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TU-EF-207-00: Advances in Breast Imaging

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis mode due to lower photon fluence per projection. This may require fast-frame acquisition and symmetric or asymmetric pixel binning in some systems. Recent studies investigated the performance of increased conversion layer thickness for contrast-enhanced imaging of the breast in dual-energy acquisition mode. In other direct conversion detectors operating in the avalanche mode, sensitivities close to the single photon response are also explored for mammography and breast tomosynthesis. The potential advantages and challenges of this approach are described. Dedicated breast CT brings x-ray imaging of the breast to true tomographic 3D imaging. It can eliminate the tissue superposition problem and does not require physical compression of the breast. Using cone beam geometry and a flat-panel detector, several hundred projections are acquired and reconstructed to near isotropic voxels. Multiplanar reconstruction facilitates viewing the breast volume in any desired orientation. Ongoing clinical studies, the current state-of-the art, and research to advance the technology are described. Learning Objectives: To understand the ongoing developments in x-ray imaging of the breast To understand the approaches and applications of spectral mammography To understand the potential advantages of distributed x-ray source arrays for digital breast tomosynthesis To understand the ongoing developments in detector technology for digital mammography and breast tomosynthesis To understand the current state-of-the-art for dedicated cone-beam breast CT and research to advance the technology. Research collaboration with Koning Corporation.

60 APPLIED LIFE SCIENCES↗

WE-EF-210-07: Development of a Minimally Invasive Photo Acoustic Imaging System for Early Prostate Cancer Detection

Purpose: The objective of this work is to design, implement and characterize a catheter-based ultrasound/photoacoustic imaging probe for early-diagnosis of prostate cancer and to aid in image-guided radiation therapy. Methods: The need to image across 6–10cm of tissue to image the whole prostate gland limits the resolution achievable with a transrectal ultrasound approach. In contrast, the urethra bisects the prostate gland, providing a minimally invasive pathway for deploying a high resolution ultrasound transducer. Utilizing a high-frequency (20MHz) ultrasound/photoacoustic probe, high-resolution structural and molecular imaging of the prostate tissue is possible. A custom 3D printed probe containing a high-frequency single-element ultrasound transducer is utilized. The diameter of the probe is designed to fit inside a Foley catheter and the probe is rotated around the central axis to achieve a circular B-scan. A custom ultrasound amplifier and receiver was set up to trigger the ultrasound pulse transmission and record the reflected signal. The reconstructed images were compared to images generated by traditional 5 MHz ultrasound transducers. Results: The preliminary results using the high-frequency ultrasound probe show that it is possible to resolve finely detailed information in a prostate tissue phantom that was not achievable with previous low-frequency ultrasound systems. Preliminary ultrasound imaging was performed on tissue mimicking phantom and sensitivity and signal-to-noise ratio of the catheter was measured. Conclusion: In order to achieve non-invasive, high-resolution, structural and molecular imaging for early-diagnosis and image-guided radiation therapy of the prostate tissue, a transurethral catheter was designed. Structural/molecular imaging using ultrasound/photoacoustic of the prostate tissue will allow for localization of hyper vascularized areas for early-stage prostate cancer diagnosis.

60 APPLIED LIFE SCIENCES↗

Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization

Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at MGD of 2.5 mGy), an increased CNR (by ∼10) for microcalcifications was observed using the Dexela 2923 MAM CMOS APS x-ray imager at a lower MGD (2.0 mGy). Conclusions: The Dexela 2923 MAM CMOS APS x-ray imager is capable to achieve a high imaging performance at spatial frequencies up to 6.7 lp/mm. Microcalcifications of 165 μm are distinguishable based on reported data and their modeling results due to the small pixel pitch of 75 μm. At the same time, potential dose reduction is expected using the studied CMOS APS x-ray imager.

60 APPLIED LIFE SCIENCES↗

Can radiomics features be reproducibly measured from CBCT images for patients with non-small cell lung cancer?

