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At least 55 records · Page 3

SU-E-T-539: Maximum Energy of Helium and Carbon Ions Clinically Needed for Spine, Lung, Prostate and Pancreas Cancer

Purpose: Maximum available kinetic energy of accelerated heavy ions is a critical parameter to consider during the establishment of a heavy ion therapy center. It dictates the maximum range in tissue and determines the size and cost of ion gantry. We have started planning our heavy ion therapy center and we report on the needed ion range. Methods: We analyzed 50 of random SBRT-spine, SBRT- lung, prostate and pancreatic cancer patients from our photon clinic. In the isocentric axial CT cut we recorded the maximum water equivalent depth (WED4Field) of PTV’s most distal edge in four cardinal directions and also in a beam direction that required the largest penetration, WEDGantry. These depths were then used to calculate the percentage of our patients we would be able to treat as a function of available maximum carbon and helium beam energy. Based on the Anterior-Posterior WED for lung patients and the maximum available ion energy we estimated the largest possible non-coplanar beam entry angle φ (deviation from vertical) in the isocentric vertical sagittal plane. Results: We found that if 430MeV/u C-12, equivalently 220MeV/u He-4, beams are available, more than 96% (98%) of all patients can be treated without any gantry restrictions (in cardinals angles only) respectively. If the energy is reduced to 400MeV/u C-12, equivalently 205MeV/u He-4, the above fractions reduce to 80% (87%) for prostate and 88% (97%) for other sites. This 7% energy decrease translates to almost 5% gantry size and cost decrease for both ions. These energy limits in combination with the WED in the AP direction for lung patients resulted in average non-coplanar angles of φ430MeV/u = 68°±8° and φ400MeV/u = 65°±10° if nozzle clearance permits them. Conclusion: We found that the two worldwide most common maximum carbon beam energies will treat above 80% of all our patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-F-J-173: Online Replanning for Dose Painting Based On Changing ADC Map of Pancreas Cancer

Purpose: The introduction of MR-guided radiation therapy (RT), e.g., MR-Linac, would allow dose painting to adapt spatial RT response revealed from MRI data during the RT delivery. The purpose of this study is to investigate the use of an online replanning method to adapt dose painting from the MRI Apparent Diffusion Coefficient (ADC) map acquired during the delivery of RT for pancreatic cancers. Methods: Original dose painting plans were created based on multi-parametric simulation MRI including T1, T2 and ADC, using a treatment planning system (MONACO, Elekta) equipped with an online replanning algorithm (WSO, warm start optimization). Multiple GTVs, identified based on various ADC levels were prescribed to different doses ranging from 50–70 Gy with simultaneous integrated boost in 28 fractions. The MRI acquired after RT were used to mimic weekly MRI, on which the changing GTVs, pancreatic head and other organs-at-risk (OAR) (duodenum, stomach, small bowel) were delineated. The adaptive plan was generated by applying WSO algorithm starting from the deformed original plan based on the weekly MRI using a deformable image registration (DIR) software (ADMIRE, Elekta). The online replanning method takes <10 min. including DIR, target delineation, WSO execution and final dose calculation. Standard IGRT repositioning and full-blown reoptimization plans were also generated to compare with the adaptive plans. Results: The online replanning method significantly improved the multiple target coverages and OAR sparing for pancreatic cancers. For example, for a case with two GTVs with prescriptions of 60 and 70 Gy in pancreatic head, V100-GTV70 (the volume covered by 100% of prescription dose for GTV with 70 Gy)/V100-GTV60/V100-CTV50/V45-duodenum were (95.1/22.2/69.5/85.7), (95.0/97.0/98.6/34.3), and (95.0/98.1/100.0/38.7) for the IGRT, adaptive and reoptimization plans, respectively. Conclusion: The introduced online adaptive replanning method can effectively account for interfractional changes including tumor spatial response during MR-guided RT delivery, allowing precise delivery of dose painting. This study was partially supported by Elekta Inc.

