dimensional magnetic resonance imaging (TR-4DMRI) with a high spatiotemporal resolution for multi-breathing cycle motion assessment. A super-resolution approach was developed to combine fast 3-dimensional (3D) cine MRI with low resolution during free breathing (FB) and high-resolution 3D static MRI during breath hold (BH) using deformable image registration. A T1-weighted, turbo field echo sequence, coronal 3D cine acquisition, partial Fourier approximation, and SENSitivity Encoding parallel acceleration were used. The same MRI pulse sequence, field of view, and acceleration techniques were applied in both FB and BH acquisitions; the intensity-based Demons deformable image registration method was used. Under an institutional review board-approved protocol, 7 volunteers were studied with 3D cine FB scan (voxel size: 5 × 5 × 5 mm3) at 2 Hz for 40 seconds and a 3D static BH scan (2 × 2 × 2 mm3). To examine the image fidelity of 3D cine and super-resolution TR-4DMRI, a mobile gel phantom with multi-internal targets was scanned at 3 speeds and compared with the 3D static image. Image similarity among 3D cine, 4DMRI, and 3D static was evaluated visually using difference image and quantitatively using voxel intensity correlation and Dice index (phantom only). Multi-breathing-cycle waveforms were extracted and compared in both phantom and volunteer images using the 3D cine as the references. Mild imaging artifacts were found in the 3D cine and TR-4DMRI of the mobile gel phantom with a Dice index of >0.95. Among 7 volunteers, the super-resolution TR-4DMRI yielded high voxel-intensity correlation (0.92 ± 0.05) and low voxel-intensity difference (<0.05). The detected motion differences between TR-4DMRI and 3D cine were -0.2 ± 0.5 mm (phantom) and -0.2 ± 1.9 mm (diaphragms). Super-resolution TR-4DMRI has been reconstructed with adequate temporal (2 Hz) and spatial (2 × 2 × 2 mm3) resolutions. Further TR-4DMRI characterization and improvement are necessary before clinical applications. Multi-breathing cycles can be examined, providing patient-specific breathing irregularities and motion statistics for future 4D radiation therapy.

Li G ，Wei J ，Kadbi M ，Moody J ，Sun A ，Zhang S ，Markova S ，Zakian K ，Hunt M ，Deasy JO ... -  《-》

A super-resolution framework for the reconstruction of T2-weighted (T2w) time-resolved (TR) 4DMRI using T1w TR-4DMRI as the guidance.

The purpose of this study was to develop T2-weighted (T2w) time-resolved (TR) four-dimensional magnetic resonance imaging (4DMRI) reconstruction technique with higher soft-tissue contrast for multiple breathing cycle motion assessment by building a super-resolution (SR) framework using the T1w TR-4DMRI reconstruction as guidance. The multi-breath T1w TR-4DMRI was reconstructed by deforming a high-resolution (HR: 2 × 2 × 2 mm3 ) volumetric breath-hold (BH, 20s) three-dimensional magnetic resonance imaging (3DMRI) image to a series of low-resolution (LR: 5 × 5 × 5 mm3 ) 3D cine images at a 2Hz frame rate in free-breathing (FB, 40 s) using an enhanced Demons algorithm, namely [T1BH →FB] reconstruction. Within the same imaging session, respiratory-correlated (RC) T2w 4DMRI (2 × 2 × 2 mm3 ) was acquired based on an internal navigator to gain HR T2w (T2HR ) in three states (full exhalation and mid and full inhalation) in ~5 min. Minor binning artifacts in the RC-4DMRI were automatically identified based on voxel intensity correlation (VIC) between consecutive slices as outliers (VIC < VICmean -σ) and corrected by deforming the artifact slices to interpolated slices from the adjacent slices iteratively until no outliers were identified. A T2HR image with minimal deformation (<1 cm at the diaphragm) from the T1BH image was selected for multi-modal B-Spline deformable image registration (DIR) to establish the T2HR -T1BH voxel correspondence. Two approaches to reconstruct T2w TR-4DMRI were investigated: (A) T2HR →[T1BH →FB]: to deform T2w HR to T1w BH only as T1w TR-4DMRI was reconstructed, and combine the two displacement vector fields (DVFs) to reconstruct T2w TR-4DMRI, and (B) [T2HR ←T1BH ]→FB: to deform T1w BH to T2w HR first and apply the deformed T1w BH to reconstruct T2w TR-4DMRI. The reconstruction times were similar, 8-12 min per volume. To validate the two methods, T2w- and T1w-mapped 4D XCAT digital phantoms were utilized with three synthetic spherical tumors (ϕ = 2.0, 3.0, and 4.0 cm) in the lower or mid lobes as the ground truth to evaluate the tumor location (the center of mass, COM), size (volume ratio, %V), and shape (Dice index). Six lung cancer patients were scanned under an IRB-approved protocol and the T2w TR-4DMRI images reconstructed from the two methods were compared based on the preservation of the three tumor characteristics. The local tumor-contained image quality was also characterized using the VIC and structure similarity (SSIM) indexes. In the 4D digital phantom, excellent tumor alignment after T2HR -T1HR DIR is achieved: ∆COM = 0.8 ± 0.5 mm, %V = 1.06 ± 0.02, and Dice = 0.91 ± 0.03, in both deformation directions using the DIR-target image as the reference. In patients, binning artifacts are corrected with improved image quality: average VIC increases from 0.92 ± 0.03 to 0.95 ± 0.01. Both T2w TR-4DMRI reconstruction methods produce similar tumor alignment errors ∆COM = 2.9 ± 0.6 mm. However, method B ([T2HR ←T1BH ]→FB) produces superior results in preserving more T2w tumor features with a higher %V = 0.99 ± 0.03, Dice = 0.81 ± 0.06, VIC = 0.85 ± 0.06, and SSIM = 0.65 ± 0.10 in the T2w TR-4DMRI images. This study has demonstrated the feasibility of T2w TR-4DMRI reconstruction with high soft-tissue contrast and adequately-preserved tumor position, size, and shape in multiple breathing cycles. The T2w-centric DIR (method B) produces a superior solution for the SR-based framework of T2w TR-4DMRI reconstruction with highly preserved tumor characteristics and local image features, which are useful for tumor delineation and motion management in radiation therapy.