Purpose: Increasing evidence suggests radiomics features extracted from computed tomography (CT) images may be useful in prognostic models for patients with nonsmall cell lung cancer (NSCLC). This study was designed to determine whether such features can be reproducibly obtained from cone-beam CT (CBCT) images taken using medical Linac onboard-imaging systems in order to track them through treatment. Methods: Test-retest CBCT images of ten patients previously enrolled in a clinical trial were retrospectively obtained and used to determine the concordance correlation coefficient (CCC) for 68 different texture features. The volume dependence of each feature was also measured using the Spearman rank correlation coefficient. Features with a high reproducibility (CCC > 0.9) that were not due to volume dependence in the patient test-retest set were further examined for their sensitivity to differences in imaging protocol, level of scatter, and amount of motion by using two phantoms. The first phantom was a texture phantom composed of rectangular cartridges to represent different textures. Features were measured from two cartridges, shredded rubber and dense cork, in this study. The texture phantom was scanned with 19 different CBCT imagers to establish the features’ interscanner variability. The effect of scatter on these features was studied by surrounding the same texture phantom with scattering material (rice and solid water). The effect of respiratory motion on these features was studied using a dynamic-motion thoracic phantom and a specially designed tumor texture insert of the shredded rubber material. The differences between scans acquired with different Linacs and protocols, varying amounts of scatter, and with different levels of motion were compared to the mean intrapatient difference from the test-retest image set. Results: Of the original 68 features, 37 had a CCC >0.9 that was not due to volume dependence. When the Linac manufacturer and imaging protocol were kept consistent, 4–13 of these 37 features passed our criteria for reproducibility more than 50% of the time, depending on the manufacturer-protocol combination. Almost all of the features changed substantially when scatter material was added around the phantom. For the dense cork, 23 features passed in the thoracic scans and 11 features passed in the head scans when the differences between one and two layers of scatter were compared. Using the same test for the shredded rubber, five features passed the thoracic scans and eight features passed the head scans. Motion substantially impacted the reproducibility of the features. With 4 mm of motion, 12 features from the entire volume and 14 features from the center slice measurements were reproducible. With 6–8 mm of motion, three features (Laplacian of Gaussian filtered kurtosis, gray-level nonuniformity, and entropy), from the entire volume and seven features (coarseness, high gray-level run emphasis, gray-level nonuniformity, sum-average, information measure correlation, scaled mean, and entropy) from the center-slice measurements were considered reproducible. Conclusions: Some radiomics features are robust to the noise and poor image quality of CBCT images when the imaging protocol is consistent, relative changes in the features are used, and patients are limited to those with less than 1 cm of motion.

60 APPLIED LIFE SCIENCES↗

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R{sup 2} = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.

61 RADIATION PROTECTION AND DOSIMETRY↗

Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. Results: The mean TRE (and standard deviation) was 0.6 ± 0.7 mm (smaller than the voxel dimension) for DIR between pre contrast and postcontrast end-inspiratory CT image data sets. No singularities were observed in the displacement vector fields. The mean HU enhancement (and standard deviation) was 37.3 ± 10.5 HU for normal lung subjects and 30.7 ± 13.5 HU for diseased lung subjects. Spatial heterogeneity of regional perfusion was found to be higher for diseased lung subjects than for normal lung subjects, i.e., a mean coefficient of variation of 2.06 vs 1.59 (p = 0.07). The average gravitationally directed gradient was strong and significant (R{sup 2} = 0.99, p < 0.01) for normal lung dogs, whereas it was moderate and nonsignificant (R{sup 2} = 0.61, p = 0.12) for diseased lung dogs. Conclusions: This canine study demonstrated the accuracy of DIR with subvoxel TREs on average, higher spatial heterogeneity of regional perfusion for diseased lung subjects than for normal lung subjects, and a strong gravitationally directed gradient for normal lung subjects, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. Further studies such as comparison with other perfusion imaging modalities will be necessary to validate the physiological significance.

