Continuous Wave of Condensation Improves the Filling of Curved Canals: a Micro-CT Study / La condensación de onda contínua mejora el selle de canales curvos: un estudio de micro-CT

Abstract The aim of this study was to compare the filling capacity in curved root canal using a new continuous wave of condensation technique (Termo Pack II, Easy Dental Equipments, Brazil) or lateral compaction. The percentage of voids in the filling of mesial root canals of mandibular molars was assessed by micro-computed tomography (micro-CT). Mesial root canals (n=24) of mandibular molars with a degree of curvature between 20° and 40° were prepared using rotary system (ProDesign Logic, Easy, Brazil) up to #35, .05 taper. The root canals were filled by using the continuous wave of condensation system or lateral compaction and AH Plus sealer (n=12). Scanning at 9 µm was performed after preparation and after filling by using micro-CT SkyScan 1176. The volumetric percentage of filling material and voids (total length and in each root canal third) were calculated. Data were analyzed using ANOVA/ Tukey and Student's t tests (α=0.05). Before the filling techniques, the root canals volume after preparation was similar (p>0.05). The root canals filled by the continuous wave of condensation technique presented the lowest percentage of voids, and the greatest percentage of filling material in total length and thirds (cervical, middle and apical) (p<0.05). Both techniques were not able of completely filling the root canals. The continuous wave of condensation technique Termo Pack II promoted better root canal filling in curved root canals, when compared with lateral compaction.

Resumen El objetivo de este estudio fue comparar la capacidad de obturación en conductos radiculares curvos utilizando una nueva técnica de condensación de onda continua (Termo Pack II, Easy Dental Equipments, Brasil) vs compactación lateral. El porcentaje de brechas en la obturación de los conductos radiculares mesiales de los molares mandibulares se evaluó mediante microtomografía computarizada (micro-CT). Se prepararon conductos radiculares mesiales (n=24) de molares mandibulares con un grado de curvatura entre 20° y 40° utilizando un sistema rotatorio (ProDesign Logic, Easy, Brasil) al #35, conicidad 0,05. Los conductos radiculares se obturaron utilizando un sistema de condensación de onda contínua o compactación lateral y cemento AH Plus (n=12). Se realizó un escaneo de 9 µm después de la preparación y después de la obturación usando el micro-CT SkyScan 1176. Se calculó el porcentaje volumétrico de material de obturación y vacíos (longitud total y en cada tercio del conducto radicular). Los datos se analizaron utilizando las pruebas ANOVA/Tukey y t de Student (α=0,05). Antes de las técnicas de obturación, el volumen de los conductos radiculares después de la preparación fue similar (p>0,05). Los conductos radiculares obturados con la técnica de condensación por onda contínua presentaron el menor porcentaje de vacíos y el mayor porcentaje de material de obturación en longitud total y en tercios (cervical, medio y apical) (p<0,05). Ambas técnicas no fueron capaces de llenar completamente los conductos radiculares. La técnica de condensación de onda contínua Termo Pack II promovió un mejor relleno del conducto radicular en conductos radiculares curvos en comparación con la compactación lateral.

X-ray scintillator lens-coupled with CMOS camera for pre-clinical cardiac vascular imaging-A feasibility study.