60 APPLIED LIFE SCIENCES↗

Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis

Highlights: • Basal autophagy impairment causes zymogen granule accumulation in acinar cells. • Pancreas-specific autophagy impairment mice cause pancreatitis at 4 weeks of age. • Pancreas-specific autophagy impairment mice developed chronic pancreatitis. Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre{sup +/-} Atg7{sup fl/fl} mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age. However, the number of zymogen granules in acinar cells drastically increased at 4 weeks of age in mice with pancreas-specific autophagy impairment. In addition to the increased number of zymogen granules, serum lipase was elevated, and the pancreas became oedematous at 4 weeks of age, suggesting pancreatitis. After 5 weeks of age, acinar cell death was accelerated, and several histological features of chronic pancreatitis were observed, including glandular atrophy and pseudotubular complexes with fibrotic changes. In conclusion, the impairment of pancreas-specific basal autophagy caused spontaneous zymogen granule accumulation in acinar cells and pancreatitis, which eventually led to chronic pancreatitis.

60 APPLIED LIFE SCIENCES↗

Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dosimetric benefit of adaptive re-planning in pancreatic cancer stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) shows promise in unresectable pancreatic cancer, though this treatment modality has high rates of normal tissue toxicity. This study explores the dosimetric utility of daily adaptive re-planning with pancreas SBRT. We used a previously developed supercomputing online re-planning environment (SCORE) to re-plan 10 patients with pancreas SBRT. Tumor and normal tissue contours were deformed from treatment planning computed tomographies (CTs) and transferred to daily cone-beam CT (CBCT) scans before re-optimizing each daily treatment plan. We compared the intended radiation dose, the actual radiation dose, and the optimized radiation dose for the pancreas tumor planning target volume (PTV) and the duodenum. Treatment re-optimization improved coverage of the PTV and reduced dose to the duodenum. Within the PTV, the actual hot spot (volume receiving 110% of the prescription dose) decreased from 4.5% to 0.5% after daily adaptive re-planning. Within the duodenum, the volume receiving the prescription dose decreased from 0.9% to 0.3% after re-planning. It is noteworthy that variation in the amount of air within a patient's stomach substantially changed dose to the PTV. Adaptive re-planning with pancreas SBRT has the ability to improve dose to the tumor and decrease dose to the nearby duodenum, thereby reducing the risk of toxicity.

61 RADIATION PROTECTION AND DOSIMETRY↗

Vitamin A deficiency induces endoplasmic reticulum stress and apoptosis in pancreatic islet cells: Implications of stearoyl-CoA desaturase 1-mediated oleic acid synthesis

Highlights: • For first time, here we report the possible underlying mechanism of vitamin A deficiency- induced pancreatic dysfunction. • Vitamin A deficiency altered the architecture and impaired the functions of pancreas. • Further, it increased the endoplasmic reticulum stress and reduced the SCD1-mediated monounsaturated fatty acid; oleic acid. • All these changes, possibly resulted in increased pancreatic islet cell death and thus decreased plasma insulin and glucagon levels. Previously, we reported that vitamin A deficiency resulted in the reduction of stearoyl-CoA desaturase 1 (SCD1) and monounsaturated fatty acid (MUFA) levels, which corroborated with attenuation of high fructose-induced hepatic steatosis. Here, we aimed at assessing the effect of vitamin A deficiency on SCD1, MUFA levels and their impact on pancreas’ structure and functions. Male weanling Wistar rats fed one of the four diets, namely control (Con), vitamin A-deficient (VAD), highfructose (HFr) and vitamin A-deficient diet with highfructose (VADHFr) for 16 weeks period. Compared to the control, feeding of VAD diet (alone or with HFr) resulted in pancreatic intra-islet vessel dilation and reduced plasma insulin, glucagon and C-peptide levels, however, glucose levels decreased only in VADHFr group. In line with plasma levels, VAD diet-fed animals displayed lower immunostaining for insulin and glucagon, which corroborated with increased apoptotic staining observed in the islet regions, possibly due to increased cellular stress, as indicated by high immunostaining for endothelial nitric oxide synthase (eNOS) and CCAAT/Enhancer-binding protein homologues protein (CHOP). On the other hand, it significantly decreased the SCD1 protein, which corroborated with reduced MUFA levels, particularly, oleic acid (C18:1), when compared to the control and HFr groups. In conclusion, chronic vitamin A deficiency altered the structure and functions of pancreas by diminishing the islet cells, possibly by inducing cellular stress-mediated apoptosis and decreasing SCD1-mediated oleic acid (C18:1) synthesis. Thus, the data suggest that unlike liver, the reduction in SCD1 and MUFA levels in the pancreas exerts deleterious effects on its functions and perturb the overall cellular metabolism.

