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OBJECTIVE To describe the technique and assess the diagnostic potential and limitations of tomosynthesis for imaging of the metacarpophalangeal joint (MCPJ) of equine cadavers; compare the tomosynthesis appearance of pathological lesions with their conventional radiographic, CT, and MRI appearances; and evaluate all imaging findings with gross lesions of a given MCPJ. SAMPLE Distal portions of 4 forelimbs from 4 equine cadavers. PROCEDURES The MCPJs underwent radiography, tomosynthesis (with a purpose-built benchtop unit), CT, and MRI; thereafter, MCPJs were disarticulated and evaluated for the presence of gross lesions. The ability to identify pathological lesions on all images was assessed, followed by semiobjective scoring for quality of the overall image and appearance of the subchondral bone, articular cartilage, periarticular margins, and adjacent trabecular bone of the third metacarpal bone, proximal phalanx, and proximal sesamoid bones of each MCPJ. RESULTS Some pathological lesions in the subchondral bone of the third metacarpal bone were detectable with tomosynthesis but not with radiography. Overall, tomosynthesis was comparable to radiography, but volumetric imaging modalities were superior to tomosynthesis and radiography for imaging of subchondral bone, articular cartilage, periarticular margins, and adjacent bone. CONCLUSIONS AND CLINICAL RELEVANCE With regard to the diagnostic characterization of equine MCPJs, tomosynthesis may be more accurate than radiography for identification of lesions within subchondral bone because, in part, of its ability to reduce superimposition of regional anatomic features. Tomosynthesis may be useful as an adjunctive imaging technique, highlighting subtle lesions within bone, compared with standard radiographic findings.

Introduction Musculoskeletal injury to extremities is a common issue for both stateside and deployed military personnel, as well as the general public. Superposition of anatomy can make diagnosis difficult using standard clinical techniques. There is a need for increased diagnostic accuracy at the point-of-care for military personnel in both training and operational environments, as well as assessment during follow-up treatment to optimize care and expedite return to service. Orthopedic tomosynthesis is rapidly emerging as an alternative to digital radiography (DR), exhibiting an increase in sensitivity for some clinical tasks, including diagnosis and follow-up of fracture and arthritis. Commercially available digital tomosynthesis systems are large complex devices. A compact device for extremity tomosynthesis (TomoE) was previously demonstrated using carbon nanotube X-ray source array technology. The purpose of this study was to prepare and evaluate the prototype device for an Institutional Review Board-approved patient wrist imaging study and provide initial patient imaging results. Materials and Methods A benchtop device was constructed using a carbon nanotube X-ray source array and a flat panel digital detector. Twenty-one X-ray projection images of cadaveric specimens and human subjects were acquired at incident angles from −20 to +20 degrees in various clinical orientations, with entrance dose calibrated to commercial digital tomosynthesis wrist scans. The projection images were processed with an iterative reconstruction algorithm in 1 mm slices. Reconstruction slice images were evaluated by a radiologist for feature conspicuity and diagnostic accuracy. Results The TomoE image quality was found to provide more diagnostic information than DR, with reconstruction slices exhibiting delineation of joint space, visual conspicuity of trabecular bone, bone erosions, fractures, and clear depiction of normal anatomical features. The scan time was 15 seconds and the skin entrance dose was verified to be 0.2 mGy. Conclusions The TomoE device image quality has been evaluated using cadaveric specimens. Dose was calibrated for a patient imaging study. Initial patient images depict a high level of anatomical detail and an increase in diagnostic value compared to DR.

Cone beam computed tomography (CBCT) is now widely used in dentistry and growing areas of medical imaging. The presence of strong metal artifacts is however a major concern of using CBCT especially in dentistry due to the presence of highly attenuating dental restorations, fixed appliances, and implants. Virtual monoenergetic images (VMIs) synthesized from dual energy CT (DECT) datasets are known to reduce metal artifacts. Although several techniques exist for DECT imaging, they in general come with significantly increased equipment cost and not available in dental clinics. The objectives of this study were to investigate the feasibility of developing a low-cost dual energy CBCT (DE-CBCT) by retrofitting a regular CBCT scanner with a carbon nanotube (CNT) x-ray source with dual focal spots and corresponding low-energy (LE) and high-energy (HE) spectral filters. A testbed with a CNT field emission x-ray source (NuRay Technology, Chang Zhou, China), a flat panel detector (Teledyne, Waterloo, Canada), and a rotating object stage was used for this feasibility study. Two distinct polychromatic x-ray spectra with the mean photon energies of 66.7keV and 86.3keV were produced at a fixed 120kVp x-ray tube voltage by using Al+Au and Al+Sn foils as the respective LE and HE filters attached to the exist window of the x-ray source. The HE filter attenuated the x-ray photons more than the LE filter. The calculated post-object air kerma rate of the HE beam was 31.7% of the LE beam. An anthropomorphic head phantom (RANDO, Nuclear Associates, Hicksville, NY) with metal beads was imaged using the testbed and the images were reconstructed using an iterative volumetric CT reconstruction algorithm. The VMIs were synthesized using an image-domain basis materials decomposition method with energy ranging from 30 to 150keV. The results were compared to the reconstructed images from a single energy clinical dental CBCT scanner (CS9300, Carestream Dental, Atlanta, GA). A significant reduction of the metal artifacts was observed in the VMI images synthesized at high energies compared to those from the same object imaged by the clinical dental CBCT scanner. The ability of the CNT x-ray source to generate the output needed to compensate the reduction of photon flux due to attenuation from the spectral filters and to maintain the CT imaging time was evaluated. The results demonstrated the feasibility of DE-CBCT imaging using the proposed approach. Metal artifact reduction was achieved in VMIs synthesized. The x-ray output needed for the proposed DE-CBCT can be generated by a fixed-anode CNT x-ray source.