60 APPLIED LIFE SCIENCES↗

SU-C-209-07: Phantoms for Digital Breast Tomosynthesis Imaging System Evaluation

Purpose: Digital Breast Tomosynthesis (DBT) is gaining importance in breast imaging. There is a need for phantoms that can be used for image evaluation and comparison. Existing commercially available phantoms for DBT are expensive and may lack clinically relevant test objects. The purpose of this study is to develop phantoms for DBT evaluation. Methods Four phantoms have been designed and constructed to assess the image quality (IQ) of two DBT systems. The first contains a spiral of 0.3 mm SiC beads in gelatin to measure the tomographic slice thickness profile and uniformity of coverage in a series of tomographic planes. The second contains simulated tumors inclined with respect to the phantom base to assess tomographic image quality. The third has a tilted array of discs with varying contrast and diameter. This phantom was imaged alone and in a stack of TE slabs giving 2 to 10 cm thickness. The fourth has a dual wedge of glandular and adipose simulating materials. One wedge contains discs with varying diameter and thickness; the other supports a mass with six simulated spicules of varying size and a cluster of simulated calcifications. The simulated glandular tissue material varies between 35 and 100% of the total thickness (5.5 cm). Results: All phantoms were scanned successfully. The best IQ comparison was achieved with the dual wedge phantom as demonstrated by the spiculated mass and calcifications. Images were evaluated by two radiologists and one physicist. The projection images and corresponding set of tomographic planes were comparable and the synthesized projection images were inferior to the projection images for both systems. Conclusion: Four phantoms were designed, constructed and imaged on two DBT systems. They successfully demonstrated performance differences between two systems, and between true and synthesized projection images. Future work will incorporate these designs into a single phantom.

60 APPLIED LIFE SCIENCES↗

SU-F-I-09: Improvement of Image Registration Using Total-Variation Based Noise Reduction Algorithms for Low-Dose CBCT

Purpose: To study the effect of total-variation based noise reduction algorithms to improve the image registration of low-dose CBCT for patient positioning in radiation therapy. Methods: In low-dose CBCT, the reconstructed image is degraded by excessive quantum noise. In this study, we developed a total-variation based noise reduction algorithm and studied the effect of the algorithm on noise reduction and image registration accuracy. To study the effect of noise reduction, we have calculated the peak signal-to-noise ratio (PSNR). To study the improvement of image registration, we performed image registration between volumetric CT and MV- CBCT images of different head-and-neck patients and calculated the mutual information (MI) and Pearson correlation coefficient (PCC) as a similarity metric. The PSNR, MI and PCC were calculated for both the noisy and noise-reduced CBCT images. Results: The algorithms were shown to be effective in reducing the noise level and improving the MI and PCC for the low-dose CBCT images tested. For the different head-and-neck patients, a maximum improvement of PSNR of 10 dB with respect to the noisy image was calculated. The improvement of MI and PCC was 9% and 2% respectively. Conclusion: Total-variation based noise reduction algorithm was studied to improve the image registration between CT and low-dose CBCT. The algorithm had shown promising results in reducing the noise from low-dose CBCT images and improving the similarity metric in terms of MI and PCC.

60 APPLIED LIFE SCIENCES↗

SU-G-BRA-09: Estimation of Motion Tracking Uncertainty for Real-Time Adaptive Imaging

Purpose: kV fluoroscopic imaging combined with MV treatment beam imaging has been investigated for intrafractional motion monitoring and correction. It is, however, subject to additional kV imaging dose to normal tissue. To balance tracking accuracy and imaging dose, we previously proposed an adaptive imaging strategy to dynamically decide future imaging type and moments based on motion tracking uncertainty. kV imaging may be used continuously for maximal accuracy or only when the position uncertainty (probability of out of threshold) is high if a preset imaging dose limit is considered. In this work, we propose more accurate methods to estimate tracking uncertainty through analyzing acquired data in real-time. Methods: We simulated motion tracking process based on a previously developed imaging framework (MV + initial seconds of kV imaging) using real-time breathing data from 42 patients. Motion tracking errors for each time point were collected together with the time point’s corresponding features, such as tumor motion speed and 2D tracking error of previous time points, etc. We tested three methods for error uncertainty estimation based on the features: conditional probability distribution, logistic regression modeling, and support vector machine (SVM) classification to detect errors exceeding a threshold. Results: For conditional probability distribution, polynomial regressions on three features (previous tracking error, prediction quality, and cosine of the angle between the trajectory and the treatment beam) showed strong correlation with the variation (uncertainty) of the mean 3D tracking error and its standard deviation: R-square = 0.94 and 0.90, respectively. The logistic regression and SVM classification successfully identified about 95% of tracking errors exceeding 2.5mm threshold. Conclusion: The proposed methods can reliably estimate the motion tracking uncertainty in real-time, which can be used to guide adaptive additional imaging to confirm the tumor is within the margin or initialize motion compensation if it is out of the margin.