60 APPLIED LIFE SCIENCES↗

Dose-shaping using targeted sparse optimization

Purpose: Dose volume histograms (DVHs) are common tools in radiation therapy treatment planning to characterize plan quality. As statistical metrics, DVHs provide a compact summary of the underlying plan at the cost of losing spatial information: the same or similar dose-volume histograms can arise from substantially different spatial dose maps. This is exactly the reason why physicians and physicists scrutinize dose maps even after they satisfy all DVH endpoints numerically. However, up to this point, little has been done to control spatial phenomena, such as the spatial distribution of hot spots, which has significant clinical implications. To this end, the authors propose a novel objective function that enables a more direct tradeoff between target coverage, organ-sparing, and planning target volume (PTV) homogeneity, and presents our findings from four prostate cases, a pancreas case, and a head-and-neck case to illustrate the advantages and general applicability of our method.Methods: In designing the energy minimization objective (E{sub tot}{sup sparse}), the authors utilized the following robust cost functions: (1) an asymmetric linear well function to allow differential penalties for underdose, relaxation of prescription dose, and overdose in the PTV; (2) a two-piece linear function to heavily penalize high dose and mildly penalize low and intermediate dose in organs-at risk (OARs); and (3) a total variation energy, i.e., the L{sub 1} norm applied to the first-order approximation of the dose gradient in the PTV. By minimizing a weighted sum of these robust costs, general conformity to dose prescription and dose-gradient prescription is achieved while encouraging prescription violations to follow a Laplace distribution. In contrast, conventional quadratic objectives are associated with a Gaussian distribution of violations, which is less forgiving to large violations of prescription than the Laplace distribution. As a result, the proposed objective E{sub tot}{sup sparse} improves tradeoff between planning goals by 'sacrificing' voxels that have already been violated to improve PTV coverage, PTV homogeneity, and/or OAR-sparing. In doing so, overall plan quality is increased since these large violations only arise if a net reduction in E{sub tot}{sup sparse} occurs as a result. For example, large violations to dose prescription in the PTV in E{sub tot}{sup sparse}-optimized plans will naturally localize to voxels in and around PTV-OAR overlaps where OAR-sparing may be increased without compromising target coverage. The authors compared the results of our method and the corresponding clinical plans using analyses of DVH plots, dose maps, and two quantitative metrics that quantify PTV homogeneity and overdose. These metrics do not penalize underdose since E{sub tot}{sup sparse}-optimized plans were planned such that their target coverage was similar or better than that of the clinical plans. Finally, plan deliverability was assessed with the 2D modulation index.Results: The proposed method was implemented using IBM's CPLEX optimization package (ILOG CPLEX, Sunnyvale, CA) and required 1-4 min to solve with a 12-core Intel i7 processor. In the testing procedure, the authors optimized for several points on the Pareto surface of four 7-field 6MV prostate cases that were optimized for different levels of PTV homogeneity and OAR-sparing. The generated results were compared against each other and the clinical plan by analyzing their DVH plots and dose maps. After developing intuition by planning the four prostate cases, which had relatively few tradeoffs, the authors applied our method to a 7-field 6 MV pancreas case and a 9-field 6MV head-and-neck case to test the potential impact of our method on more challenging cases. The authors found that our formulation: (1) provided excellent flexibility for balancing OAR-sparing with PTV homogeneity; and (2) permitted the dose planner more control over the evolution of the PTV's spatial dose distribution than conventional objective functions. In particular, E{sub tot}{sup sparse}-optimized plans for the pancreas case and head-and-neck case exhibited substantially improved sparing of the spinal cord and parotid glands, respectively, while maintaining or improving sparing for other OARs and markedly improving PTV homogeneity. Plan deliverability for E{sub tot}{sup sparse}-optimized plans was shown to be better than their associated clinical plans, according to the two-dimensional modulation index.Conclusions: These results suggest that our formulation may be used to improve dose-shaping and OAR-sparing for complicated disease sites, such as the pancreas or head and neck. Furthermore, our objective function and constraints are linear and constitute a linear program, which converges to the global minimum quickly, and can be easily implemented in treatment planning software. Thus, the authors expect fast translation of our method to the clinic where it may have a positive impact on plan quality for challenging disease sites.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly benefit from the addition of MRI and especially functional MR techniques.

