Numerical modelling of biopotential field for detection of breast tumour

Breast cancer is a disease characterised by the uncontrolled growth of abnormal cells. These cancer cells can travel through the body by way of blood or lymph nodes. Previous studies have indicated that, changes in the electrical properties of abnormal breast are more significant compared to the breast normal tissues. In the present study, a simple 2D models of breast (close to realistic), with and without artificially inserted malignant cancer were simulated, based upon electrical activity within the breast. We developed an inhomogeneous female breast model, closer to the actual, by considering a breast as a hemisphere with various layers of unequal thickness in supine condition. In order to determine the potential distribution developed due to a dipole source, isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method. Significant changes in the potential distribution were recoded in the malignant and normal breast regions. The surface potential decreases about 0.5%, for the small malignant region of surface area 13 mm(2) (spherical diameter=2mm). And it (surface potential) decreases about 16.4% for large malignant surface area of 615 mm(2) (spherical diameter=14 mm). Hence, the results show that, the sizes of tumours result in the reduction of surface potential and follows a fourth order polynomial equation. Thus, biofield analysis yields promising results in the detection of the breast cancer of various sizes.     

Viscoelasticity-based MR elastography of skeletal muscle

An in vivo multifrequency magnetic resonance elastography (MRE) protocol was developed for studying the viscoelastic properties of human skeletal muscle in different states of contraction. Low-frequency shear vibrations in the range of 25-62.5 Hz were synchronously induced into the femoral muscles of seven volunteers and measured in a cross-sectional view by encoding the fast-transverse shear wave component parallel to the muscle fibers. The so-called springpot model was used for deriving two viscoelastic constants, μ and α, from the dispersion functions of the complex shear modulus in relaxed and in loaded muscle. Representing the shear elasticity parallel to the muscle fibers, μ increased in all volunteers upon contraction from 2.68 ± 0.23 kPa to 3.87 ± 0.50 kPa. Also α varied with load, indicating a change in the geometry of the mechanical network of muscle from relaxation (α = 0.253 ± 0.009) to contraction (α = 0.270 ± 0.009). These results provide a reference for a future assessment of muscular dysfunction using rheological parameters.     

A three-dimensional quality-guided phase unwrapping method for MR elastography

Magnetic resonance elastography (MRE) uses accumulated phases that are acquired at multiple, uniformly spaced relative phase offsets, to estimate harmonic motion information. Heavily wrapped phase occurs when the motion is large and unwrapping procedures are necessary to estimate the displacements required by MRE. Two unwrapping methods were developed and compared in this paper. The first method is a sequentially applied approach. The three-dimensional MRE phase image block for each slice was processed by two-dimensional unwrapping followed by a one-dimensional phase unwrapping approach along the phase-offset direction. This unwrapping approach generally works well for low noise data. However, there are still cases where the two-dimensional unwrapping method fails when noise is high. In this case, the baseline of the corrupted regions within an unwrapped image will not be consistent. Instead of separating the two-dimensional and one-dimensional unwrapping in a sequential approach, an interleaved three-dimensional quality-guided unwrapping method was developed to combine both the two-dimensional phase image continuity and one-dimensional harmonic motion information. The quality of one-dimensional harmonic motion unwrapping was used to guide the three-dimensional unwrapping procedures and it resulted in stronger guidance than in the sequential method. In this work, in vivo results generated by the two methods were compared.     

Improvement in diagnosis of breast tumour using ultrasound elastography and echography: A phantom based analysis

Due to the isoechoic nature of lesions and their poor contrast with neighbouring tissue, a lesion may remain undetected in ultrasound B mode imaging for cancerous tissue. Imaging of the elastic properties of tissue provides new information which is collateral to tissue pathology. This study provides quantitative analysis of improvements in tumour diagnosis when the ultrasound B mode imaging is combined with elastography. Quantification was based on the textural parameters measured from the ultrasound B mode image and strain measured from the elastogram. The ability of a parameter to discriminate between diseased cases and normal cases was evaluated using receiver operating characteristic (ROC) analysis. Polyacrylamide gel based tissue mimicking phantoms with embedded inclusions of varying stiffness were used for the analysis.     