We present the design and characterization of an X-ray imaging system consisting of an off-the-shelf CMOS sensor optically coupled to a CsI scintillator. The camera can perform both high-resolution and functional cardiac imaging. High-resolution 3D imaging requires microfocus X-ray tubes and expensive detectors, while pre-clinical functional cardiac imaging requires high flux pulsed (clinical) X-ray tubes and high-end cameras. Our work describes an X-ray camera, namely an "optically coupled X-ray(OCX) detector," used for both the aforementioned applications with no change in the specifications. We constructed the imaging detector with two different CMOS optical imaging cameras called CMOS sensors, 1.A monochrome CMOS sensor coupled with an f1.4 lens and 2.an RGB CMOS sensor coupled with an f0.95 prime lens. The imaging system consisted of our X-ray camera, micro-focus X-ray source (50kVp and 1mA), and a rotary stage controlled from a personal computer (PC) and LabVIEW interface. The detective quantum efficiency (DQE) of the imaging system(monochrome) estimated using a cascaded linear model was 17% at 10 lp/mm. The system modulation transfer function (MTF) and the noise power spectrum (NPS) were inputs to the DQE estimation. Because of the RGB camera's low quantum efficiency (QE), the OCX detector DQE was 19% at 5 lp/mm. The contrast to noise ratio (CNR) at different frame rates was studied using the capillary tubes filled with various dilutions of iodinated contrast agents. In-vivo cardiac angiography demonstrated that blood vessels of the order of 100 microns or above were visible at 40 frames per second despite the low X-ray flux. For high-resolution 3D imaging, the system was characterized by imaging a cylindrical micro-CT contrast phantom and comparing it against images from a commercial scanner.

Efficacy of 30% and 38% Silver Diamine Fluoride in Arresting Caries Lesions After Different Application Times: An in Vitro Study

Abstract Objective: To evaluate the efficacy of silver diamine fluoride (SDF) in arresting dentin caries lesions when applied under different concentrations and times. Material and Methods: Forty-two bovine blocks were selected and fixed in 24-well plates. Each well received a mixed bacterial inoculum added to the culture medium with 5% sucrose. The plates were incubated in microaerophilia (7 days) for caries formation, confirmed by micro-CT (M1). SDF was applied over the carious lesions for different times and concentrations (n=6): SDF 30% - immediate removal, 1 minute and 3 minutes; SDF 38%, - immediate removal, 1 minute and 3 minutes. The group without treatment was the control. Then, the samples were again scanned by micro-CT (M2) and submitted to a second cariogenic challenge for 21 days. Then, a final scan was performed (M3). Results: Mean pH at the culture medium and lesion depth were compared using Kruskal-Wallis and Wilcoxon tests. 38% SDF showed the lowest metabolic activity of the biofilm. All 38% groups and 30% 1 and 3 minutes did not show an increase in mean lesion depth comparing M3 with M1. However, only 30% 3 minutes and 38% 1 and 3 minutes showed a significant reduction of lesion depth. Conclusion: The minimum application time of 30% SDF to arrest dentin caries lesion was 1 minute, while 38% SDF arrested with application and immediate removal.

Developing diagnostic assessment of breast lumpectomy tissues using radiomic and optical signatures.

High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e-11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e-14). Extending the radiomics approach to high-dimensional optical data-termed "optomics" in this study-offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.

High-resolution fast-tomography brain-imaging beamline at the Taiwan Photon Source.

The new Brain Imaging Beamline (BIB) of the Taiwan Photon Source (TPS) has been commissioned and opened to users. The BIB and in particular its endstation are designed to take advantage of bright unmonochromatized synchrotron X-rays and target fast 3D imaging, ∼1 ms exposure time plus very high ∼0.3 µm spatial resolution. A critical step in achieving the planned performances was the solution to the X-ray induced damaging problems of the detection system. High-energy photons were identified as their principal cause and were solved by combining tailored filters/attenuators and a high-energy cut-off mirror. This enabled the tomography acquisition throughput to reach >1 mm3 min-1, a critical performance for large-animal brain mapping and a vital mission of the beamline.

Three-dimensional non-destructive visualization of teeth enamel microcracks using X-ray micro-computed tomography.

Although the topic of tooth fractures has been extensively analyzed in the dental literature, there is still insufficient information about the potential effect of enamel microcracks (EMCs) on the underlying tooth structures. For a precise examination of the extent of the damage to the tooth structure in the area of EMCs, it is necessary to carry out their volumetric [(three-dimensional (3D)] evaluation. The aim of this study was to validate an X-ray micro-computed tomography ([Formula: see text]CT) as a technique suitable for 3D non-destructive visualization and qualitative analysis of teeth EMCs of different severity. Extracted human maxillary premolars were examined using a [Formula: see text]CT instrument ZEISS Xradia 520 Versa. In order to separate crack, dentin, and enamel volumes a Deep Learning (DL) algorithm, part of the Dragonfly's segmentation toolkit, was utilized. For segmentation needs we implemented Dragonfly's pre-built UNet neural network. The scanning technique which was used made it possible to recognize and detect not only EMCs that are visible on the outer surface but also those that are buried deep inside the tooth. The 3D visualization, combined with DL assisted segmentation, enabled the evaluation of the dynamics of an EMC and precise examination of its position with respect to the dentin-enamel junction.