60 APPLIED LIFE SCIENCES↗

SU-G-JeP3-14: Positioning and Dosimetric Uncertainties in Image-Guided Radiation Therapy with Respiratory Gating

Purpose: To investigate quantitatively positioning and dosimetric uncertainties due to 4D-CT intra-phase motion in the internal-target-volume (ITV) associated with radiation therapy using respiratory-gating for patients setup with image-guidance-radiation-therapy (IGRT) using free-breathing or average-phase CT-images. Methods: A lung phantom with an embedded tissue-equivalent target is imaged with CT while it is stationary and moving. Four-sets of structures are outlined: (a) the actual target on CT-images of the stationary-target, (b) ITV on CT-images for the free-moving phantom, (c) ITV’s from the ten different phases (10–100%) and (d) ITV on the CT-images generated from combining 3 phases: 40%–50%–60%. The variations in volume, length and center-position of the ITV’s and their effects on dosimetry during dose delivery for patients setup with image-guidance are investigated. Results: Intra-phase motion due to breathing affects the volume, center position and length of the ITVs from different respiratory-phases. The ITV’s vary by about 10% from one phase to another. The largest ITV is measured on the free breathing CT images and the smallest is on the stationary CT-images. The ITV lengths vary by about 4mm where it may shrink or elongated depending on the motion-phase. The center position of the ITV varies between the different motion-phases which shifts upto 10mm from the stationary-position which is nearly equal to motion-amplitude. This causes systematic shifts during dose delivery with beam gating using certain phases (40%–50%–60%) for patients setup with IGRT using free-breathing or average-phase CT-images. The dose coverage of the ITV depends on the margins used for treatment-planning-volume where margins larger than the motion-amplitudes are needed to ensure dose coverage of the ITV. Conclusion: Volume, length, and center position of the ITV’s change between the different motion phases. Large systematic shifts are induced by respiratory-gating with ITVs on certain phases when patients are setup with IGRT using free-breathing or average-phase CT-images.

60 APPLIED LIFE SCIENCES↗

TU-FG-209-11: Validation of a Channelized Hotelling Observer to Optimize Chest Radiography Image Processing for Nodule Detection: A Human Observer Study

Purpose: To validate the use of a Channelized Hotelling Observer (CHO) model for guiding image processing parameter selection and enable improved nodule detection in digital chest radiography. Methods: In a previous study, an anthropomorphic chest phantom was imaged with and without PMMA simulated nodules using a GE Discovery XR656 digital radiography system. The impact of image processing parameters was then explored using a CHO with 10 Laguerre-Gauss channels. In this work, we validate the CHO’s trend in nodule detectability as a function of two processing parameters by conducting a signal-known-exactly, multi-reader-multi-case (MRMC) ROC observer study. Five naive readers scored confidence of nodule visualization in 384 images with 50% nodule prevalence. The image backgrounds were regions-of-interest extracted from 6 normal patient scans, and the digitally inserted simulated nodules were obtained from phantom data in previous work. Each patient image was processed with both a near-optimal and a worst-case parameter combination, as determined by the CHO for nodule detection. The same 192 ROIs were used for each image processing method, with 32 randomly selected lung ROIs per patient image. Finally, the MRMC data was analyzed using the freely available iMRMC software of Gallas et al. Results: The image processing parameters which were optimized for the CHO led to a statistically significant improvement (p=0.049) in human observer AUC from 0.78 to 0.86, relative to the image processing implementation which produced the lowest CHO performance. Conclusion: Differences in user-selectable image processing methods on a commercially available digital radiography system were shown to have a marked impact on performance of human observers in the task of lung nodule detection. Further, the effect of processing on humans was similar to the effect on CHO performance. Future work will expand this study to include a wider range of detection/classification tasks and more observers, including experienced chest radiologists.

