Phantom Samples Research Articles

Development and preclinical evaluation of a patient-specific high energy x-ray phase sensitive breast tomosynthesis system.

This article reports the first x-ray phase sensitive breast tomosynthesis (PBT) system that is aimed for direct translation to clinical practice for the diagnosis of breast cancer. To report the preclinical evaluation and comparison of the newly built PBT system with a conventional digital breast tomosynthesis (DBT) system. The PBT system is developed based on a comprehensive inline phase contrast theoretical model. The system consists of a polyenergetic microfocus x-ray source and a flat panel detector mounted on an arm that is attached to a rotating gantry. It acquires nine projections over a 15° angular span in a stop-and-shoot manner. A dedicated phase retrieval algorithm is integrated with a filtered back-projection method that reconstructs tomographic slices. The American College of Radiology (ACR) accreditation phantom, a contrast detail (CD) phantom and mastectomy tissue samples were imaged at the same glandular dose levels by both the PBT and a standard of care DBT system for image quality characterizations and comparisons. The PBT imaging scores with the ACR phantom are in good to excellent range and meet the quality assurance criteria set by the Mammography Quality Standard Act. The CD phantom image comparison and associated statistical analyses from two-alternative forced-choice reader studies confirm the improvement offered by the PBT system in terms of contrast resolution, spatial resolution, and conspicuity. The artifact spread function (ASF) analyses revealed a sizable lateral spread of metal artifacts in PBT slices as compared to DBT slices. Signal-to-noise ratio values for various inserts of the ACR and CD phantoms further validated the superiority of the PBT system. Mastectomy sample images acquired by the PBT system showed a superior depiction of microcalcifications vs the DBT system. The PBT imaging technology can be clinically employed for improving the accuracy of breast cancer screening and diagnosis.

Digital adaptive optics based on digital lateral shearing of the computed pupil field for point scanning retinal swept source OCT

A novel non-iterative digital adaptive optics technique is presented in which the wavefront error is calculated using the phase difference between the pupil field and its digital copies translated by a pixel along the horizontal and vertical direction in the pupil plane. This method provides slope data per pixel, thus can generate > 50k local slope data samples for a circular pupil of diameter 256 pixels with high accuracy and dynamic range. It offers more than 12x faster computational speed in comparison to the sub-aperture based digital adaptive optics method. Furthermore, it is independent of any system parameters, the light distribution in the pupil plane, or the intensity of the image. The technique is useful in applications such as interferometric or digital holography based microscopy, metrology, and as digital wavefront sensor in adaptive optics, where focusing of light in the sample is involved that creates a guide star or where the sample itself exhibits guide star-like structures. This technique is implemented in a point scanning swept-source OCT at 1060 nm, and a large wavefront error with a peak to valley of 20 radians and root mean square error of 0.71 waves is detected and corrected in case of a micro-beads phantom sample. Also, human photoreceptor images are recovered from aberrated retinal OCT volumes acquired at eccentricities of 2 and 2.5 degrees from the fovea in vivo.

Active Thermography for Non-invasive Inspection of an Artwork on Poplar Panel: Novel Approach Using Principal Component Thermography and Absolute Thermal Contrast

The conservation of the works of art represent a topic of global interest. The development of effective tools based on advanced technology for analysing and monitoring their health-state is essential to assuring their preservation. In fact, detecting and preventing the formation of defective areas or assessing for an accurate pre-restoration analysis are the main objectives of non-destructive inspection. Active thermography is a well-known non-invasive imaging technique and reliable tool for providing a fast and low-cost analysis of a work of art. In this study we combine the potential of Principal Component Thermography and of Absolute Thermal Contrast to analyse thermal images acquired in-situ on a poplar panel painting representing an original artwork dating in the end of XVI century. We first optimized the thermal stimulation parameters in the laboratory using special phantom samples. These samples were specially made by reproducing in high fidelity the structural properties and materials of the artwork in order to perform effectively the preliminary tests. Then we moved the equipment in-situ by performing the non-destructive inspection directly on the real artwork. We have developed a specific experimental protocol that combines active thermography with two specific and appropriate image processing modalities that allowed us the effective detection of various types of defects in the painting layer. We report a complete analysis and deep discussion concerning the detection and characterization of the defects. Results show that our diagnostic protocol is a powerful tool in assessing the pre-restoration health-state and suitable for in situ analysis of wood artworks.