Analytic modeling of breast elastography

The elastic moduli of tumors change during their pathological evolution. Elastographic imaging has potential for detecting and characterizing cancers by mapping the stiffness distribution in tissues. In this paper a micromechanics-based analytical method was developed to detect the location, size, and elastic modulus of a tumor mass embedded in a symmetric two-dimensional breast tissue. A closed-form solution for the strain elastograms (forward problem) was derived. A computational algorithm for the inverse problem was developed for the detection, localization, and characterization of a heterogeneous mass embedded in a breast tissue. Numerical examples were presented to evaluate the proposed method's performance. The detectability of a tumor mass was estimated with respect to lesion location, size, and modulus contrast ratio. It was shown that the micromechanics theory provides a powerful tool for the diagnosis of breast cancer.     

Thresholds for detecting and characterizing focal lesions using steady-state MR elastography

An objective contrast-detail analysis was performed in this study to assess the low contrast detectability of a clinical prototype harmonic magnetic resonance elastographic imaging system. Elastographic imaging was performed on gelatin phantoms containing spherical inclusions of varying size and modulus contrast. The results demonstrate that lesions as small as 5 mm can be detected with a minimum modulus contrast of 14 dB. However, the shear modulus of such small lesions was not accurately recovered. In general, the shear modulus of larger focal lesions was accurately (i.e., within 25% of the true value) recovered. The minimum modulus contrast needed to detect focal lesions was observed to decrease with increasing lesion size.     

Liver fibrosis: non-invasive assessment with MR elastography

The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis. Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study. The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0, no fibrosis, to F4, cirrhosis. MR elastography was performed by transmitting low-frequency (65 Hz) mechanical waves into the liver with a transducer placed at the back of the patients. The MR pulse sequence was a motion-sensitized spin-echo sequence, phase-locked to the mechanical excitation. The phase maps were processed to obtain shear elasticity and shear viscosity maps. The mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was 2.24 +/- 0.23 kPa in the 11 patients without substantial fibrosis (F0-F1 grades), 2.56 +/- 0.24 kPa in the four patients with substantial fibrosis (F2-F3) and 4.68 +/- 1.61 kPa in the 10 patients with cirrhosis (F4). The differences between groups were statistically significant (p 相似文献   

High-resolution multi-parameter DNA flow cytometry enables detection of tumour and stromal cell subpopulations in paraffin-embedded tissues

The accuracy of DNA ploidy measurements of paraffin-embedded tissues is limited by the lack of resolution and the inability to identify the DNA diploid population unequivocally in bimodal DNA histograms. A multi-parameter DNA flow cytometric method has been developed that enables the simultaneous detection of neoplastic and stromal cells in samples from dewaxed 50 microm sections or 2 mm diameter punches of archival tissue blocks. The method combines heat pretreatment in sodium citrate buffer and subsequent enzymatic dissociation with a collagenase/dispase mixture. Cells were simultaneously stained for keratin (FITC), vimentin (R-PE), and DNA (PI) before flow cytometric analysis. The method was applied to 12 paraffin-embedded cervical carcinomas and four colorectal carcinomas. In all cervical cancers, distinct keratin-positive and vimentin-positive cell populations were observed. While the exclusive vimentin-positive cell fractions always yielded unimodal DNA content distributions, bimodal distributions were observed for the keratin-positive cell fractions in nine cervical carcinomas, whereas one cervical carcinoma showed three distinct G0G1 populations. Coefficients of variation of the G0G1 peaks ranged from 1.70% to 4.79%. Average background, aggregate, and debris values were 14.7% (vimentin-positive fraction) and 33.8% (keratin-positive fraction). Flow sorting confirmed that the exclusively vimentin-positive cell fractions represent different normal stromal and infiltrate cells that can serve as an internal ploidy reference enabling discrimination between DNA hypo-diploid and DNA hyper-diploid tumour cell subpopulations. The neoplastic origin of the keratin-vimentin co-expressing cells from two cervical carcinomas was confirmed by genotyping of flow-sorted samples revealing loss of heterozygosity (LOH) of 6p. This improved method obviates the need for fresh/frozen tumour tissue for high-resolution DNA ploidy measurements and enables the isolation of highly purified tumour subpopulations for subsequent genotyping.     

