Collision-avoiding imaging trajectories for linac mounted cone-beam CT.

BACKGROUND: Some patients cannot be imaged with cone-beam CT for image-guided radiation therapy because their size, pose, or fixation devices cause collisions with the machine. OBJECTIVE: To investigate imaging trajectories that avoid such collisions by using virtual isocenter and variable magnification during acquisition while yielding comparable image quality. METHODS: The machine components most likely to collide are the gantry and kV detector. A virtual isocenter trajectory continuously moves the patient during gantry rotation to maintain an increased separation between the two. With dynamic magnification, the kV detector is dynamically moved to increase clearance for an angular range around the potential collision point while acquiring sufficient data to maintain the field-of-view. Both strategies were used independently and jointly with the resultant image quality evaluated against the standard circular acquisition. RESULTS: Collision avoiding trajectories show comparable contrast and resolution to standard techniques. For an anthropomorphic phantom, the RMSE is <7×10- 4, multi-scale structural similarity index is >0.97, and visual image fidelity is >0.96 for all trajectories when compared to a standard circular scan. CONCLUSIONS: The proposed trajectories avoid machine-patient collisions while providing comparable image quality to the current standard thereby enabling CBCT imaging for patients that could not otherwise be scanned.

Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization.

Modern standards for radiation treatment do not take into account tumor oxygenation for radiation treatment planning. Strong correlation between tumor oxygenation and radiation treatment success suggests that oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. We have developed an OGRT protocol for rodents. Electron paramagnetic resonance (EPR) imaging is used for recording oxygen maps with high spatial resolution and excellent accuracy better than 1 torr. Radiation is delivered with an animal intensity modulated radiation therapy (IMRT) XRAD225Cx micro-CT/ therapy system. The radiation plan is delivered in two steps. First, a uniform 15% tumor control dose (TCD15) is delivered to the whole tumor. In the second step, an additional booster dose amounting to the difference between TCD98 and TCD15 is delivered to radio-resistant, hypoxic tumor regions. Delivery of the booster dose is performed using a multiport conformal beam protocol. For radiation beam shaping we used individual radiation blocks 3D-printed from tungsten infused ABS polymer. Calculation of beam geometry and the production of blocks is performed next to the EPR imager, immediately after oxygen imaging. Preliminary results demonstrate the sub-millimeter precision of the radiation delivery and high dose accuracy. The efficacy of the radiation treatment is currently being tested on syngeneic FSa fibrosarcoma tumors grown in the legs of C3H mice.

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment.

Current strategies to target tumors with nanomedicines rely on passive delivery via the enhanced permeability and retention effect, leveraging the disorganized tumor microvasculature to promote macromolecule extravasation and the reduced lymphatic and venous drainage that favor retention. Nonetheless, FDA approvals and clinical use of nanomedicines have lagged, reflecting failure to display superiority over conventional formulations. Here, we have exploited image-guided X-irradiation to augment nanoparticle accumulation in tumors. A single 5 Gy dose of radiation, below that required to significantly delay tumor growth, can markedly enhance delivery of macromolecules and nanoparticles. The radiation effect was independent of endothelial cell integrity, suggesting a primary role for damage to microvascular pericytes and/or interstitial extracellular matrix. Significantly, radiation-guided delivery potentiated the therapeutic effects of PEGylated liposomal doxorubicin on experimental tumors. Applied to patients, these results suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity.

Approaching Oxygen-Guided Intensity-Modulated Radiation Therapy.

