Ultra-low-dose vs. standard-of-care-dose CT of the chest in patients with post-COVID-19 conditions-a prospective intra-patient multi-reader study.

OBJECTIVES: To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions. METHODS: We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated. RESULTS: Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001). CONCLUSION: ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views. CLINICAL RELEVANCE STATEMENT: Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients.

Design, Implementation, and Evaluation of a Head and Neck MRI RF Array Integrated with a 511 keV Transmission Source for Attenuation Correction in PET/MR.

The goal of this work is to further improve positron emission tomography (PET) attenuation correction and magnetic resonance (MR) sensitivity for head and neck applications of PET/MR. A dedicated 24-channel receive-only array, fully-integrated with a hydraulic system to move a transmission source helically around the patient and radiofrequency (RF) coil array, is designed, implemented, and evaluated. The device enables the calculation of attenuation coefficients from PET measurements at 511 keV including the RF coil and the particular patient. The RF coil design is PET-optimized by minimizing photon attenuation from coil components and housing. The functionality of the presented device is successfully demonstrated by calculating the attenuation map of a water bottle based on PET transmission measurements; results are in excellent agreement with reference values. It is shown that the device itself has marginal influence on the static magnetic field B0 and the radiofrequency transmit field B1 of the 3T PET/MR system. Furthermore, the developed RF array is shown to outperform a standard commercial 16-channel head and neck coil in terms of signal-to-noise ratio (SNR) and parallel imaging performance. In conclusion, the presented hardware enables accurate calculation of attenuation maps for PET/MR systems while improving the SNR of corresponding MR images in a single device without degrading the B0 and B1 homogeneity of the scanner.

Intra-fractional lung tumor motion monitoring using arbitrary gantry angles during radiotherapy treatment.

Intensity-based 2D/3D registration using kilo-voltage (kV) and mega-voltage (MV) on-board imaging is a promising approach for real-time tumor motion tracking. So far, the performance of the kV images as well as kV-MV image pairs for 2D/3D registration using only one gantry angle (in anterior-posterior (AP) direction) has been investigated on patient data. In stereotactic body radiation therapy (SBRT), however, various gantry angles are typically used. This study attempts to answer the question of whether automatic 2D/3D registration is possible using kV images as well as kV-MV image pairs for gantry angles other than the AP direction. We also investigated the effect of additional portal MV images paired with kV images to improve 2D/3D registration in extracting cranio-caudal (CC) and AP displacement at arbitrary gantry angles and different fractions. The kV and MV image sequences as well as 3D volume data from five patients suffering from non-small cell lung cancer undergoing SBRT were used. Diaphragm motion served as the reference signal. The CC and AP displacements resulting from the registration results were compared with the corresponding reference motion signal. Pearson correlation coefficients (R value) was used to calculate the similarity measure between reference signal and the extracted displacements resulting from the registration. Signals we found that using 2D/3D registration tumor motion in 5 degrees of freedom (DOF) with kV images and in 6 degrees of freedom with kV-MV image pairs can be extracted for most gantry angles in all patients. Furthermore, our results have shown that the use of kV-MV image pairs increases the overall chance of tumor visibility and therefore leads to more successful extraction of CC as well as AP displacements for almost all gantry angles in all patients. We observed an improvement in registration of at least 0.29% more gantry angle for all patients when we used kV-MV images compared to kV images alone. In addition, an improvement in the R-value was observed in up to 16 fractions in various patients.

Characterization, number, and spatial organization of nerve fibers in the human cervical vagus nerve and its superior cardiac branch.