60 APPLIED LIFE SCIENCES↗

SU-E-J-72: Dosimetric Study of Cone-Beam CT-Based Radiation Treatment Planning Using a Patient-Specific Stepwise CT-Density Table

Purpose: To assess dose calculation accuracy of cone-beam CT (CBCT) based treatment plans using a patient-specific stepwise CT-density conversion table in comparison to conventional CT-based treatment plans. Methods: Unlike CT-based treatment planning which use fixed CT-density table, this study used patient-specific CT-density table to minimize the errors in reconstructed mass densities due to the effects of CBCT Hounsfield unit (HU) uncertainties. The patient-specific CT-density table was a stepwise function which maps HUs to only 6 classes of materials with different mass densities: air (0.00121g/cm3), lung (0.26g/cm3), adipose (0.95g/cm3), tissue (1.05 g/cm3), cartilage/bone (1.6g/cm3), and other (3g/cm3). HU thresholds to define different materials were adjusted for each CBCT via best match with the known tissue types in these images. Dose distributions were compared between CT-based plans and CBCT-based plans (IMRT/VMAT) for four types of treatment sites: head and neck (HN), lung, pancreas, and pelvis. For dosimetric comparison, PTV mean dose in both plans were compared. A gamma analysis was also performed to directly compare dosimetry in the two plans. Results: Compared to CT-based plans, the differences for PTV mean dose were 0.1% for pelvis, 1.1% for pancreas, 1.8% for lung, and −2.5% for HN in CBCT-based plans. The gamma passing rate was 99.8% for pelvis, 99.6% for pancreas, and 99.3% for lung with 3%/3mm criteria, and 80.5% for head and neck with 5%/3mm criteria. Different dosimetry accuracy level was observed: 1% for pelvis, 3% for lung and pancreas, and 5% for head and neck. Conclusion: By converting CBCT data to 6 classes of materials for dose calculation, 3% of dose calculation accuracy can be achieved for anatomical sites studied here, except HN which had a 5% accuracy. CBCT-based treatment planning using a patient-specific stepwise CT-density table can facilitate the evaluation of dosimetry changes resulting from variation in patient anatomy.

60 APPLIED LIFE SCIENCES↗

Preliminary results on the feasibility of using ultrasound to monitor intrafractional motion during radiation therapy for pancreatic cancer

Purpose: Substantial intrafraction organ motion during radiation therapy (RT) for pancreatic cancer is well recognized as a major limiting factor for accurate delivery of RT. The aim of this work is to determine the feasibility of monitoring the intrafractional motion of the pancreas or surrounding structures using ultrasound for RT delivery. Methods: Transabdominal ultrasound (TAUS) and 4DCT data were acquired on ten pancreatic cancer patients during radiation therapy process in a prospective study. In addition, TAUS and MRI were collected for five healthy volunteers. The portal vein (PV) and the head of the pancreas (HP) along with other structures were contoured on these images. Volume changes, distance between the HP and PV, and motion difference between the HP and PV were measured to examine whether PV can be used as a motion surrogate for HP. TAUS images were acquired and processed using a research version of the Clarity autoscan ultrasound system (CAUS). Motion monitoring was performed with the ultrasound probe mounted on an arm fixed to the couch. Video segments of the monitoring sessions were captured. Results: On TAUS, PV is better visualized than HP. The measured mean volume deviation for all patients for the HP and PV was 1.4 and 0.6 ml, respectively. The distance between the HP and PV was close to a constant with 0.22 mm mean deviation throughout the ten breathing phases. The mean of the absolute motion difference for all patients was 1.7 ± 0.8 mm in LR, 1.5 ± 0.5 mm in AP, and 2.3 ± 0.7 mm in SI, suggesting that the PV is a good surrogate for HP motion estimation. By using this surrogate, the HP motion tracking using TAUS was demonstrated. Conclusions: Large intrafractional organ motion due to respiratory and/or bowel motion is a limiting factor in administering curative radiation doses to pancreatic tumors. The authors investigate the use of real-time ultrasound to track pancreas motion. Due to the poor visibility of the pancreas head on an ultrasound image, the portal vein is identified as a surrogate. The authors have demonstrated the feasibility of tracking HP motion through the localization of the PV using TAUS. This will potentially allow real-time tracking of intrafractional motion to justify small PTV-margins and to account for unusual motions, thus, improving normal tissue sparing.