Nonlinear photoacoustic imaging dedicated to thermal-nonlinearity characterization

We proposed a nonlinear photoacoustic (PA) technique as a new imaging contrast mechanism for tissue thermal-nonlinearity characterization. When a sine-modulated Gaussian temperature field is introduced by a laser beam, in view of the temperature dependence of the thermal diffusivity, the nonlinear PA effect occurs, which leads to the production of second-harmonic PA (SHPA) signals. By extracting the fundamental frequency PA and SHPA signal amplitudes of samples through the lock-in technique, a parameter that only reflects nonlinear thermal-diffusivity characteristics of the sample then can be obtained. The feasibility of the technique for thermal-nonlinearity characterization has been studied on phantom samples. In vitro biological tissues have been studied by this method to demonstrate its medical imaging capability, prefiguring great potential of this new method in medical imaging applications.

Extraction of 3D quantitative maps using EDS-STEM tomography and HAADF-EDS bimodal tomography

Electron tomography has been widely applied to three-dimensional (3D) morphology characterization and chemical analysis at the nanoscale. A HAADF-EDS bimodal tomographic (HEBT) reconstruction technique has been developed to extract high resolution element-specific information. However, the reconstructed elemental maps cannot be directly converted to quantitative compositional information. In this work, we propose a quantification approach for obtaining elemental weight fraction maps from the HEBT reconstruction technique using the physical parameters extracted from a Monte Carlo code, MC X-ray. A similar quantification approach is proposed for the EDS-STEM tomographic reconstruction. The performance of the two quantitative reconstruction methods, using the simultaneous iterative reconstruction technique, are evaluated and compared for a simulated dataset of a two-dimensional phantom sample. The effects of the reconstruction parameters including the number of iterations and the weight of the HAADF signal are discussed. Finally, the two approaches are applied to an experimental dataset to show the 3D structure and quantitative elemental maps of a particle of flux melted metal-organic framework glass.

Shear Wave Generation by Remotely Stimulating Aluminum Patches With a Transient Magnetic Field and Its Preliminary Application in Elastography.

This article presents shear wave generation by remotely stimulating aluminum patches through a transient magnetic field, and its preliminary application in the cross-correlation approach based ultrasound elastography. A transient magnetic field is employed to remotely vibrate the patch actuators through the Lorentz force. The origin, and the characteristics of the Lorentz force are confirmed using an interferometric laser probe. The shear wave displacement fields generated in the soft medium are studied through the ultrafast ultrasound imaging. The potential of the shear wave fields generated through the patch actuators for the cross-correlation approach based elastography is confirmed through experiments on an agar phantom sample. Under a transient magnetic field of changing rate of 10.44kT/s, the patch actuator generates a shear wave source of amplitude of 100 μm in a polyvinyl alcohol (PVA) phantom sample. The shear wave fields created by experiments agree qualitatively well with those by theory. From the shear wave velocity map computed from 100 frames of shear wave fields, the boundaries of cylindrical regions of different stiffness can be clearly recognized, which are completely concealed in the ultrasound image. Shear wave fields in the level of 100 μm can be remotely generated in soft medium through stimulating aluminum patches with a transient magnetic field, and qualitative shear wave velocity maps can be reconstructed from the shear wave fields generated. The proposed method allows potential application of the cross-correlation approach based elastography in intravascular-based or catheter-based cardiology.

Inverse modeling for quantitative X-ray microanalysis applied to 2D heterogeneous materials

Current quantitative X-ray microanalysis methods are only available for homogeneous materials. This paper presents a newly developed inverse modeling algorithm to determine both the structure and composition of two-dimensional (2D) heterogeneous materials from a series of X-ray intensity measurements under different beam energies and beam positions. It utilizes an iterative process of forward modeling to determine the optimal specimen to minimize the relative differences between the simulated and experimental characteristic X-ray intensities. The Monte Carlo method is used for the forward modeling to predict the X-ray radiation for a given specimen and experimental setup. Several examples of applications are presented for different types of samples with one-dimensional (1D) and 2D structures, in which the simulated X-ray intensities from phantom samples are used as input. Most of the results obtained from our algorithm agree well with the phantom samples. Some discrepancies are found for the voxels located at deeper depths of the 2D samples. And the discrepancies may be attributed to errors from the Monte Carlo simulations and from the variation of the X-ray range with beam energy. As a proof-of-concept work, this paper confirms the feasibility of our inverse modeling algorithm applied to 2D heterogeneous materials.