A deep learning-integrated micro-CT image analysis pipeline for quantifying rice lodging resistance-related traits.

Lodging is a common problem in rice, reducing its yield and mechanical harvesting efficiency. Rice architecture is a key aspect of its domestication and a major factor that limits its high productivity. The ideal rice culm structure, including major_axis_culm, minor axis_culm, and wall thickness_culm, is critical for improving lodging resistance. However, the traditional method of measuring rice culms is destructive, time consuming, and labor intensive. In this study, we used a high-throughput micro-CT-RGB imaging system and deep learning (SegNet) to develop a high-throughput micro-CT image analysis pipeline that can extract 24 rice culm morphological traits and lodging resistance-related traits. When manual and automatic measurements were compared at the mature stage, the mean absolute percentage errors for major_axis_culm, minor_axis_culm, and wall_thickness_culm in 104 indica rice accessions were 6.03%, 5.60%, and 9.85%, respectively, and the R2 values were 0.799, 0.818, and 0.623. We also built models of bending stress using culm traits at the mature and tillering stages, and the R2 values were 0.722 and 0.544, respectively. The modeling results indicated that this method can quantify lodging resistance nondestructively, even at an early growth stage. In addition, we also evaluated the relationships of bending stress to shoot dry weight, culm density, and drought-related traits and found that plants with greater resistance to bending stress had slightly higher biomass, culm density, and culm area but poorer drought resistance. In conclusion, we developed a deep learning-integrated micro-CT image analysis pipeline to accurately quantify the phenotypic traits of rice culms in ∼4.6 min per plant; this pipeline will assist in future high-throughput screening of large rice populations for lodging resistance.

Tuneable in-situ nanoCT workflow using FIB/SEM.

Inspired by the standard computed tomography, a new method of 3D X-ray imaging embedded in FIB-SEM microscope is proposed. The unique combination of TEM-like specimen stage enabling in lens STEM detection (referred to as CompuStage), nanomanipulator (referred to as EasyLift) facilitating in-situ sample transfer from bulk sample to TEM-like stage and pixelated in-situ Timepix X-ray detector in Helios G4 FX FIB-SEM system offers an unprecedented workflow. Motivated by common circular CT scan known from microCT world, the object under study is placed on CompuStage rod which enables two possible rotation (in TEM/SEM terminology called tilt) movements - α-tilt - rotation of the CompuStage rod around its axis, and ß-tilt - rotation around axis perpendicular to CompuStage rod. ß-tilt rotation enables a circular movement of the sample while α-tilt sets the correct position of sample with respect to target and detector. Thin metal lamella of suitable material welded to EasyLift manipulator needle is used as an X-ray target. The final target-sample geometry - position, distance - can be fine-tuned using position control of CompuStage and EasyLift and in-situ monitored by SEM. Both sample and target can also be easily prepared in-situ. Radiographs are recorded by Timepix detector with inherent noise-free operation and energy filtration. For the 3D reconstruction standard microCT reconstruction algorithm is used with the procedure adjusted for the format and quality of nanoCT images. The experiments were carried out on Helios G4 FX DualBeam using titanium and tungsten targets and various semiconductor samples. The ultimate resolution of the proposed method in orders of tens of nanometers was achieved both by the possibility of close target to sample positioning and of adjustment of primary beam energy down to low energies reducing the interaction volume in the target. Since the lower energy radiation is well suited for life-science, the method was also tested on several bio-samples using silver target. The silver target, thanks to its massive low energy Lα line, allowed to distinguish subtle structures in the resin embedded stained mouse brain and also to observe and reconstruct canaliculi in the mouse bone (earlier reported by Dierolf et al. 2010, Nature 467 436).

