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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.

Purpose Stationary computed tomography (s-CT) conceptually offers several advantages over existing rotating gantry-based CT. Over the last 40 yr, s-CT has been investigated using different technological approaches. We are developing a s-CT system specifically for head/brain imaging using carbon nanotube (CNT)-based field emission x-ray source array technology. The noncircular geometry requires different assessment approaches as compared to circular geometries. The purpose of the present study is to investigate whether the CNT source array meets the requirements for stationary head CT (s-HCT). Methods Multiple prototype CNT x-ray source arrays were manufactured based on the system requirements obtained from simulation. Source characterization was performed using a benchtop setup consisting of an x-ray source array with 45 distributed focal spots, each operating at 120 kVp, and an electronic control system (ECS) for high speed control of the x-ray output from individual focal spots. Due to the forward-angled geometry of the linear anode, the projected focal spot shape is expected to vary at wide angle views. A pinhole method was implemented to determine the effective focal spot size (FSS) in the imaging plane at a range of angular viewpoints with a flat panel detector. The output spectrum and half value layer (HVL) were also evaluated for a range of viewing angles to characterize the beam quality across the fan-beam. Dosimetry was performed on a simulated scan to evaluate total exposure. Results The prototype CNT x-ray source array demonstrated adequate specifications for a s-HCT imaging machine. The source array was operated at 120 kVp with long-term stability over a full year of regular laboratory use. Multiple cathode current measurements were used to confirm submicrosecond accuracy with regards to exposure time and subsequently dose control. All 45 focal spots were measured with an average value of 1.26 (±0.04) mm × 1.21 (±0.03) mm (equivalent to IEC 1,0). The x-ray spectrum was found to be appropriately filtered based on sources used in existing rotary CT systems. A stable and reliable output of 0.04 mAs per emitter and a resulting dose of 0.015 mGy per projection were observed over several months of rigorous phantom imaging. Dose per projection was regulated by the ECS and measured with ±0.5% tolerance. Conclusions The CNT x-ray source array was found to meet the requirements for the proposed stationary head CT scanner, with regard to FSS, beam quality, and dose precision. The remaining challenges are related to the overall system design of a nonrotating CT scanner with distributed sources. The next phase of the project will incorporate multiple CNT source arrays with multirow detectors in a proof-of-concept study and analysis of a fully functional s-HCT system.

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.

BACKGROUND: Screen detected and incidental pulmonary nodules are increasingly common. Current guidelines recommend tissue sampling of solid nodules >8 mm. Bronchoscopic biopsy poses the lowest risk but is paired with the lowest diagnostic yield when compared to CT-guided biopsy or surgery. A need exists for a safe, mobile, low radiation dose, intra-procedural method to localize biopsy instruments within target nodules. This retrospective cross sectional reader feasibility study evaluates the ability of clinicians to identify pulmonary nodules using a prototype carbon nanotube radiation enabled stationary digital chest tomosynthesis system. METHODS: Patients with pulmonary nodules on prior CT imaging were recruited and consented for imaging with stationary digital chest tomosynthesis. Five pulmonologists of varying training levels participated as readers. Following review of patient CT and a thoracic radiologist’s interpretation of nodule size and location the readers were tasked with interpreting the corresponding tomosynthesis scan to identify the same nodule found on CT. RESULTS: Fifty-five patients were scanned with stationary digital chest tomosynthesis. The median nodule size was 6 mm (IQR =4–13 mm). Twenty nodules (37%) were greater than 8 mm. The radiation entrance dose for s-DCT was 0.6 mGy. A significant difference in identification of nodules using s-DCT was seen for nodules

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.