The outcome of cancer radiation treatment is strongly correlated with tumor oxygenation. The aim of this study is to use oxygen tension distributions in tumors obtained using Electron Paramagnetic Resonance (EPR) imaging to devise better tumor radiation treatment. The proposed radiation plan is delivered in two steps. In the first step, a uniform 50% tumor control dose (TCD50) is delivered to the whole tumor. For the second step an additional dose boost is delivered to radioresistant, hypoxic tumor regions. FSa fibrosarcomas grown in the gastrocnemius of the legs of C3H mice were used. Oxygen tension images were obtained using a 250 MHz pulse imager and injectable partially deuterated trityl OX63 (OX71) spin probe. Radiation was delivered with a novel animal intensity modulated radiation therapy (IMRT) XRAD225Cx microCT/radiation therapy delivery system. In a simplified scheme for boost dose delivery, the boost area is approximated by a sphere, whose radius and position are determined using an EPR O2 image. The sphere that irradiates the largest fraction of hypoxic voxels in the tumor was chosen using an algorithm based on Receiver Operator Characteristic (ROC) analysis. We used the fraction of irradiated hypoxic volume as the true positive determinant and the fraction of irradiated normoxic volume as the false positive determinant in the terms of that analysis. The most efficient treatment is the one that demonstrates the shortest distance from the ROC curve to the upper left corner of the ROC plot. The boost dose corresponds to the difference between TCD90 and TCD50 values. For the control experiment an identical radiation dose to the normoxic tumor area is delivered.

Dynamic intensity-weighted region of interest imaging for conebeam CT.

BACKGROUND: Patient dose from image guidance in radiotherapy is small compared to the treatment dose. However, the imaging beam is untargeted and deposits dose equally in tumor and healthy tissues. It is desirable to minimize imaging dose while maintaining efficacy. OBJECTIVE: Image guidance typically does not require full image quality throughout the patient. Dynamic filtration of the kV beam allows local control of CT image noise for high quality around the target volume and lower quality elsewhere, with substantial dose sparing and reduced scatter fluence on the detector. METHODS: The dynamic Intensity-Weighted Region of Interest (dIWROI) technique spatially varies beam intensity during acquisition with copper filter collimation. Fluence is reduced by 95% under the filters with the aperture conformed dynamically to the ROI during cone-beam CT scanning. Preprocessing to account for physical effects of the collimator before reconstruction is described. RESULTS: Reconstructions show image quality comparable to a standard scan in the ROI, with higher noise and streak artifacts in the outer region but still adequate quality for patient localization. Monte Carlo modeling shows dose reduction by 10-15% in the ROI due to reduced scatter, and up to 75% outside. CONCLUSIONS: The presented technique offers a method to reduce imaging dose by accepting increased image noise outside the ROI, while maintaining full image quality inside the ROI.

Lung texture in serial thoracic CT scans: assessment of change introduced by image registration.

PURPOSE: The aim of this study was to quantify the effect of four image registration methods on lung texture features extracted from serial computed tomography (CT) scans obtained from healthy human subjects. METHODS: Two chest CT scans acquired at different time points were collected retrospectively for each of 27 patients. Following automated lung segmentation, each follow-up CT scan was registered to the baseline scan using four algorithms: (1) rigid, (2) affine, (3) B-splines deformable, and (4) demons deformable. The registration accuracy for each scan pair was evaluated by measuring the Euclidean distance between 150 identified landmarks. On average, 1432 spatially matched 32 × 32-pixel region-of-interest (ROI) pairs were automatically extracted from each scan pair. First-order, fractal, Fourier, Laws' filter, and gray-level co-occurrence matrix texture features were calculated in each ROI, for a total of 140 features. Agreement between baseline and follow-up scan ROI feature values was assessed by Bland-Altman analysis for each feature; the range spanned by the 95% limits of agreement of feature value differences was calculated and normalized by the average feature value to obtain the normalized range of agreement (nRoA). Features with small nRoA were considered "registration-stable." The normalized bias for each feature was calculated from the feature value differences between baseline and follow-up scans averaged across all ROIs in every patient. Because patients had "normal" chest CT scans, minimal change in texture feature values between scan pairs was anticipated, with the expectation of small bias and narrow limits of agreement. RESULTS: Registration with demons reduced the Euclidean distance between landmarks such that only 9% of landmarks were separated by ≥1 mm, compared with rigid (98%), affine (95%), and B-splines (90%). Ninety-nine of the 140 (71%) features analyzed yielded nRoA > 50% for all registration methods, indicating that the majority of feature values were perturbed following registration. Nineteen of the features (14%) had nRoA < 15% following demons registration, indicating relative feature value stability. Student's t-tests showed that the nRoA of these 19 features was significantly larger when rigid, affine, or B-splines registration methods were used compared with demons registration. Demons registration yielded greater normalized bias in feature value change than B-splines registration, though this difference was not significant (p = 0.15). CONCLUSIONS: Demons registration provided higher spatial accuracy between matched anatomic landmarks in serial CT scans than rigid, affine, or B-splines algorithms. Texture feature changes calculated in healthy lung tissue from serial CT scans were smaller following demons registration compared with all other algorithms. Though registration altered the values of the majority of texture features, 19 features remained relatively stable after demons registration, indicating their potential for detecting pathologic change in serial CT scans. Combined use of accurate deformable registration using demons and texture analysis may allow for quantitative evaluation of local changes in lung tissue due to disease progression or treatment response.