60 APPLIED LIFE SCIENCES↗

Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

60 APPLIED LIFE SCIENCES↗

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Toward Personalized Dosimetry with {sup 32}P Microparticle Therapy for Advanced Pancreatic Cancer

Purpose: To develop a Monte Carlo model for patient-specific dosimetry of {sup 32}P microparticle localized internal radionuclide therapy for advanced pancreatic cancer. Methods and Materials: Spherical tumor geometries and a pancreatic phantom were modeled, as well as different 3-dimensional non-uniform clinical pancreatic geometries based on patient-specific ultrasound images. The dosimetry simulations modeled the dose distribution due to the energy spectrum of emitted beta particles. Results: The average dose for small (3-cm diameter) and large (6-cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and 128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on the basis of patient data, the mean doses delivered to the tumor were calculated to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the smallest tumor volumes. The calculated dose distributions are highly non-uniform. For the largest tumor studied, the pancreas received approximately 6% of the tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor studied exhibited the most dynamic changes in volume in response to the treatment, the dose to tumor and pancreas is significantly underestimated if a static tumor volume is assumed. Conclusions: These results demonstrate the dosimetry of {sup 32}P microparticle localized internal radionuclide therapy for pancreatic cancer and the possibility of developing personalized treatment strategies. The results also highlight the importance of considering the effects of non-uniform dose distributions and dynamic change of tumor mass during treatment on the dosimetry of the tumor and critical organs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

WE-G-BRD-01: A Data-Driven 4D-MRI Motion Model to Estimate Full Field-Of-View Abdominal Motion From 2D Image Navigators During MR-Linac Treatment

Purpose: To estimate full field-of-view abdominal respiratory motion from fast 2D image navigators using a 4D-MRI based motion model. This will allow for radiation dose accumulation mapping during MR-Linac treatment. Methods: Experiments were conducted on a Philips Ingenia 1.5T MRI. First, a retrospectively ordered 4D-MRI was constructed using 3D transient-bSSFP with radial in-plane sampling. Motion fields were calculated through 3D non-rigid registration. From these motion fields a PCA-based abdominal motion model was constructed and used to warp a 3D reference volume to fast 2D cine-MR image navigators that can be used for real-time tracking. To test this procedure, a time-series consisting of two interleaved orthogonal slices (sagittal and coronal), positioned on the pancreas or kidneys, were acquired for 1m38s (dynamic scan-time=0.196ms), during normal, shallow, or deep breathing. The coronal slices were used to update the optimal weights for the first two PCA components, in order to warp the 3D reference image and construct a dynamic 4D-MRI time-series. The interleaved sagittal slices served as an independent measure to test the model’s accuracy and fit. Spatial maps of the root-mean-squared error (RMSE) and histograms of the motion differences within the pancreas and kidneys were used to evaluate the method. Results: Cranio-caudal motion was accurately calculated within the pancreas using the model for normal and shallow breathing with an RMSE of 1.6mm and 1.5mm and a histogram median and standard deviation below 0.2 and 1.7mm, respectively. For deep-breathing an underestimation of the inhale amplitude was observed (RMSE=4.1mm). Respiratory-induced antero-posterior and lateral motion were correctly mapped (RMSE=0.6/0.5mm). Kidney motion demonstrated good motion estimation with RMSE-values of 0.95 and 2.4mm for the right and left kidney, respectively. Conclusion: We have demonstrated a method that can calculate dynamic 3D abdominal motion in a large volume, while acquiring real-time cine-MR images for MR-guided radiotherapy.

60 APPLIED LIFE SCIENCES↗

SU-F-J-43: Positional Variation of Implanted Fiducial Markers Over the Course of Image Guided Radiotherapy for Pancreatic Cancer