BACKGROUND: Electrical stimulation of the vagus nerve (VN) is a therapy for epilepsy, obesity, depression, and heart diseases. However, whole nerve stimulation leads to side effects. We examined the neuroanatomy of the mid-cervical segment of the human VN and its superior cardiac branch to gain insight into the side effects of VN stimulation and aid in developing targeted stimulation strategies. METHODS: Nerve specimens were harvested from eight human body donors, then subjected to immunofluorescence and semiautomated quantification to determine the signature, quantity, and spatial distribution of different axonal categories. RESULTS: The right and left cervical VN (cVN) contained a total of 25,489 ± 2781 and 23,286 ± 3164 fibers, respectively. Two-thirds of the fibers were unmyelinated and one-third were myelinated. About three-quarters of the fibers in the right and left cVN were sensory (73.9 ± 7.5 % versus 72.4 ± 5.6 %), while 13.2 ± 1.8 % versus 13.3 ± 3.0 % were special visceromotor and parasympathetic, and 13 ± 5.9 % versus 14.3 ± 4.0 % were sympathetic. Special visceromotor and parasympathetic fibers formed clusters. The superior cardiac branches comprised parasympathetic, vagal sensory, and sympathetic fibers with the left cardiac branch containing more sympathetic fibers than the right (62.7 ± 5.4 % versus 19.8 ± 13.3 %), and 50 % of the left branch contained sensory and sympathetic fibers only. CONCLUSION: The study indicates that selective stimulation of vagal sensory and motor fibers is possible. However, it also highlights the potential risk of activating sympathetic fibers in the superior cardiac branch, especially on the left side.

Real-time 2D/3D registration using kV-MV image pairs for tumor motion tracking in image guided radiotherapy.

Intra-fractional respiratory motion during radiotherapy leads to a larger planning target volume (PTV). Real-time tumor motion tracking by two-dimensional (2D)/3D registration using on-board kilo-voltage (kV) imaging can allow for a reduction of the PTV though motion along the imaging beam axis cannot be resolved using only one projection image. We present a retrospective patient study investigating the impact of paired portal mega-voltage (MV) and kV images on registration accuracy. Material and methods. We used data from 10 patients suffering from non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) lung treatment. For each patient we acquired a planning computed tomography (CT) and sequences of kV and MV images during treatment. We compared the accuracy of motion tracking in six degrees-of-freedom (DOF) using the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs. Results. Motion along cranial-caudal direction could accurately be extracted when using only the kV sequence but in AP direction we obtained large errors. When using kV-MV pairs, the average error was reduced from 2.9 mm to 1.5 mm and the motion along AP was successfully extracted. Mean registration time was 188 ms. Conclusion. Our evaluation shows that using kV-MV image pairs leads to improved motion extraction in six DOF and is suitable for real-time tumor motion tracking with a conventional LINAC.

Source-detector trajectory optimization for CBCT metal artifact reduction based on PICCS reconstruction.

Precise instrument placement plays a critical role in all interventional procedures, especially percutaneous procedures such as needle biopsies, to achieve successful tumor targeting and increased diagnostic accuracy. C-arm cone beam computed tomography (CBCT) has the potential to precisely visualize the anatomy in direct vicinity of the needle and evaluate the adequacy of needle placement during the intervention, allowing for instantaneous adjustment in case of misplacement. However, even with the most advanced C-arm CBCT devices, it can be difficult to identify the exact needle position on CBCT images due to the strong metal artifacts around the needle. In this study, we proposed a framework for customized trajectory design in CBCT imaging based on Prior Image Constrained Compressed Sensing (PICCS) reconstruction with the goal of reducing metal artifacts in needle-based procedures. We proposed to optimize out-of-plane rotations in three-dimensional (3D) space and minimize projection views while reducing metal artifacts at specific volume of interests (VOIs). An anthropomorphic thorax phantom with a needle inserted inside and two tumor models as the imaging targets were used to validate the proposed approach. The performance of the proposed approach was also evaluated for CBCT imaging under kinematic constraints by simulating some collision areas on the geometry of the C-arm. We compared the result of optimized 3D trajectories using the PICCS algorithm and 20 projections with the result of a circular trajectory with sparse view using PICCS and Feldkamp, Davis, and Kress (FDK), both using 20 projections, and the circular FDK method with 313 projections. For imaging targets 1 and 2, the highest values of structural similarity index measure (SSIM) and universal quality index (UQI) between the reconstructed image from the optimized trajectories and the initial CBCT image at the VOI was calculated 0.7521, 0.7308 and 0.7308, 0.7248 respectively. These results significantly outperformed the FDK method (with 20 and 313 projections) and the PICCS method (20 projections) both using the circular trajectory. Our results showed that the proposed optimized trajectories not only significantly reduce metal artifacts but also suggest a dose reduction for needle-based CBCT interventions, considering the small number of projections used. Furthermore, our results showed that the optimized trajectories are compatible with spatially constrained situations and enable CBCT imaging under kinematic constraints when the standard circular trajectory is not feasible.