HiSStology: high spectral and spatial resolution magnetic resonance imaging detection of vasculature validated by histology and micro-computed tomography.

High spectral and spatial resolution (HiSS) data, acquired with echo-planar spectroscopic imaging (EPSI), can be used to acquire water spectra from each small image voxel. These images are sensitive to changes in local susceptibility caused by superparamagnetic iron oxide particles (SPIO); therefore, we hypothesized that images derived from HiSS data are very sensitive to tumor neovasculature following injection of SPIO. Accurate image registration was used to validate HiSS detection of neovasculature with histology and micro-computed tomographic (microCT) angiography. Athymic nude mice and Copenhagen rats were inoculated with Dunning AT6.1 prostate tumor cells in the right hind limb. The tumor region was imaged pre- and post-intravenous injection of SPIO. Three-dimensional assemblies of the CD31-stained histologic slices of the mouse legs and the microCT images of the rat vascular casts were registered with EPSI. The average distance between HiSS-predicted regions of high vascular density on magnetic resonance imaging and CD31-stained regions on histology was 200 µm. Similarly, vessels identified by HiSS in the rat images coincided with vasculature in the registered microCT image. The data demonstrate a strong correlation between tumor vasculature identified using HiSS and two gold standards: histology and microCT angiography.

High-resolution MRI of excised human prostate specimens acquired with 9.4T in detection and identification of cancers: validation of a technique.

PURPOSE: To evaluate feasibility of high-resolution, high-field ex vivo prostate magnetic resonance imaging (MRI) as an aid to guide pathologists' examination and develop in vivo MRI methods. MATERIALS AND METHODS: Unfixed excised prostatectomy specimens (n = 9) were obtained and imaged immediately after radical prostatectomy under an Institutional Review Board-approved protocol. High-resolution T2-weighted (T2W) MRI of specimens were acquired with a Bruker 9.4 T scanner to correlate with whole-mount histology. Additionally, T2 and apparent diffusion coefficient (ADC) maps were generated. RESULTS: By visual inspection of the nine prostate specimens imaged, high-resolution T2W MRI showed improved anatomical detail compared to published low-resolution images acquired at 4 T as published by other investigators. Benign prostatic hyperplasia, adenocarcinomas, curvilinear duct architecture distortion due to adenocarcinomas, and normal radial duct distribution were readily identified. T2 was ≈10 msec longer (P < 0.03) and the ADC was ≈1.4 times larger (P < 0.002) in the normal peripheral zone compared to the peripheral zone with prostate cancer. CONCLUSION: Differences in T2 and ADC between benign and malignant tissue are consistent with in vivo data. High-resolution, high-field MRI has the potential to improve the detection and identification of prostate structures. The protocols and techniques developed in this study could augment routine pathological analysis of surgical specimens and guide treatment of prostate cancer patients.

Small Animal IMRT Using 3D-Printed Compensators.

PURPOSE: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. METHODS AND MATERIALS: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. RESULTS: Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. CONCLUSIONS: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

3D anatomical model for teaching canine lumbosacral epidural anesthesia.

