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At least 145 records · Page 8

SU-F-J-139: Amplitude of Low Frequency Fluctuation(ALFF) and Regional Homogeneity (ReHo) Study of the Respiration Motion Control Byhypnosis

Purpose: Respiration control by hypnosis is a method in reducing the detriment to the healthy organs or organizations for patients during radiotherapy, especially for lung and abdomen cancer (Fig.1). It’s hypothesized that there exists alterations neurological brain activity during the hypnosis state of respiratory motion control in comparison with resting state. Methods: Thirteen healthy volunteers were organized to participate in a hypnosis experiment that consisted of two sectional scans of functional magnetic resonance imaging (fMRI), rest state condition (RSC) scanning and hypnosis state condition (HSC) scanning. In addition, the coronal section of the lung was scanned during both conditions. During the hypnosis scan, the volunteers were under the hypnotists’ guidance to keep peace and stable respiration. To evaluate the altered physiological performance of hypnosis in the respiratory control, three conventional indicators ALFF/fALFF (0.01–0.08Hz) and ReHo, were applied to identify the difference. Results: Compared with RSC, HSC showed significant (p<0.05) higher ReHo in superior temporal gyrus, middle temporal gyrus, frontal lobe, middle occipital gyrus, parietal lobe, cerebellum anterior Lobe and lingual gyrus, and left brainstem (Fig.2). While significant lower ReHo in middle frontal gyrus, superior frontal gyrus, inferior semi-lunar lobule, sub-lobar and limbic lobe (Fig.2). As for the ALFF results, significant higher value of HSC was observed in superior temporal gyrus, middle temporal gyrus, middle occipital gyrus, middle occipital gyrus, cerebellum anterior lobe, lingual gyrus, sub-lobar, limbic lobe, and lower in cerebellum posterior lobe, inferior semi-lunar lobule, inferior parietal lobule right middle frontal gyrus, cerebellar tonsil (Fig.3). The results of fALFF were similar to ALFF (Fig.4). The above results demonstrated that most significant regions of brain were uniform between ReHo and ALFF/fALFF. Conclusion: Hypnosis is a new psychological and helpful technology for respiration control. This study provides new insights of neurological brain activity during hypnosis of respiration control. This work is supported by grants from Guangdong Innovative Research Team Program of China (Grant No. 2011S013), National 863 Programs of China (Grant Nos. 2012AA02A604 and 2015AA043203), the National High-tech R&D Program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917)

60 APPLIED LIFE SCIENCES↗

SU-F-J-151: Evaluation of a Magnetic Resonance Image Gated Radiotherapy System Using a Motion Phantom and Radiochromic Film

Purpose: Magnetic resonance image (MRI) guided radiotherapy enables gating directly on target position for soft-tissue targets in the lung and abdomen. We present a dosimetric evaluation of a commercially-available FDA-approved MRI-guided radiotherapy system’s gating performance using a MRI-compatible respiratory motion phantom and radiochromic film. Methods: The MRI-compatible phantom was capable of one-dimensional motion. The phantom consisted of a target rod containing high-contrast target inserts which moved inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical target, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal and actual tumor trajectories (two free-breathing trajectories and one repeated-breath hold) were used. Gamma comparison at 5%/3mm was used to measure fidelity to the static target dose distribution. Results: Without gating, gamma pass rates were 24–47% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% of the target allowed outside the gating boundary, the gamma pass rate was 99.6%. Relaxing the gating window to 5 mm resulted in gamma pass rate of 98.6% with repeated breath holds. For all motion trajectories gated with 3 mm margin and 10% allowed out, gamma pass rates were between 64–100% (mean:87.5%). For a 5 mm margin and 10% allowed out, gamma pass rates were between 57–98% (mean: 82.49%), significantly lower than for 3 mm by paired t-test (p=0.01). Conclusion: We validated the performance of respiratory gating based on real-time cine MRI images with the only FDA-approved MRI-guided radiotherapy system. Our results suggest that repeated breath hold gating should be used when possible for best accuracy. A 3 mm gating margin is statistically significantly more accurate than a 5 mm gating margin.