弥散张量磁共振成像的新进展

弥散张量磁共振成像技术是近年来出现的一项新技术,由于其对脑白质纤维具有高度敏感性以致在临床上的应用日益广泛,并为人体中枢神经系统的深入研究提供了有效的工具。     

Hyaluronan-modified magnetic nanoclusters for detection of CD44-overexpressing breast cancer by MR imaging

We fabricated hyaluronan-modified magnetic nanoclusters (HA-MNCs) for detection of CD44-overexpressing breast cancer using magnetic resonance (MR) imaging. CD44 is closely associated with cancer growth, including proliferation, metastasis, invasion, and angiogenesis. Hence, pyrenyl hyaluronan (Py-HA) conjugates were synthesized as CD44-targetable surfactants with hyaluronan (HA) and 1-pyrenylbutyric acid (Py) to modify hyaluronan on hydrophobic magnetic nanocrystals. Subsequently, HA-MNCs were fabricated using the nano-emulsion method; magnetic nanocrystals were simultaneously self-assembled with Py-HA conjugates, and their physical and magnetic properties depended on the degree of substitution (DS) of Py in Py-HA conjugates. HA-MNCs exhibited superior targeting efficiency with MR sensitivity as well as excellent biocompatibility through in?vitro/in?vivo studies. This suggests that HA-MNCs can be a potent cancer specific molecular imaging agent via targeted detection of CD44 with MR imaging.     

Diffusion tensor MR imaging of principal directions: a tensor tomography approach

A novel approach to reconstructing the principal directions of a diffusion tensor field directly from magnetic resonance imaging (MRI) data using a tensor tomography data acquisition approach was developed. If tensor eigenvalues are assumed to be known, the reconstruction of principal directions requires fewer measurements than the reconstruction of the full tensor field. The tensor tomography data acquisition method (rotating diffusion gradients) leads to a unique reconstruction of principal directions, whereas the conventional MRI acquisition technique (stationary diffusion gradients) leads to an ambiguous reconstruction of principal directions when the same number of measurements are used. A computer-generated phantom was used to simulate the diffusion tensor field in the mid-ventricular region of the myocardium. The principal directions of the diffusion tensor field were assumed to align with the fibre structure of the myocardium. An iterative algorithm was used to reconstruct the principal directions. Computer simulations verify that the proposed method provides accurate reconstruction of the principal directions of a diffusion tensor field.     

扩散张量MR成像研究

本文一方面综述了8年来国际上扩散张量磁共振成像(DTI)的研究进展情况。包括总结了到目前为止所使用的4种提高DTI成像精度的方法，并指出精度的提高依赖于成像中脉冲序列的优化、实验方法的完善和后处理算法两个方面。文中比较了目前研究扩散张量的两种基本模型：扩散张量模型和q-空间模型。指出这两种模型侧重应用于不同的场合。前者侧重于研究器官或宏观组织中的扩散，而后者侧重于研究小到细胞尺度(μm量级)的扩散行为。两者在应用研究方面是互补的，所要求的实验条件是有差别的。另一方面结合文献对扩散张量模型的实验条件进行了理论分析。认为b因子取得过高并不合理。并用DTI实验数据和结果进行了初步验证。为了改进扩散张量模型本文探讨了考虑多指数衰减的设想。文中综述了DTI的导出量和一些实验结果，在此基础上分析了设计和优化各向异性指标(DAI)的原则。对于DTI的重要导出结果神经纤维柬成像(fiber tractography)重点分析了造成其成像精度不高的主要因素，指出了改进纤维束传导方向甄选算法和寻求纤维束方向场的几何性质是两种可能的解决办法。     

An octahedral shear strain-based measure of SNR for 3D MR elastography

A signal-to-noise ratio (SNR) measure based on the octahedral shear strain (the maximum shear strain in any plane for a 3D state of strain) is presented for magnetic resonance elastography (MRE), where motion-based SNR measures are commonly used. The shear strain, γ, is directly related to the shear modulus, μ, through the definition of shear stress, τ = μγ. Therefore, noise in the strain is the important factor in determining the quality of motion data, rather than the noise in the motion. Motion and strain SNR measures were found to be correlated for MRE of gelatin phantoms and the human breast. Analysis of the stiffness distributions of phantoms reconstructed from the measured motion data revealed a threshold for both strain and motion SNR where MRE stiffness estimates match independent mechanical testing. MRE of the feline brain showed significantly less correlation between the two SNR measures. The strain SNR measure had a threshold above which the reconstructed stiffness values were consistent between cases, whereas the motion SNR measure did not provide a useful threshold, primarily due to rigid body motion effects.     

