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SU-E-J-159: Analysis of Total Imaging Uncertainty in Respiratory-Gated Radiotherapy

Purpose: In respiratory-gated radiotherapy, the gating phase during treatment delivery needs to coincide with the corresponding phase determined during the treatment plan. However, because radiotherapy is performed based on the image obtained for the treatment plan, the time delay, motion artifact, volume effect, and resolution in the images are uncertain. Thus, imaging uncertainty is the most basic factor that affects the localization accuracy. Therefore, these uncertainties should be analyzed. This study aims to analyze the total imaging uncertainty in respiratory-gated radiotherapy. Methods: Two factors of imaging uncertainties related to respiratory-gated radiotherapy were analyzed. First, CT image was used to determine the target volume and 4D treatment planning for the Varian Realtime Position Management (RPM) system. Second, an X-ray image was acquired for image-guided radiotherapy (IGRT) for the BrainLAB ExacTrac system. These factors were measured using a respiratory gating phantom. The conditions applied during phantom operation were as follows: respiratory wave form, sine curve; respiratory cycle, 4 s; phantom target motion amplitude, 10, 20, and 29 mm (which is maximum phantom longitudinal motion). The target and cylindrical marker implanted in the phantom coverage of the CT images was measured and compared with the theoretically calculated coverage from the phantom motion. The theoretical position of the cylindrical marker implanted in the phantom was compared with that acquired from the X-ray image. The total imaging uncertainty was analyzed from these two factors. Results: In the CT image, the uncertainty between the target and cylindrical marker’s actual coverage and the coverage of CT images was 1.19 mm and 2.50mm, respectively. In the Xray image, the uncertainty was 0.39 mm. The total imaging uncertainty from the two factors was 1.62mm. Conclusion: The total imaging uncertainty in respiratory-gated radiotherapy was clinically acceptable. However, an internal margin should be added to account for the total imaging uncertainty.

60 APPLIED LIFE SCIENCES↗

TH-A-BRF-11: Image Intensity Non-Uniformities Between MRI Simulation and Diagnostic MRI

Purpose: MRI simulation for MRI-based radiotherapy demands that patients be setup in treatment position, which frequently involves use of alternative radiofrequency (RF) coil configurations to accommodate immobilized patients. However, alternative RF coil geometries may exacerbate image intensity non-uniformities (IINU) beyond those observed in diagnostic MRI, which may challenge image segmentation and registration accuracy as well as confound studies assessing radiotherapy response when MR simulation images are used as baselines for evaluation. The goal of this work was to determine whether differences in IINU exist between MR simulation and diagnostic MR images. Methods: ACR-MRI phantom images were acquired at 3T using a spin-echo sequence (TE/TR:20/500ms, rBW:62.5kHz, TH/skip:5/5mm). MR simulation images were obtained by wrapping two flexible phased-array RF coils around the phantom. Diagnostic MR images were obtained by placing the phantom into a commercial phased-array head coil. Pre-scan normalization was enabled in both cases. Images were transferred offline and corrected for IINU using the MNI N3 algorithm. Coefficients of variation (CV=σ/μ) were calculated for each slice. Wilcoxon matched-pairs and Mann-Whitney tests compared CV values between original and N3 images and between MR simulation and diagnostic MR images. Results: Significant differences in CV were detected between original and N3 images in both MRI simulation and diagnostic MRI groups (p=0.010, p=0.010). In addition, significant differences in CV were detected between original MR simulation and original and N3 diagnostic MR images (p=0.0256, p=0.0016). However, no significant differences in CV were detected between N3 MR simulation images and original or N3 diagnostic MR images, demonstrating the importance of correcting MR simulation images beyond pre-scan normalization prior to use in radiotherapy. Conclusions: Alternative RF coil configurations used in MRI simulation can Result in significant IINU differences compared to diagnostic MR images. The MNI N3 algorithm reduced MR simulation IINU to levels observed in diagnostic MR images. Funding provided by Advancing a Healthier Wisconsin.

60 APPLIED LIFE SCIENCES↗

Using dual-energy x-ray imaging to enhance automated lung tumor tracking during real-time adaptive radiotherapy

Purpose: Real-time, markerless localization of lung tumors with kV imaging is often inhibited by ribs obscuring the tumor and poor soft-tissue contrast. This study investigates the use of dual-energy imaging, which can generate radiographs with reduced bone visibility, to enhance automated lung tumor tracking for real-time adaptive radiotherapy. Methods: kV images of an anthropomorphic breathing chest phantom were experimentally acquired and radiographs of actual lung cancer patients were Monte-Carlo-simulated at three imaging settings: low-energy (70 kVp, 1.5 mAs), high-energy (140 kVp, 2.5 mAs, 1 mm additional tin filtration), and clinical (120 kVp, 0.25 mAs). Regular dual-energy images were calculated by weighted logarithmic subtraction of high- and low-energy images and filter-free dual-energy images were generated from clinical and low-energy radiographs. The weighting factor to calculate the dual-energy images was determined by means of a novel objective score. The usefulness of dual-energy imaging for real-time tracking with an automated template matching algorithm was investigated. Results: Regular dual-energy imaging was able to increase tracking accuracy in left–right images of the anthropomorphic phantom as well as in 7 out of 24 investigated patient cases. Tracking accuracy remained comparable in three cases and decreased in five cases. Filter-free dual-energy imaging was only able to increase accuracy in 2 out of 24 cases. In four cases no change in accuracy was observed and tracking accuracy worsened in nine cases. In 9 out of 24 cases, it was not possible to define a tracking template due to poor soft-tissue contrast regardless of input images. The mean localization errors using clinical, regular dual-energy, and filter-free dual-energy radiographs were 3.85, 3.32, and 5.24 mm, respectively. Tracking success was dependent on tumor position, tumor size, imaging beam angle, and patient size. Conclusions: This study has highlighted the influence of patient anatomy on the success rate of real-time markerless tumor tracking using dual-energy imaging. Additionally, the importance of the spectral separation of the imaging beams used to generate the dual-energy images has been shown.