60 APPLIED LIFE SCIENCES↗

Sci-Thur PM – Colourful Interactions: Highlights 07: Canadian Computed Tomography Survey: National Diagnostic Reference Levels

Purpose: The Canadian Computed (CT) Tomography Survey sought to collect CT technology and dose index data (CTDI and DLP) at the national level in order to establish national diagnostic reference levels (DRLs) for seven common CT examinations of standard-sized adults and pediatric patients. Methods: A single survey booklet (consisting of four sections) was mailed to and completed for each participating CT scanner. Survey sections collected data on (i) General facility and scanner information, (ii) routine protocols (as available), (iii) individual patient data (as applied) and (iv) manual CTDI measurements. Results: Dose index (CTDIvol and DLP) and associated patient data from 24 280 individual patient exam sequences was analyzed for seven common CT examinations performed in Canada: Adult Head, Chest, Abdomen/Pelvis, and Chest/Abdomen/Pelvis, and Pediatric Head, Chest, and Abdomen. Pediatric examination data was sub-divided into three age ranges: 0–3, 3–7 and 7–13 years. DRLs (75th percentile of dose index distributions) were found for all thirteen groups. Further analysis also permitted segmentation of examination data into 8 sub-groups, whose dose index data was displayed along with group histograms – showing relative contribution of axial vs. helical, contrast use (C+ vs. C-), and application of fixed current vs. dose reduction (DR) – 75th percentiles of DR sub-groups were, in almost all cases, lower than whole group (examination) DRLs. Conclusions: The analysis and summaries presented in the pending survey report can serve to aid local CT imaging optimization efforts within Canada and also contribute further to international efforts in radiation protection of patients.

60 APPLIED LIFE SCIENCES↗

Development and cross‐validation of a circumference‐based predictive equation to estimate body fat in an active population

Abstract Objective The U.S. Army uses sex‐specific circumference‐based prediction equations to estimate percent body fat (%BF) to evaluate adherence to body composition standards. The equations are periodically evaluated to ensure that they continue to accurately assess %BF in a diverse population. The objective of this study was to develop and validate alternative field expedient equations that may improve upon the current Army Regulation (AR) body fat (%BF) equations. Methods Body size and composition were evaluated in a representatively sampled cohort of 1904 active‐duty Soldiers (1261 Males, 643 Females), using dual‐energy X‐ray absorptiometry (%BF DXA ), and circumferences obtained with 3D imaging and manual measurements. Sex stratified linear prediction equations for %BF were constructed using internal cross validation with %BF DXA as the criterion measure. Prediction equations were evaluated for accuracy and precision using root mean squared error, bias, and intraclass correlations. Equations were externally validated in a convenient sample of 1073 Soldiers. Results Three new equations were developed using one to three circumference sites. The predictive values of waist, abdomen, hip circumference, weight and height were evaluated. Changing from a 3‐site model to a 1‐site model had minimal impact on measurements of model accuracy and performance. Male‐specific equations demonstrated larger gains in accuracy, whereas female‐specific equations resulted in minor improvements in accuracy compared to existing AR equations. Equations performed similarly in the second external validation cohort. Conclusions The equations developed improved upon the current AR equation while demonstrating robust and consistent results within an external population. The 1‐site waist circumference‐based equation utilized the abdominal measurement, which aligns with associated obesity related health outcomes. This could be used to identify individuals at risk for negative health outcomes for earlier intervention.

Taylor, Kathryn M.↗

A Method to Recognize Anatomical Site and Image Acquisition View in X-ray Images

A method was developed to recognize anatomical site and image acquisition view automatically in 2D X-ray images that are used in image-guided radiation therapy. The purpose is to enable site and view dependent automation and optimization in the image processing tasks including 2D-2D image registration, 2D image contrast enhancement, and independent treatment site confirmation. The X-ray images for 180 patients of six disease sites (the brain, head-neck, breast, lung, abdomen, and pelvis) were included in this study with 30 patients each site and two images of orthogonal views each patient. A hierarchical multiclass recognition model was developed to recognize general site first and then specific site. Each node of the hierarchical model recognized the images using a feature extraction step based on principal component analysis followed by a binary classification step based on support vector machine. Given two images in known orthogonal views, the site recognition model achieved a 99% average F1 score across the six sites. If the views were unknown in the images, the average F1 score was 97%. If only one image was taken either with or without view information, the average F1 score was 94%. The accuracy of the site-specific view recognition models was 100%.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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↗

