Super-resolution reconstruction of time-resolved four-dimensional computed tomography (TR-4DCT) with multiple...

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.

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.

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 mm³) free-breathing (FB) 3D cine MR^FB images in 40 s (2 Hz) and a high-resolution (highR: 2 × 2 × 2 mm³) 3D breath-hold (BH) MR^BH image for each patient. A CT (1 × 1 × 3 mm³) image was selected from 10-bin RC-4DCT with minimal binning artifacts and a close diaphragm match (<1 cm) to the MR^BH image. A mutual-information-based Freeform deformable image registration (DIR) was used to register the CT and MR^BH via the opposite directions (namely F1: $$ and F2: $$ ) to establish CT-MR voxel correspondences. An intensity-based enhanced Demons DIR was then applied for $$ , in which the original MR^BH was used in D1: $$ , while the deformed MR^BH 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^FB, tumor volume ratio (TVR) referenced to MR^BH, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|∆COM^D1-D2|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR-4DCT images.

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^FB 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^D1-D2| = 1.2 ± 0.8 mm between D1 and D2 reconstructions.

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.