Using µCT in live larvae of a large wood-boring beetle to study tracheal oxygen supply during development.

How respiratory structures vary with, or are constrained by, an animal's environment is of central importance to diverse evolutionary and comparative physiology hypotheses. To date, quantifying insect respiratory structures and their variation has remained challenging due to their microscopic size, hence only a handful of species have been examined. Several methods for imaging insect respiratory systems are available, in many cases however, the analytical process is lethal, destructive, time consuming and labour intensive. Here, we explore and test a different approach to measuring tracheal volume using X-ray micro-tomography (µCT) scanning (at 15 µm resolution) on living, sedated larvae of the cerambycid beetle Cacosceles newmannii across a range of body sizes at two points in development. We provide novel data on resistance of the larvae to the radiation dose absorbed during µCT scanning, repeatability of imaging analyses both within and between time-points and, structural tracheal trait differences provided by different image segmentation methods. By comparing how tracheal dimension (reflecting metabolic supply) and basal metabolic rate (reflecting metabolic demand) increase with mass, we show that tracheal oxygen supply capacity increases during development at a comparable, or even higher rate than metabolic demand. Given that abundant gas delivery capacity in the insect respiratory system may be costly (due to e.g. oxygen toxicity or space restrictions), there are probably balancing factors requiring such a capacity that are not linked to direct tissue oxygen demand and that have not been thoroughly elucidated to date, including CO2 efflux. Our study provides methodological insights and novel biological data on key issues in rapidly quantifying insect respiratory anatomy on live insects.

Nondestructive Quantitative Evaluation of Yarns and Fabrics and Determination of Contact Area of Fabrics Using the X-ray Microcomputed Tomography System for Skin-Textile Friction Analysis.

In different mechanical conditions, repetitive friction in combination with pressure, shear, temperature, and moisture leads to skin discomfort and imposes the risks of developing skin injuries such as blisters and pressure ulcers, frequently reported in athletes, military personnel, and in people with compromised skin conditions and/or immobility. Textiles next to skin govern the skin microclimate, have the potential to influence the mechanical contact with skin, and contribute to skin comfort and health. The adhesion-friction theory suggests that contact area is a critical factor to influence adhesion, and therefore, friction force. Friction being a surface phenomenon, most of the studies concentrated on the surface profile or topographic analysis of textiles. This study investigated both the surface profiles and the inner construction of the fabrics through X-ray microcomputed tomographic three-dimensional image analysis. A novel nondestructive method to evaluate yarn and fabric structural details quantitatively and calculate contact area (in fiber area %) experimentally has been reported in this paper. Plain and satin-woven fabrics with different thread densities and made from 100% cotton ring-spun yarns with two different linear densities (40 and 60 Ne) were investigated in this study. The measurements from the tomographic images (pixel size: 1.13 µm) and the fiber area % analysis were in good agreement to comprehend and compare the yarn and fabric properties reported. The fiber area % as reported in this paper can be used to evaluate the skin-textile interfaces and quantitatively determine the contact area under different physical, mechanical, and microclimatic conditions to understand the actual skin-textile interaction during any physical activity or sports. The proposed method can be helpful in engineering textiles to enhance skin comfort and prevent injuries, such as blisters and pressure ulcers, in diversified application areas, including but not limited to, sports and healthcare apparel, military apparel, and firefighter's protective clothing. In addition, the images were capable of precisely evaluating yarn diameters, crimp %, and packing factor as well as fabric thickness, volumetric densities, and cover factors as compared with those obtained from theoretical evaluation and existing classical test methods. All these findings suggest that the proposed new method can reliably be used to quantify the yarn and fabric characteristics, compare their functionality, and understand the structural impacts in an objective and nondestructive way.

3D printed bismuth oxide-polylactic acid composites for radio-mimetic computed tomography spine phantoms.