Nie X ，Saleh Z ，Kadbi M ，Zakian K ，Deasy J ，Rimner A ，Li G ... -  《-》

Enhanced super-resolution reconstruction of T1w time-resolved 4DMRI in low-contrast tissue using 2-step hybrid deformable image registration.

Deformable image registration (DIR) in low-contrast tissues is often suboptimal because of low visibility of landmarks, low driving-force to deform, and low penalty for misalignment. We aim to overcome the shortcomings for improved reconstruction of time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI). Super-resolution TR-4DMRI reconstruction utilizes DIR to combine high-resolution (highR:2x2x2mm3 ) breath-hold (BH) and low-resolution (lowR:5x5x5mm3 ) free-breathing (FB) 3D cine (2Hz) images to achieve clinically acceptable spatiotemporal resolution. A 2-step hybrid DIR approach was developed to segment low-dynamic-range (LDR) regions: low-intensity lungs and high-intensity "bodyshell" (=body-lungs) for DIR refinement after conventional DIR. The intensity in LDR regions was renormalized to the full dynamic range (FDR) to enhance local tissue contrast. A T1-mapped 4D XCAT digital phantom was created, and seven volunteers and five lung cancer patients were scanned with two BH and one 3D cine series per subject to compare the 1-step conventional and 2-step hybrid DIR using: (a) the ground truth in the phantom, (b) highR-BH references, which were used to simulate 3D cine images by down-sampling and Rayleigh-noise-adding, and (c) cross-verification between two TR-4DMRI images reconstructed from two BHs. To assess DIR improvement, 8-17 blood vessel bifurcations were used in volunteers, and lung tumor position, size, and shape were used in phantom and patients, together with the voxel intensity correlation (VIC), structural similarity (SSIM), and cross-consistency check (CCC). The 2-step hybrid DIR improves contrast and DIR accuracy. In volunteers, it improves low-contrast alignment from 6.5 ± 1.8 mm to 3.3 ± 1.0 mm. In phantom, it improves tumor center of mass alignment (COM = 1.3 ± 0.2 mm) and minimizes DIR directional difference. In patients, it produces almost-identical tumor COM, size, and shape (dice> 0.85) as the reference. The VIC and SSIM are significantly increased and the number of CCC outliers are reduced by half. The 2-step hybrid DIR improves low-contrast-tissue alignment and increases lung tumor fidelity. It is recommended to adopt the 2-step hybrid DIR for TR-4DMRI reconstruction.

Nie X ，Huang K ，Deasy J ，Rimner A ，Li G ... -  《Journal of Applied Clinical Medical Physics》

Introduction of a pseudo demons force to enhance deformation range for robust reconstruction of super-resolution time-resolved 4DMRI.