X-ray Computed Tomography (CT) is an indispensable imaging modality in the diagnosis of traumatic brain injury and brain hemorrhage. While the technology and the associated system components have been refined over the last several decades, all modern CT systems still rely on the principle of rotating sources and detectors. The rotating gantry adds a high degree of complexity to the overall system design, and could be eliminated in favor of a configuration of stationary x-ray sources and detectors. Such a change could potentially enable CT systems to be better suited for austere environments. Furthermore, the image acquisition speed would no longer be limited by the maximum rotating speed of the gantry. Unfortunately, due to the size and bulk of existing commercial x-ray sources, such a configuration is impossible to build with a sufficient number of focal spots. Recently, carbon nanotube (CNT) x-ray source arrays have been used in various stationary imaging configurations to generate diagnostic quality tomosynthesis images in the fields of mammography, dentistry, and orthopedics. In this study, we present a potential stationary head CT (s-HCT) design which combines projection data from 3 separate but parallel imaging planes for a complete CT fan-beam reconstruction. The proposed scanner consists of 3 CNT x-ray source arrays with a large number distributed focal spots each, and an Electronic Control System (ECS) for high speed control of the x-ray exposure from each focal spot. The projection data was collected by an array of multi-row detectors. For this unique imaging configuration, a customized geometry calibration procedure was developed. A linear collimator was designed and constructed for the reduction of cone-angle scatter. Finally, volumetric CT slice data was acquired through z-axis translation of the imaging object.

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.

Purpose: Carbon nanotube (CNT) based field-emission x-ray source arrays allow the development of robust stationary computed tomography (CT) imaging systems with no gantry movement. There are many technical considerations that constrain the optimal system design. The aim of this work is to assess the image quality of a proposed Stationary Head CT (sHCT) system through simulation. Methods: In our previous work, we defined a system design consisting of three parallel imaging planes. Each plane consists of a CNT x-ray source array with a large number of linearly distributed focal spots and three strip detector modules. Each imaging plane is rotated 120° with respect to the adjacent plane to provide maximum projection view coverage of the region of interest (ROI). An iterative reconstruction algorithm based on the ASTRA toolbox was developed for the specific sHCT system. The ACR 464 phantom and a set of clinical head CT data were used to assess the system design and image quality. Imaging performance was evaluated both quantitatively and qualitatively. Results: The simulation results suggest that the proposed sHCT design is feasible and high-fidelity CT images can be obtained. The reconstructed image of the ACR 464 phantom reproduces accurate CT numbers. The reconstructed CT images for the human head confirm the capability of this prototype for identifying low contrast pathologies. Conclusion: A three-plane sHCT system is evaluated in this work. The iterative reconstruction algorithm produces high image quality in terms of uniformity, signal-to-noise ratio, signal-to-contrast ratio and structural information. Further work on the optimization of the current sHCT system will focus on speed up of volumetric image data collection in system hardware and further improvement of the reconstruction image quality through regularization and incorporating of machine leaning techniques.

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.

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.

The imaging evaluation of cystic fibrosis currently relies on chest radiography or computed tomography. Recently, digital chest tomosynthesis has been proposed as an alternative. We have developed a stationary digital chest tomosynthesis (s-DCT) system based on a carbon nanotube (CNT) linear x-ray source array. This system enables tomographic imaging without movement of the x-ray tube and allows for physiological gating. The goal of this study was to evaluate the feasibility of clinical CF imaging with the s-DCT system. CF patients undergoing clinically indicated chest radiography were recruited for the study and imaged on the s-DCT system. Three board-certified radiologists reviewed both the CXR and s-DCT images for image quality relevant to CF. CF disease severity was assessed by Brasfield score on CXR and chest tomosynthesis score on s-DCT. Disease severity measures were also evaluated against subject pulmonary function tests. Fourteen patients underwent s-DCT imaging within 72 h of their chest radiograph imaging. Readers scored the visualization of proximal bronchi, small airways and vascular pattern higher on s-DCT than CXR. Correlation between the averaged Brasfield score and averaged tomosynthesis disease severity score for CF was -0.73, p = 0.0033. The CF disease severity score system for tomosynthesis had high correlation with FEV1 (r = -0.685) and FEF 25–75% (r = -0.719) as well as good correlation with FVC (r = -0.582). We demonstrate the potential of CNT x-ray-based s-DCT for use in the evaluation of cystic fibrosis disease status in the first clinical study of s-DCT. • Carbon nanotube-based linear array x-ray tomosynthesis systems have the potential to provide diagnostically relevant information for patients with cystic fibrosis without the need for a moving gantry. • Despite the short angular span in this prototype system, lung features such as the proximal bronchi, small airways and pulmonary vasculature have improved visualization on s-DCT compared with CXR. Further improvements are anticipated with longer linear x-ray array tubes. • Evaluation of disease severity in CF patients is possible with s-DCT, yielding improved visualization of important lung features and high correlation with pulmonary function tests at a relatively low dose.

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.