60 APPLIED LIFE SCIENCES↗

Super-resolution reconstruction in frequency, image, and wavelet domains to reduce through-plane partial voluming in MRI

Purpose: To compare and evaluate the use of super-resolution reconstruction (SRR), in frequency, image, and wavelet domains, to reduce through-plane partial voluming effects in magnetic resonance imaging. Methods: The reconstruction of an isotropic high-resolution image from multiple thick-slice scans has been investigated through techniques in frequency, image, and wavelet domains. Experiments were carried out with thick-slice T2-weighted fast spin echo sequence on the Academic College of Radiology MRI phantom, where the reconstructed images were compared to a reference high-resolution scan using peak signal-to-noise ratio (PSNR), structural similarity image metric (SSIM), mutual information (MI), and the mean absolute error (MAE) of image intensity profiles. The application of super-resolution reconstruction was then examined in retrospective processing of clinical neuroimages of ten pediatric patients with tuberous sclerosis complex (TSC) to reduce through-plane partial voluming for improved 3D delineation and visualization of thin radial bands of white matter abnormalities. Results: Quantitative evaluation results show improvements in all evaluation metrics through super-resolution reconstruction in the frequency, image, and wavelet domains, with the highest values obtained from SRR in the image domain. The metric values for image-domain SRR versus the original axial, coronal, and sagittal images were PSNR = 32.26 vs 32.22, 32.16, 30.65; SSIM = 0.931 vs 0.922, 0.924, 0.918; MI = 0.871 vs 0.842, 0.844, 0.831; and MAE = 5.38 vs 7.34, 7.06, 6.19. All similarity metrics showed high correlations with expert ranking of image resolution with MI showing the highest correlation at 0.943. Qualitative assessment of the neuroimages of ten TSC patients through in-plane and out-of-plane visualization of structures showed the extent of partial voluming effect in a real clinical scenario and its reduction using SRR. Blinded expert evaluation of image resolution in resampled out-of-plane views consistently showed the superiority of SRR compared to original axial and coronal image acquisitions. Conclusions: Thick-slice 2D T2-weighted MRI scans are part of many routine clinical protocols due to their high signal-to-noise ratio, but are often severely affected by through-plane partial voluming effects. This study shows that while radiologic assessment is performed in 2D on thick-slice scans, super-resolution MRI reconstruction techniques can be used to fuse those scans to generate a high-resolution image with reduced partial voluming for improved postacquisition processing. Qualitative and quantitative evaluation showed the efficacy of all SRR techniques with the best results obtained from SRR in the image domain. The limitations of SRR techniques are uncertainties in modeling the slice profile, density compensation, quantization in resampling, and uncompensated motion between scans.

60 APPLIED LIFE SCIENCES↗

Using compressive sensing to recover images from PET scanners with partial detector rings

Purpose: Most positron emission tomography/computed tomography (PET/CT) scanners consist of tightly packed discrete detector rings to improve scanner efficiency. The authors’ aim was to use compressive sensing (CS) techniques in PET imaging to investigate the possibility of decreasing the number of detector elements per ring (introducing gaps) while maintaining image quality. Methods: A CS model based on a combination of gradient magnitude and wavelet domains (wavelet-TV) was developed to recover missing observations in PET data acquisition. The model was designed to minimize the total variation (TV) and L1-norm of wavelet coefficients while constrained by the partially observed data. The CS model also incorporated a Poisson noise term that modeled the observed noise while suppressing its contribution by penalizing the Poisson log likelihood function. Three experiments were performed to evaluate the proposed CS recovery algorithm: a simulation study, a phantom study, and six patient studies. The simulation dataset comprised six disks of various sizes in a uniform background with an activity concentration of 5:1. The simulated image was multiplied by the system matrix to obtain the corresponding sinogram and then Poisson noise was added. The resultant sinogram was masked to create the effect of partial detector removal and then the proposed CS algorithm was applied to recover the missing PET data. In addition, different levels of noise were simulated to assess the performance of the proposed algorithm. For the phantom study, an IEC phantom with six internal spheres each filled with F-18 at an activity-to-background ratio of 10:1 was used. The phantom was imaged twice on a RX PET/CT scanner: once with all detectors operational (baseline) and once with four detector blocks (11%) turned off at each of 0 °, 90 °, 180 °, and 270° (partially sampled). The partially acquired sinograms were then recovered using the proposed algorithm. For the third test, PET images from six patient studies were investigated using the same strategy of the phantom study. The recovered images using WTV and TV as well as the partially sampled images from all three experiments were then compared with the fully sampled images (the baseline). Comparisons were done by calculating the mean error (%bias), root mean square error (RMSE), contrast recovery (CR), and SNR of activity concentration in regions of interest drawn in the background as well as the disks, spheres, and lesions. Results: For the simulation study, the mean error, RMSE, and CR for the WTV (TV) recovered images were 0.26% (0.48%), 2.6% (2.9%), 97% (96%), respectively, when compared to baseline. For the partially sampled images, these results were 22.5%, 45.9%, and 64%, respectively. For the simulation study, the average SNR for the baseline was 41.7 while for WTV (TV), recovered image was 44.2 (44.0). The phantom study showed similar trends with 5.4% (18.2%), 15.6% (18.8%), and 78% (60%), respectively, for the WTV (TV) images and 33%, 34.3%, and 69% for the partially sampled images. For the phantom study, the average SNR for the baseline was 14.7 while for WTV (TV) recovered image was 13.7 (11.9). Finally, the average of these values for the six patient studies for the WTV-recovered, TV, and partially sampled images was 1%, 7.2%, 92% and 1.3%, 15.1%, 87%, and 27%, 25.8%, 45%, respectively. Conclusions: CS with WTV is capable of recovering PET images with good quantitative accuracy from partially sampled data. Such an approach can be used to potentially reduce the cost of scanners while maintaining good image quality.