The purpose of this study was to enhance the deformation range of demons-based deformable image registration (DIR) for large respiration-induced organ motion in the reconstruction of time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI) for multi-breath motion simulation. A demons-based DIR algorithm was modified to enhance the deformation range for TR-4DMRI reconstruction using the super-resolution approach. A pseudo demons force was introduced to accelerate the coarse deformation in a multi-resolution (n = 3) DIR approach. The intensity gradient of a voxel was applied to its neighboring (5 × 5 × 5) voxels with a weight of Gaussian probability profile (σ = 1 voxel) to extend the demons force, especially on those voxels that have little intensity gradience but high-intensity difference. A digital 4DMRI phantom with 3-8 cm diaphragmatic motions was used for DIR comparison. Six volunteers were scanned with two high-resolution (highR: 2 × 2 × 2 mm3 ) breath-hold (BH) 3DMR images at full inhalation (BHI) and full exhalation (BHE) and low-resolution (lowR: 5 × 5 × 5 mm3 ) free-breathing (FB) 3DMR cine images (2 Hz) under an IRB-approved protocol. A cross-consistency check (CCC) (BHI→FB←BHE), with voxel intensity correlation (VIC) and inverse consistency error (ICE), was introduced for cross-verification of TR-4DMRI reconstruction. Using the digital phantom, the maximum deformable magnitude is doubled using the modified DIR from 3 to 6 cm at the diaphragm. In six human subjects, the first 15-iteration DIR using the pseudo force deforms 200 ± 150% more than the original force, and succeeds in all 12 cases, whereas the original demons-based DIR failed in 67% of tested cases. Using the pseudo force, high VIC (>0.9) and small ICE (1.6 ± 0.6 mm) values are observed for DIR of BHI&BHE, BHI→FB, and BHE→FB. The CCC identifies four questionable cases, in which two cases need further DIR refinement, without missing true negative. The introduction of a pseudo demons force enhances the largest deformation magnitude up to 6 cm. The cross-consistency check ensures the quality of TR-4DMRI reconstruction. Further investigation is ongoing to fully characterize TR-4DMRI for potential multi-breathing-cycle radiotherapy simulation.

Li G ，Sun A ，Nie X ，Moody J ，Huang K ，Zhang S ，Sharma S ，Deasy J ... -  《-》

Clinical evaluation of 4D MRI in the delineation of gross and internal tumor volumes in comparison with 4DCT.

To evaluate clinical utility of respiratory-correlated (RC) four-dimensional magnetic resonance imaging (4DMRI) for lung tumor delineation and motion assessment, in comparison with the current clinical standard of 4D computed tomography (4DCT). A prospective T2-weighted (T2w) RC-4DMRI technique was applied to acquire coronal 4DMRI images for 14 lung cancer patients (16 lesions) during free breathing (FB) under an IRB-approved protocol, together with a breath-hold (BH) T1w 3DMRI and axial 4DMRI. Clinical simulation CT and 4DCT were acquired within 2 h. An internal navigator was applied to trigger amplitude-binned 4DMRI acquisition whereas a bellows or real-time position management (RPM) was used in the 4DCT reconstruction. Six radiation oncologists manually delineated the gross and internal tumor volumes (GTV and ITV) in 399 3D images using programmed clinical workflows under a tumor delineation guideline. The ITV was the union of GTVs within the breathing cycle without margin. Average GTV and motion range were assessed and ITV variation between 4DMRI and 4DCT was evaluated using the Dice similarity index, mean distance agreement (MDA), and volume difference. The mean tumor volume is similar between 4DCT (GTV4DCT  = 1.0, as the reference) and T2w-4DMRI (GTVT2wMR  = 0.97), but smaller in T1w MRI (GTVT1wMR  = 0.76), suggesting possible peripheral edema around the tumor. Average GTV variation within the breathing cycle (22%) in 4DMRI is slightly greater than 4DCT (17%). GTV motion variation (-4 to 12 mm) and ITV variation (∆VITV =-25 to 95%) between 4DCT and 4DMRI are large, confirmed by relatively low ITV similarity (Dice = 0.72 ± 0.11) and large MDA = 2.9 ± 1.5 mm. Average GTVs are similar between T2w-4DMRI and 4DCT, but smaller by 25% in T1w BH MRI. Physician training and breathing coaching may be necessary to reduce ITV variability between 4DMRI and 4DCT. Four-dimensional magnetic resonance imaging is a promising and viable technique for clinical lung tumor delineation and motion assessment.

Zhang J ，Srivastava S ，Wang C ，Beckham T ，Johnson C ，Dutta P ，Shepherd A ，Mechalakos J ，Hunt M ，Wu A ，Rimner A ，Li G ... -  《Journal of Applied Clinical Medical Physics》