Extension of the Stoichiometric Calibration of CT Hounsfield values to Metallic Materials

Abstract Nowadays, patients with metallic implants undergoing radiotherapy may suffer from inaccuracy in the treatment plan caused by the implant. To ensure a precise plan an accurate relation between Hounsfield values of the computer tomographic (CT) images and the electron density of the elements and material mixtures is indispensable. In order to extend the stoichiometric calibration approach known for tissues to the regime of metallic materials, the basic physical equations as well as approximations in the parametrization and fitting are carefully reviewed. CT images of a standard calibration phantom and pure metallic samples up to the atomic number Z = 29 were acquired for various energies. Hounsfield values were determined on an extended Hounsfield scale which allows the mapping of material having high atomic number Z. It is found that from basic physics an empirical factorization of the cross-sections into a function of Z and a function of photon energy E is not allowed over a wide range of Z. Specifically, the parameterization for tissue like materials cannot be prolonged to materials with high-Z. Thus, the calibration is subdivided into regions of materials and its accuracy is quantified in each region. It depends, among others, on the knowledge of the X-ray photon spectra, the segmentation of the material samples and the empirical parameterization of the linear-attenuation coefficient.

Algebraic reconstruction of 3D spatial EPR images from high numbers of noisy projections: An improved image reconstruction technique for high resolution fast scan EPR imaging

A novel method for reconstructing 3D spatial EPR images from large numbers of noisy projections was developed that minimizes mean square error between the experimental projections and those from the reconstructed image. The method utilizes raw projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of the paramagnetic probe without the need for deconvolution techniques that are poorly suited for processing of high noise projections. A numerical phantom was reconstructed for method validation. Reconstruction time for the matrix of 1283 voxels and 16,384 noiseless projections was 4.6 min for a single iteration. The algorithm converged quickly, reaching R2 ~ 0.99975 after the very first iteration. An experimental phantom sample with nitroxyl radical was measured. With 16,384 projections and a field gradient of 8 G/cm, resolutions of 0.4 mm were achieved for a cubical area of 25 × 25 × 25 mm3. Reconstruction was sufficiently fast and memory efficient making it suitable for applications with large 3D matrices and fully determined system of equations. The developed algorithm can be used with any gradient distribution and does not require adjustable filter parameters that makes for simple application. A thorough analysis of the strengths and limitations of this method for 3D spatial EPR imaging is provided.

Conversion of Laser Ultrasonic Tomography Data to the DICOM Standard

An experimental setup for laser ultrasonic tomography of biological tissues has been developed. Experimental studies of phantom samples were conducted. A program for converting graphic data of laser ultrasonic tomography into a standard medical format has been developed.

New and rapid pulse sequences for two-dimensional D-T1 correlation measurements

Longitudinal relaxation time (T1), transverse relaxation time (T2) and diffusion coefficient (D) values have been widely used for the characterizations of materials using low field Time Domain Nuclear Magnetic Resonance (TD-NMR). Each parameter can be determined using one-dimensional techniques or their values and correlations by multi-dimensional experiments such as T1-T2, D-T2, and T1-D-T2. In this work, we studied four D-T1 sequences for TD-NMR combining Stejskal-Tanner Pulse Gradient Spin Echo (PGSE) diffusion measurement with Inversion-Recovery (IR), Saturation-Recovery (SR), Small-Angle Continuous Wave Free Precession (CWFP-T1) and Small-Angle Flip-Flop (SAFF) for T1 measurement. The results show that rapid D-T1 measurements can be obtained with single shot CWFP-T1 and SAFF sequences. The two sequences were two and eight time fast than sequences based on SR and IR, respectively. Although the two fast sequences yield low signal-to-noise ratio signal, they can be as fast as the traditional D-T2 experiment, or even faster, because it is not necessary to wait a recycle delay of 5 T1. Another advantage of the CWFP-T1 and SAFF methods, when compared to the one based on SR or CPMG (for D-T2) are the low specific absorption rate (SAR) of these sequences due the low flip angles in the sequences, that reduces the sample heating problem. These sequences were initially studied using phantom samples. They also were used to study plant tissues to observe the anisotropic diffusion in asparagus. Therefore, they can be useful methods for practical application in TD-NMR.

Simultaneously Reducing Cutting Force and Tissue Damage in Needle Insertion With Rotation.