Rationale and Objectives: A linear array of carbon nanotube-enabled x-ray sources allows for stationary digital breast tomosynthesis (sDBT), during which projection views are collected without the need to move the x-ray tube. This work presents our initial clinical experience with a first-generation sDBT device. Materials and Methods: Following informed consent, women with a “suspicious abnormality” (Breast Imaging Reporting and Data System 4), discovered by digital mammography and awaiting biopsy, were also imaged by the first generation sDBT. Four radiologists participated in this paired-image study, completing questionnaires while interpreting the mammograms and sDBT image stacks. Areas under the receiver operating characteristic curve were used to measure reader performance (likelihood of correctly identifying malignancy based on pathology as ground truth), while a multivariate analysis assessed preference, as readers compared one modality to the next when interpreting diagnostically important image features. Results: Findings from 43 women were available for analysis, in whom 12 cases of malignancy were identified by pathology. The mean areas under the receiver operating characteristic curve was significantly higher (p < 0.05) for sDBT than mammography for all breast density categories and breast thicknesses. Additionally, readers preferred sDBT over mammography when evaluating mass margins and shape, architectural distortion, and asymmetry, but preferred mammography when characterizing microcalcifications. Conclusion: Readers preferred sDBT over mammography when interpreting soft-tissue breast features and were diagnostically more accurate using images generated by sDBT in a Breast Imaging Reporting and Data System 4 population. However, the findings also demonstrated the need to improve microcalcification conspicuity, which is guiding both technological and image-processing design changes in future sDBT devices.

Purpose: Scatter reduction remains a challenge for chest tomosynthesis. The purpose of this study was to validate a lowdose patient-specific method of scatter correction in a large animal model and implement the technique in a human imaging study in a population with known lung lesions. Method: The porcine and human subjects were imaged with an experimental stationary digital chest tomosynthesis system. Full field projection images were acquired, as well as with a customized primary sampling device for sparse sampling of the primary signal. A primary sampling scatter correction algorithm was used to compute scatter from the primary beam information. Sparse scatter was interpolated and used to correct projections prior to reconstruction. Reconstruction image quality was evaluated over multiple acquisitions in the animal subject to quantify the impact of lung volume discrepancies between scans. Results: Variations in lung volume between the full field and primary sample projection images induced mild variation in computed scatter maps, due to acquisitions during separate breath holds. Reconstruction slice images from scatter corrected datasets including both similar and dissimilar breath holds were compared and found to have minimal differences. Initial human images are included. Conclusions: We have evaluated the prototype low-dose, patient-specific scatter correction in an in-vivo porcine model currently incorporated into a human imaging study. The PSSC technique was found to tolerate some lung volume variation between scans, as it has a minimal impact on reconstruction image quality. A human imaging study has been initiated and a reader comparison will determine clinical efficacy.

Objectives: A practical approach to three-dimensional (3D) intraoral imaging would have many potential applications in clinical dentistry. Stationary intraoral tomosynthesis (sIOT) is an experimental 3D imaging technology that holds promise. The purpose of this study was to explore synthetic radiography as a tool to improve the clinical utility of the images generated by an sIOT scan. Methods: Extracted tooth specimens containing either caries adjacent to restorations (CAR) or vertical root fractures (VRF) were imaged by sIOT and standard dental radiography devices. Qualitative assessments were used to compare the conspicuity of these pathologies in the standard radiographs and in a set of multi-view synthetic radiographs generated from the information collected by sIOT. Results: The sIOT-based synthetic 2D radiographs contained less artefact than the image slices in the reconstructed 3D stack, which is the conventional approach to displaying information from a tomosynthesis scan. As a single sIOT scan can be used to generate synthetic radiographs from multiple viewing angles, the interproximal space was less likely to be obscured in the synthetic images compared to the standard radiograph. Additionally, the multi-view synthetic radiographs can potentially improve the display of CAR and VRFs as compared to a single standard radiograph. Conclusions: This preliminary experience combining synthetic radiography and sIOT in extracted tooth models is encouraging and supports the ongoing study of this promising approach to 3D intraoral imaging with many potential applications.