Silicone phantoms fabricated with multi-material extrusion 3D printing technology mimicking imaging properties of soft tissues in CT.

Recently, 3D printing has been widely used to fabricate medical imaging phantoms. So far, various rigid 3D printable materials have been investigated for their radiological properties and efficiency in imaging phantom fabrication. However, flexible, soft tissue materials are also needed for imaging phantoms for simulating several clinical scenarios where anatomical deformations is important. Recently, various additive manufacturing technologies have been used to produce anatomical models based on extrusion techniques that allow the fabrication of soft tissue materials. To date, there is no systematic study in the literature investigating the radiological properties of silicone rubber materials/fluids for imaging phantoms fabricated directly by extrusion using 3D printing techniques. The aim of this study was to investigate the radiological properties of 3D printed phantoms made of silicone in CT imaging. To achieve this goal, the radiodensity as described as Hounsfield Units (HUs) of several samples composed of three different silicone printing materials were evaluated by changing the infill density to adjust their radiological properties. A comparison of HU values with a Gammex Tissue Characterization Phantom was performed. In addition, a reproducibility analysis was performed by creating several replicas for specific infill densities. A scaled down anatomical model derived from an abdominal CT was also fabricated and the resulting HU values were evaluated. For the three different silicone materials, a spectrum ranging from -639 to +780 HU was obtained on CT at a scan setting of 120 kVp. In addition, using different infill densities, the printed materials were able to achieve a similar radiodensity range as obtained in different tissue-equivalent inserts in the Gammex phantom (238 HU to -673 HU). The reproducibility results showed good agreement between the HU values of the replicas compared to the original samples, confirming the reproducibility of the printed materials. A good agreement was observed between the HU target values in abdominal CT and the HU values of the 3D-printed anatomical phantom in all tissues.

Additively manufactured test phantoms for mimicking soft tissue radiation attenuation in CBCT using Polyjet technology.

OBJECTIVES: To develop and validate a simple approach for building cost-effective imaging phantoms for Cone Beam Computed Tomography (CBCT) using a modified Polyjet additive manufacturing technology where a single material can mimic a range of human soft-tissue radiation attenuation. MATERIALS AND METHODS: Single material test phantoms using a cubic lattice were designed in 3-Matic 15.0 software . Keeping the individual cubic lattice volume constant, eight different percentage ratio (R) of air: material from 0% to 70% with a 10% increment were assigned to each sample. The phantoms were printed in three materials, namely Vero PureWhite, VeroClear and TangoPlus using Polyjet technology. The CT value analysis, non-contact profile measurement and microCT-based volumetric analysis was performed for all the samples. RESULTS: The printed test phantoms produced a grey value spectrum equivalent to the radiation attenuation of human soft tissues in the range of -757 to +286 HU on CT. The results from dimensional comparison analysis of the printed phantoms with the digital test phantoms using non-contact profile measurement showed a mean accuracy of 99.07 % and that of micro-CT volumetric analysis showed mean volumetric accuracy of 84.80-94.91%. The material and printing costs of developing 24 test phantoms was 83.00 Euro. CONCLUSIONS: The study shows that additive manufacturing-guided macrostructure manipulation modifies successfully the radiographic visibility of a material in CBCT imaging with 1 mm3 resolution, helping customization of imaging phantoms.