Rotational needle insertion is commonly used in needle biopsy to improve cutting performance. The application of rotational motion for needle insertion has been shown to efficiently reduce the cutting force. However, studies have found that needle rotation can increase tissue damage due to the tissue winding effect. The bidirectional rotation of a needle during insertion can be a solution to avoid tissue winding while maintaining a low cutting force. In this study, needle insertion with bidirectional rotation was investigated by conducting mechanical and optical experiments. First, needle insertion tests were performed on gelatin-based tissue phantom samples to understand the effect of bidirectional needle rotation on the cutting force. Subsequently, the effective strain, which is an indicator of tissue damage, was observed at the cross-sections of samples in the axial and radial directions of the needle by using the digital image correlation (DIC) technology. The primary findings of this study are as follows: (1) higher needle insertion speeds result in higher cutting forces and effective strains that occur at the axial cross-section, (2) increase in the needle rotation reduces the cutting force and effective strain at the axial cross-section but increases the effective strain at the radial cross-section, (3) application of bidirectional rotation decreases the mean effective strain at the radial cross-section by 10%-25% while maintaining a low cutting force. In clinical applications, bidirectional rotation can be a useful strategy to simultaneously reduce the cutting force and tissue damage, which leads to better cutting performance and lower risks of bleeding and hematoma.

A phantom system for assessing the effects of membrane lipids on water proton relaxation.

Quantitative MRI (qMRI) is a method for the non-invasive study of brain-structure-associated changes expressed with measurable units. The qMRI-derived parameters have been shown to reflect brain tissue composition such as myelin content. Nevertheless, it remains a major challenge to identify and quantify the contributions of specific molecular components to the MRI signal. Here, we describe a phantom system that can be used to evaluate the contribution of membrane lipids to qMRI-derived parameters. We used a hydration-dehydration dry film technique to formulate liposomes that can be used as a model of the bilayer lipid membrane. The liposomes were comprised of the most abundant types of lipid found in the human brain. We then applied clinically available qMRI techniques with adjusted bias corrections in order to test the ability of the phantom system to estimate multiple qMRI parameters such as proton density (PD), T1 , T2 , T2 * and magnetization transfer. In addition, we accurately measured the phantom sample water fraction (normalized PD). A similar protocol was also applied to the human brain in vivo. The phantom system allows for a reliable estimation of qMRI parameters for phantoms composed of various lipid types using a clinical MRI scanner. We also found a comparable reproducibility between the phantom and in vivo human brain qMRI estimations. To conclude, we have successfully created a biologically relevant liposome phantom system whose lipid composition can be fully controlled. Our lipid system and analysis can be used to measure the contributions to qMRI parameters of membrane lipids found in the human brain under scanning conditions that are relevant to in vivo human brain scans. Such a model system can be used to test the contributions of lipidomic changes in normal and pathological brain states.

Denoising Raman spectra by Wiener estimation with a numerical calibration dataset.

Most denoising methods that are currently used in the processing of Raman spectra require significant user interaction in order to optimize their performance across a range of signal-to-noise ratios. In this study, we proposed a method based on the principle of spectral integration followed by Wiener estimation using a numerical calibration dataset, which eliminates the need of experimental measurements for calibration as in the previous Wiener estimation based denoising method. The new method was tested on three types of samples, including a phantom sample, human fingernail and leukemia cells. Compared to two common denoising methods, i.e. moving-average filtering and Savitzky-Golay filtering, the performance of the proposed method is significantly less sensitive to the choices of parameters. Moreover, this method provides comparable or even better denoising performance in the cases with low signal-to-noise ratios.

Using T1 as a direct detection dimension in two-dimensional time-domain NMR experiments using CWFP regime

The transverse relaxation time (T2), measured with Carr-Purcell-Meiboom-Gill (CPMG) sequence, has been widely used to obtain the direct dimension data in two-dimension time domain NMR (2D TD-NMR). In this paper we are demonstrating that Continuous Wave Free Precession sequence, with low flip angle (CWFP-T1), can be an alternative to CPMG as direct detection dimension. CWFP-T1 is a fast single shot sequence, like CPMG, and yields an exponential signal governed predominantly by the longitudinal (T1) relaxation time. To obtain the correlations between T1 and T2 (T1-T2 maps) we are proposing the use of CPMG-CWFP-T1 pulse sequence. In this sequence CPMG encodes T2 information (indirect dimension) that modulates the CWFP-T1 (direct dimension) signal amplitudes. CPMG-CWFP-T1 experiments were compared with classical 2D sequences such as Saturation-Recovery-CPMG (SR-CPMG) and Inversion-Recovery-CPMG (IR-CPMG) sequence and yields similar results in phantom sample. The experimental time for the 2D sequences, using single scan, shows that SR-CPMG ≤ CPMG-CWFP-T1 < IR-CPMG. Experimental and simulated results demonstrated that 2D-CPMG-CWFP-T1 maps have higher resolution in T1 dimension than the techniques that uses CPMG as direct dimension. CPMG-CWFP-T1 sequence was also applied to study beef samples, and 2D maps showed higher resolution in the two fat signals than the classical IR-CPMG method.