Adipocyte induced arterial calcification is prevented with sodium thiosulfate

Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes, and adipocytes exposed to elevated phosphorus can induce calcification of VSMC in a paracrine manner. Sodium thiosulfate inhibited this calcification and decreased the secretin of leptin and VEGF from adipocytes. These results suggest that adipocyte exposure to elevated phosphorus may be a pathogenic factor in calcification observed in the skin in calciphylaxis and other diseases.

60 APPLIED LIFE SCIENCES↗

Tracing the dynamic expression of the Nfκb2 gene during inflammatory processes by in vivo bioluminescence imaging in transgenic mice

Highlights: • Construct a mouse transgenic model line which could trace the p100/p50 expression by luciferase in vivo. • Nfκb2 could express in all mouse tissues and the luciferase expression could represent Nfκb2 expression in most tissues. • Lps induced inflammation could increase luciferase expression in certain stage. • In the IBD model, the fluorescence expression in mouse abdomen was coincide with the intestine after DSSfeed. Nfκb2(p52/p100) plays essential roles in many chronic inflammatory diseases. Tracing the dynamic expression of Nfκb2 during different biological processes in vivo can provide valuable clues to understand the biological functions of this gene and develop anti-inflammatory drugs. In this study, B6-Tg(Nfκb2-luc){sup Mlit} transgenic mouse line, a mouse model in which the expression of firefly luciferase gene is under the control of a 14.6-kb mouse Nfκb2 promoter, was generated to monitor the expression of p52/p100 in vivo. Bioluminescence imaging was used for tracking the luciferase signal in living mice in a variety of inflammatory processes, including LPS-induced sepsis and inflammatory bowel disease (IBD). The data of in vivo bioluminescence imaging in this mouse model showed that luciferase activity coincided with the endogenous p52/p100 expression. Moreover, dexamethasone or aspirin, two routine anti-inflammatory drugs, could decrease the high-level expression of luciferase induced by LPS. Overall, our results suggest that the B6-Tg(Nfκb2-luc){sup Mlit} mice represent a valuable reporter mouse model not only to monitor the expression of p52/p100 in physiological or pathological processes but also to evaluate the effects of various anti-inflammatory drug treatments in vivo.

60 APPLIED LIFE SCIENCES↗

Adaptations for gas exchange enabled the elongation of lepidopteran proboscises

The extensive biodiversification of butterflies and moths (Lepidoptera) is partly attributed to their unique mouthparts (proboscis [Pr]) that can span in length from less than 1 mm to over 280mm in Darwin's sphinx moths. Lepi-doptera, similar to other insects, are believed to inhale and exhale respiratory gases only through valve-like spi-racles on their thorax and abdomen, making gas exchange through the narrow tracheae (Tr) challenging for the elongated Pr. How Lepidoptera overcome distance effects for gas transport to the Pr is an open question that is important to understanding how the Pr elongated over evolutionary time. Here, we show with scanning electron microscopy and X-ray imaging that distance effects on gas exchange are overcome by previously unreported micropores on the Pr surface and by superhydrophobic Tr that prevent water loss and entry. We find that the density of micropores decreases monotonically along the Pr length with the maxima proportional to the Pr length and that micropore diameters produce a Knudsen number at the boundary between the slip and transition flow regimes. By numerical estimation, we further show that the respiratory gas exchange for the Pr predominantly occurs via diffusion through the micropores. In conclusion, these adaptations are key innovations vital to Pr elongation, which likely facilitated lepidopteran biodiversification and the radiation of angiosperms by coevolutionary processes.