PURPOSE: To assess the visibility of microcalcifications in images generated by a first-generation carbon-nanotube (CNT)-enabled stationary digital breast tomosynthesis (sDBT) device, using magnified 2D mammography and conventional, moving-source DBT as references for comparison. METHODS: Lumpectomy specimens were imaged by magnified mammography and two 3D mammography approaches, including sDBT and moving-source DBT. The planar size of individual microcalcifications was measured in the reconstructed image stacks of sDBT and moving-source DBT and compared to the magnified mammography image. An artifact spread function (ASF) was used to assess the depth dimensions of the microcalcifications displayed through the reconstructed image stacks. Breast-imaging specialists rated their preference for one imaging modality over another when interpreting microcalcifications in the magnified mammography image and synthetic slab images from sDBT and moving-source DBT. RESULTS. The planar size of individual microcalcifications was similar in images generated by sDBT and moving-source DBT when the sDBT projections were binned to match the pixel size used by the moving-source DBT system. However, the unique structure of sDBT allowed for a wider-angle span of projection views and operation of the detector in full-resolution mode without significantly compromising the scan time. In this configuration, the planar sizes of individual microcalcifications displayed by sDBT was more similar to magnified mammography than moving-source DBT, and the microcalcifications had a narrower ASF through depth. Readers preferred sDBT over moving-source DBT when assessing microcalcifications in synthetic slab images, although magnified mammography was rated highest overall. CONCLUSIONS. The sDBT system displayed microcalcifications as well as conventional, moving-source DBT when the effective pixel size of the detector was matched. However, with the detector in its full-resolution mode, sDBT displayed microcalcifications with greater clarity. Readers still preferred images generated by magnified mammography over both 3D mammography approaches. This finding is guiding continued hardware and software development to optimize the sDBT technology.

Purpose. Report advances being made in synthetic mammography applied to carbon nanotube-enabled stationary digital breast tomosynthesis (sDBT). Methods. The potential value of adding Laplacian decomposition, feature-enhancement algorithms, and weighted recombination to the tunable forward-projection steps developed previously to generate synthetic mammograms for sDBT was studied in this phantom-based comparison of sDBT to full field digital mammography (FFDM) and moving-source or conventional DBT. Contrast-to-noise ratio (CNR) and the full-width-at-half-maximum (FWHM) of the signal intensity were used to compare the display of microcalcification and mass features in the FFDM image and the synthetic images generated by sDBT and DBT. These findings guided modifications in the sDBT image processing chain, seeking to maximize the display of clinically-important features in the sDBT-based synthetic image. Results. Decomposing each reconstructed image slice into its high, mid, and low-frequency components yielded images emphasizing a different feature of clinical importance: microcalcifications, masses, and background density. Applying feature-enhancement algorithms to these images followed by weighted recombination during forward projection yielded an sDBT-based synthetic image that displayed masses with a higher CNR than the FFDM image and the synthetic image generated by DBT. Additionally, microcalcifications that could be visualized in all three modalities were displayed with a higher CNR in the synthetic images generated by DBT and sDBT compared to the FFDM image. Conclusion. Adding Laplacian decomposition, feature-enhancement, and weighted recombination steps to the image processing chain that generates a synthetic image from information collected by sDBT improved the display of clinicallyimportant features. Advancing the synthetic mammography capability of sDBT is important, as it will help complete the evolution of this promising technology to a viable clinical tool.

Purpose. Explore the potential value of displaying information collected by stationary intraoral tomosynthesis (sIOT) as multi-view synthetic radiographs, using vertical root fractures (VRFs) as a model system. Methods. Filled and unfilled extracted tooth roots containing artificially-induced VRFs were imaged by sIOT and standard periapical radiography. sIOT collected 7 views across a 12° angle span, providing information for an image processing chain that included reconstruction, weighting, and forward projection to generate a set a synthetic two-dimensional (2D) images. Qualitative assessments of fracture conspicuity were used for comparison. Results. The conspicuity of VRFs changed significantly with the angle of imaging, suggesting benefit to displaying a set of synthetic images across a span of viewing angles. Although high-density in-plane and out-of-plane artifacts, which could limit the conspicuity of VRFs, were prominent in the three-dimensional (3D) stack of reconstructed image slices, these artifacts were minimal in the synthetic radiographs. As such, some fractures were displayed more clearly in the synthetic 2D images compared to the reconstructed 3D image stack. Also, in some cases, the fractures were more conspicuous in the sIOT-generated synthetic images than the standard periapical radiographs. Conclusion. Multi-view synthetic radiography can improve the display of VRFs in images generated by sIOT. As such, this approach to dental imaging may offer a useful clinical tool, with potential application to a host of imaging tasks.

