Pancreatic ductal adenocarcinoma (PDA) has the worst outcome of any solid tumor [
1]. Whereas surgical resection remains the mainstay therapy, 80% of patients with non-metastatic disease have unresectable tumors that are unlikely to be down-staged after standard chemo-radiation therapy, due to the geometric relationship of the primary tumor to the surrounding vasculature [
2]. Nevertheless, the overall survival rates in the patient group undergoing margin negative resection after neoadjuvant therapy are 2–3 times of the unresectable patient group [
3,
4]. Stereotactic body radiation therapy (SBRT) has shown to improve local tumor control rates, yet has disappointing down-staging rates. Alternatively, radiation therapy (RT) with simultaneous integrated boost (SIB) to cancerous tissue surrounding tumor infiltrating vasculature has the potential to sterilize tumor around the vessels that have precluded resectability [
5,
6]. However there are significant technical challenges associated with accurately escalating (boosting) radiation dose to the vessel/tumor interface due to substantial internal organ motion in the upper abdominal region. [
7‐
10] SBRT with SIB to tumor/vessel interface is further complicated by the fact that the motion of the cancerous tissue surrounding the tumor infiltrating vessels may be different from center of the pancreas tumor [
11]. Per standard clinical practice in our institution, a free-breathing (FB) contrast enhanced helical CT and a four dimensional CT (4D-CT) are performed to quantify the motion. Depending on patient compliance, 4D-CT can either be performed right after FB-CT with a sufficient amount of contrast left over in the blood vessels to enhance vasculature visibility, or after a long breathing coaching session to reach a stable respiration pattern required for a successful 4D-CT acquisition, when the contrast in the region of interest has already diminished. Risks associated with radiation dose and contrast agents also prevent this procedure from being repetitively performed on patients. [
12,
13] The problem is further compounded by poor CT soft tissue contrast and 4D-CT stitching artifacts [
14]. For these reasons, 4D-CT with delayed intravenous and oral contrasts often has limited value to evaluate soft tissue and blood vessel respiratory motion.
Recently the interest in using magnetic resonance imaging (MRI) in pancreas radiotherapy has increased. The superior soft tissue contrast and versatile imaging sequences of MRI can facilitate margin definitions in SBRT-SIB. Frequent imaging procedures necessary for organ motion characterization are also impeded by radiation dose from 4D-CT while not an issue in MRI. Since current MRI speed is insufficient to capture the three-dimensional motion of upper abdominal organs in real time, four dimensional MRI (4D-MRI) was developed to reconstruct motion encoded images from multiple breathing cycles. Early 4D-MRI was reconstructed by sorting 2D cine images from consecutive slices, thus its quality was degraded by severe stitching artifacts [
15‐
17]. The artifacts were eliminated with new 4D-MRI techniques based on 3D acquisition sequences [
18] and k-space sorting such as the recently developed self-gated 4D-MRI technique with 3D radial sampling and k-space sorting [
16,
19]. The new class of 4D-MRI sequences also provides high isotropic resolution that was unachievable with 2D cine based 4D-MRI.
Recently, slab-selective excitation was proposed to improve vessel-tissue contrast and overall image quality in 3D radial-sampling-based 4D-MRI [
20]. This approach exploits the in-flow effect. As fresh blood first enters the imaging volume of interest and experiences fewer RF-pulses than stationary tissues, blood signal is markedly higher than that of tissue, creating appreciable vessel-tissue contrast for various types of cancers including the pancreatic cancer. However, its ability of quantifying the pancreatic tumor and tumor infiltrating vessel motion has not been studied and compared with the current state of the art method 4D-CT.
To quantify this ability, the current study aims to exploit the technological potential of contrast free vessel highlighting in combination with the high resolution 4D-MRI method for a pancreatic patient cohort. The goal is to show the reproducibility and consistency of this novel 4D-MR method. Through the comparison with 4D-CT, we specifically evaluate the respiratory motion trajectories for both the tumor and the tumor infiltrating blood vessels that used to define potential boost volumes in the pancreas SIB treatment.