Extension of the open-source TIGRE toolbox for proton imaging.

Proton irradiation is a well-established method to treat deep-seated tumors in radio oncology. Usually, an X-ray computed tomography (CT) scan is used for treatment planning. Since proton therapy is based on the precise knowledge of the stopping power describing the energy loss of protons in the patient tissues, the Hounsfield units of the planning CT have to be converted. This conversion introduces range errors in the treatment plan, which could be reduced, if the stopping power values were extracted directly from an image obtained using protons instead of X-rays. Since protons are affected by multiple Coulomb scattering, reconstruction of the 3D stopping power map results in limited image quality if the curved proton path is not considered. This work presents a substantial code extension of the open-source toolbox TIGRE for proton CT (pCT) image reconstruction based on proton radiographs including a curved proton path estimate. The code extension and the reconstruction algorithms are GPU-based, allowing to achieve reconstruction results within minutes. The performance of the pCT code extension was tested with Monte Carlo simulated data using three phantoms (Catphan® high resolution and sensitometry modules and a CIRS patient phantom). In the simulations, ideal and non-ideal conditions for a pCT setup were assumed. The obtained mean absolute percentage error was found to be below 1% and up to 8 lp/cm could be resolved using an idealized setup. These findings demonstrate that the presented code extension to the TIGRE toolbox offers the possibility for other research groups to use a fast and accurate open-source pCT reconstruction.

Realistic 3D printed CT imaging tumor phantoms for validation of image processing algorithms.

Medical imaging phantoms are widely used for validation and verification of imaging systems and algorithms in surgical guidance and radiation oncology procedures. Especially, for the performance evaluation of new algorithms in the field of medical imaging, manufactured phantoms need to replicate specific properties of the human body, e.g., tissue morphology and radiological properties. Additive manufacturing (AM) technology provides an inexpensive opportunity for accurate anatomical replication with customization capabilities. In this study, we proposed a simple and cheap protocol using Fused Deposition Modeling (FDM) technology to manufacture realistic tumor phantoms based on the filament 3D printing technology. Tumor phantoms with both homogenous and heterogeneous radiodensity were fabricated. The radiodensity similarity between the printed tumor models and real tumor data from CT images of lung cancer patients was evaluated. Additionally, it was investigated whether a heterogeneity in the 3D printed tumor phantoms as observed in the tumor patient data had an influence on the validation of image registration algorithms. A radiodensity range between -217 to 226 HUs was achieved for 3D printed phantoms using different filament materials; this range of radiation attenuation is also observed in the human lung tumor tissue. The resulted HU range could serve as a lookup-table for researchers and phantom manufactures to create realistic CT tumor phantoms with the desired range of radiodensities. The 3D printed tumor phantoms also precisely replicated real lung tumor patient data regarding morphology and could also include life-like heterogeneity of the radiodensity inside the tumor models. An influence of the heterogeneity on accuracy and robustness of the image registration algorithms was not found.

Ultra-low-dose CT vs. chest X-ray in non-traumatic emergency department patients - a prospective randomised crossover cohort trial.