Polylactic acid (PLA) composite filaments with varying concentrations of bismuth oxide microparticle additives were fabricated for use with commercially available fused filament fabrication (FFF) printing systems for the production of spine phantoms that mimic the radiopacity of bone. Thermal analysis showed that the additives had limited impact on the glass transition temperature and melting point of the filaments, allowing for their use in commercial FFF systems with standard printer settings. The ultimate strength of the printed test specimens was found to reduce slightly when bismuth oxide was added in high concentrations, with a moderate reduction of 12% compared to PLA at the highest concentration of 30 wt%. The modulus of the specimens increased by up to 24% with the addition of the additive. The radiopacity of specimens printed with the composite filaments were measured by X-ray microcomputed tomography (micro-CT) and clinical computed tomography (CT). The CT number was found to increase by approximately 196 HU per wt% of bismuth oxide added to the filaments. A phantom model of a cervical spine deformity was successfully printed by FFF with a composite filament which was calibrated to mimic the radiopacity of cervical and cortical bone. The results indicate that the composite filaments have direct applicability for the production of phantoms used for education and preoperative planning.

Topography of Primary Molar Pulp Chamber Floor: A Scanning Electron Microscopy and Micro-Computed Tomography Analysis

ABSTRACT Objective: To determine in vitro the frequency, shape, type, diameter, and patency of accessory canals in the primary molars pulp chamber floor. Material and Methods: Sixteen healthy primary molars were evaluated by micro-computed tomography and scanning electron microscopy. Descriptive analyses of the frequency, shape (round, oval, or irregular), type (blind, true, or hidden), patency and diameter of the accessory canals were performed. Results: Half of the teeth presented accessory canals, 62.5% of which were located in the upper molars and 37.5% in the lower molars. The most frequent shape was irregular. In three-dimensional analysis, blind accessory canals (12.5%) and with patency (18.7%) of the teeth were observed. The average accessory canal diameter was 51.97 µm (± 26.03 µm). Conclusion: Upper molars showed a higher frequency of accessory canals with larger diameters. The irregular shape was the most frequent. 18.7% of accessory channels showed patency.

An open, modular, and flexible micro X-ray computed tomography system for research.

In this paper, a modular and open micro X-ray Computed Tomography (µXRCT) system is presented, which was set up during the last years at the Institute of Applied Mechanics (CE) of the University of Stuttgart and earlier at the Institute of Computational Engineering of Ruhr-University Bochum. The system is characterized by its intrinsic flexibility resulting from the modular and open design on each level and the opportunity to implement advanced experimental in situ setups. On the one hand, the presented work is intended to support researchers interested in setting up an experimental XRCT system for the microstructural characterization of materials. On the other hand, it aims to support scientists confronted with the decision to set up a system on their own or to buy a commercial scanner. In addition to the presentation of the various hardware components and the applied modular software concept, the technical opportunities of the open and modular hard- and software design are demonstrated by implementing a simple and reliable method for the compensation of bad detector pixels to enhance the raw data quality of the projections. A detailed investigation of the performance of the presented system with regard to the achievable spatial resolution is presented. XRCT datasets of three different applications are finally shown and discussed, demonstrating the wide scope of options of the presented system.

Coronary micro-computed tomography angiography in mice.

Coronary computed tomography angiography is an established technique in clinical practice and a valuable tool in the diagnosis of coronary artery disease in humans. Imaging of coronaries in preclinical research, i.e. in small animals, is very difficult due to the high demands on spatial and temporal resolution. Mice exhibit heart rates of up to 600 beats per minute motivating the need for highest detector framerates while the coronaries show diameters below 100 µm indicating the requirement for highest spatial resolution. We herein use a custom built micro-CT equipped with dedicated reconstruction algorithms to illustrate that coronary imaging in mice is possible. The scanner provides a spatial and temporal resolution sufficient for imaging of smallest, moving anatomical structures and the dedicated reconstruction algorithms reduced radiation dose to less than 1 Gy but do not yet allow for longitudinal studies. Imaging studies were performed in ten mice administered with a blood-pool contrast agent. Results show that the course of the left coronary artery can be visualized in all mice and all major branches can be identified for the first time using micro-CT. This reduces the gap in cardiac imaging between clinical practice and preclinical research.