60 APPLIED LIFE SCIENCES↗

Visualization of High Latitude Ion Upflow in Support of the Image Mission

The study of the magnetosphere is a 400 year old science that began with the publication by Gilbert, in 1600, of his hypotheses that the Earth was a giant magnet. Since then we have learned many things about the magnetosphere, particularly in the last 40 years of the space age, but we still have many unanswered questions. In spite of the many thousands of observations of this system we still lack a global understanding of how it works. This is due to its large size and tenuous nature that mean that any measurement made of the fields or particles involved only give one a knowledge of the local conditions at a given time. To gain a global perspective through such observations would require the simultaneous operation of thousands of satellites spread throughout the magnetospheric system in addition to observations made on the ground. Such a program would be impractical at least from financial considerations. What is needed for the advancement of magnetospheric physics is to develop the same capabilities that astrophysicists, solar physicists and meteorologists have been using for years --- the ability to stand back from the object under study and see it in its entirety. The challenge for doing this for the magnetosphere is that the particle densities are very low and the material is, for the most part, not luminous. In the last 25 years several ideas have been proposed that would allow at least the imaging of certain portions of the magnetosphere. These include imaging of the plasmasphere through the resonant scattering of solar 304 A from He+ ions, imaging of various hot plasma populations (i.e. the ring current, plasmasheet, upflowing ionospheric ions, etc.) from the neutral atoms that result when ions of these populations charge exchange with the hydrogen geocorona, and imaging the aurora at various wavelengths in the far ultraviolet. In addition, a novel technique for probing various boundaries in the magnetosphere by bouncing low frequency radio waves off of them has been extensively studied. Such a technique is analogous to the way the under water world can be probed with sonar. About five years ago NASA convened a science working group to study the possibility of flying a magnetospheric imaging mission. This resulted in a number of proposals for such a mission, one of which was selected to be the first MIDEX mission, to be launched in early 2000. The mission is called IMAGE (Imager for Magnetopause to Aurora Global Exploration) and its P.I. is J. Burch at SwRI. The IMAGE spacecraft will carry imagers to view the plasmasphere, aurora, ring current, inner plasmasheet, and upflowing ionospheric ions as well as a radio sounder to probe the location, shape and dynamics of the magnetopause, plasmapause, etc. Between its selection last April and the non advocacy mission review, which takes place next spring, the IMAGE teams needs to further refine the design of the mission and its instruments. The theory and modeling (T&M) subgroup of this team has the task of demonstrating what kind of images the instruments on IMAGE will see as well as showing that useful scientific information can be extracted from such images. As a central element to the efforts of the T&M subgroup we have decided to simulate and create synthetic images for the magnetic cloud event of October, 1995. In this event a large cloud, with high plasma densities and strong magnetic fields, ejected from the sun collided with the earth's magnetosphere triggering a three day period of intense magnetic storms and substorms. This event was observed from a number of different spacecraft and on the ground so we have a good data set to work with. In our work we will place the IMAGE spacecraft in the magnetosphere on its proposed orbit, with its proposed instruments, to see what it would see had it been there. Existing models of the plasmasphere, ring current and magnetopause will be run for this event to give the structures for the imaging instruments. There are several models which are lacking and which need to be developed. These include a model for the cusp, the inner plasmasheet and the upflowing ions. My task this summer was to develop the upflowing ion model and use it to create synthetic images.

Wilson, Gordon R.↗

The Athena Microscopic Imager Investigation

The Athena science payload on the Mars Exploration Rovers (MER) includes the Microscopic Imager (MI) [1]. The MI is a fixed-focus camera mounted on the end of an extendable instrument arm, the Instrument Deployment Device (IDD; see Figure 1).The MI was designed to acquire images at a spatial resolution of 30 microns/pixel over a broad spectral range (400 - 700 nm; see Table 1). Technically, the microscopic imager is not a microscope: it has a fixed magnification of 0.4 and is intended to produce images that simulate a geologist s view through a common hand lens. In photographers parlance, the system makes use of a macro lens. The MI uses the same electronics design as the other MER cameras [2, 3] but has optics that yield a field of view of 31 31 mm across a 1024 1024 pixel CCD image (Figure 2). The MI acquires images using only solar or skylightillumination of the target surface. A contact sensor is used to place the MI slightly closer to the target surface than its best focus distance (about 66 mm), allowing concave surfaces to be imaged in good focus. Because the MI has a relatively small depth of field (3 mm), a single MI image of a rough surface will contain both focused and unfocused areas. Coarse focusing will be achieved by moving the IDD away from a rock target after the contact sensor is activated. Multiple images taken at various distances will be acquired to ensure good focus on all parts of rough surfaces. By combining a set of images acquired in this way, a completely focused image can be assembled. Stereoscopic observations can be obtained by moving the MI laterally relative to its boresight. Estimates of the position and orientation of the MI for each acquired image will be stored in the rover computer and returned to Earth with the image data. The MI optics will be protected from the Martian environment by a retractable dust cover. The dust cover includes a Kapton window that is tinted orange to restrict the spectral bandpass to 500-700 nm, allowing color information to be obtained by taking images with the dust cover open and closed. The MI will image the same materials measured by other Athena instruments (including surfaces prepared by the Rock Abrasion Tool), as well as rock and soil targets of opportunity. Subsets of the full image array can be selected and/or pixels can be binned to reduce data volume. Image compression will be used to maximize the information contained in the data returned to Earth. The resulting MI data will place other MER instrument data in context and aid in petrologic and geologic interpretations of rocks and soils on Mars.