Background: Ultra-low-dose CT (ULDCT) examinations of the chest at only twice the radiation dose of a chest X-ray (CXR) now offer a valuable imaging alternative to CXR. This trial prospectively compares ULDCT and CXR for the detection rate of diagnoses and their clinical relevance in a low-prevalence cohort of non-traumatic emergency department patients. Methods: In this prospective crossover cohort trial, 294 non-traumatic emergency department patients with a clinically indicated CXR were included between May 2nd and November 26th of 2019 (www.clinicaltrials.gov: NCT03922516). All participants received both CXR and ULDCT, and were randomized into two arms with inverse reporting order. The detection rate of CXR was calculated from 'arm CXR' (n = 147; CXR first), and of ULDCT from 'arm ULDCT' (n = 147; ULDCT first). Additional information reported by the second exam in each arm was documented. From all available clinical and imaging data, expert radiologists and emergency physicians built a compound reference standard, including radiologically undetectable diagnoses, and assigned each finding to one of five clinical relevance categories for the respective patient. Findings: Detection rates for main diagnoses by CXR and ULDCT (mean effective dose: 0.22 mSv) were 9.1% (CI [5.2, 15.5]; 11/121) and 20.1% (CI [14.2, 27.7]; 27/134; P = 0.016), respectively. As an additional imaging modality, ULDCT added 9.1% (CI [5.2, 15.5]; 11/121) of main diagnoses to prior CXRs, whereas CXRs did not add a single main diagnosis (0/134; P < 0.001). Notably, ULDCT also offered higher detection rates than CXR for all other clinical relevance categories, including findings clinically irrelevant for the respective emergency department visit with 78.5% (CI [74.0, 82.5]; 278/354) vs. 16.2% (CI [12.7, 20.3]; 58/359) as a primary modality and 68.2% (CI [63.3, 72.8]; 245/359) vs. 2.5% (CI [1.3, 4.7]; 9/354) as an additional imaging modality. Interpretation: In non-traumatic emergency department patients, ULDCT of the chest offered more than twice the detection rate for main diagnoses compared to CXR. Funding: The Department of Biomedical Imaging and Image-guided Therapy of Medical University of Vienna received funding from Siemens Healthineers (Erlangen, Germany) to employ two research assistants for one year.

Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-11C]WAY-100635 independent of arterial sampling.

UNLABELLED: image- derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT(1A)) with [carbonyl-(11)C]WAY-100635 before and after hormone treatment. METHODS: Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10 min onward (IDIF+VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT(1A) receptor quantification was achieved with arterial input functions (AIF) and IDIF+VIF using a two-tissue compartment model. RESULTS: Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p>0.4) and below 2% for plasma to whole-blood ratios (p>0.4). Variability was slightly higher for parent fractions (VARmax=24% at 5 min, p<0.05 and VAR<13% after 20 min, p>0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference Δ=-7.6 ± 16.9 kBq/ml, p>0.1), whereas AIFs exhibited a delay (Δ=4 ± 6.4s, p<0.05) and higher peak width (Δ=15.9 ± 5.2s, p<0.001). Linear regression analysis showed strong agreement for 5-HT(1A) binding as obtained with AIF and IDIF+VIF at baseline (R(2)=0.95), after treatment (R(2)=0.93) and when pooling all scans (R(2)=0.93), with slopes and intercepts in the range of 0.97 to 1.07 and -0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF. CONCLUSIONS: Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT(1A) receptors. This holds true for 5-HT(1A) binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetic characteristics.

Using statistical measures for automated comparison of in-beam PET data.

PURPOSE: Positron emission tomography (PET) is considered to be the state of the art technique to monitor particle therapy in vivo. To evaluate the beam delivery the measured PET image is compared to a predicted ß(+)-distribution. Nowadays the range assessment is performed by a group of experts via visual inspection. This procedure is rather time consuming and requires well trained personnel. In this study an approach is presented to support human decisions in an automated and objective way. METHODS: The automated comparison presented uses statistical measures, namely, Pearson's correlation coefficient (PCC), to detect ion beam range deviations. The study is based on 12 in-beam PET patient data sets recorded at GSI and 70 artificial beam range modifications per data set. The range modifications were 0, 4, 6, and 10 mm water equivalent path length (WEPL) in positive and negative beam directions. The reference image to calculate the PCC was both an unmodified simulation of the activity distribution (Test 1) and a measured in-beam PET image (Test 2). Based on the PCCs sensitivity and specificity were calculated. Additionally the difference between modified and unmodified data sets was investigated using the Wilcoxon rank sum test. RESULTS: In Test 1 a sensitivity and specificity over 90% was reached for detecting modifications of ±10 and ±6 mm WEPL. Regarding Test 2 a sensitivity and specificity above 80% was obtained for modifications of ±10 and -6 mm WEPL. The limitation of the method was around 4 mm WEPL. CONCLUSIONS: The results demonstrate that the automated comparison using PCC provides similar results in terms of sensitivity and specificity compared to visual inspections of in-beam PET data. Hence the method presented in this study is a promising and effective approach to improve the efficiency in the clinical workflow in terms of particle therapy monitoring by means of PET.