Orthopedic tomosynthesis is emerging as an attractive alternative to digital radiography (DR), with increased sensitivity for some clinical tasks, including fracture diagnosis and staging and follow-up of arthritis. Commercially available digital tomosynthesis (DTS) systems are complex, room-sized devices. A compact tomosynthesis system for extremity imaging (TomoE) was previously demonstrated using carbon nanotube (CNT) x-ray source array technology. The purpose of this study was to evaluate the prototype device in preparation for an Institutional Review Board (IRB)- approved patient imaging study and evaluate initial patient images. A tabletop device was constructed using a short CNT x-ray source array, operated in three positions, and a flat panel digital detector. Twenty-one x-ray projection images were acquired at incident angles from -20 to +20 degrees in various clinical orientations, with entrance doses matched to commercial in-room DTS scanners. The projection images were reconstructed with an iterative reconstruction technique in 1mm slices. Cadaveric specimen and initial participant images were reviewed by radiologists for feature conspicuity and diagnostic accuracy. TomoE image quality was found to be superior to DR, with reconstruction slices exhibiting visual conspicuity of trabecular bone, delineation of joint space, bone erosions, fractures, and clear depiction of normal anatomical features. The scan time was fifteen seconds with mechanical translation. Skin entrance dose was verified to be 0.2mGy. TomoE device image quality has been evaluated in cadaveric specimens and dose was calibrated for a patient imaging study. Initial patient images depict a high level of anatomical detail an increase in diagnostic value compared to DR.

Purpose: Chest tomosynthesis is an attractive alternative to computed tomography (CT) for lung nodule screening, but reductions in image quality caused by radiation scatter remains an important limitation. Conventional anti-scatter grids result in higher patient dose, and alternative approaches are needed. The purpose of this study was to validate a lowdose patient-specific approach to scatter correction for an upcoming human imaging study. Method: A primary sampling device (PSD) was designed and scatter correction algorithm incorporated into an experimental stationary digital chest tomosynthesis (s-DCT) system for this study to directly compute scatter from the primary beam information. Phantom and an in-vivo porcine subject were imaged. Total scan time was measured and image quality evaluated. Results: Comparison of reconstruction slice images from uncorrected and scatter-corrected projection images reveals improved image quality, with increased feature conspicuity. Each scan in the current setup required twelve seconds, in addition to one second for PSD retraction, for a total scan time of 25 seconds. Conclusions: We have evaluated the prototype low-dose, patient-specific scatter correction methodology using phantom studies in preparation for a clinical trial. Incorporating only 5% of additional patient dose, the reconstruction slices exhibit increased visual conspicuity of anatomical features, with the primary drawback of increased total scan time. Though used for tomosynthesis, the technique can be easily translated to digital radiography in lieu of an anti-scattering grid.

Registration is widely used in image-guided therapy and image-guided surgery to estimate spatial correspondences between organs of interest between planning and treatment images. However, while high-quality computed tomography (CT) images are often available at planning time, limited angle acquisitions are frequently used during treatment because of radiation concerns or imaging time constraints. This requires algorithms to register CT images based on limited angle acquisitions. We, therefore, formulate a 3D/2D registration approach which infers a 3D deformation based on measured projections and digitally reconstructed radiographs of the CT. Most 3D/2D registration approaches use simple transformation models or require complex mathematical derivations to formulate the underlying optimization problem. Instead, our approach entirely relies on differentiable operations which can be combined with modern computational toolboxes supporting automatic differentiation. This then allows for rapid prototyping, integration with deep neural networks, and to support a variety of transformation models including fluid flow models. We demonstrate our approach for the registration between CT and stationary chest tomosynthesis (sDCT) images and show how it naturally leads to an iterative image reconstruction approach.

Purpose Technological advancements in dental radiography have improved oral care on many fronts, yet diagnostic efficacy for some of the most common oral conditions, such as caries, dental cracks and fractures, and periodontal disease, remains relatively low. Driven by the clinical need for a better diagnostic yield for these and other dental conditions, we initiated the development of a stationary intraoral tomosynthesis (s-IOT) imaging system using carbon nanotube (CNT) x-ray source array technology. Here, we report the system characterization and preliminary imaging evaluation of a clinical prototype s-IOT system approved for human use. Methods The clinical prototype s-IOT system is comprised of a multibeam CNT x-ray source array, high voltage generator, control electronics, collimator cone, and dynamic digital intraoral detector. During a tomosynthesis scan, each x-ray source is operated sequentially at fixed, nominal tube current of 7 mA and user-specified pulse width. Images are acquired by a digital intraoral detector and the reconstruction algorithm generates slice information in real time for operator review. In this study, the s-IOT system was characterized for tube output, dosimetry, and spatial resolution. Manufacturer specifications were validated, such as tube current, kVp, and pulse width. Tube current was measured with an oscilloscope on the analog output of the anode power supply. Pulse width, kVp, and peak skin dose were measured with a dosimeter with ion chamber and high voltage accessory. In-plane spatial resolution was evaluated via measurement of MTF and imaging of a line pair phantom. Spatial resolution in the depth direction was evaluated via artifact spread measurement. The size of the collimated radiation field was evaluated for compliance with FDA regulations. A dental phantom and human specimens of varying pathologies were imaged on a clinical 2D intraoral imaging system as well as s-IOT for comparison and to explore potential clinical applications. Results The measured tube current, kVp, and pulse width values were within 3% of the set values. A cumulative peak skin dose of 1.12 mGy was measured for one complete tomosynthesis scan using a 50-ms pulse per projection view. Projection images and reconstruction slices revealed MTF values ranging from 8.1 to 9.3 cycles/mm. Line pair imaging verified this result. The radiation field was found to meet the FDA requirements for intraoral imaging devices. Tomosynthesis reconstruction slice images of the dental phantom and human specimens provided depth resolution, allowing visibility of anatomical features that cannot be seen in the 2D intraoral images. Conclusions The clinical prototype s-IOT device was evaluated and found to meet all manufacturer specifications. Though the system capability is higher, initial investigations are targeting a low-dose range comparable to a single 2D radiograph. Preliminary studies indicated that s-IOT provides increased image quality and feature conspicuity at a dose comparable to a single 2D intraoral radiograph.