K E Herkenhoff↗

Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography

BACKGROUND: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall-motion analysis. Interpretation of dobutamine stress echocardiography is observer-dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. METHODS AND RESULTS: Twenty-nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5-3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. CONCLUSION: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.

Non-NASA Center↗

Synthetic Foveal Imaging Technology

Synthetic Foveal imaging Technology (SyFT) is an emerging discipline of image capture and image-data processing that offers the prospect of greatly increased capabilities for real-time processing of large, high-resolution images (including mosaic images) for such purposes as automated recognition and tracking of moving objects of interest. SyFT offers a solution to the image-data processing problem arising from the proposed development of gigapixel mosaic focal-plane image-detector assemblies for very wide field-of-view imaging with high resolution for detecting and tracking sparse objects or events within narrow subfields of view. In order to identify and track the objects or events without the means of dynamic adaptation to be afforded by SyFT, it would be necessary to post-process data from an image-data space consisting of terabytes of data. Such post-processing would be time-consuming and, as a consequence, could result in missing significant events that could not be observed at all due to the time evolution of such events or could not be observed at required levels of fidelity without such real-time adaptations as adjusting focal-plane operating conditions or aiming of the focal plane in different directions to track such events. The basic concept of foveal imaging is straightforward: In imitation of a natural eye, a foveal-vision image sensor is designed to offer higher resolution in a small region of interest (ROI) within its field of view. Foveal vision reduces the amount of unwanted information that must be transferred from the image sensor to external image-data-processing circuitry. The aforementioned basic concept is not new in itself: indeed, image sensors based on these concepts have been described in several previous NASA Tech Briefs articles. Active-pixel integrated-circuit image sensors that can be programmed in real time to effect foveal artificial vision on demand are one such example. What is new in SyFT is a synergistic combination of recent advances in foveal imaging, computing, and related fields, along with a generalization of the basic foveal-vision concept to admit a synthetic fovea that is not restricted to one contiguous region of an image.

Hoenk, Michael↗

Computational Ghost Imaging for Remote Sensing

This work relates to the generic problem of remote active imaging; that is, a source illuminates a target of interest and a receiver collects the scattered light off the target to obtain an image. Conventional imaging systems consist of an imaging lens and a high-resolution detector array [e.g., a CCD (charge coupled device) array] to register the image. However, conventional imaging systems for remote sensing require high-quality optics and need to support large detector arrays and associated electronics. This results in suboptimal size, weight, and power consumption. Computational ghost imaging (CGI) is a computational alternative to this traditional imaging concept that has a very simple receiver structure. In CGI, the transmitter illuminates the target with a modulated light source. A single-pixel (bucket) detector collects the scattered light. Then, via computation (i.e., postprocessing), the receiver can reconstruct the image using the knowledge of the modulation that was projected onto the target by the transmitter. This way, one can construct a very simple receiver that, in principle, requires no lens to image a target. Ghost imaging is a transverse imaging modality that has been receiving much attention owing to a rich interconnection of novel physical characteristics and novel signal processing algorithms suitable for active computational imaging. The original ghost imaging experiments consisted of two correlated optical beams traversing distinct paths and impinging on two spatially-separated photodetectors: one beam interacts with the target and then illuminates on a single-pixel (bucket) detector that provides no spatial resolution, whereas the other beam traverses an independent path and impinges on a high-resolution camera without any interaction with the target. The term ghost imaging was coined soon after the initial experiments were reported, to emphasize the fact that by cross-correlating two photocurrents, one generates an image of the target. In CGI, the measurement obtained from the reference arm (with the high-resolution detector) is replaced by a computational derivation of the measurement-plane intensity profile of the reference-arm beam. The algorithms applied to computational ghost imaging have diversified beyond simple correlation measurements, and now include modern reconstruction algorithms based on compressive sensing.

Erkmen, Baris I.↗

Fully Integrated Ultra-thin Intraoperative Micro-imager for Cancer Detection Using Upconverting Nanoparticles

Abstract Purpose Intraoperative detection and removal of microscopic residual disease (MRD) remain critical to the outcome of cancer surgeries. Today’s minimally invasive surgical procedures require miniaturization and surgical integration of highly sensitive imagers to seamlessly integrate into the modern clinical workflow. However, current intraoperative imagers remain cumbersome and still heavily dependent on large lenses and rigid filters, precluding further miniaturization and integration into surgical tools. Procedures We have successfully engineered a chip-scale intraoperative micro-imager array—without optical filters or lenses—integrated with lanthanide-based alloyed upconverting nanoparticles (aUCNPs) to achieve tissue imaging using a single micro-chip. This imaging platform is able to leverage the unique optical properties of aUCNPs (long luminescent lifetime, high-efficiency upconversion, no photobleaching) by utilizing a time-resolved imaging method to acquire images using a 36-by-80-pixel, 2.3 mm $$\times$$ × 4.8 mm silicon-based electronic imager micro-chip, that is, less than 100-µm thin. Each pixel incorporates a novel architecture enabling automated background measurement and cancellation. We have validated the performance, spatial resolution, and the background cancellation scheme of the imaging platform, using resolution test targets and mouse prostate tumor sample intratumorally injected with aUCNPs. To demonstrate the ability to image MRD, or tumor margins, we evaluated the imaging platform in visualizing a single-cell thin section of the injected prostate tumor sample. Results Tested on USAF resolution targets, the imager is able to achieve a resolution of 71 µm. We have also demonstrated successful background cancellation, achieving a signal-to-background ratio of 8 when performing ex vivo imaging on aUCNP-injected prostate tumor sample, improved from originally 0.4. The performance of the imaging platform on single-cell layer sections was also evaluated and the sensor achieved a signal-to-background ratio of 4.3 in resolving cell clusters with sizes as low as 200 cells. Conclusion The imaging system proposed here is a scalable chip-scale ultra-thin alternative for bulky conventional intraoperative imagers. Its novel pixel architecture and background correction scheme enable visualization of microscopic-scale residual disease while remaining completely free of lenses and filters, achieving an ultra-miniaturized form factor—critical for intraoperative settings.