Multiwavelength photoacoustic temperature measurement with phantom and ex-vivo tissue

Photoacoustic temperature measurement is a new type of thermometric technology with noninvasive, real-time, high precision and space resolution. For improving the measurement accuracy and reliability, the method of using a multiwavelength photoacoustic signal to monitor the temperature named as multiwavelength photoacoustic temperature measurement was proposed in this paper. Based on the basic photoacoustic effect theory, the theoretical feasibility of this method was analyzed. And the experimental results from the phantom and ex-vivo tissue samples indicate that the multiwavelength photoacoustic temperature measurement can effectively reduce the error to smaller than 0.1 °C, and increase the accuracy of temperature measurement by more than two times. Our study demonstrated that the multiwavelength photoacoustic temperature measurement can potentially be a valuable method for temperature measurement during photothermal therapy or other clinic applications.

Mesoscale characterization of continuous fiber reinforced composites through machine learning: Fiber chirality

A method of quantifying fiber chirality, the twist of continuous fibers through a volume, is defined and applied to both phantom data and real data. Specifically, a field quantity termed the fiber chirality based on the anti-symmetric part of the gradient of the fiber orientation is introduced. For this method of estimation, the input is the set of fiber positions gathered from the stack of images which represent the sample volumes. The phantom sample is generated and several different real continuous fiber reinforced matrix composites are experimentally characterized. Each phantom dataset contains a bundle of fibers that rotate about a center axis with a user-defined angle at each step in the z-direction. The chirality of the fibers is calculated based on the pre-characterized positions using a machine learning algorithm. To validate the method of quantification, our chirality estimation method results in a colormap with an angle of rotation that becomes increasingly more similar to the user-defined angle with decreasing inter-slice distance. Fiber positions from real data are then input into the estimation method and the results are compared.

Fabrication, Measurement and Time Decay of the Electromagnetic Properties of Semi-Solid Water-Based Phantoms.

This paper presents a complete and detailed description of the fabrication and measurement of the electromagnetic properties of water-based semi-solid phantoms with emphasis on the analysis of the time evolution of the complex permittivity of several samples stored in different conditions. A known recipe for a 2/3 muscle equivalent phantom is used as test material, and the several phantom sample properties are measured with an in-house developed coaxial probe technique. It is shown that the storing condition is of paramount importance to extend the lifetime of a given phantom. This behavior stems from the way the storing condition affects the water evaporation rate of the sample. In particular, while an unprotected sample can preserve its electromagnetic properties only for a few days, a very well-sealed one can last at least up to a year.

Development of multifunctional Overhauser-enhanced magnetic resonance imaging for concurrent in vivo mapping of tumor interstitial oxygenation, acidosis and inorganic phosphate concentration

Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content.

Spatially-offset Raman spectroscopy for monitoring mineralization of bone tissue engineering scaffolds: feasibility study based on phantom samples.

Using phantom samples, we investigated the feasibility of spatially-offset Raman spectroscopy (SORS) as a tool for monitoring non-invasively the mineralization of bone tissue engineering scaffold in-vivo. The phantom samples consisted of 3D-printed scaffolds of poly-caprolactone (PCL) and hydroxyapatite (HA) blends, with varying concentrations of HA, to mimic the mineralisation process. The scaffolds were covered by a 4 mm layer of skin to simulate the real in-vivo measurement conditions. At a concentration of HA approximately 1/3 that of bone (~0.6 g/cm3), the characteristic Raman band of HA (960 cm−1) was detectable when the PCL:HA layer was located at 4 mm depth within the scaffold (i.e. 8 mm below the skin surface). For the layers of the PCL:HA immediately under the skin (i.e. top of the scaffold), the detection limit of HA was 0.18 g/cm3, which is approximately one order of magnitude lower than that of bone. Similar results were also found for the phantoms simulating uniform and inward gradual mineralisation of the scaffold, indicating the suitability of SORS to detect early stages of mineralisation. Nevertheless, the results also show that the contribution of the materials surrounding the scaffold can be significant and methods for subtraction need to be investigated in the future. In conclusion, these results indicate that spatially-offset Raman spectroscopy is a promising technique for in-vivo longitudinal monitoring scaffold mineralization and bone re-growth.