Purpose. Investigate synthetic mammography approaches for carbon nanotube (CNT)-enabled stationary digital breast tomosynthesis (sDBT). Methods. Projection images of breast-mimicking phantoms containing soft-tissue masses and microcalcification clusters collected by sDBT were used to develop weighted-intensity forward-projection algorithms that generated a synthetic mammogram from the reconstructed 3D image space. Reconstruction was accomplished by an adapted fan-volume modification of the simultaneous iterative reconstruction technique. Detectability indices were used to quantify mass and calcification visibility. The image processing chain was then applied to projection views collected by sDBT on women with “suspicious” breast lesions detected by standard screening 2D digital mammography. Results. Quantifying detectability allowed correlation between the visibility of clinically-important image features and the order of the polynomial weighting function used during forward projection. The range of weighted functions exists between the extremes of an average-intensity projection (zero-order) and maximum-intensity projection (infinite-order), with lower order weights emphasizing soft-tissue features and higher-order weights emphasizing calcifications. Application of these algorithms to patient images collected by sDBT, coupled with dense-artifact reduction and background equalization steps, produced synthetic mammograms on which additional post-processing approaches can be explored, with the actual mammogram providing a reference for comparison. Conclusions. An image-processing chain with adjustable weighting during forward projection, dense-artifact reduction, and background equalization can yield a range of sDBT-based synthetic mammograms that display clinically-important features differently, potentially improving the ability to appreciate the association of masses and calcifications.

Tomosynthesis imaging has been demonstrated as an alternative to MRI and CT for orthopedic imaging. Current commercial tomosynthesis scanners are large in-room devices. The goal of this study was to evaluate the feasibility of designing a compact tomosynthesis device for extremity imaging at the point-of-care utilizing a carbon nanotube (CNT) x-ray source array. The feasibility study was carried out using a short linear CNT source array with limited number of x-ray emitting focal spots. The short array was mounted on a translation stage and moved linearly to mimic imaging configurations with up to 40 degrees angular coverage at a source-to-detector distance of 40cm. The receptor was a 12x12cm flat panel digital detector. An anthropomorphic phantom and cadaveric wrist specimens were imaged at 55kVp under various exposure conditions. The projection images were reconstructed with an iterative reconstruction algorithm. Image quality was assessed by musculoskeletal radiologists. Reconstructed tomosynthesis slice images were found to display a higher level of detail than projection images due to reduction of superposition. Joint spaces and abnormalities such as cysts and bone erosion were easily visualized. Radiologists considered the overall utility of the tomosynthesis images superior to conventional radiographs. This preliminary study demonstrated that the CNT x-ray source array has the potential to enable tomosynthesis imaging of extremities at the point-of-care. Further studies are necessary to optimize the system and x-ray source array configurations in order to construct a dedicated device for diagnostic and interventional applications.

Purpose: To assess the visibility of microcalcifications in images generated by a first-generation carbon-nanotube (CNT)-enabled stationary digital breast tomosynthesis (sDBT) device, using magnified 2D mammography and conventional, moving-source DBT as references for comparison. Methods: Lumpectomy specimens were imaged by magnified mammography and two 3D mammography approaches, including sDBT and moving-source DBT. The planar size of individual microcalcifications was measured in the reconstructed image stacks of sDBT and moving-source DBT and compared to the magnified mammography image. An artifact spread function (ASF) was used to assess the depth dimensions of the microcalcifications displayed through the reconstructed image stacks. Breast-imaging specialists rated their preference for one imaging modality over another when interpreting microcalcifications in the magnified mammography image and synthetic slab images from sDBT and moving-source DBT. Results: The planar size of individual microcalcifications was similar in images generated by sDBT and moving-source DBT when the sDBT projections were binned to match the pixel size used by the moving-source DBT system. However, the unique structure of sDBT allowed for a wider-angle span of projection views and operation of the detector in full-resolution mode without significantly compromising the scan time. In this configuration, the planar sizes of individual microcalcifications displayed by sDBT was more similar to magnified mammography than moving-source DBT, and the microcalcifications had a narrower ASF through depth. Readers preferred sDBT over moving-source DBT when assessing microcalcifications in synthetic slab images, although magnified mammography was rated highest overall. Conclusions: The sDBT system displayed microcalcifications as well as conventional, moving-source DBT when the effective pixel size of the detector was matched. However, with the detector in its full-resolution mode, sDBT displayed microcalcifications with greater clarity. Readers still preferred images generated by magnified mammography over both 3D mammography approaches. This finding is guiding continued hardware and software development to optimize the sDBT technology.