Purpose: Pancreas is a soft-tissue organ, implanted fiducials can change positions due to migration or tissue deformation. This study quantified positional variation of fiducials in IGRT for pancreatic cancer. Methods: 20 patients had at least 3 gold fiducials implanted in pancreas under EUS guidance. Patients had 4D-CT simulation for gated treatment. Daily gated OBI kV images (Turebeam) were used for positional alignment with fiducials for total of 25 or 28 fractions. Relative distances among 3 fiducials (d{sub 1–} {sub 2}, d{sub 1–3}, d{sub 2–3}) were measured from 4D-CT end-of-expiration phase bin; and from gated kV images in first, mid, and last fraction (n=180). Results: The median duration between implant and simulation was 11 (range 0–41) days. The median duration between simulation and first fraction was 17 (range 8–24) days. The median relative distance was 12 (range 4–78) mm for d{sub 1–2}, 24 (range 6–80) mm for d{sub 1–3}, and 19 (range 5–63) mm for d{sub 2–3}. The median deviation was 1 mm for d{sub 1–2}, d{sub 1–3}, d{sub 2–3} between simulation and first fraction, first and mid fraction, mid and last fraction (n=180). Two patients (10%) had deviation >= 5 mm (5, 11 mm) between simulation and first fraction. One patient (5%) had deviation >= 5 mm (11 mm) between first and mid fraction. No patient (0%) had deviation >= 5 mm between mid and last fraction. In all 3 cases with deviation >=5 mm, only one fiducial was significantly deviated. No clear evidence that deviation size was associated with time interval between implant and first fraction. Conclusion: Implanted gold fiducials were quite stable over time in their relative positions in pancreas. Our data suggested at least 3 fiducials are needed. In cases that one fiducial was significantly deviated in daily kV images, this fiducial should be excluded in image guidance.

60 APPLIED LIFE SCIENCES↗

Reduced volume of diabetic pancreatic islets in rodents detected by synchrotron X-ray phase-contrast microtomography and deep learning network

The pancreatic islet is a highly structured micro-organ that produces insulin in response to rising blood glucose. Here we develop a label-free and automatic imaging approach to visualize the islets in situ in diabetic rodents by the synchrotron radiation X-ray phase-contrast microtomography (SRμCT) at the ID17 station of the European Synchrotron Radiation Facility. The large-size images (3.2 mm × 15.97 mm) were acquired in the pancreas in STZ-treated mice and diabetic GK rats. Each pancreas was dissected by 3000 reconstructed images. The image datasets were further analysed by a self-developed deep learning method, AA-Net. All islets in the pancreas were segmented and visualized by the three-dimension (3D) reconstruction. After quantifying the volumes of the islets, we found that the number of larger islets (=>1500 μm 3 ) was reduced by 2-fold (wt 1004 ± 94 vs GK 419 ± 122, P < 0.001) in chronically developed diabetic GK rat, while in STZ-treated diabetic mouse the large islets were decreased by half (189 ± 33 vs 90 ± 29, P < 0.001) compared to the untreated mice. Our study provides a label-free tool for detecting and quantifying pancreatic islets in situ. It implies the possibility of monitoring the state of pancreatic islets in vivo diabetes without labelling.

59 BASIC BIOLOGICAL SCIENCES↗

Dual-energy CT in the obese: a preliminary retrospective review to evaluate quality and feasibility of the single-source dual-detector implementation

Purpose: To determine the feasibility of performing dual-energy CT with a single-source spectral detector system in obese patients. Materials and methods: Retrospective, IRB-approved review of 28 patients weighing ≥ 270 lbs (122 kg) who underwent CT of the abdomen on a single-source spectral detector system was performed. Two blinded, independent radiologists rated relative preference between conventional CT images taken at 120 kVp (CCT120) and monoenergetic 70 keV equivalent (MonoE70) as well as iodine map image quality in the spleen, pancreas, kidneys, and liver. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between conventional CT and MonoE70 images and correlated with body habitus markers of weight, height, and abdominal diameter. Results: MonoE70 images were preferred by radiologists 100% of the time (1-sample t test, p < 0.0001) over conventional CCT120 images. Noise was significantly lower; SNR and CNR were significantly higher in MonoE70 images than in CCT120 images (paired t tests, p < 0.0001). Mean iodine map rating (scale 1–5) was 4.54 ± 0.58, denoting near homogenous and complete iodine mapping through the spleen, pancreas, kidneys, and liver for the majority of patients. Body habitus markers were not significantly correlated with image preference score; noise; MonoE70 SNR; MonoE70 CNR; change in noise, SNR, or CNR from CCT120 to MonoE70, or iodine map quality; ordinal and linear regression, p = 0.2547, p = 0.6837, p = 0.1888, p = 0.5489, p = 0.9830, p = 0.8849, p = 0.8741, p = 0.1522, respectively. Conclusion: The single-source spectral detector implementation of dual-energy CT provides viable, high-quality imaging for obese patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