59 BASIC BIOLOGICAL SCIENCES↗

Cloning and expressing a highly functional and substrate specific farnesoic acid o-methyltransferase from the Asian citrus psyllid ( Diaphorina citri Kuwayama)

The Asian citrus psyllid, Diaphorina citri , transmits a phloem-limited bacterium, Candidatus ‘Liberibacter’ asiaticus that causes citrus greening disease. Because juvenile hormone (JH) plays an important role in adult and nymphal development, we studied the final steps in JH biosynthesis in D. citri . A putative JH acid methyltransferase ortholog gene ( jmt D) and its cognate cDNA were identified by searching D. citri genome database. Expression analysis shows expression in all life stages. In adults, it is expressed in the head-thorax, (containing the corpora allata), and the abdomen (containing ovaries and male accessory glands). A 3D protein model identified the catalytic groove with catalytically active amino acids and the S-adenosyl methionine (SAM)-binding loop. The cDNA was expressed in Escherichia coli cells and the purified enzyme showed high preference for farnesoic acid (FA) and homoFA ( k cat of 0.752 × 10 –3 and 0.217 × 10 –3 s –1 , respectively) as compared to JH acid I (JHA I) ( cis/trans/cis ; 2 Z , 6 E , 10 cis ), JHA III (2 E , 6 E , 10cis ), and JHA I ( trans / cis / cis ; 2 E , 2 Z , 10 cis ) ( k cat of 0.081 × 10 –3 , 0.013 × 10 –3 , and 0.003 × 10 –3 s –1 , respectively). This suggests that this ortholog is a Dc FA-o-methyl transferase gene ( fmt D), not a jmt D, and that JH biosynthesis in D. citri proceeds from FA to JH III through methyl farnesoate (MF). Dc FA-o-MT does not require Ca 2+ , Mg 2+ or Zn 2+ , however, Zn 2+ (1 mM) completely inhibits the enzyme probably by binding H115 at the active groove. This represents the first purified FA-o-MT from Hemiptera with preferred biological activity for FA and not JHA.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Bioluminescence Tomography–Guided Radiation Therapy for Preclinical Research

Purpose: In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm. Methods and Materials: The BLT system was designed to dock with the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary charge-coupled device (CCD) camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were used as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate BLT localization capability for various source geometries. Results: Online BLT was able to recover the CoM of the embedded light source with an average accuracy of 1 mm compared to that with CBCT localization. Differences between BLT- and CBCT-guided irradiation shown on the films were consistent with the source localization revealed in the BLT and CBCT images. In vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors. Conclusions: The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, nonpalpable, or orthotopic tumor models.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Purpose: To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition. Methods and Materials: Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components, namely, bone, red marrow (RM), and yellow marrow (YM). DECT-derived marrow fat fraction was validated using histology of lumbar vertebrae obtained from cadavers. The fractions of RM (RMF = RM/total marrow) and YMF were calculated in each skeletal region to assess the correlation of marrow composition with sites and ages. Treatment planning was simulated to target irradiation differentially at a higher dose (18 Gy) to either RM or YM and a lower dose (12 Gy) to the rest of the skeleton. Results: A significant correlation between fat fractions obtained from DECT and cadaver histology samples was observed (r=0.861, P<.0001, Pearson). The RMF decreased in the head, neck, and chest was significantly inversely correlated with age but did not show any significant age-related changes in the abdomen and pelvis regions. Conformity of radiation to targets (RM, YM) was significantly dependent on skeletal sites. The radiation exposure was significantly reduced (P<.05, t test) to organs at risk (OARs) in RM and YM irradiation compared with standard total marrow irradiation (TMI). Conclusions: Whole-body DECT offers a new imaging technique to visualize and measure skeletal-wide marrow composition. The DECT-based treatment planning offers volumetric and site-specific precise radiation dosimetry of RM and YM, which varies with aging. Our proposed method could be used as a functional compartment of TMI for further targeted radiation to specific bone marrow environment, dose escalation, reduction of doses to OARs, or a combination of these factors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Rebamipide ameliorates radiation-induced intestinal injury in a mouse model

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13 Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. - Highlights: • The first study on the therapeutic effects of rebamipide in radiation injury. • Irradiation destructed microscopic structures and intestinal barrier. • Rebamipide recovered intestinal barrier function and tight junction components. • Rebamipide reduced the levels of pro-inflammatory cytokines and MMP 9. • Intestinal cell proliferation and β-catenin expression increased by rebamipide.