Stationary intraoral tomosynthesis (sIOT) is an experimental imaging approach using a fixed array of carbon nanotubeenabled x-ray sources to produce a series of projections from which three-dimensional information can be reconstructed and displayed. Customized to the dental workspace, the first-generation sIOT tube is compact, easy-to-operate, and designed to interface with standard digital intraoral detectors. The purpose of this work was to explore the utility of the sIOT device across a range of dental pathologies and thereby identify limitations potentially amenable to correction through post-acquisition processing. Phantoms, extracted human teeth, and cadaveric specimens containing caries, fractures, and dilacerated roots, often associated with amalgam restorations, were imaged using tube settings that match the kVp and mA used in conventional clinical 2D intraoral imaging. An iterative reconstruction approach generated a stack of image slices through which the reader scrolls to appreciate depth relationships. Initial experience demonstrated an improved ability to visualize occlusal caries, interproximal caries, crown and root fractures, and root dilacerations when compared to 2D imaging. However, artifacts around amalgam restorations and metal implants proved problematic, leading to the incorporation of an artifact reduction step in the post-acquisition processing chain. These findings support the continued study of sIOT as a viable limited-angle tomography tool for dental applications and provide a foundation for the ongoing development of image processing steps to maximize the diagnostic utility of the displayed images.

High resolution imaging of the chest is dependent on a breath hold maintained throughout the imaging time. However, pediatric and comatose patients are unable to follow respiration commands. Gated tomosynthesis could offer a lower dose, high in-plane resolution imaging modality, but current systems are unable to prospectively gate in a reasonable scan time. In contrast, a carbon nanotube (CNT) based linear x-ray source array offers both the angular span and precise control necessary to generate x-ray projections for gated tomosynthesis. The goal of this study was to explore the first clinical use of the CNT linear x-ray source array for gated clinical chest imaging. Eighteen pediatric cystic fibrosis patients were recruited for this study, with 13 usable image sets. The s-GDCT system consists of a CNT linear x-ray source array coupled with a digital detector. A respiration signal derived from a respiratory belt served as a gating signal with sources fired sequentially when the imaging window and maximum inspiration window coincided. Images were reconstructed and reviewed for motion blur and ability to identify major anatomical structures. Image quality was highly dependent on quality of the respiration gating signal, and a correlation was found between qualitative image quality and height of the respiration peak. We demonstrate the first prospectively gated evaluation of the stationary digital chest tomosynthesis patients in pediatric patients. Though further refinements in projection selection and respiratory gating approaches are necessary, this study demonstrates the potential utility of this low dose imaging approach.

Background The first generation stationary intraoral tomosynthesis (sIOT) device, developed at University of North Carolina (UNC), provides 3-D information in intraoral imaging with a speed and dose comparable with those of traditional intraoral radiography. Initial research shows promise in several diagnostic tasks, including caries and fracture detection. However, the original iterative reconstruction produces artifacts adjacent to metal restorations. Two new iterative reconstructions with metal artifact reduction (MAR1 and MAR2) have been developed. MAR1 segments the metal out before reconstruction and adds it back after reconstruction. MAR2 minimizes the artifact amplified at each iteration by dividing the projected error by the number of slices. Objective(s) The aim of this study was to compare the effectiveness of metal artifact reduction in tomosynthesis. Study Design Pilot samples of 2 extracted premolars with amalgam restorations were imaged by using the sIOT system. Reconstructions were generated using the original, MAR1, and MAR2 algorithms. Using line density plots, artifact pixel intensity and artifact width were measured for the original, MAR1, and MAR2 algorithms. Results The difference between average dentin pixel intensity and artifact pixel intensity for sample 1 was 8016, –5781, and 759 for the original, MAR1, and MAR2 reconstructions, respectively. Artifact width was 2.61 mm, 0.82 mm, and 1.38 mm, respectively. For sample 2, the difference in intensity was 8248, –5399, and 93, respectively. Artifact width was 1.71 mm, 1.06 mm, and 0.81 mm, respectively. Discussion/Conclusions MAR1 and MAR2 reduced the intensity of the artifacts; however, reduction by MAR2 was more pronounced. MAR1 produced radiopaque artifacts, whereas MAR2 produced radiolucent artifacts. MAR1 and MAR2 reduced the width of the artifacts, but the extent was reversed between the samples. The results support the value of MAR for tomosynthesis and suggests that MAR2 may be more effective. Continued development of artifact reduction techniques is needed with a more in-depth study using a larger sample size.

