Breast imaging using 3D electrical impedence tomography

Aim: To determine the diagnostic efficiency of 3D Eletrical Impedance Tomography (EIT) compared to Mammography (MG) and Ultrasonography (USG) in imaging the breast. Materials and Methods: A group of 88 patients presenting with various breast complaints was examined using combined Mammography and Ultrasonography (MG & USG) or either of these modalities alone. The same patients were then examined using the 3D EIT imaging system "MEIK". The findings were then compared. The sensitivity of these modalities for this group of patients were later determined and statistically analysed. Results: Of the total of 88 patients, 59 findings were "suspicious" by any of the 3 modalities alone or by their combination. EIT had a sensitivity of 77.8 % compared to MG with a sensitivity of 83.3 % and USG with a sensitivity of 94.4 % regarding cases of fibrocystic mastitis. For cases involving cysts, EIT had 100 % sensitivity which was the same as that for USG compared to MG with a sensitivity of only 81 %. Among cases of fibroadenoma, EIT had a sensitivity of just 68.8 % compared to MG with a sensitivity of 87.5 % and USG with a sensitivity of 75 %. Finally among cases of carcinoma, EIT had a sensitivity of 75 % compared to the sensitivity of 100 % of MG and USG in our group of patients. The study revealed that there was no overall significant difference in sensitivity between MG-USG (p = 0.219) and MG-EIT (p = 0.779) and USG-EIT (p = 0.169). However, in regard to identifying cysts there was significant difference in the sensitivity of MG compared to USG & EIT suggesting that EIT has a role in these cases. Conclusion: Electrical impedance could be used as an adjunct to Mammography and Ultrasonography for breast cancer detection. However, the differentiation of malignant from benign lesions based on impedance measurements needs further investigation. Multifrequency electrical impedance imaging appears the most promising for detecting breast malignancies but methodological improvements need to be made to realise its potential.     

Genes into geometry: imaging for mouse development in 3D

Mammalian development is a sophisticated program coordinated by a complex set of genetic and physiological factors. Alterations in anatomy or morphology provide intrinsic measures of progress in or deviations from this program. Emerging three-dimensional imaging methods now allow for more sophisticated morphological assessment than ever before, enabling comprehensive phenotyping, visualization of anatomical context and patterns, automated and quantitative morphological analysis, as well as improved understanding of the developmental time course. Furthermore, these imaging tools are becoming increasingly available and will consequently play a prominent role in elucidating the factors that direct and influence mammalian development.     

Characterization of the growth plate-bone interphase region using cryo-FIB SEM 3D volume imaging

The interphase region at the base of the growth plate includes blood vessels, cells and mineralized tissues. In this region, cartilage is mineralized and replaced with bone. Blood vessel extremities permeate this space providing nutrients, oxygen and signaling factors. All these different components form a complex intertwined 3D structure. Here we use cryo-FIB SEM to elaborate this 3D structure without removing the water. As it is challenging to image mineralized and unmineralized tissues in a hydrated state, we provide technical details of the parameters used. We obtained two FIB SEM image stacks that show that the blood vessels are in intimate contact not only with cells, but in some locations also with mineralized tissues. There are abundant red blood cells at the extremities of the vessels. We also documented large multinucleated cells in contact with mineralized cartilage and possibly also with bone. We observed membrane bound mineralized particles in these cells, as well as in blood serum, but not in the hypertrophic chondrocytes. We confirm that there is an open pathway from the blood vessel extremities to the mineralizing cartilage. Based on the sparsity of the mineralized particles, we conclude that mainly ions in solution are used for mineralizing cartilage and bone, but these are augmented by the supply of mineralized particles.     

Effect of verification imaging on in vivo dosimetry results using Gafchromic EBT3 film