59 BASIC BIOLOGICAL SCIENCES↗

Angular-spectral filtering of recoil protons for optimization of fast neutron imaging employing proton converters

Fast neutron imaging is an important capability for diverse applications such as inertial confinement fusion diagnostics, cargo security, nuclear nonproliferation and arms control, and industrial inspection. Traditional phosphor image plates can be enhanced for fast neutron imaging using hydrogenous plastic converters which allow fast neutrons to scatter off hydrogen nuclei to produce energetic protons that can be recorded by the image plate. However, protons emitted by image plates are not constrained in their emission angle, which contributes to the blur of the resulting image. Here, we investigate two methods that can alter the spatial extent of converted protons that deposit energy in the image plate: reducing the converter thickness, and introducing a proton filter between the plastic converter and image plate to reduce the contribution of lower-energy, off-axis protons to the image. Here we determine the optimal plastic converter thickness for maximizing the signal intensity to be 2–3 mm through Monte Carlo simulations, and we benchmark this result against experimental measurements with a deuterium-tritium (DT) neutron generator. Next, we evaluate the image smearing and signal loss for various converters to show that solely reducing the converter thickness has the expected effect of reducing the blur from proton image smearing of the sharpness of an edge recorded on the image plate at the cost of reducing the signal intensity. The use of a proton filter is shown to achieve a similar improvement of edge sharpness as reducing the converter thickness while also sacrificing the signal intensity. We conclude that the use of proton energy filtering can improve the sharpness of fast neutron images in situations where the converter thickness cannot be reduced below some practical minimum. For more intense neutron sources, the signal intensity is of less concern, and optimizing the resolution of the image plate and therefore of the imaging system could have greater value. In these applications, proton filters may allow for improved fast neutron imaging measurements.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Anatomical noise in contrast-enhanced digital mammography. Part I. Single-energy imaging

Purpose: The use of an intravenously injected iodinated contrast agent could help increase the sensitivity of digital mammography by adding information on tumor angiogenesis. Two approaches have been made for clinical implementation of contrast-enhanced digital mammography (CEDM), namely, single-energy (SE) and dual-energy (DE) imaging. In each technique, pairs of mammograms are acquired, which are then subtracted with the intent to cancel the appearance of healthy breast tissue to permit sensitive detection and specific characterization of lesions. Patterns of contrast agent uptake in the healthy parenchyma, and uncanceled signal from background tissue create a 'clutter' that can mask or mimic an enhancing lesion. This type of 'anatomical noise' is often the limiting factor in lesion detection tasks, and thus, noise quantification may be useful for cascaded systems analysis of CEDM and for phantom development. In this work, the authors characterize the anatomical noise in CEDM clinical images and the authors evaluate the influence of the x-ray energy used for acquisition, the presence of iodine in the breast, and the timing of imaging postcontrast administration on anatomical noise. The results are presented in a two-part report, with SE CEDM described here, and DE CEDM in Part II. Methods: A power law is used to model anatomical noise in CEDM images. The exponent, {beta}, which describes the anatomical structure, and the constant {alpha}, which represents the magnitude of the noise, are determined from Wiener spectra (WS) measurements on images. A total of 42 SE CEDM cases from two previous clinical pilot studies are assessed. The parameters {alpha} and {beta} are measured both from unprocessed images and from subtracted images. Results: Consistent results were found between the two SE CEDM pilot studies, where a significant decrease in {beta} from a value of approximately 3.1 in the unprocessed images to between about 1.1 and 1.8 in the subtracted images was observed. Increasing the x-ray energy from that used in conventional DM to those of typical SE CEDM spectra with mean energies above 33 keV significantly decreased {alpha} by about a factor of 19, in agreement with theory. Compared to precontrast images, in the unprocessed postcontrast images at 30 s postinjection, {alpha} was larger by about 7.4 Multiplication-Sign 10{sup -7} mm{sup 2} and {beta} was decreased by 0.2. While {alpha} did not vary significantly with the time after contrast administration, {beta} from the unprocessed image WS increased linearly, and {beta} from subtracted image WS increased with an initial quadratic relationship that plateaued by about 5 min postinjection. Conclusions: The presence of an iodinated contrast agent in the breast produced small, but significant changes in the power law parameters of unprocessed CEDM images compared to the precontrast images. Image subtraction in SE CEDM significantly reduced anatomical noise compared to conventional DM, with a reduction in both {alpha} and {beta} by about a factor of 2. The data presented here, and in Part II of this work, will be useful for modeling of CEDM backgrounds, for systems characterization and for lesion detectability experiments using models that account for anatomical noise.

60 APPLIED LIFE SCIENCES↗

Progressive cone beam CT dose control in image-guided radiation therapy

Purpose: Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction. Methods: A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction. The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation. Results: In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved. Conclusions: PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.