Multiscale pink-beam microCT imaging at the ESRF-ID17 biomedical beamline.

Recent trends in hard X-ray micro-computed tomography (microCT) aim at increasing both spatial and temporal resolutions. These challenges require intense photon beams. Filtered synchrotron radiation beams, also referred to as `pink beams', which are emitted by wigglers or bending magnets, meet this need, owing to their broad energy range. In this work, the new microCT station installed at the biomedical beamline ID17 of the European Synchrotron is described and an overview of the preliminary results obtained for different biomedical-imaging applications is given. This new instrument expands the capabilities of the beamline towards sub-micrometre voxel size scale and simultaneous multi-resolution imaging. The current setup allows the acquisition of tomographic datasets more than one order of magnitude faster than with a monochromatic beam configuration.

Cranial morphology of the tanystropheid Macrocnemus bassanii unveiled using synchrotron microtomography.

The genus Macrocnemus is a member of the Tanystropheidae, a clade of non-archosauriform archosauromorphs well known for their very characteristic, elongated cervical vertebrae. Articulated specimens are known from the Middle Triassic of Alpine Europe and China. Although multiple articulated specimens are known, description of the cranial morphology has proven challenging due to the crushed preservation of the specimens. Here we use synchrotron micro computed tomography to analyse the cranial morphology of a specimen of the type species Macrocnemus bassanii from the Besano Formation of Monte San Giorgio, Ticino, Switzerland. The skull is virtually complete and we identify and describe the braincase and palatal elements as well the atlas-axis complex for the first time. Moreover, we add to the knowledge of the morphology of the skull roof, rostrum and hemimandible, and reconstruct the cranium of M. bassanii in 3D using the rendered models of the elements. The circumorbital bones were found to be similar in morphology to those of the archosauromorphs Prolacerta broomi and Protorosaurus speneri. In addition, we confirm the palatine, vomer and pterygoid to be tooth-bearing palatal bones, but also observed heterodonty on the pterygoid and the palatine.

Dual source hybrid spectral micro-CT using an energy-integrating and a photon-counting detector.

Preclinical micro-CT provides a hotbed in which to develop new imaging technologies, including spectral CT using photon counting detector (PCD) technology. Spectral imaging using PCDs promises to expand x-ray CT as a functional imaging modality, capable of molecular imaging, while maintaining CT's role as a powerful anatomical imaging modality. However, the utility of PCDs suffers due to distorted spectral measurements, affecting the accuracy of material decomposition. We attempt to improve material decomposition accuracy using our novel hybrid dual-source micro-CT system which combines a PCD and an energy integrating detector. Comparisons are made between PCD-only and hybrid CT results, both reconstructed with our iterative, multi-channel algorithm based on the split Bregman method and regularized with rank-sparse kernel regression. Multi-material decomposition is performed post-reconstruction for separation of iodine (I), gold (Au), gadolinium (Gd), and calcium (Ca). System performance is evaluated first in simulations, then in micro-CT phantoms, and finally in an in vivo experiment with a genetically modified p53fl/fl mouse cancer model with Au, Gd, and I nanoparticle (NP)-based contrasts agents. Our results show that the PCD-only and hybrid CT reconstructions offered very similar spatial resolution at 10% MTF (PCD: 3.50 lp mm-1; hybrid: 3.47 lp mm-1) and noise characteristics given by the noise power spectrum. For material decomposition we note successful separation of the four basis materials. We found that hybrid reconstruction reduces RMSE by an average of 37% across all material maps when compared to PCD-only of similar dose but does not provide much difference in terms of concentration accuracy. The in vivo results show separation of targeted Au and accumulated Gd NPs in the tumor from intravascular iodine NPs and bone. Hybrid spectral micro-CT can benefit nanotechnology and cancer research by providing quantitative imaging to test and optimize various NPs for diagnostic and therapeutic applications.