Purpose To develop a 3D anatomical model for teaching canine epidural anesthesia (3DMEA) and to assess its efficacy for teaching and learning prior to the use of live animals. Methods The creation of 3DMEA was based on 3D optical scanning and 3D printing of canine bone pieces of the fifth to the seventh lumbar vertebrae, sacrum and pelvis. A total of 20 male dogs were scheduled for castration. 20 veterinary students watched a video showing epidural anesthesia in dogs before the clinical attempt and were assigned to control or 3DMEA groups. Students in the 3DMEA group trained in the model after the video. For the clinical trial, the epidural procedure was performed by students under the veterinary supervision. When observed the absence of response to nociceptive stimuli, the epidural was considered successful. Then, all students answered a questionnaire evaluating the main difficulty founded in the technique and its degree of difficulty. Results The 3DMEA group reported a lower degree of difficulty to perform the epidural anesthesia technique when compared with the control group (p=0.0037). The 3DMEA reproduced the anatomical structures, allowing the perception of the distance of needle in relation to the iliac prominences during epidural anesthesia. Its mobility allowed simulation of the animal in standing position and sternal recumbency. Conclusion The use of 3DMEA demonstrated greater efficacy in the execution of the technique, being effective in the teaching and learning process before the epidural anesthesia in live animals.

Characterization of response to radiation mediated gene therapy by means of multimodality imaging.

Imaging techniques are under development to facilitate early analysis of spatial patterns of tumor response to combined radiation and antivascular gene therapy. A genetically modified, replication defective adenoviral vector (Ad.EGR-TNFalpha), injected intratumorally, mediates infected cells to express tumor necrosis factor alpha (TNFalpha), which is increased after exposure to radiation. The goal of this study was to characterize an image based "signature" for response to this combined radiation and gene therapy in mice with human prostate xenografts. This study is part of an imaged guided therapy project where such a signature would be useful in guiding subsequent treatments. Changes in the tumor micro-environment were assessed using MRI registered with electron paramagnetic resonance imaging which provides images of tissue oxygenation. Dynamic contrast-enhanced MRI was used to assess tissue perfusion. When compared with null vector (control) treatment, the ratio of contrast agent (Gd-DTPA-BMA) washout rate to uptake rate was lower (P = 0.001) after treatment, suggesting a more balanced perfusion. Concomitantly, oxygenation significantly increased in the treated animals and decreased or did not change in the control animals (P < 0.025). This is the first report of minimally invasive, quantitative, absolute oxygen measurements correlated with tissue perfusion in vivo.

Region-of-interest image reconstruction with intensity weighting in circular cone-beam CT for image-guided radiation therapy.

Imaging plays a vital role in radiation therapy and with recent advances in technology considerable emphasis has been placed on cone-beam CT (CBCT). Attaching a kV x-ray source and a flat panel detector directly to the linear accelerator gantry has enabled progress in target localization techniques, which can include daily CBCT setup scans for some treatments. However, with an increasing number of CT scans there is also an increasing concern for patient exposure. An intensity-weighted region-of-interest (IWROI) technique, which has the potential to greatly reduce CBCT dose, in conjunction with the chord-based backprojection-filtration (BPF) reconstruction algorithm, has been developed and its feasibility in clinical use is demonstrated in this article. A nonuniform filter is placed in the x-ray beam to create regions of two different beam intensities. In this manner, regions outside the target area can be given a reduced dose but still visualized with a lower contrast to noise ratio. Image artifacts due to transverse data truncation, which would have occurred in conventional reconstruction algorithms, are avoided and image noise levels of the low- and high-intensity regions are well controlled by use of the chord-based BPF reconstruction algorithm. The proposed IWROI technique can play an important role in image-guided radiation therapy.

Characterization of a novel phantom for three-dimensional in vitro cell experiments.

A novel intensity-modulated radiation therapy (IMRT) phantom for use in three-dimensional in vitro cell experiments, based on a commercially available system (CIRS Inc., Norfolk, VA), was designed and fabricated. The water-equivalent plastic phantom can, with a set of water-equivalent plastic inserts, enclose 1-3 multi-well tissue culture plates. Dosimetry within the phantom was assessed using thermoluminescence dosimeters (TLDs) and film. The phantom was loaded with three tissue culture plates, and an array of TLDs or a set of three films was placed underneath each plate within the phantom, and then irradiated using an IMRT plan created for it. Measured doses from each dosimeter were compared to those acquired from the treatment planning system. The percent differences between TLD measurements and the corresponding points in the treatment plan ranged from 1.3% to 2.9%, differences which did not show statistical significance. Average point-by-point percent dose differences for each film plane ranged from 1.6% to 3.1%. The percentage dose difference for which 95% of the points in the film matched those corresponding to the calculated dose plane to within 3.0% ranged from 2.8% to 4.2%. The good agreement between predicted and measured dose shows that the phantom is a useful and efficient tool for three-dimensional in vitro cell experiments.