61 RADIATION PROTECTION AND DOSIMETRY↗

TU-EF-BRA-02: Longitudinal Proton Spin Relaxation and T1-Imaging

NMR, and Proton Density MRI of the 1D Patient - Anthony Wolbarst Net Voxel Magnetization, m(x,t). T1-MRI; The MRI Device - Lisa Lemen ‘Classical’ NMR; FID Imaging in 1D via k-Space - Nathan Yanasak Spin-Echo; S-E/Spin Warp in a 2D Slice - Ronald Price Magnetic resonance imaging not only reveals the structural, anatomic details of the body, as does CT, but also it can provide information on the physiological status and pathologies of its tissues, like nuclear medicine. It can display high-quality slice and 3D images of organs and vessels viewed from any perspective, with resolution better than 1 mm. MRI is perhaps most extraordinary and notable for the plethora of ways in which it can create unique forms of image contrast, reflective of fundamentally different biophysical phenomena. As with ultrasound, there is no risk from ionizing radiation to the patient or staff, since no X-rays or radioactive nuclei are involved. Instead, MRI harnesses magnetic fields and radio waves to probe the stable nuclei of the ordinary hydrogen atoms (isolated protons) occurring in water and lipid molecules within and around cells. MRI consists, in essence, of creating spatial maps of the electromagnetic environments around these hydrogen nuclei. Spatial variations in the proton milieus can be related to clinical differences in the biochemical and physiological properties and conditions of the associated tissues. Imaging of proton density (PD), and of the tissue proton spin relaxation times known as T1 and T2, all can reveal important clinical information, but they do so with approaches so dissimilar from one another that each is chosen for only certain clinical situations. T1 and T2 in a voxel are determined by different aspects of the rotations and other motions of the water and lipid molecules involved, as constrained by the local biophysical surroundings within and between its cells – and they, in turn, depend on the type of tissue and its state of health. Three other common applications of MRI exploit its capability to detect and image distinct movements of fluids: MR angiography (MRA), which rivals CT angiography but often requires no contrast medium, monitors the bulk flow of blood; functional MRI ( f MRI), distinguishes the perfusion of oxygenated blood from that of de-oxygenated, and lights up parts of the brain that are activated by a stimulus, rather like PET; and diffusion tensor imaging (DTI) indicates the diffusion of free water along tracts of axons, thereby bringing nerve trunks into view. There are variants on all of these themes, and on others as well. Magnetic Resonance Spectroscopy (MRS), for example, can perform non-invasive ‘virtual biopsies’ that allow identification of certain cancers and other lesions. And an MRI-guided needle biopsy can sample brain tissue from a region only millimeters in dimensions. MRI, however, involves deeper and more complex aspects of physics, technology, and biology than do most other imaging modalities, and it is widely considered to be correspondingly more difficult to learn. We could probably cover all of this rather comprehensively if we had 50 hours available rather than 2 ̶ but, to paraphrase a former Secretary of Defense, you tell your story in the time you have allotted. The four presenters and another physicist, Kevin King from GE, have combined their efforts to co-author a single slide show that describes essentials of MRI as simply as possible. It is obviously far from thorough, but hopefully it will succeed in explaining some of the basics in a simplified but still valid fashion; in providing a taste of the numerous capabilities and complexities of the modality; and in whetting your appetite to learn more. Part I. NMR, and Proton Density MRI of the 1D Patient (Wolbarst), begins with an introductory case study that illustrates a half dozen ways in which MRI provides valuable clinical information. It then explores the nuclear magnetic resonance (NMR) phenomenon, which underlies MRI. NMR can be introduced with either of two approaches. In the first, one thinks (loosely) of the nuclei of hydrogen atoms as (rotating and charged and therefore) magnetic objects, whose spin-axes tend to align in a strong external magnetic field, much like a compass needle. As with the Bohr atom, this spin-up/spin-down picture is a highly abridged version of the full quantum mechanical treatment, but still it leads to some useful, legitimate pictures of the NMR process occurring within a voxel: When RF photons of the correct (Larmor) frequency elevate protons in a fixed magnetic field out of their lower-energy spin state into the upper, the NMR phenomenon is indicated by the detectable absorption of RF power. With the addition of a linear gradient field along a multi-voxel, one-dimensional patient/phantom, as well, we can determine the water content of each compartment – an example of a real MRI study, albeit in 1D. Part I concludes with a discussion of the net magnetization at position x, m0(x), under conditions of dynamic thermal equilibrium, which leads into: Part II. Net Voxel Magnetization, m(x,t); T1-MRI; The MRI Device (Lemen), investigates the biophysics of the form of proton spin relaxation process characterized by the time T1. It then moves on to the creation of an MR image that displays the spatial variation in the values of this clinically relevant parameter, again in 1D. Finally, the design and workings of a clinical MRI machine are sketched, in preparation for: Part III. ‘Classical’ NMR; FID Imaging in 1D via k-Space (Yanasak) presents the second standard approach to NMR and MRI, the classical model. It focuses on the time dependence of the net nuclear magnetization, m(x,t), the overall magnetic field generated by the cohort of protons in the voxel at position x. Quite remarkably, this nuclear net magnetization itself acts in a strong magnetic field like a gyroscope in a gravitational field. This tack is better for explaining Free Induction Decay (FID), which involves a brief introduction to the Fourier transform and k-space. This leads to conventional Spin-Echo (S-E) reconstruction techniques for creating clinical images from raw data, and sets the stage for: Part IV. Spin-Echo; S-E / Spin Warp in a 2D Slice (Price) discusses application of the S- E sequence of radiofrequency pulses and gradient magnetic fields to the 1D patient. T2 is introduced but not explained. This Part also considers how to manipulate the image acquisition parameters so as to generate clinical pictures with contrast dominated by spatial variations in PD, T1, or T2. We conclude by demonstrating the spin-warp approach to imaging in 2D with a simple 2×2, 4-voxel example. Much of this material is presented in more detail in the chapter “MRI of the One-dimensional Patient, Part I”, in Advances in Medical Physics, Vol 5 (2014). Copies are on display at the Medical Physics Publishing booth. Learning Objectives: The participant will learn about the processes of NMR and T1 spin relaxation in a tissue voxel in a uniform magnetic field. The participant will learn about combining spin-up/spin-down NMR and T1 processes with a linear gradient to effect frequency-encoding of voxel spatial position. This approach can be used to create proton density and T1 MRI maps, respectively, of the contents of multi-voxel 1D phantoms. The participant will learn about how the ‘classical’ model of NMR it can generate Free Induction Decay (FID) images of 1D phantoms, which involves the use of the Fourier transform in k-space. This can lead simply into standard Spin-Echo images. The participant will learn about extending Spin-Echo imaging into 2 and more dimensions.