In this work, the apparent treatment dose that kV planar or CBCT imaging contributes to Gafchromic EBT3 film used for in vivo dosimetry, was investigated. Gafchromic EBT3 film pieces were attached to a variety of phantoms and irradiated using the linear accelerator’s built-in kV imaging system, in both kV planar mode and CBCT mode. To evaluate the sensitivity of the film in the clinical scenario where dose contributions are received from both imaging and treatment, additional pieces of film were irradiated using base doses of 50 cGy and then irradiated using selected kV planar and CBCT techniques. For kV planar imaging, apparent treatment doses of up to 3.4 cGy per image pair were seen. For CBCT, apparent treatment doses ranged from 0.22 cGy to 3.78 cGy. These apparent doses were reproducible with and without the inclusion of the 50 cGy base dose. The contribution of apparent treatment dose from both planar kV as well as CBCT imaging can be detected, even in conjunction with an actual treatment dose. The magnitude of the apparent dose was found to be dependent on patient geometry, scanning protocol, and measurement location. It was found that the apparent treatment dose from the imaging could add up to 8% of additional uncertainty to the in vivo dosimetry result, if not taken into account. It is possible for this apparent treatment dose to be accounted for by subtraction of the experimentally determined apparent doses from in vivo measurements, as demonstrated in this work.     

A reliability and validity study for Scolioscan: a radiation-free scoliosis assessment system using 3D ultrasound imaging

Background

Radiographic evaluation for patients with scoliosis using Cobb method is the current gold standard, but radiography has radiation hazards. Several groups have recently demonstrated the feasibility of using 3D ultrasound for the evaluation of scoliosis. Ultrasound imaging is radiation-free, comparatively more accessible, and inexpensive. However, a reliable and valid 3D ultrasound system ready for clinical scoliosis assessment has not yet been reported. Scolioscan is a newly developed system targeted for scoliosis assessment in clinics by using coronal images of spine generated by a 3D ultrasound volume projection imaging method. The aim of this study is to test the reliability of spine deformity measurement of Scolioscan and its validity compared to the gold standard Cobb angle measurements from radiography in adolescent idiopathic scoliosis (AIS) patients.

Methods

Prospective study divided into two stages: 1) Investigation of intra- and inter- reliability between two operators for acquiring images using Scolioscan and among three raters for measuring spinal curves from those images; 2) Correlation between the Cobb angle obtained from radiography by a medical doctor and the spine curve angle obtained using Scolioscan (Scolioscan angle). The raters for ultrasound images and the doctors for evaluating radiographic images were mutually blinded. The two stages of tests involved 20 (80 % females, total of 26 angles, age of 16.4?±?2.7 years, and Cobb angle of 27.6?±?11.8°) and 49 (69 % female, 73 angles, 15.8?±?2.7 years and 24.8?±?9.7°) AIS patients, respectively. Intra-class correlation coefficients (ICC) and Bland-Altman plots and root-mean-square differences (RMS) were employed to determine correlations, which interpreted based on defined criteria.

Results

We demonstrated a very good intra-rater and intra-operator reliability for Scolioscan angle measurement with ICC larger than 0.94 and 0.88, respectively. Very good inter-rater and inter-operator reliability was also demonstrated, with both ICC larger than 0.87. For the thoracic deformity measurement, the RMS were 2.5 and 3.3° in the intra- and inter-operator tests, and 1.5 and 3.6° in the intra- and inter-rater tests, respectively. The RMS differences were 3.1, 3.1, 1.6, 3.7° in the intra- and inter-operator and intra- and inter-rater tests, respectively, for the lumbar angle measurement. Moderate to strong correlations (R²?>?0.72) were observed between the Scolioscan angles and Cobb angles for both the thoracic and lumbar regions. It was noted that the Scolioscan angle slightly underestimated the spinal deformity in comparison with Cobb angle, and an overall regression equation y?=?1.1797x (R²?=?0.76) could be used to translate the Scolioscan angle (x) to Cobb angle (y) for this group of patients. The RMS difference between Scolioscan angle and Cobb angle was 4.7 and 6.2°, with and without the correlation using the overall regression equation.

Conclusions

We showed that Scolioscan is reliable for measuring coronal deformity for patients with AIS and appears promising in screening large numbers of patients, for progress monitoring, and evaluation of treatment outcomes. Due to it being radiation-free and relatively low-cost, Scolioscan has potential to be widely implemented and may contribute to reducing radiation dose during serial monitoring.