Oxygen-Guided Radiation Therapy.

PURPOSE: It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. METHODS AND MATERIALS: For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. RESULTS: We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P = .04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. CONCLUSIONS: This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.

Electron paramagnetic resonance oxygen image hypoxic fraction plus radiation dose strongly correlates with tumor cure in FSa fibrosarcomas.

PURPOSE: Tumor hypoxia has long been known to produce resistance to radiation. In this study, electron paramagnetic resonance (EPR) oxygen imaging was investigated for its power to predict the success of tumor control according to tumor oxygenation level and radiation dose. METHODS AND MATERIALS: A total of 34 EPR oxygen images were obtained from the legs of C3H mice bearing 0.5-cm(3) FSa fibrosarcomas under both normal (air breathing) and clamped tumor conditions. Under the same conditions as those during which the images were obtained, the tumors were irradiated to a variety of doses near the FSa dose at which 50% of tumors were cured. Tumor tissue was distinguished from normal tissue using co-registration of the EPR oxygen images with spin-echo magnetic resonance imaging of the tumor and/or stereotactic localization. The tumor voxel statistics in the EPR oxygen image included the mean and median partial pressure of oxygen and the fraction of tumor voxels below the specified partial pressure of oxygen values of 3, 6, and 10 mm Hg. Bivariate logistic regression analysis using the radiation dose and each of the EPR oxygen image statistics to determine which best separated treatment failure from success. RESULTS: The measurements of the dose at which 50% of tumors were cured were similar to those found in published data for this syngeneic tumor. Bivariate analysis of 34 tumors demonstrated that tumor cure correlated with dose (p = 0.004) and with a <10 mm Hg hypoxic fraction (p = 0.023). CONCLUSION: Our results have shown that, together, radiation dose and EPR image hypoxic fraction separate the population of FSa fibrosarcomas that are cured from those that fail, thus predicting curability.

Exact reconstruction of volumetric images in reverse helical cone-beam CT.

Helical scanning configuration has been used widely in diagnostic cone-beam computed tomography (CBCT) for acquiring data sufficient for exact image reconstruction over an extended volume. In image-guided radiation therapy (IGRT) and other applications of CBCT, it can be difficult, if not impossible, to implement mechanically a multiple-turn helical trajectory on the imaging systems due to hardware constraints. However, imaging systems in these applications often allow for the implementation of a reverse helical trajectory in which the rotation direction changes between two consecutive turns. Because the reverse helical trajectory satisfies Tuy's condition, when projections of the imaged object are nontruncated, it yields data sufficient for exact image reconstruction within the reverse helix volume. The recently developed chord-based algorithms such as the backprojection filtration (BPF) algorithm can readily be applied to reconstructing images on chords of a reverse helical trajectory, and they can thus reconstruct an image within a volume covered by the chords. Conversely, the chord-based algorithms cannot reconstruct images within regions that are not intersected by chords. In a reverse helix volume, as shown below, chordless regions exist in which no images can thus be reconstructed by use of the chord-based algorithms. In this work, based upon Pack-Noo's formula, a shift-invariant filtered backprojection (FBP) algorithm is derived for exact image reconstruction within the reverse helix volume, including the chordless region. Numerical studies have also been conducted to demonstrate the chordless region in a reverse helix volume and to validate the FBP algorithm for image reconstruction within the chordless region. Results of the numerical studies confirm that the FBP algorithm can exactly reconstruct an image within the entire reverse helix volume, including the chordless region. It is relatively straightforward to extend the FBP algorithm to reconstruct images for general trajectories, including reverse helical trajectories with variable pitch, tilted axis, and/or additional segments between turns.