60 APPLIED LIFE SCIENCES↗

TU-EF-BRA-03: Free Induction Decay (without the Decay) and Spin-Echo Imaging

NMR, and Proton Density MRI of the 1D Patient - Anthony Wolbarst Net Voxel Magnetization, m(x,t). T1-MRI; The MRI Device - Lisa Lemen ‘Classical’ NMR; FID Imaging in 1D via k-Space - Nathan Yanasak Spin-Echo; S-E/Spin Warp in a 2D Slice - Ronald Price Magnetic resonance imaging not only reveals the structural, anatomic details of the body, as does CT, but also it can provide information on the physiological status and pathologies of its tissues, like nuclear medicine. It can display high-quality slice and 3D images of organs and vessels viewed from any perspective, with resolution better than 1 mm. MRI is perhaps most extraordinary and notable for the plethora of ways in which it can create unique forms of image contrast, reflective of fundamentally different biophysical phenomena. As with ultrasound, there is no risk from ionizing radiation to the patient or staff, since no X-rays or radioactive nuclei are involved. Instead, MRI harnesses magnetic fields and radio waves to probe the stable nuclei of the ordinary hydrogen atoms (isolated protons) occurring in water and lipid molecules within and around cells. MRI consists, in essence, of creating spatial maps of the electromagnetic environments around these hydrogen nuclei. Spatial variations in the proton milieus can be related to clinical differences in the biochemical and physiological properties and conditions of the associated tissues. Imaging of proton density (PD), and of the tissue proton spin relaxation times known as T1 and T2, all can reveal important clinical information, but they do so with approaches so dissimilar from one another that each is chosen for only certain clinical situations. T1 and T2 in a voxel are determined by different aspects of the rotations and other motions of the water and lipid molecules involved, as constrained by the local biophysical surroundings within and between its cells – and they, in turn, depend on the type of tissue and its state of health. Three other common applications of MRI exploit its capability to detect and image distinct movements of fluids: MR angiography (MRA), which rivals CT angiography but often requires no contrast medium, monitors the bulk flow of blood; functional MRI ( f MRI), distinguishes the perfusion of oxygenated blood from that of de-oxygenated, and lights up parts of the brain that are activated by a stimulus, rather like PET; and diffusion tensor imaging (DTI) indicates the diffusion of free water along tracts of axons, thereby bringing nerve trunks into view. There are variants on all of these themes, and on others as well. Magnetic Resonance Spectroscopy (MRS), for example, can perform non-invasive ‘virtual biopsies’ that allow identification of certain cancers and other lesions. And an MRI-guided needle biopsy can sample brain tissue from a region only millimeters in dimensions. MRI, however, involves deeper and more complex aspects of physics, technology, and biology than do most other imaging modalities, and it is widely considered to be correspondingly more difficult to learn. We could probably cover all of this rather comprehensively if we had 50 hours available rather than 2 ̶ but, to paraphrase a former Secretary of Defense, you tell your story in the time you have allotted. The four presenters and another physicist, Kevin King from GE, have combined their efforts to co-author a single slide show that describes essentials of MRI as simply as possible. It is obviously far from thorough, but hopefully it will succeed in explaining some of the basics in a simplified but still valid fashion; in providing a taste of the numerous capabilities and complexities of the modality; and in whetting your appetite to learn more. Part I. NMR, and Proton Density MRI of the 1D Patient (Wolbarst), begins with an introductory case study that illustrates a half dozen ways in which MRI provides valuable clinical information. It then explores the nuclear magnetic resonance (NMR) phenomenon, which underlies MRI. NMR can be introduced with either of two approaches. In the first, one thinks (loosely) of the nuclei of hydrogen atoms as (rotating and charged and therefore) magnetic objects, whose spin-axes tend to align in a strong external magnetic field, much like a compass needle. As with the Bohr atom, this spin-up/spin-down picture is a highly abridged version of the full quantum mechanical treatment, but still it leads to some useful, legitimate pictures of the NMR process occurring within a voxel: When RF photons of the correct (Larmor) frequency elevate protons in a fixed magnetic field out of their lower-energy spin state into the upper, the NMR phenomenon is indicated by the detectable absorption of RF power. With the addition of a linear gradient field along a multi-voxel, one-dimensional patient/phantom, as well, we can determine the water content of each compartment – an example of a real MRI study, albeit in 1D. Part I concludes with a discussion of the net magnetization at position x, m0(x), under conditions of dynamic thermal equilibrium, which leads into: Part II. Net Voxel Magnetization, m(x,t); T1-MRI; The MRI Device (Lemen), investigates the biophysics of the form of proton spin relaxation process characterized by the time T1. It then moves on to the creation of an MR image that displays the spatial variation in the values of this clinically relevant parameter, again in 1D. Finally, the design and workings of a clinical MRI machine are sketched, in preparation for: Part III. ‘Classical’ NMR; FID Imaging in 1D via k-Space (Yanasak) presents the second standard approach to NMR and MRI, the classical model. It focuses on the time dependence of the net nuclear magnetization, m(x,t), the overall magnetic field generated by the cohort of protons in the voxel at position x. Quite remarkably, this nuclear net magnetization itself acts in a strong magnetic field like a gyroscope in a gravitational field. This tack is better for explaining Free Induction Decay (FID), which involves a brief introduction to the Fourier transform and k-space. This leads to conventional Spin-Echo (S-E) reconstruction techniques for creating clinical images from raw data, and sets the stage for: Part IV. Spin-Echo; S-E / Spin Warp in a 2D Slice (Price) discusses application of the S- E sequence of radiofrequency pulses and gradient magnetic fields to the 1D patient. T2 is introduced but not explained. This Part also considers how to manipulate the image acquisition parameters so as to generate clinical pictures with contrast dominated by spatial variations in PD, T1, or T2. We conclude by demonstrating the spin-warp approach to imaging in 2D with a simple 2×2, 4-voxel example. Much of this material is presented in more detail in the chapter “MRI of the One-dimensional Patient, Part I”, in Advances in Medical Physics, Vol 5 (2014). Copies are on display at the Medical Physics Publishing booth. Learning Objectives: The participant will learn about the processes of NMR and T1 spin relaxation in a tissue voxel in a uniform magnetic field. The participant will learn about combining spin-up/spin-down NMR and T1 processes with a linear gradient to effect frequency-encoding of voxel spatial position. This approach can be used to create proton density and T1 MRI maps, respectively, of the contents of multi-voxel 1D phantoms. The participant will learn about how the ‘classical’ model of NMR it can generate Free Induction Decay (FID) images of 1D phantoms, which involves the use of the Fourier transform in k-space. This can lead simply into standard Spin-Echo images. The participant will learn about extending Spin-Echo imaging into 2 and more dimensions.