60 APPLIED LIFE SCIENCES↗

Wearable radio-frequency sensing of respiratory rate, respiratory volume, and heart rate

Abstract Many health diagnostic systems demand noninvasive sensing of respiratory rate, respiratory volume, and heart rate with high user comfort. Previous methods often require multiple sensors, including skin-touch electrodes, tension belts, or nearby off-the-body readers, and hence are uncomfortable or inconvenient. This paper presents an over-clothing wearable radio-frequency sensor study, conducted on 20 healthy participants (14 females) performing voluntary breathing exercises in various postures. Two prototype sensors were placed on the participants, one close to the heart and the other below the xiphoid process to couple to the motion from heart, lungs and diaphragm, by the near-field coherent sensing principle. We can achieve a satisfactory correlation of our sensor with the reference devices for the three vital signs: heart rate ( r = 0.95), respiratory rate ( r = 0.93) and respiratory volume ( r = 0.84). We also detected voluntary breath-hold periods with an accuracy of 96%. Further, the participants performed a breathing exercise by contracting abdomen inwards while holding breath, leading to paradoxical outward thorax motion under the isovolumetric condition, which was detected with an accuracy of 83%.

60 APPLIED LIFE SCIENCES↗

Combined computed tomography and position-resolved X-ray diffraction of an intact Roman-era Egyptian portrait mummy

Hawara Portrait Mummy 4, a Roman-era Egyptian portrait mummy, was studied with computed tomography (CT) and with CT-guided synchrotron X-ray diffraction mapping. These are the first X-ray diffraction results obtained non-invasively from objects within a mummy. The CT data showed human remains of a 5-year-old child, consistent with the female (but not the age) depicted on the portrait. Physical trauma was not evident in the skeleton. Diffraction at two different mummy-to-detector separations allowed volumetric mapping of features including wires and inclusions within the wrappings and the skull and femora. Additionally, the largest uncertainty in origin determination was approximately 1.5 mm along the X-ray beam direction, and diffraction- and CT-determined positions matched. Diffraction showed that the wires were a modern dual-phase steel and showed that the 7 × 5 × 3 mm inclusion ventral of the abdomen was calcite. Tracing the 00.2 and 00.4 carbonated apatite (bone's crystalline phase) reflections back to their origins produced cross-sectional maps of the skull and of femora; these maps agreed with transverse CT slices within approximately 1 mm. Coupling CT and position-resolved X-ray diffraction, therefore, offers considerable promise for non-invasive studies of mummies.

60 APPLIED LIFE SCIENCES↗

PpIX‐enabled fluorescence‐based detection and photodynamic priming of platinum‐resistant ovarian cancer cells under fluid shear stress

Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

59 BASIC BIOLOGICAL SCIENCES↗

Application of the optically stimulated luminescence (OSL) technique for mouse dosimetry in micro-CT imaging

