72 Current Medical Imaging Reviews, 2010, 6, 72-81 1573-4056/10 $55.00+.00 ©2010 Bentham Science Publishers Ltd. Recent Development of Low-dose X-ray Cone-beam Computed Tomography Jing Wang* ,1,2 , Zhengrong Liang 3 , Hongbing Lu 4 , and Lei Xing 1 1 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA 2 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 3 Departments of Radiology and Computer Science, Stony Brook University, Stony Brook, NY 11794, USA 4 Department of Biomedical Engineering/Computer Application, Fourth Military Medical University, Xi’an, Shaanxi 710032, China Abstract: Cone-beam computed tomography (CBCT) is an emerging medical imaging modality used for various clinical applications. However, radiation dose to patients is a major limiting factor for its utility in some applications such as daily patient setup and future adaptive therapy in radiotherapy. In this article, we summarize recent development for dose re- duction in CBCT. In particular, we discuss several noise reduction strategies for low-dose CBCT with a low mAs proto- col. Keywords: Cone-beam CT, low-dose, noise reduction. I. INTRODUCTION With the development of large area flat-panel detectors, cone-beam computed tomography (CBCT) has become an emerging medical imaging modality and been widely used for various clinical applications such as for breast imaging and image-guided radiation therapy (IGRT) [1-28]. Com- pared with conventional digital mammography, CBCT breast imaging provides volumetric information which potentially can improve lesion detection accuracy with increased radia- tion dose. In radiation therapy, integration of the CBCT with a linear accelerator makes it possible to acquire a high- resolution volumetric image of a patient at a treatment posi- tion. There is growing interest in using on-board CBCT for a patient treatment position setup and dose reconstruction in radiotherapy [8, 29-31]. The repeated use of CBCT during a course of radiotherapy treatment has raised concerns of extra radiation dose delivered to patients [32-35]. For example, it has been reported [34] that the dose delivered from Varian’s CBCT system with current clinical protocols for pelvic area is more than 3 cGy for central tissue, about 5 cGy for most of the peripheral tissues and 11 cGy to femoral head. If CBCT is used daily for patient setup, the total CBCT imag- ing dose delivered to patient could be extremely high in a course of intensity-modulated radiation therapy (IMRT) treatment. The extra radiation exposure to normal tissue dur- ing kV-CBCT will significantly increase the probability of stochastic risk of inducing cancer and genetic defects. The CBCT dose needs to be minimized to fully realize its advan- tages in these clinical applications. CBCT imaging dose is affected by many factors includ- ing tube potential (kVp), tube current and exposure time *Address correspondence to this author at the Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Tel: 214-645-7635 Fax: 214-645-2885; E-mail: jing.wang@utsouthwestern.edu (mAs), beam quality, beam collimation, etc. Dose reduction for CBCT can be achieved via X-ray beam collima- tion/filtration or using a low mAs protocol. In this article, we summarize recent development of dose reduction techniques for CBCT including different design of beam collimators, iterative image reconstruction algorithms for CBCT based on undersampled projection views, and noise reduction tech- niques for low-dose CBCT with a low mAs protocol. II. COLLIMATOR-BASED METHODS CBCT imaging dose can be reduced by using X-ray fil- ters or collimators. In commercial scanners, two types of filters, i.e., flat filters and bowtie filters, are usually em- ployed to reduce patient dose. The flat filters, typically made of aluminum or copper, are used to attenuate the X-ray spec- trum uniformly across the entire field of view (FOV) to re- move low-energy X-rays. The bowtie filters are employed to modify the intensity of the X-ray beam inside the FOV. The patient cross section is typically oval-shaped and the bowtie filter is designed to compensate for the variable path length of X-ray beam through the patient. Several different collimators have been proposed to fur- ther reduce radiation dose in CBCT. For example, Chityala et al. [36] proposed a concept of region-of-interest (ROI) CT where only ROI is irradiated with high-dose X-rays while outside of ROI is irradiated at a lower dose. Moor et al. [37] added a zonal filter to the CBCT X-ray tube of the Elekta Synergy linear accelerator to produce an un-attenuated beam for a central “target zone” and a partially attenuated beam for an outer “set-up zone”. By using such collimator, doses along the axis of rotation were reduced by up to 50% in both target and set-up zones. Contrast-to-noise ratio (CNR) in- creased by up to 15% in zonally filtered CBCT images com- pared to full-field images due to the reduced scatter signal from attenuated beam. Chen et al. [2] and Lai et al. [38] pro- posed to use a volume-of-interest (VOI) filter for breast