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 Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brain tissue. Most MRT studies have been conducted at synchrotron facilities. With the aim to make this promising treatment more available, we have built the first desktop image-guided MRT device based on carbon nanotube x-ray technology. In the current study, our purpose was to evaluate the effects of MRT on the rodent normal brain tissue using our device and compare it with the effect of the integrated equivalent homogenous dose. Methods Twenty-four, 8-week-old male C57BL/6 J mice were randomly assigned to three groups: MRT, broad-beam (BB) and sham. The hippocampal region was irradiated with two parallel microbeams in the MRT group (beam width = 300 μm, center-to-center = 900 μm, 160 kVp). The BB group received the equivalent integral dose in the same area of their brain. Rotarod, marble burying and open-field activity tests were done pre- and every month post-irradiation up until 8 months to evaluate the cognitive changes and potential irradiation side effects on normal brain tissue. The open-field activity test was substituted by Barnes maze test at 8th month. A multilevel model, random coefficients approach was used to evaluate the longitudinal and temporal differences among treatment groups. Results We found significant differences between BB group as compared to the microbeam-treated and sham mice in the number of buried marble and duration of the locomotion around the open-field arena than shams. Barnes maze revealed that BB mice had a lower capacity for spatial learning than MRT and shams. Mice in the BB group tend to gain weight at the slower pace than shams. No meaningful differences were found between MRT and sham up until 8-month follow-up using our measurements. Conclusions Applying MRT with our newly developed prototype compact CNT-based image-guided MRT system utilizing the current irradiation protocol can better preserve the integrity of normal brain tissue. Consequently, it enables applying higher irradiation dose that promises better tumor control. Further studies are required to evaluate the full extent effects of this novel modality. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0864-2) contains supplementary material, which is available to authorized users.

Despite recent advances in dental radiography, the diagnostic accuracies for some of the most common dental diseases have not improved significantly, and in some cases remain low. Intraoral x-ray is the most commonly used x-ray diagnostic tool in dental clinics. It however suffers from the typical limitations of a 2D imaging modality including structure overlap. Cone-beam computed tomography (CBCT) uses high radiation dose and suffers from image artifacts and relatively low resolution. The purpose of this study is to investigate the feasibility of developing a stationary intraoral tomosynthesis (s-IOT) using spatially distributed carbon nanotube (CNT) x-ray array technology, and to evaluate its diagnostic accuracy compared to conventional 2D intraoral x-ray. A bench-top s-IOT device was constructed using a linear CNT based X-ray source array and a digital intraoral detector. Image reconstruction was performed using an iterative reconstruction algorithm. Studies were performed to optimize the imaging configuration. For evaluation of s-IOT’s diagnostic accuracy, images of a dental quality assurance phantom, and extracted human tooth specimens were acquired. Results show s-IOT increases the diagnostic sensitivity for caries compared to intraoral x-ray at a comparable dose level.

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.

Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.

Scatter radiation severely degrades the image quality. Measurement-based scatter correction methods sample the scatter signal at sparsely distributed points, from which the scatter profile is estimated and deterministically removed from the projection image. The estimation of the scatter profile is generally done through a spline interpolation and the resulting scatter profile is quite smooth. Consequently, the noise is intact and the signal-to-noise ratio is reduced in the projection image after scatter correction, leading to image artifacts and increased noise in the reconstruction images. We propose a simple and effective method, referred to as filtered scatter-to-primary ratio ([Formula: see text]-SPR) estimation, to estimate the scatter profile using the sparsely sampled scatter signal. Using the primary sampling device and the stationary digital tomosynthesis systems previously developed in our lab, we evaluated and compared the [Formula: see text]-SPR method in comparison with existing methods in terms of contrast ratio, signal difference-to-noise ratio, and modulation transfer function. A significant improvement in image quality is observed in both the projection and the reconstruction images using the proposed method.

Microbeam radiation therapy (MRT) is a promising preclinical modality for cancer treatment, with remarkable preferential tumoricidal effects, that is, tumor eradication without damaging normal tissue functions. Significant lifespan extension has been demonstrated in brain tumor-bearing small animals treated with MRT. So far, MRT experiments can only be performed in a few synchrotron facilities around the world. Limited access to MRT facilities prevents this enormously promising radiotherapy technology from reaching the broader biomedical research community and hinders its potential clinical translation. We recently demonstrated, for the first time, the feasibility of generating microbeam radiation in a laboratory environment using a carbon nanotube x-ray source array and performed initial small animal studies with various brain tumor models. This new nanotechnology-enabled microbeam delivery method, although still in its infancy, has shown promise for achieving comparable therapeutic effects to synchrotron MRT and has offered a potential pathway for clinical translation.