60 APPLIED LIFE SCIENCES↗

TH-AB-209-01: Making Benchtop X-Ray Fluorescence Computed Tomography (XFCT) Practical for in Vivo Imaging by Integration of a Dedicated High-Performance X-Ray Source in Conjunction with Micro-CT Functionality

Purpose: To make benchtop x-ray fluorescence computed tomography (XFCT) practical for routine preclinical imaging tasks with gold nanoparticles (GNPs) by deploying, integrating, and characterizing a dedicated high-performance x-ray source and addition of simultaneous micro-CT functionality. Methods: Considerable research effort is currently under way to develop a polychromatic benchtop cone-beam XFCT system capable of imaging GNPs by stimulation and detection of gold K-shell x-ray fluorescence (XRF) photons. Recently, an ad hoc high-power x-ray source was incorporated and used to image the biodistribution of GNPs within a mouse, postmortem. In the current work, a dedicated x-ray source system featuring a liquid-cooled tungsten-target x-ray tube (max 160 kVp, ∼3 kW power) was deployed. The source was operated at 125 kVp, 24 mA. The tube’s compact dimensions allowed greater flexibility for optimizing both the irradiation and detection geometries. Incident x-rays were shaped by a conical collimator and filtered by 2 mm of tin. A compact “OEM” cadmium-telluride x-ray detector was implemented for detecting XRF/scatter spectra. Additionally, a flat panel detector was installed to allow simultaneous transmission CT imaging. The performance of the system was characterized by determining the detection limit (10-second acquisition time) for inserts filled with water/GNPs at various concentrations (0 and 0.010–1.0 wt%) and embedded in a small-animal-sized phantom. The phantom was loaded with 0.5, 0.3, and 0.1 wt% inserts and imaged using XFCT and simultaneous micro-CT. Results: An unprecedented detection limit of 0.030 wt% was experimentally demonstrated, with a 33% reduction in acquisition time. The reconstructed XFCT image accurately localized the imaging inserts. Micro-CT imaging did not provide enough contrast to distinguish imaging inserts from the phantom under the current conditions. Conclusion: The system is immediately capable of in vivo preclinical XFCT imaging with GNPs. Micro-CT imaging will require optimization of irradiation parameters to improve contrast. Supported by NIH/NCI grant R01CA155446; This investigation was supported by NIH/NCI grant R01CA155446.

60 APPLIED LIFE SCIENCES↗

TH-AB-209-10: Breast Cancer Identification Through X-Ray Coherent Scatter Spectral Imaging

Purpose: We have previously described the development and testing of a coherent-scatter spectral imaging system for identification of cancer. Our prior evaluations were performed using either tissue surrogate phantoms or formalin-fixed tissue obtained from pathology. Here we present the first results from a scatter imaging study using fresh breast tumor tissues obtained through surgical excision. Methods: A coherent-scatter imaging system was built using a clinical X-ray tube, photon counting detectors, and custom-designed coded-apertures. System performance was characterized using calibration phantoms of biological materials. Fresh breast tumors were obtained from patients undergoing mastectomy and lumpectomy surgeries for breast cancer. Each specimen was vacuum-sealed, scanned using the scatter imaging system, and then sent to pathology for histological workup. Scatter images were generated separately for each tissue specimen and analyzed to identify voxels containing malignant tissue. The images were compared against histological analysis (H&E + pathologist identification of tumors) to assess the match between scatter-based and histological diagnosis. Results: In all specimens scanned, the scatter images showed the location of cancerous regions within the specimen. The detection and classification was performed through automated spectral matching without the need for manual intervention. The scatter spectra corresponding to cancer tissue were found to be in agreement with those reported in literature. Inter-patient variability was found to be within limits reported in literature. The scatter images showed agreement with pathologist-identified regions of cancer. Spatial resolution for this configuration of the scanner was determined to be 2–3 mm, and the total scan time for each specimen was under 15 minutes. Conclusion: This work demonstrates the utility of coherent scatter imaging in identifying cancer based on the scatter properties of the tissue. It presents the first results from coherent scatter imaging of fresh (unfixed) breast tissue using our coded-aperture scatter imaging approach for cancer identification.