The development and testing of a digital PET phantom for the evaluation of tumor volume segmentation techniques.

Methods for accurate tumor volume segmentation of positron emission tomography (PET) images have been under investigation in recent years partly as a result of the increased use of PET in radiation treatment planning (RTP). None of the developed automated or semiautomated segmentation methods, however, has been shown reliable enough to be regarded as the standard. One reason for this is that there is no source of well characterized and reliable test data for evaluating such techniques. The authors have constructed a digital tumor phantom to address this need. The phantom was created using the Zubal phantom as input to the SimSET software used for PET simulations. Synthetic tumors were placed in the lung of the Zubal phantom to provide the targets for segmentation. The authors concentrated on the lung, since much of the interest to include PET in RTP is for nonsmall cell lung cancer. Several tests were performed on the phantom to ensure its close resemblance to clinical PET scans. The authors measured statistical quantities to compare image intensity distributions from regions-of-interest (ROIs) placed in the liver, the lungs, and tumors in phantom and clinical reconstructions. Using ROIs they also made measurements of autocorrelation functions to ensure the image texture is similar in clinical and phantom data. The authors also compared the intensity profile and appearance of real and simulated uniform activity spheres within uniform background. These measurements, along with visual comparisons of the phantom with clinical scans, indicate that the simulated phantom mimics reality quite well. Finally, they investigate and quantify the relationship between the threshold required to segment a tumor and the inhomogeneity of the tumor's image intensity distribution. The tests and various measurements performed in this study demonstrate how the phantom can offer a reliable way of testing and investigating tumor volume segmentation in PET.

Immobilization Using Dental Material Casts Facilitates Accurate Serial and Multimodality Small Animal Imaging.

Custom disposable patient immobilization systems that conform to the patient's body contours are commonly used to facilitate accurate repeated patient setup for imaging and treatment in radiation therapy. However, in small-animal imaging, immobilization is often overlooked or done in a way that is not conducive to reproducible positioning. This has a negative impact on the potential for accurate analysis of serial or multimodality imaging. We present the use of vinyl polysiloxane dental impression material for immobilization of mice for imaging. Four different materials were examined to identify any potential artifacts using magnetic resonance techniques. A water phantom placed inside the cast was used at 4.7 T with magnetic resonance imaging and showed no effect at the center of the image when compared with images without the cast. A negligible effect was seen near the ends of the coil. Each material had no detectable signal using electron paramagnetic resonance imaging at 9 mT. The use of dental material also greatly enhances the use of fiducial markers that can be embedded in the mold. Therefore, image registration is simplified as the immobilization of the animal and fiducials together helps in translating from one image coordinate system to another.

Late toxicity after post-prostatectomy intensity modulated radiation therapy: Evaluating normal-tissue sparing guidelines.

PURPOSE: Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. METHODS AND MATERIALS: 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. RESULTS: With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. CONCLUSIONS: More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Low-dose X-ray radiotherapy-radiodynamic therapy via nanoscale metal-organic frameworks enhances checkpoint blockade immunotherapy.

Checkpoint blockade immunotherapy relies on energized cytotoxic T cells attacking tumour tissue systemically. However, for many cancers, the reliance on T cell infiltration leads to low response rates. Conversely, radiotherapy has served as a powerful therapy for local tumours over the past 100 years, yet is rarely sufficient to cause systemic tumour rejection. Here, we describe a treatment strategy that combines nanoscale metal-organic framework (nMOF)-enabled radiotherapy-radiodynamic therapy with checkpoint blockade immunotherapy for both local and systemic tumour elimination. In mouse models of breast and colorectal cancer, intratumorally injected nMOFs treated with low doses of X-ray irradiation led to the eradication of local tumours and, when loaded with an inhibitor of the immune checkpoint molecule indoleamine 2,3-dioxygenase, the irradiated nMOFs led to consistent abscopal responses that rejected distal tumours. By combining the advantages of local radiotherapy and systemic tumour rejection via synergistic X-ray-induced in situ vaccination and indoleamine 2,3-dioxygenase inhibition, nMOFs may overcome some of the limitations of checkpoint blockade in cancer treatment.