A new imaging technology has emerged that uses carbon nanotubes (CNT) as the electron emitter (cathode) for the X-ray tube. Since the performance of the CNT cathode is controlled by simple voltage manipulation, CNT-enabled X-ray sources are ideal for the repetitive imaging steps needed to capture three-dimensional information. As such, they have allowed the development of a gated micro-computed tomography (CT) scanner for small animal research as well as stationary tomosynthesis, an experimental technology for large field-of-view human imaging. The small animal CT can acquire images at specific points in the respiratory and cardiac cycles. Longitudinal imaging therefore becomes possible and has been applied to many research questions, ranging from tumor response to the noninvasive assessment of cardiac output. Digital tomosynthesis (DT) is a low-dose and low-cost human imaging tool that captures some depth information. Known as three-dimensional mammography, DT is now used clinically for breast imaging. However, the resolution of currently-approved DT is limited by the need to swing the X-ray source through space to collect a series of projection views. An array of fixed and distributed CNT-enabled sources provides the solution and has been used to construct stationary DT devices for breast, lung, and dental imaging. To date, over 100 patients have been imaged on Institutional Review Board-approved study protocols. Early experience is promising, showing an excellent conspicuity of soft-tissue features, while also highlighting technical and post-acquisition processing limitations that are guiding continued research and development. Additionally, CNT-enabled sources are being tested in miniature X-ray tubes that are capable of generating adequate photon energies and tube currents for clinical imaging. Although there are many potential applications for these small field-of-view devices, initial experience has been with an X-ray source that can be inserted into the mouth for dental imaging. Conceived less than 20 years ago, CNT-enabled X-ray sources are now being manufactured on a commercial scale and are powering both research tools and experimental human imaging devices. WIREs Nanomed Nanobiotechnol 2018, 10:e1475. doi: 10.1002/wnan.1475 This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Stationary digital breast tomosynthesis (sDBT) is an emerging technology in which the single rotating x-ray tube is replaced by a fixed array of multiple carbon nanotube-enabled sources, providing a higher spatial and temporal resolution. As such, sDBT offers a promising platform for contrast-enhanced (CE) imaging. However, given the minimal enhancement above background with standard operational tube settings and iodine dosing, CE breast imaging requires additional acquisition steps to isolate the iodine signal, using either temporal or dual energy subtraction (TS or DES) protocols. Also, correcting for factors that limit contrast is critical, and scatter and noise pose unique challenges during tomosynthesis. This phantom-based study of CE sDBT compared different postacquisition scatter correction approaches on the quality of the reconstructed image slices. Beam-pass collimation was used to sample scatter indirectly, from which an interpolated scatter map was obtained for each projection image. Scatter-corrected projections provided the information for reconstruction. Comparison between the application of different scatter maps demonstrated the significant effect that processing has on the contrast-to-noise ratio and feature detectability ([Formula: see text]) in the final displayed images and emphasized the critical importance of scatter correction during DES.

Few investigations have been published demonstrating the in vivo contrast characteristics of phase-change perfluorocarbon droplets. In this study, we examine the properties of low boiling point nanoscale droplets compared to microbubbles with respect to image enhancement and circulation time. To accomplish this, we develop a custom pulse sequence to vaporize and image droplets using the Verasonics research platform. Results show that droplets can produce similar contrast compared to microbubbles, and can circulate for significantly longer than microbubbles, depending on formulation. Finally, this study demonstrates a novel concept in contrast-enhanced ultrasound: capture of droplet-generated contrast wash-out in the target organ.

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published demonstrating the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low boiling point nanoscale PCCAs evaluated in vivo, and compare data to conventional microbubbles with respect to contrast generation and circulation properties. In order to do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results show that droplets can produce similar contrast enhancement to microbubbles (7.29 to 18.24 dB over baseline, depending on formulation), and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also demonstrates for the first time the ability to capture contrast wash-out kinetics of the target organ as a measure of vascular perfusion.

Information regarding the contributions of the authors was not included in the original publication. In the original format of the paper submitted for review, the author order was Phillips, Puett, Sheeran, Miller, Matsunaga, and Dayton. This order was agreed on by all authors to properly acknowledge levels of contribution according to standard biomedical convention with primary contributor first and senior author last. However, the authors wish to note that because of the standard format style of JASA, the authors in the published document are grouped by institution. Dr. Phillips, as first author, conducted all of the studies in the manuscript, analyzed data, wrote the manuscript, and performed editing. Mr. Puett and Mr. Sheeran assisted with data collection and analysis, as did Dr. Miller. Dr. Matsunaga provided expertise as to the nanodroplet formulations. Dr. Dayton was the senior author on this work, contributed to study concept and design, applied for the funding, and edited the manuscript.

Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100-300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 × 10(6) per cm(3) resulted in mean lesion volumes of 80.4 ± 33.1 mm(3) and 52.8 ± 14.2 mm(3) (mean ± s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, compared to a lesion volume of 1.0 ± 0.8 mm(3) in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site.

Both pefluorocarbon microbubbles and nanodroplets have been investigated as enhancers of high intensity focused ultrasound (HIFU) thermal ablation, however microbubbles often lead to surface or skin lesions. We have designed and investigated a dual-perfluorocarbon (PFC) nanodroplet which has the benefits of sufficiently small size to extravasate from tumors, enhanced stability at body temperature, and sufficiently low acoustic threshold for vaporization. In vitro, microbubbles enhanced thermal depostion at the target site by 21%, but were found to cause surface heating up to 60.2±2.2°C. Nanodroplets caused no more surface heating (10.1±1.1°C) than the temperature rise observed in agent-free controls (9.8±0.8°C), and enhanced heating at the target by 51%. Circulation time of the nanodroplets was investigated in vivo. HIFU (1 MHz, 4.06 MPa, CW, 15 seconds) was applied to rat livers (n=3) up to 95 minutes after nanodroplet injection, and any thermal enhancement was detected simultaneously by MR thermometry. Temperature rises of up to 55 degrees above body temperature were observed out to 95 minutes. HIFU applied to control livers without nanodroplets induced only a 22°C maximal temperature rise. These results suggest that the nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 hours and could reduce focused ultrasound surgical procedure times by as much as 5 fold by more quickly ablating a larger region of tissue, without compromising safety.