60 APPLIED LIFE SCIENCES↗

Quantitative Imaging with a Mobile Phone Microscope

Use of optical imaging for medical and scientific applications requires accurate quantification of features such as object size, color, and brightness. High pixel density cameras available on modern mobile phones have made photography simple and convenient for consumer applications; however, the camera hardware and software that enables this simplicity can present a barrier to accurate quantification of image data. This issue is exacerbated by automated settings, proprietary image processing algorithms, rapid phone evolution, and the diversity of manufacturers. If mobile phone cameras are to live up to their potential to increase access to healthcare in low-resource settings, limitations of mobile phone–based imaging must be fully understood and addressed with procedures that minimize their effects on image quantification. Here we focus on microscopic optical imaging using a custom mobile phone microscope that is compatible with phones from multiple manufacturers. We demonstrate that quantitative microscopy with micron-scale spatial resolution can be carried out with multiple phones and that image linearity, distortion, and color can be corrected as needed. Using all versions of the iPhone and a selection of Android phones released between 2007 and 2012, we show that phones with greater than 5 MP are capable of nearly diffraction-limited resolution over a broad range of magnifications, including those relevant for single cell imaging. We find that automatic focus, exposure, and color gain standard on mobile phones can degrade image resolution and reduce accuracy of color capture if uncorrected, and we devise procedures to avoid these barriers to quantitative imaging. By accommodating the differences between mobile phone cameras and the scientific cameras, mobile phone microscopes can be reliably used to increase access to quantitative imaging for a variety of medical and scientific applications.

59 BASIC BIOLOGICAL SCIENCES↗

RockFlow: Fast Generation of Synthetic Source Rock Images Using Generative Flow Models

Image-based evaluation methods are a valuable tool for source rock characterization. The time and resources needed to obtain images has spurred development of machine-learning generative models to create synthetic images of pore structure and rock fabric from limited image data. While generative models have shown success, existing methods for generating 3D volumes from 2D training images are restricted to binary images and grayscale volume generation requires 3D training data. Shale characterization relies on 2D imaging techniques such as scanning electron microscopy (SEM), and grayscale values carry important information about porosity, kerogen content, and mineral composition of the shale. Here, we introduce RockFlow, a method based on generative flow models that creates grayscale volumes from 2D training data. We apply RockFlow to baseline binary micro-CT image volumes and compare performance to a previously proposed model. We also show the extension of our model to 2D grayscale data by generating grayscale image volumes from 2D SEM and dual modality nanoscale shale images. The results show that our method underestimates the porosity and surface area on the binary baseline datasets but is able to generate realistic grayscale image volumes for shales. With improved binary data preprocessing, we believe that our model is capable of generating synthetic porous media volumes for a very broad class of rocks from shale to carbonates to sandstone.

58 GEOSCIENCES↗

First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole

We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of ~40 μas, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.

79 ASTRONOMY AND ASTROPHYSICS↗

Operation and Performance of the Mars Exploration Rover Imaging System on the Martian Surface

This slide presentation details the Mars Exploration Rover (MER) imaging system. Over 144,000 images have been gathered from all Mars Missions, with 83.5% of them being gathered by MER. Each Rover has 9 cameras (Navcam, front and rear Hazcam, Pancam, Microscopic Image, Descent Camera, Engineering Camera, Science Camera) and produces 1024 x 1024 (1 Megapixel) images in the same format. All onboard image processing code is implemented in flight software and includes extensive processing capabilities such as autoexposure, flat field correction, image orientation, thumbnail generation, subframing, and image compression. Ground image processing is done at the Jet Propulsion Laboratory's Multimission Image Processing Laboratory using Video Image Communication and Retrieval (VICAR) while stereo processing (left/right pairs) is provided for raw image, radiometric correction; solar energy maps,triangulation (Cartesian 3-spaces) and slope maps.

imaging↗

Dependence of Adaptive Cross-correlation Algorithm Performance on the Extended Scene Image Quality

Recently, we reported an adaptive cross-correlation (ACC) algorithm to estimate with high accuracy the shift as large as several pixels between two extended-scene sub-images captured by a Shack-Hartmann wavefront sensor. It determines the positions of all extended-scene image cells relative to a reference cell in the same frame using an FFT-based iterative image-shifting algorithm. It works with both point-source spot images as well as extended scene images. We have demonstrated previously based on some measured images that the ACC algorithm can determine image shifts with as high an accuracy as 0.01 pixel for shifts as large 3 pixels, and yield similar results for both point source spot images and extended scene images. The shift estimate accuracy of the ACC algorithm depends on illumination level, background, and scene content in addition to the amount of the shift between two image cells. In this paper we investigate how the performance of the ACC algorithm depends on the quality and the frequency content of extended scene images captured by a Shack-Hatmann camera. We also compare the performance of the ACC algorithm with those of several other approaches, and introduce a failsafe criterion for the ACC algorithm-based extended scene Shack-Hatmann sensors.

wave-front sensing and control↗