Research Systems

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences were: T1-weighted, T2-weighted, zero-echo time (ZTE), and two ultra-short echo time sequences with 20 μs (UTE1) and 2 ms (UTE2) echo times. CT data were manually segmented into air, soft tissue, and bone to obtain the RTP reference. Bias field corrected MR images were automatically segmented into the same tissue classes using a fuzzy c-means segmentation algorithm with multiple images as input. Similarities between segmented CT and automatic segmented MR (ASMR) images were evaluated using Dice coefficient. Three ASMR images with high similarity index were used for further RTP. Three beam arrangements were investigated. Dose distributions were compared by analysing dose volume histograms. The highest Dice coefficients were obtained for the ZTE-UTE2 combination and for the T1-UTE1-T2 combination when ZTE was unavailable. Both combinations, along with UTE1-UTE2, often used to generate ASMR images, were used for further RTP. Using 1 beam, MR based RTP underestimated the dose to be delivered to the target (range: 1.4%-7.6%). When more complex beam configurations were used, the calculated dose using the ZTE-UTE2 combination was the most accurate, with 0.7% deviation from CT, compared to 0.8% for T1-UTE1-T2 and 1.7% for UTE1-UTE2. The presented MR-only based workflow for RTP on a SARRP enables both accurate organ delineation and dose calculations using multiple MR sequences. This method can be useful in longitudinal studies where CT’s cumulative radiation dose might contribute to the total dose.

Shandra Gutierrez, Benedicte Descamps, Christian Vanhove

Download Paper

The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature...

Current glioblastoma (GB) small animal models for cranial radiation therapy (RT) use simple single beam technologies, which differ from the advanced conformal image-guided radiation techniques used in clinical practice. This technological disparity presents a major disadvantage for the development of new therapeutic approaches. Hence, we established a F98 GB rat model using magnetic resonance imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small Animal Radiation Research Platform (SARRP). Ten Fischer rats were inoculated with F98 tumor cells. When the tumor reached a volume of approximately 27 mm(3) on T2-weighted MR images, the animals were randomized into a treatment group (n = 5) receiving RT and concomitant temozolomide, and a sham group (n = 5) receiving control injections. For the treated animals, contrast-enhanced T1-weighted MR images were acquired followed by a cone-beam computed tomography (CBCT) on the SARRP system. Both scans were co-registered; MRI was used to define the target whereas CBCT was used for calculating a dose plan (20 Gy, three non-coplanar arc beams, 3 × 3 mm collimator). Tumor volumes were evaluated on follow-up contrast-enhanced T1-weighted MR images. Verification of treatment accuracy with γH2AX immunohistochemical staining was performed. Tumors in the control animals showed rapid proliferation during follow-up, encompassing almost the entire right cerebral hemisphere at day 12-15. Treated animals showed no significant tumor growth from 2 to 9 days post RT. γH2AX results confirmed the accuracy of dose delivery. This model, which is quite similar to the approach in the clinic, is valid for combined RT and chemotherapy of GB in rats.

Bolcaen J, Descamps B, Deblaere K, Boterberg T, Hallaert G, Van den Broecke C, Decrock E, Vral A, Leybaert L, Vanhove C, Goethals I.

Download Paper

PURPOSE: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.)...

Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural...

The goal of radiation treatment is to irradiate cancer cells (i.e., a target region) without destroying adjacent healthy tissue. Thus, it is advantageous to form the beam so that it best approximates the target, thereby reducing the amount of dose absorbed in critical regions outside the target area. While multi-leaf collimators are common in human clinical systems, small animal radiotherapy systems are typically limited to a set of fixed-size collimators. For these systems, dose painting can be used for conformal dose delivery, but is significantly slower than a multi-leaf collimator. As a compromise solution, a variable rectangular collimator has been developed for the Small Animal Radiation Research Platform (SARRP). This enables more efficient dose painting via the decomposition of a 2D target region into a minimum number of rectangles of variable size, which is the topic of this paper. The proposed method consists of several distinct steps and was implemented on the SARRP Treatment Planning System (TPS).

Cho N., Wong J., Kazanzides P.

Download Paper

The current Small Animal Radiation Research Platform (SARRP) is poor for localizing small soft tissue targets for irradiation or tumor models growing in a soft tissue environment. Therefore, an imaging method complementary to x-ray CT is required to localize the soft tissue target’s Center of Mass (CoM) to within 1 mm. In this paper, we report the development of an integrated x-ray/bioluminescence imaging/tomography (BLI/BLT) system to provide a pre-clinical, high resolution irradiation system. This system can be used to study radiation effects in small animals under the conebeam computed tomography (CBCT) imaging guidance by adding the bioluminescence imaging (BLI) system as a standalone system which can also be docked onto the SARRP. The proposed system integrates two robotic rotating stages and an x-ray source rated at maximum 130 kVp and having a small variable focal spot. A high performance and low noise CCD camera mounted in a light-tight housing along with an optical filter assembly is used for multiwavelength BL imaging and tomography. A three-mirror arrangement is implemented to eliminate the need of rotating the CCD camera for acquiring multiple views. The mirror system is attached to a motorized stage to capture images in angles between 0-90o (for the standalone system). C

S. Eslami ; Y. Yang ; J. Wong ; M. S. Patterson ; I. Iordachita

Download Paper

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A...

In this work, the suitability and performance of a mouse-size MOSFET (Mousefet) phantom is investigated for routine quality assurance (QA) of the small animal radiation research platform (SARRP). This Mousefet phantom is a simple construction consisting of five micro-MOSFETS custom integrated in a quincunx pattern within a tissue-equivalent phantom, allowing repeat/multiple QA tasks to be quickly performed in one experimental set-up. The Mousefet phantom is particularly evaluated for facilitating SARRP QA tasks which may warrant daily evaluation, including output constancy, isocenter congruency test and cone beam computed tomography (CBCT) image geometric accuracy. Results for the output constancy measurements showed a maximum daily variation of less than 2.6% for all MOSFETS, in consonance with observations from concurrent ion chamber measurements. It is also shown that the design of the Mousefet phantom allows the output check data to be used for prompt verification of beam energy and cone profile constancy. For the isocenter congruency test, it is demonstrated that the Mousefet phantom can detect 0.3 mm deviations of the CBCT isocenter from the radiation isocenter. Meanwhile, results for CBCT image geometric accuracy were consistently found to be within 2% of the expected value. Other CBCT image quality parameters could also be assessed in terms of image intensity constancy, noise and image uniformity. Overall, the results establish the Mousefet phantom as a simple and time-efficient multipurpose tool that could be employed effectively for routine QA of the SARRP.

Ngwa W, Tsiamas P, Zygmanski P, Makrigiorgos GM, Berbeco RI.

Download Paper