Technical note: A PET/MR coil with an integrated, orbiting 511 keV transmission source for PET/MR imaging validated in an animal study.

BACKGROUND: MR-based methods for attenuation correction (AC) in PET/MRI either neglect attenuation of bone, or use MR-signal derived information about bone, which leads to a bias in quantification of tracer uptake in PET. In a previous study, we presented a PET/MRI specific MR coil with an integrated transmission source (TX) system allowing for direct measurement of attenuation. In phantom measurements, this system successfully reproduced the linear attenuation coefficient of water. PURPOSE: The purpose of this study is to validate the TX system in a clinical setting using animals and to show its applicability compared to standard clinical methods. METHODS: As test subject, a 15-kg piglet was injected with 53 MBq of 18F-NaF. The µ-map obtained with the TX system and the reconstructed activity distribution were compared to four established AC methods: a Dixon sequence, an ultra-short echo time (UTE) sequence, a CT scan, and a 511 keV transmission scan using a Siemens ECAT EXACT HR+ as the reference. The PET/MRI measurements were performed on a Siemens Biograph mMR to obtain the µ-map using the TX system as well as the Dixon and UTE sequence directly followed by the CT and ECAT measurements. RESULTS: The reconstructed activity distribution using the TX system for AC showed similar results compared to the reference (<5% difference in hot regions) and outperformed the MR-based methods as implemented in the PET/MRI system (<10% difference in hot regions). However, the additional hardware of the TX system adds complexity to the acquisition process. CONCLUSION: Our porcine study demonstrates the feasibility of post-injection transmission scans using the developed TX system in a clinical setting. This makes it a useful tool for PET/MRI in cases where transmission information is needed for AC. Potential applications are studies using larger animals where state-of-the-art atlas-based or artificial intelligence AC methods are not available.

3D printed patient-specific thorax phantom with realistic heterogenous bone radiopacity using filament printer technology.

Current medical imaging phantoms are usually limited by simplified geometry and radiographic skeletal homogeneity, which confines their usage for image quality assessment. In order to fabricate realistic imaging phantoms, replication of the entire tissue morphology and the associated CT numbers, defined as Hounsfield Unit (HU) is required. 3D printing is a promising technology for the production of medical imaging phantoms with accurate anatomical replication. So far, the majority of the imaging phantoms using 3D printing technologies tried to mimic the average HU of soft tissue human organs. One important aspect of the anthropomorphic imaging phantoms is also the replication of realistic radiodensities for bone tissues. In this study, we used filament printing technology to develop a CT-derived 3D printed thorax phantom with realistic bone-equivalent radiodensity using only one single commercially available filament. The generated thorax phantom geometry closely resembles a patient and includes direct manufacturing of bone structures while creating life-like heterogeneity within bone tissues. A HU analysis as well as a physical dimensional comparison were performed in order to evaluate the density and geometry agreement between the proposed phantom and the corresponding CT data. With the achieved density range (-482 to 968 HU) we could successfully mimic the realistic radiodensity of the bone marrow as well as the cortical bone for the ribs, vertebral body and dorsal vertebral column in the thorax skeleton. In addition, considering the large radiodensity range achieved a full thorax imaging phantom mimicking also soft tissues can become feasible. The physical dimensional comparison using both Extrema Analysis and Collision Detection methods confirmed a mean surface overlap of 90% and a mean volumetric overlap of 84,56% between the patient and phantom model. Furthermore, the reproducibility analyses revealed a good geometry and radiodensity duplicability in 24 printed cylinder replicas. Thus, according to our results, the proposed additively manufactured anthropomorphic thorax phantom has the potential to be efficiently used for validation of imaging- and radiation-based procedures in precision medicine.