     

Micro CT and Micro MR imaging of 3D architecture of animal skeleton

Quantitative assessment of three-dimensional (3D) trabecular structural characteristics may improve our ability to understand the pathophysiology of osteoporosis, to test the efficacy of pharmaceutical intervention, and to estimate bone biomechanical properties. Considerable progress has been made in advanced imaging techniques for noninvasive and/or nondestructive assessment of 3D trabecular structure and connectivity. Micro computed tomography (microCT) has been used to measure 3D trabecular bone structure in rats, both in vivo and in vitro. It can directly quantify 3D trabecular bone structure such as trabecular volume, trabecular thickness, number, separation, structure model index, degree of anisotropy, and connectivity, in a model-independent manner. We have used microCT to study ovariectomy (OVX) induced osteopenia in rats and its treatment with agents such as estrogen, and sodium fluoride. We have demonstrated that 3D microCT can quantify mouse trabecular and cortical bone structure with an isotropic resolution of 9 microm(3). It is also useful for studying osteoporosis in mice and in phenotypes of transgenic mice or gene knockout mice. MicroCT can be used to quantify osteogenesis in mouse Ilizarov leg lengthening procedures, to quantify osteoconduction in a rat cranial defect model, and to quantify cortical bone porosity. Recently, microCT using high intensity and tight collimation synchrotron radiation to achieve spatial resolution of 1-2 microm has provided the capability to assess additional features such as resorption cavities. Unlike microCT, micro magnetic resonance imaging (IMRI) is nonionizing. Recently, the ability of microMRI to assess osteoporosis in animal models has been explored. Using a small, high-efficiency coil in a high-field imager, microMRI can give resolutions sufficient to discriminate individual trabeculae. We have shown that, with appropriate settings, it is possible to image trabecular bone in rats in vivo and in vitro. In our study of OVX rats, analysis of microMR images can demonstrate differences in rat trabecular bone that are not detected by DXA measurements. In a rabbit OA model, with the OA induced by meniscectomy or anterior cruciate ligament transection, MRI shows decreased cartilage thickness, subchondral osteosclerosis and osteophytes, while radiographs can only show subchondral osteosclerosis and osteophytes could not be found. Advanced imaging methods are able to measure 3D trabecular structure and connectivity in arbitrary orientations in a highly automated, objective, non-user-specific manner, allowing greater numbers of samples for unbiased comparisons between controls and the disordered or treated. They can be utilized on a large sample leading to fewer sampling errors. They are non-destructive allowing multiple tests such as biomechanical testing and chemical analysis on the same sample; and non-invasive permitting longitudinal studies and reducing the number of animals needed.     

Radiotherapy setup displacements in breast cancer patients: 3D surface imaging experience

Aim

In this study, we intend to compare two different setup procedures for female breast cancer patients.

Radiation injury of the parotid glands during treatment for head and neck cancer: assessment using dynamic contrast-enhanced MR imaging

The parotid gland is an important organ at risk of complications of radiotherapy for head and neck cancer. In this study, we examined the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of radiation injury to the parotid glands. DCE-MRI was performed before and 3 months after radiotherapy in patients treated for head and neck cancer. DCE-MRI was analyzed using the pharmacokinetic model proposed by Tofts and Kermode to produce three DCE parameters: k(trans), v(e) and v(p). These parameters were correlated with the dose of radiation delivered to the parotid glands and the degree of radiation-induced parotid atrophy. The mean radiation dose received by the parotid glands was 47.1 ± 6.6 Gy. All patients received concurrent chemotherapy. There was a significant rise in all three parameters after therapy (P < 0.0001). Baseline v(e) and v(p) and the post-treatment rise in v(e) correlated with parotid gland atrophy (P = 0.0008, 0.0003 and 0.0022, respectively). DCE-MRI has the potential to be used as a non-invasive technique for predicting and assessing radiation injury in the parotid glands.     

A biplanar reconstruction method based on 2D and 3D contours: application to the distal femur

A three-dimensional (3D) reconstruction algorithm based on contours identification from biplanar radiographs is presented. It requires, as technical prerequisites, a method to calibrate the biplanar radiographic environment and a surface generic object (anatomic atlas model) representing the structure to be reconstructed. The reconstruction steps consist of: the definition of anatomical regions, the identification of 2D contours associated to these regions, the calculation of 3D contours and projection onto the radiographs, the associations between points of the X-rays contours and points of the projected 3D contours, the optimization of the initial solution and the optimized object deformation to minimize the distance between X-rays contours and projected 3D contours. The evaluation was performed on 8 distal femurs comparing the 3D models obtained to CT-scan reconstructions. Mean error for each distal femur was 1 mm.     