60 APPLIED LIFE SCIENCES↗

TU-F-CAMPUS-J-05: Effect of Uncorrelated Noise Texture On Computed Tomography Quantitative Image Features

Purpose: To investigate the relationship between quantitative image features (i.e. radiomics) and statistical fluctuations (i.e. electronic noise) in clinical Computed Tomography (CT) using the standardized American College of Radiology (ACR) CT accreditation phantom and patient images. Methods: Three levels of uncorrelated Gaussian noise were added to CT images of phantom and patients (20) acquired in static mode and respiratory tracking mode. We calculated the noise-power spectrum (NPS) of the original CT images of the phantom, and of the phantom images with added Gaussian noise with means of 50, 80, and 120 HU. Concurrently, on patient images (original and noise-added images), image features were calculated: 14 shape, 19 intensity (1st order statistics from intensity volume histograms), 18 GLCM features (2nd order statistics from grey level co-occurrence matrices) and 11 RLM features (2nd order statistics from run-length matrices). These features provide the underlying structural information of the images. GLCM (size 128x128) was calculated with a step size of 1 voxel in 13 directions and averaged. RLM feature calculation was performed in 13 directions with grey levels binning into 128 levels. Results: Adding the electronic noise to the images modified the quality of the NPS, shifting the noise from mostly correlated to mostly uncorrelated voxels. The dramatic increase in noise texture did not affect image structure/contours significantly for patient images. However, it did affect the image features and textures significantly as demonstrated by GLCM differences. Conclusion: Image features are sensitive to acquisition factors (simulated by adding uncorrelated Gaussian noise). We speculate that image features will be more difficult to detect in the presence of electronic noise (an uncorrelated noise contributor) or, for that matter, any other highly correlated image noise. This work focuses on the effect of electronic, uncorrelated, noise and future work shall examine the influence of changes in quantum noise on the features. J. Oliver was supported by NSF FGLSAMP BD award HRD #1139850 and the McKnight Doctoral Fellowship.

60 APPLIED LIFE SCIENCES↗

SU-D-BRA-03: Analysis of Systematic Errors with 2D/3D Image Registration for Target Localization and Treatment Delivery in Stereotactic Radiosurgery

Purpose: Determine systematic deviations between 2D/3D and 3D/3D image registrations with six degrees of freedom (6DOF) for various imaging modalities and registration algorithms on the Varian Edge Linac. Methods: The 6DOF systematic errors were assessed by comparing automated 2D/3D (kV/MV vs. CT) with 3D/3D (CBCT vs. CT) image registrations from different imaging pairs, CT slice thicknesses, couch angles, similarity measures, etc., using a Rando head and a pelvic phantom. The 2D/3D image registration accuracy was evaluated at different treatment sites (intra-cranial and extra-cranial) by statistically analyzing 2D/3D pre-treatment verification against 3D/3D localization of 192 Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy treatment fractions for 88 patients. Results: The systematic errors of 2D/3D image registration using kV-kV, MV-kV and MV-MV image pairs using 0.8 mm slice thickness CT images were within 0.3 mm and 0.3° for translations and rotations with a 95% confidence interval (CI). No significant difference between 2D/3D and 3D/3D image registrations (P>0.05) was observed for target localization at various CT slice thicknesses ranging from 0.8 to 3 mm. Couch angles (30, 45, 60 degree) did not impact the accuracy of 2D/3D image registration. Using pattern intensity with content image filtering was recommended for 2D/3D image registration to achieve the best accuracy. For the patient study, translational error was within 2 mm and rotational error was within 0.6 degrees in terms of 95% CI for 2D/3D image registration. For intra-cranial sites, means and std. deviations of translational errors were −0.2±0.7, 0.04±0.5, 0.1±0.4 mm for LNG, LAT, VRT directions, respectively. For extra-cranial sites, means and std. deviations of translational errors were - 0.04±1, 0.2±1, 0.1±1 mm for LNG, LAT, VRT directions, respectively. 2D/3D image registration uncertainties for intra-cranial and extra-cranial sites were comparable. Conclusion: The Varian Edge radiosurgery 6DOF-based system, can perform 2D/3D image registration with high accuracy for target localization in image-guided stereotactic radiosurgery. The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society.

60 APPLIED LIFE SCIENCES↗