Factors for conversion between human and automatic read-outs of CDMAM images.

PURPOSE: According to the European protocol for the quality control of the physical and technical aspects of mammography screening (EPQCM) image quality of digital mammography devices has to be assessed using human evaluation of the CDMAM contrast-detail phantom. This is accomplished by the determination of threshold thicknesses of gold disks with different diameters (0.08-2 mm) and revealed to be very time consuming. Therefore a software solution based on a nonprewhitening matched filter (NPW) model was developed at the University of Nijmegen. Factors for the conversion from automatic to human readouts have been determined by Young et al. [Proc. SPIE 614206, 1-13 (2006) and Proc. SPIE 6913, 69131C1 (2008)] using a huge amount of data of both human and automatic readouts. These factors depend on the observer groups and are purely phenomenological. The authors present an alternative approach to determine the factors by using the Rose observer model. METHODS: Their method uses the Rose theory which gives a relationship between threshold contrast, diameter of the object and number of incident photons. To estimate the conversion factors for the five diameters from 0.2 to 0.5 mm they exposed with five different current-time products which resulted in 25 equations with five unknowns. RESULTS: The theoretical conversion factors (in dependence of the diameters) amounted to be 1.61 ± 0.02 (0.2 mm diameter), 1.67 ± 0.02 (0.25 mm), 1.85 ± 0.02 (0.31 mm), 2.09 ± 0.02 (0.4 mm), and 2.28 ± 0.02 (0.5 mm). The corresponding phenomenological factors found in literature are 1.74 (0.2 mm), 1.78 (0.25 mm), 1.83 (0.31 mm), 1.88 (0.4 mm), and 1.93 (0.5 mm). CONCLUSIONS: They transferred the problem of determining the factors to a well known observer model which has been examined for many years and is also well established. This method reveals to be reproduceable and produces factors comparable to the phenomenological ones.

Validation for 2D/3D registration. II: The comparison of intensity- and gradient-based merit functions using a new gold standard data set.

PURPOSE: A new gold standard data set for validation of 2D/3D registration based on a porcine cadaver head with attached fiducial markers was presented in the first part of this article. The advantage of this new phantom is the large amount of soft tissue, which simulates realistic conditions for registration. This article tests the performance of intensity- and gradient-based algorithms for 2D/3D registration using the new phantom data set. METHODS: Intensity-based methods with four merit functions, namely, cross correlation, rank correlation, correlation ratio, and mutual information (MI), and two gradient-based algorithms, the backprojection gradient-based (BGB) registration method and the reconstruction gradient-based (RGB) registration method, were compared. Four volumes consisting of CBCT with two fields of view, 64 slice multidetector CT, and magnetic resonance-T1 weighted images were registered to a pair of kV x-ray images and a pair of MV images. A standardized evaluation methodology was employed. Targets were evenly spread over the volumes and 250 starting positions of the 3D volumes with initial displacements of up to 25 mm from the gold standard position were calculated. After the registration, the displacement from the gold standard was retrieved and the root mean square (RMS), mean, and standard deviation mean target registration errors (mTREs) over 250 registrations were derived. Additionally, the following merit properties were computed: Accuracy, capture range, number of minima, risk of nonconvergence, and distinctiveness of optimum for better comparison of the robustness of each merit. RESULTS: Among the merit functions used for the intensity-based method, MI reached the best accuracy with an RMS mTRE down to 1.30 mm. Furthermore, it was the only merit function that could accurately register the CT to the kV x rays with the presence of tissue deformation. As for the gradient-based methods, BGB and RGB methods achieved subvoxel accuracy (RMS mTRE down to 0.56 and 0.70 mm, respectively). Overall, gradient-based similarity measures were found to be substantially more accurate than intensity-based methods and could cope with soft tissue deformation and enabled also accurate registrations of the MR-T1 volume to the kV x-ray image. CONCLUSIONS: In this article, the authors demonstrate the usefulness of a new phantom image data set for the evaluation of 2D/3D registration methods, which featured soft tissue deformation. The author's evaluation shows that gradient-based methods are more accurate than intensity-based methods, especially when soft tissue deformation is present. However, the current nonoptimized implementations make them prohibitively slow for practical applications. On the other hand, the speed of the intensity-based method renders these more suitable for clinical use, while the accuracy is still competitive.

