Super-resolution reconstruction of time-resolved four-dimensional computed tomography (TR-4DCT) with multiple breathing cycles based on TR-4DMRI.

Background: Respiratory motion irregularities in lung cancer patients are common and can be severe during multi-fractional (∼20 mins/fraction) radiotherapy. However, the current clinical standard of motion management is to use a single-breath respiratory-correlated four-dimension computed tomography (RC-4DCT or 4DCT) to estimate tumor motion to delineate the internal tumor volume (ITV), covering the trajectory of tumor motion, as a treatment target.

Purpose: To develop a novel multi-breath time-resolved (TR) 4DCT using the super-resolution reconstruction framework with TR 4D magnetic resonance imaging (TR-4DMRI) as guidance for patient-specific breathing irregularity assessment, overcoming the shortcomings of RC-4DCT, including binning artifacts and single-breath limitations.

Methods: Six lung cancer patients participated in the IRB-approved protocol study to receive multiple T1w MRI scans, besides an RC-4DCT scan on the simulation day, including 80 low-resolution (lowR: 5 × 5 × 5 mm) free-breathing (FB) 3D cine MR images in 40 s (2 Hz) and a high-resolution (highR: 2 × 2 × 2 mm) 3D breath-hold (BH) MR image for each patient. A CT (1 × 1 × 3 mm) image was selected from 10-bin RC-4DCT with minimal binning artifacts and a close diaphragm match (<1 cm) to the MR image. A mutual-information-based Freeform deformable image registration (DIR) was used to register the CT and MR via the opposite directions (namely F1: and F2: ) to establish CT-MR voxel correspondences. An intensity-based enhanced Demons DIR was then applied for , in which the original MR was used in D1: , while the deformed MR was used in D2: . The deformation vector fields (DVFs) obtained from each DIR were composed to apply to the deformed CT (D1) and original CT (D2) to reconstruct TR-4DCT images. A digital 4D-XCAT phantom at the end of inhalation (EOI) and end of exhalation (EOE) with 2.5 cm diaphragmatic motion and three spherical targets (ϕ = 2, 3, 4 cm) were first tested to reconstruct TR-4DCT. For each of the six patients, TR-4DCT images at the EOI, middle (MID), and EOE were reconstructed with both D1 and D2 approaches. TR-4DCT image quality was evaluated with mean distance-to-agreement (MDA) at the diaphragm compared with MR, tumor volume ratio (TVR) referenced to MR, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|∆COM|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR-4DCT images.

Results: In the phantom, TR-4DCT quality is assessed by MDA = 2.0 ± 0.8 mm at the diaphragm, TVR = 0.8 ± 0.0 for all tumors, and DICE = 0.83 ± 0.01, 0.85 ± 0.02, 0.88 ± 0.01 for ϕ = 2, 3, 4 cm tumors, respectively. In six patients, the MDA in diaphragm match is -1.6 ± 3.1 mm (D1) and 1.0 ± 3.9 mm (D2) between the reconstructed TR-4DCT and lowR MR among 18 images (3 phases/patient). The tumor similarity is TVR = 1.2 ± 0.2 and DICE = 0.70 ± 0.07 for D1 and TVR = 1.4 ± 0.3 (D2) and DICE = 0.73 ± 0.07 for D2. The tumor position difference is |∆COM| = 1.2 ± 0.8 mm between D1 and D2 reconstructions.

Conclusion: The feasibility of super-resolution reconstruction of multi-breathing-cycle TR-4DCT is demonstrated and image quality at the diaphragm and tumor is assessed in both the 4D-XCAT phantom and six lung cancer patients. The similarity of D1 and D2 reconstruction suggests consistent and reliable DIR results. Clinically, TR-4DCT has the potential for breathing irregularity assessment and dosimetry evaluation in radiotherapy.