A fast method for implicit surface reconstruction based on radial basis functions network from 3D scattered points

A method for arbitrary surface reconstruction from 3D large scattered points is proposed in this paper. According to the properties of 3D points, e.g. the non-uniform distribution and unknown topology, an implicit surface model is adopted based on radial basis functions network. And because of the property of locality of radial basis function, the method is fast and robust in surface reconstruction. Furthermore, an adapted K-Means algorithm is used to reduce reconstruction centers. For features completeness, two effective methods are introduced to extract the feature points before the adapted K-Means algorithm. Experiment results show that the presented approach is a good solution for reconstruction from 3D large scattered points.     

Construction of 3D human distal femoral surface models using a 3D statistical deformable model

Construction of 3D geometric surface models of human knee joint is always a challenge in biomedical engineering. This study introduced an improved statistical shape model (SSM) method that only uses 2D images of a joint to predict the 3D joint surface model. The SSM was constructed using 40 distal femur models of human knees. In this paper, a series validation and parametric analysis suggested that more than 25 distal femur models are needed to construct the SSM; each distal femur should be described using at least 3000 nodes in space; and two 2D fluoroscopic images taken in 45° directions should be used for the 3D surface shape prediction. Using this SSM method, ten independent distal femurs from 10 independent living subjects were predicted using their 2D plane fluoroscopic images. The predicted models were compared to their native 3D distal femur models constructed using their 3D MR images. The results demonstrated that using two fluoroscopic images of the knee, the overall difference between the predicted distal femur surface and the MR image-based surface was 0.16±1.16 mm. These data indicated that the SSM method could be a powerful method for construction of 3D surface geometries of the distal femur.     

Glycoprotein profiling of stem cells using lectin microarray based on surface plasmon resonance imaging

Lectin microarrays have emerged as a novel platform for glycan analysis during recent years. Here, we have combined surface plasmon resonance imaging (SPRi) with the lectin microarray for rapid and label-free profiling of stem cells. In this direction, 40 lectins from seven different glyco-binding motifs and three different cell lines—mouse embryonic stem cells (mESCs), mouse-induced pluripotent stem cells (miPSCs), and mouse embryonic fibroblast stem cells (MEFs)—were used. Pluripotent mouse stem cells were clearly distinguished from non-pluripotent stem cells. Eight lectins—DBA, MAL, PHA_E, PHA_L, EEL, AAL, PNA, and SNA—generated maximal value to define pluripotency of mouse stem cells in our experiments. The discriminant function based on lectin reactivities was highly accurate for the determination of stem cell pluripotency. These results suggested that glycomic analysis of stem cells leads to a novel comprehensive approach for quality control in cell-based therapy and regenerative medicine.     

A 3D modeling method to calculate the surface areas of coral branches

The quantification of physiological and biochemical parameters in coral branches require normalization to a stable factor, such as the tissue biomass or surface area. Three dimensional (3D) animation software (Gmax^®) was evaluated for estimating the surface area of simple coral branches. The software was highly predictive of the known surface areas of small (20–60 mm long) plastic rods and cones (r ² > 0.99), and of small (30–60 mm) Acropora millepora branches (r ² = 0.98) whose surface area had been obtained using the traditional wax-weight method. Two normalization parameters, 3D modeled surface area and tissue biomass (measured as protein), were then compared for A. millepora branches collected in summer and winter. In winter, protein and surface area were correlated (r ² > 0.61), but not in summer, indicating that choice of normalizing parameter will influence the outcome of experimental analyses.     

Inverse probability weighting estimation of the volume under the ROC surface in the presence of verification bias

In diagnostic medicine, the volume under the receiver operating characteristic (ROC) surface (VUS) is a commonly used index to quantify the ability of a continuous diagnostic test to discriminate between three disease states. In practice, verification of the true disease status may be performed only for a subset of subjects under study since the verification procedure is invasive, risky, or expensive. The selection for disease examination might depend on the results of the diagnostic test and other clinical characteristics of the patients, which in turn can cause bias in estimates of the VUS. This bias is referred to as verification bias. Existing verification bias correction in three‐way ROC analysis focuses on ordinal tests. We propose verification bias‐correction methods to construct ROC surface and estimate the VUS for a continuous diagnostic test, based on inverse probability weighting. By applying U‐statistics theory, we develop asymptotic properties for the estimator. A Jackknife estimator of variance is also derived. Extensive simulation studies are performed to evaluate the performance of the new estimators in terms of bias correction and variance. The proposed methods are used to assess the ability of a biomarker to accurately identify stages of Alzheimer's disease.