Perfluorocarbon microbubbles are known to enhance high intensity focused ultrasound (HIFU) ablation by cavitation. However, they can result in superficial skin heating, minimizing their clinical translation. Perfluorocarbon nanodroplets activate only at the higher pressures present at the acoustic focus. We hypothesized that a mixed perfluorocarbon nanodroplet formulation would minimize surface heating while still enhancing ablation. Tissue-mimicking phantoms containing microbubbles or nanodroplets were sonicated (1 MHz, 15 W, 60 s) to assess heating and lesion formation in vitro. Microbubbles or nanodroplets were injected into rats (n = 3) and HIFU (1 MHz, 15 W, 15 s) was focused into each liver while under MRI guidance. Temperature throughout the liver was tracked by MR thermometry. In vitro, microbubbles caused excess surface heating during HIFU, whereas nanodroplets did not. In vivo, microbubbles typically circulate for less than 15 min. In comparison, the nanodroplets remained viable in circulation for at least 96 min. HIFU lesions of consistent volume were produced during this time and reached the same maximal temperature rise (Δ550 °C). In the absence of nanodroplets or microbubbles, significantly greater power (25 W) and twice as much time (30 s) was required to generate an ablation lesion in the liver. These results demonstrate the ability of nanodroplets to more safely shorten ablation procedures.

Phase-change contrast agents (PCCAs) consist of liquid perfluorocarbon droplets that can be vaporized into gas-filled microbubbles by pulsed ultrasound waves at diagnostic pressures and frequencies. These activatable contrast agents provide benefits of longer circulating times and smaller sizes relative to conventional microbubble contrast agents. However, optimizing ultrasound-induced activation of these agents requires coordinated pulse sequences not found on current clinical systems, in order to both initiate droplet vaporization and image the resulting microbubble population. Specifically, the activation process must provide a spatially uniform distribution of microbubbles and needs to occur quickly enough to image the vaporized agents before they migrate out of the imaging field of view. The development and evaluation of protocols for PCCA-enhanced ultrasound imaging using a commercial array transducer are described. The developed pulse sequences consist of three states: (1) initial imaging at sub-activation pressures, (2) activating droplets within a selected region of interest, and (3) imaging the resulting microbubbles. Bubble clouds produced by the vaporization of decafluorobutane and octafluoropropane droplets were characterized as a function of focused pulse parameters and acoustic field location. Pulse sequences were designed to manipulate the geometries of discrete microbubble clouds using electronic steering, and cloud spacing was tailored to build a uniform vaporization field. The complete pulse sequence was demonstrated in the water bath and then in vivo in a rodent kidney. The resulting contrast provided a significant increase (>15 dB) in signal intensity.

Background Phase-shift nanoemulsions (PSNEs) provide cavitation sites when the perfluorocarbon (PFC) nanodroplets (ND) are vaporized to microbubbles by acoustic energy. Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites. However, spatial control over the ablation region can be problematic when cavitation is used to enhance heating. This study explored relationships between vaporization, ablation, and the PSNE concentration in vitro to optimize the acoustic intensity and insonation time required for spatially controlled ablation enhancement using a PSNE that included a volatile PFC component. Methods HIFU (continuous wave at 1 MHz; insonation times of 5, 10, 15, and 20 s; cool-down times of 2, 4, and 6 s; peak negative pressures of 2, 3, and 4 MPa) was applied to albumin-acrylamide gels containing PFC agents (1:1 mix of volatile decafluorobutane and more stable dodecafluoropentane at 105 to 108 PFC ND per milliliter) or agent-free controls. Vaporization fields (microbubble clouds) were imaged by conventional ultrasound, and ablation lesions were measured directly by calipers. Controlled ablation was defined as the production of ‘cigar’-shaped lesions corresponding with the acoustic focal zone. This control was considered to be lost when ablation occurred in prefocal vaporization fields having a predominantly ‘tadpole’ or oblong shape. Results Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity. Working with the maximum concentration-intensity combinations resulting in controlled ablation demonstrated a dose-responsive relationship between insonation time and volumes of both the vaporization fields (approximately 20 to 240 mm3) and the ablation lesions (1 to 135 mm3) within them. Conclusions HIFU ablation was enhanced by this PSNE and could be achieved using intensities ≤650 W/cm2. Although the ablation lesions were located within much larger microbubble clouds, optimum insonation times and intensities could be selected to achieve an ablation lesion of desired size and location for a given PSNE concentration. This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.