First application of the GPU-based software framework TIGRE for proton CT image reconstruction.

In proton therapy, the knowledge of the proton stopping power, i.e. the energy deposition per unit length within human tissue, is essential for accurate treatment planning. One suitable method to directly measure the stopping power is proton computed tomography (pCT). Due to the proton interaction mechanisms in matter, pCT image reconstruction faces some challenges: the unique path of each proton has to be considered separately in the reconstruction process adding complexity to the reconstruction problem. This study shows that the GPU-based open-source software toolkit TIGRE, which was initially intended for X-ray CT reconstruction, can be applied to the pCT image reconstruction problem using a straight line approach for the proton path. This simplified approach allows for reconstructions within seconds. To validate the applicability of TIGRE to pCT, several Monte Carlo simulations modeling a pCT setup with two Catphan® modules as phantoms were performed. Ordered-Subset Simultaneous Algebraic Reconstruction Technique (OS-SART) and Adaptive-Steepest-Descent Projection Onto Convex Sets (ASD-POCS) were used for image reconstruction. Since the accuracy of the approach is limited by the straight line approximation of the proton path, requirements for further improvement of TIGRE for pCT are addressed.

Toward on-the-fly trajectory optimization for C-arm CBCT under strong kinematic constraints.

Cone beam computed tomography (CBCT) has become a vital tool in interventional radiology. Usually, a circular source-detector trajectory is used to acquire a three-dimensional (3D) image. Kinematic constraints due to the patient size or additional medical equipment often cause collisions with the imager while performing a full circular rotation. In a previous study, we developed a framework to design collision-free, patient-specific trajectories for the cases in which circular CBCT is not feasible. Our proposed trajectories included enough information to appropriately reconstruct a particular volume of interest (VOI), but the constraints had to be defined before the intervention. As most collisions are unpredictable, performing an on-the-fly trajectory optimization is desirable. In this study, we propose a search strategy that explores a set of trajectories that cover the whole collision-free area and subsequently performs a search locally in the areas with the highest image quality. Selecting the best trajectories is performed using simulations on a prior diagnostic CT volume which serves as a digital phantom for simulations. In our simulations, the Feature SIMilarity Index (FSIM) is used as the objective function to evaluate the imaging quality provided by different trajectories. We investigated the performance of our methods using three different anatomical targets inside the Alderson-Rando phantom. We used FSIM and Universal Quality Image (UQI) to evaluate the final reconstruction results. Our experiments showed that our proposed trajectories could achieve a comparable image quality in the VOI compared to the standard C-arm circular CBCT. We achieved a relative deviation less than 10% for both FSIM and UQI metrics between the reconstructed images from the optimized trajectories and the standard C-arm CBCT for all three targets. The whole trajectory optimization took approximately three to four minutes.

Short Scan Source-detector Trajectories for Target-based CBCT.

We proposed a target-based cone beam computed tomography (CBCT) imaging framework in order to optimize a free three dimensional (3D) source-detector trajectory by incorporating prior 3D image data. We aim to enable CBCT systems to provide topical information about a region of interest (ROI) using a short-scan trajectory with a reduced number of projections. The best projection views are selected by maximizing an objective function fed by the image quality by means of applying different x-ray positions on the digital phantom data. Finally, an optimized trajectory is selected which is applied to a C-arm device able to perform general source-detector positioning. An Alderson-Rando head phantom is used in order to investigate the performance of the proposed framework. Our experiments showed that the optimized trajectory could achieve a comparable image quality in the ROI with respect to the reference C-arm CBCT while using approximately one-quarter of projections. An angular range of 156° was used for the optimized trajectory.