Assessment of the human bone lacuno-canalicular network at the nanoscale and impact of spatial resolution.

Recently, increasing attention has been given to the study of osteocytes, the cells that are thought to play an important role in bone remodeling and in the mechanisms of bone fragility. The interconnected osteocyte system is deeply embedded inside the mineralized bone matrix and lies within a closely fitted porosity known as the lacuno-canalicular network. However, quantitative data on human samples remain scarce, mostly measured in 2D, and there are gaps to be filled in terms of spatial resolution. In this work, we present data on femoral samples from female donors imaged with isotropic 3D spatial resolution by magnified X-ray phase nano computerized-tomography. We report quantitative results on the 3D structure of canaliculi in human femoral bone imaged with a voxel size of 30 nm. We found that the lacuno-canalicular porosity occupies on average 1.45% of the total tissue volume, the ratio of the canalicular versus lacunar porosity is about 37.7%, and the primary number of canaliculi stemming from each lacuna is 79 on average. The examination of this number at different distances from the surface of the lacunae demonstrates branching in the canaliculi network. We analyzed the impact of spatial resolution on quantification by comparing parameters extracted from the same samples imaged with 120 nm and 30 nm voxel sizes. To avoid any bias related to the analysis region, the volumes at 120 nm and 30 nm were registered and cropped to the same field of view. Our results show that the measurements at 120 and 30 nm are strongly correlated in our data set but that the highest spatial resolution provides more accurate information on the canaliculi network and its branching properties.

The impact of respiratory gating on improving volume measurement of murine lung tumors in micro-CT imaging.

Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. However, preclinical imaging faces unique challenges that emphasize the gap between mouse and man. One example is the difference in breathing patterns and breath-holding ability, which can dramatically affect tumor burden assessment in lung tissue. As part of a co-clinical trial studying immunotherapy and radiotherapy in sarcomas, we are using micro-CT of the lungs to detect and measure metastases as a metric of disease progression. To effectively utilize metastatic disease detection as a metric of progression, we have addressed the impact of respiratory gating during micro-CT acquisition on improving lung tumor detection and volume quantitation. Accuracy and precision of lung tumor measurements with and without respiratory gating were studied by performing experiments with in vivo images, simulations, and a pocket phantom. When performing test-retest studies in vivo, the variance in volume calculations was 5.9% in gated images and 15.8% in non-gated images, compared to 2.9% in post-mortem images. Sensitivity of detection was examined in images with simulated tumors, demonstrating that reliable sensitivity (true positive rate (TPR) ≥ 90%) was achievable down to 1.0 mm3 lesions with respiratory gating, but was limited to ≥ 8.0 mm3 in non-gated images. Finally, a clinically-inspired "pocket phantom" was used during in vivo mouse scanning to aid in refining and assessing the gating protocols. Application of respiratory gating techniques reduced variance of repeated volume measurements and significantly improved the accuracy of tumor volume quantitation in vivo.

Study of drug particle distributions within mini-tablets using synchrotron X-ray microtomography and superpixel image clustering.

Uniform drug distribution within fast disintegrating tablets is a key quality measure to ensure a reliable, steady, and targeted release of the contained active pharmaceutical ingredients. In this work, the drug particle distribution in mini-tablets was studied with synchrotron phase contrast X-ray microtomography. Mini-tablets had a weight of 9.5 mg and a drug load from 2.5% to 20%. Moxidectin, a drug used for treatment of parasitic infections, was used as a model compound. Drug content covered a range from 91% to 121% of the target dose. A linear iterative clustering (SLIC) superpixel method was used for segmentation, analysis, and visualization of the spatial distribution of individual tablet components (i.e., pores, excipients, and drug). Results show that the drug was not uniformly distributed within the tablet, revealing an increasing drug load towards the tablets' outer boundaries and thus indicative of a radial displacement of drug particles during compaction. The presented method can be used for the quantitative analysis of drug content and drug distribution within pharmaceutical tablets, allowing for the optimization of fast disintegrating formulations. The results also affirm that that drug loads up to 20% will not lead to segregation for moxidectin.