Microbeam radiation therapy (MRT) uses an array of high-dose, narrow (~100 μm) beams separated by a fraction of a millimeter to treat various radio-resistant, deep-seated tumors. MRT has been shown to spare normal tissue up to 1000 Gy of entrance dose while still being highly tumoricidal. Current methods of tumor localization for our MRT treatments require MRI and X-ray imaging with subject motion and image registration that contribute to the measurement error. The purpose of this study is to develop a novel form of imaging to quickly and accurately assist in high resolution target positioning for MRT treatments using X-ray fluorescence (XRF). The key to this method is using the microbeam to both treat and image. High Z contrast media is injected into the phantom or blood pool of the subject prior to imaging. Using a collimated spectrum analyzer, the region of interest is scanned through the MRT beam and the fluorescence signal is recorded for each slice. The signal can be processed to show vascular differences in the tissue and isolate tumor regions. Using the radiation therapy source as the imaging source, repositioning and registration errors are eliminated. A phantom study showed that a spatial resolution of a fraction of microbeam width can be achieved by precision translation of the mouse stage. Preliminary results from an animal study showed accurate iodine profusion, confirmed by CT. The proposed image guidance method, using XRF to locate and ablate tumors, can be used as a fast and accurate MRT treatment planning system.

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 µm wide and spaced at 900 µm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Purpose: Microbeam radiation therapy (MRT) uses narrow planes of high dose radiation beams to treat cancerous tumors. This experimental therapy method based on synchrotron radiation has been shown to spare normal tissue at up to 1000 Gy of peak entrance dose while still being effective in tumor eradication and extending the lifetime of tumor-bearing small animal models. Motion during treatment can lead to significant movement of microbeam positions resulting in broader beam width and lower peak to valley dose ratio (PVDR), which reduces the effectiveness of MRT. Recently, the authors have demonstrated the feasibility of generating microbeam radiation for small animal treatment using a carbon nanotube (CNT) x-ray source array. The purpose of this study is to incorporate physiological gating to the CNT microbeam irradiator to minimize motion-induced microbeam blurring. Methods: The CNT field emission x-ray source array with a narrow line focal track was operated at 160 kVp. The x-ray radiation was collimated to a single 280 μm wide microbeam at entrance. The microbeam beam pattern was recorded using EBT2 Gafchromic© films. For the feasibility study, a strip of EBT2 film was attached to an oscillating mechanical phantom mimicking mouse chest respiratory motion. The servo arm was put against a pressure sensor to monitor the motion. The film was irradiated with three microbeams under gated and nongated conditions and the full width at half maximums and PVDRs were compared. An in vivo study was also performed with adult male athymic mice. The liver was chosen as the target organ for proof of concept due to its large motion during respiration compared to other organs. The mouse was immobilized in a specialized mouse bed and anesthetized using isoflurane. A pressure sensor was attached to a mouse's chest to monitor its respiration. The output signal triggered the electron extraction voltage of the field emission source such that x-ray was generated only during a portion of the mouse respiratory cycle when there was minimum motion. Parallel planes of microbeams with 12.4 Gy/plane dose and 900 μm pitch were delivered. The microbeam profiles with and without gating were analyzed using γ-H2Ax immunofluorescence staining. Results: The phantom study showed that the respiratory motion caused a 50% drop in PVDR from 11.5 when there is no motion to 5.4, whereas there was only a 5.5% decrease in PVDR for gated irradiation compared to the no motion case. In thein vivo study, the histology result showed gating increased PVDR by a factor of 2.4 compared to the nongated case, similar to the result from the phantom study. The full width at tenth maximum of the microbeam decreased by 40% in gating in vivo and close to 38% with phantom studies. Conclusions: The CNT field emission x-ray source array can be synchronized to physiological signals for gated delivery of x-ray radiation to minimize motion-induced beam blurring. Gated MRT reduces valley dose between lines during long-time radiation of a moving object. The technique allows for more precise MRT treatments and makes the CNT MRT device practical for extended treatment.