A Systematic Approach to 4D Radiation Therapy – Integration of 4D Medical Imaging into 4D Radiation Therapy

Maria Chan, Yulin Song


Historically, the evolution of radiation oncology has been closely linked to the advances in medical imaging. Recent breakthroughs in imaging technology, particularly 4D medical imaging, have injected new momentum into radiation oncology, shedding new light on revitalizing this century old treatment modality. This eventually led to the creation of a primitive form of 4D radiation therapy (4DRT). 4DRT can be defined as a combination of using 4D imaging to guide radiation treatment planning, correcting for daily set-up errors through either patient repositioning or plan adaptation, and controlling radiation delivery based on internal or external fiducials that can be continuously tracked. 4DRT introduces the time dimension into the 3DRT in order to compensate for patient motion/changes occurring either during a single fraction (intra-fractional) or between successive fractions (inter-fractional). The major advantages of 4DRT are high-precision dose conformity, minimized normal tissue complication probability, and possible further dose escalation to the target. To maximize the potential benefits of 4D medical imaging and promising improvements in patient survival and quality of life, an integrative and systemic approach to 4DRT is essential. Without such an integrated multi-disciplinary strategy, 4DRT would only remain as an ideal concept. Here, we propose a comprehensive approach that integrates 4D medical imaging into each of the key steps in 4DRT, including 4D simulation, 4D treatment planning, and 4D treatment delivery.

4D Simulation
The 4D imaging modalities, including 4DCT, 4DMRI, 4DPET, and 4DSPECT, should be used to provide needed clinical information. To provide a time-stamped indication of the motion stage (amplitude or phase), external or internal fiducial markers should be used for monitoring patient motion in 4DCT imaging. With this tracking information, image acquisition can be prospectively gated and the acquired images can be retrospectively sorted into image bins reflecting the different respiratory phases. One of the three respiratory tracking techniques should be considered: (1) optical tracking methods using an infrared laser with reflectors placed on thorax or abdomen, (2) use of a spirometer to measure tidal ventilation volume, (3) use of Bellows pressure sensor below diaphragm for monitoring anatomical volume change.

4D Treatment Planning
An internal target volume (ITV) with more precise margin covering the moving clinical target volume (CTV) should be delineated on either 4DCT or 4DMRI. In addition, PET or SPECT 3D images should also be employed to accurately determine the true extent of the CTV. A full 4DCT image (multiple 3DCT images) acquired at each of the respiratory phases (at least eight) should be used to create an independent treatment plan for each phase. The physician contoured target and organs at risk (OAR) should be preserved through deformable image registration. Plans should be computed using adaptive dose calculation technique.

4D Treatment Delivery
On-site Imaging for Patient Setup: The 2D/3D/4D imaging of the patient in the treatment position should be used to improve setup accuracy. These include multiple 2D x-ray imaging, optical 3D superficial imaging, kV cone-beam CT (CBCT) imaging, helical MVCT imaging, and 4DCT imaging.

Real-time Target Tracking: Superficial motion tracking and external surrogates are useful in determining the extent of respiratory motion, but are not sufficient for tracking tumor motion and change in volume and shape. Therefore, internal fiducial markers should be implanted into or around the target to minimize ionization radiation to the patient.

Real-time Dose Delivery: Real-time treatment delivery should be guided by a target tracking feedback system. Currently, this has not been feasible in most of the clinics. The key is the combination of the individual 4DRT components to form a clinically feasible approach.


4D, radiation therapy, medical imaging

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