Purpose: Micro-CT is considered to be a powerful tool to investigate various models of disease on anesthetized animals. In longitudinal studies, the radiation dose delivered by the micro-CT to the same animal is a major concern as it could potentially induce spurious effects in experimental results. Optically stimulated luminescence dosimeters (OSLDs) are a relatively new kind of detector used in radiation dosimetry for medical applications. The aim of this work was to assess the dose delivered by the CT component of a micro-SPECT (single-photon emission computed tomography)/CT camera during a typical whole-body mouse study, using commercially available OSLDs based on Al{sub 2}O{sub 3}:C crystals.Methods: CTDI (computed tomography dose index) was measured in micro-CT with a properly calibrated pencil ionization chamber using a rat-like phantom (60 mm in diameter) and a mouse-like phantom (30 mm in diameter). OSLDs were checked for reproducibility and linearity in the range of doses delivered by the micro-CT. Dose measurements obtained with OSLDs were compared to those of the ionization chamber to correct for the radiation quality dependence of OSLDs in the low-kV range. Doses to tissue were then investigated in phantoms and cadavers. A 30 mm diameter phantom, specifically designed to insert OSLDs, was used to assess radiation dose over a typical whole-body mouse imaging study. Eighteen healthy female BALB/c mice weighing 27.1 ± 0.8 g (1 SD) were euthanized for small animal measurements. OLSDs were placed externally or implanted internally in nine different locations by an experienced animal technician. Five commonly used micro-CT protocols were investigated.Results: CTDI measurements were between 78.0 ± 2.1 and 110.7 ± 3.0 mGy for the rat-like phantom and between 169.3 ± 4.6 and 203.6 ± 5.5 mGy for the mouse-like phantom. On average, the displayed CTDI at the operator console was underestimated by 1.19 for the rat-like phantom and 2.36 for the mouse-like phantom. OSLDs exhibited a reproducibility of 2.4% and good linearity was found between 60 and 450 mGy. The energy scaling factor was calculated to be between 1.80 ± 0.16 and 1.86 ± 0.16, depending on protocol used. In phantoms, mean doses to tissue over a whole-body CT examination were ranging from 186.4 ± 7.6 to 234.9 ± 7.1 mGy. In mice, mean doses to tissue in the mouse trunk (thorax, abdomen, pelvis, and flanks) were between 213.0 ± 17.0 and 251.2 ± 13.4 mGy. Skin doses (3 OSLDs) were much higher with average doses between 350.6 ± 25.3 and 432.5 ± 34.1 mGy. The dose delivered during a topogram was found to be below 10 mGy. Use of the multimouse bed of the system gave a significantly 20%–40% lower dose per animal (p < 0.05).Conclusions: Absorbed doses in micro-CT were found to be relatively high. In micro-SPECT/CT imaging, the micro-CT unit is mainly used to produce a localization frame. As a result, users should pay attention to adjustable CT parameters so as to minimize the radiation dose and avoid any adverse radiation effects which may interfere with biological parameters studied.

61 RADIATION PROTECTION AND DOSIMETRY↗

Sample size requirements for estimating effective dose from computed tomography using solid-state metal-oxide-semiconductor field-effect transistor dosimetry

Purpose: Effective dose (ED) is a widely used metric for comparing ionizing radiation burden between different imaging modalities, scanners, and scan protocols. In computed tomography (CT), ED can be estimated by performing scans on an anthropomorphic phantom in which metal-oxide-semiconductor field-effect transistor (MOSFET) solid-state dosimeters have been placed to enable organ dose measurements. Here a statistical framework is established to determine the sample size (number of scans) needed for estimating ED to a desired precision and confidence, for a particular scanner and scan protocol, subject to practical limitations. Methods: The statistical scheme involves solving equations which minimize the sample size required for estimating ED to desired precision and confidence. It is subject to a constrained variation of the estimated ED and solved using the Lagrange multiplier method. The scheme incorporates measurement variation introduced both by MOSFET calibration, and by variation in MOSFET readings between repeated CT scans. Sample size requirements are illustrated on cardiac, chest, and abdomen–pelvis CT scans performed on a 320-row scanner and chest CT performed on a 16-row scanner. Results: Sample sizes for estimating ED vary considerably between scanners and protocols. Sample size increases as the required precision or confidence is higher and also as the anticipated ED is lower. For example, for a helical chest protocol, for 95% confidence and 5% precision for the ED, 30 measurements are required on the 320-row scanner and 11 on the 16-row scanner when the anticipated ED is 4 mSv; these sample sizes are 5 and 2, respectively, when the anticipated ED is 10 mSv. Conclusions: Applying the suggested scheme, it was found that even at modest sample sizes, it is feasible to estimate ED with high precision and a high degree of confidence. As CT technology develops enabling ED to be lowered, more MOSFET measurements are needed to estimate ED with the same precision and confidence.

61 RADIATION PROTECTION AND DOSIMETRY↗