Two-dimensional waveform analysis in MR elastography of skeletal muscles

A method for direct determination of anisotropic elastic coefficients using two-dimensional shear wave patterns is introduced. Thereby, the symmetry of the wave patterns is approximated by a squared elliptic equation yielding an explicit relation between waveform and elasticity. The method is used to analyse MR elastography wave images of the biceps acquired by a continuous harmonic excitation at the distal tendon of the muscle. Typically V-shaped wave patterns were observed in this type of tissue, which could be well reproduced by the proposed elliptic approximation of the waveform assuming incompressibility and a transverse isotropic model of elasticity. Without additional experiments, the analysis of straightness, slope and interferences of the wave fronts enabled us to deduce two Young's moduli and one shear modulus, which fully describe the anisotropy of the elasticity of muscles. The results suggest strong anisotropy of the living human biceps causing a shear wave speed parallel to the muscle fibres that is approximately four times faster than the perpendicular shear wave speed.     

Preliminary assessment of one-dimensional MR elastography for use in monitoring focused ultrasound therapy

The purpose of this work is to assess a fast technique that measures tissue stiffness and temperature during focused ultrasound thermal therapy (FUS). A one-dimensional (1D) MR elastography (MRE) pulse sequence was evaluated for the purpose of obtaining rapid measurements of thermally induced changes in tissue stiffness and temperature for monitoring FUS treatments. The accuracy of the 1D measurement was studied by comparing tissue displacements measured by 1D MRE with those measured by the well-established 2D MRE pulse sequence. The reproducibility of the 1D MRE measurement was assessed, in gel phantoms and ex vivo porcine tissue, for varied FUS intensity levels (31.5-199.9 W cm(-2)) and over a range of displacements at the focus (0.1-1 microm). Temperature elevations in agarose gel phantoms were measured using 1D MRE and calibrated using fiberoptic-thermometer-based measurements. The 1D MRE displacement measurements are highly correlated with those obtained with the 2D technique (R(2) = 0.88-0.93), indicating that 1D MRE can successfully measure tissue displacement. Ten repeated trials at each FUS power level yielded a minimum detectable displacement change of 0.2 microm in phantoms and 0.4 microm in tissue (at 95% confidence level). The 1D MRE temperature measurements correlated well with temperature changes measured simultaneously with fiberoptic thermometers (R(2) = 0.97). The 1D MRE technique is capable of detecting tissue displacements as low as 0.4 microm, which is an order of magnitude smaller than 5 microm displacements expected during FUS therapy (Le et al 2005 AIP Conf. Proc.: Ther. Ultrasound 829 186-90). Additionally, 1D MRE was shown to provide adequate measurements of temperature elevations in tissue. These findings indicate that 1D MRE may be an effective tool for monitoring FUS treatments.     

Unipolar MR elastography: Theory,numerical analysis and implementation

In MR elastography (MRE), zeroth moment balanced motion‐encoding gradients (MEGs) are incorporated into MRI sequences to induce a phase shift proportional to the local displacement caused by external actuation. To maximize the signal‐to‐noise ratio (SNR), fractional encoding is employed, i.e., the MEG duration is reduced below the wave period. Here, gradients encode primarily the velocity of the motion‐reducing encoding efficiency. Thus, in GRE‐MRE, T₂* decay and motion sensitivity have to be balanced, imposing a lower limit on repetition times (TRs). We propose to use a single trapezoidal gradient, a “unipolar gradient”, to directly encode spin displacement. Such gradients cannot be used in conventional sequences as they exhibit a large zeroth moment and dephase magnetization. By time‐reversing a spoiled SSFP sequence, the spoiling gradient becomes an efficient unipolar MEG. The proposed “unipolar MRE” technique benefits from this approach in three ways: first, displacement encoding is split over multiple TRs increasing motion sensitivity; second, spoiler and MEG coincide, allowing a reduction in TR; third, motion sensitivity of a typical unipolar lobe is of an order of magnitude higher than a bipolar MEG of equal duration. In this work, motion encoding using unipolar MRE is analyzed using the extended phase graph (EPG) formalism with a periodic motion propagator. As an approximation, the two‐transverse TR approximation for diffusion‐weighted SSFP is extended to incorporate cyclic motion. A complex encoding efficiency metric is introduced to compare the displacement fields of unipolar and conventional GRE‐MRE sequences in both magnitude and phase. The derived theoretical encoding equations are used to characterize the proposed sequence using an extensive parameter study. Unipolar MRE is validated against conventional GRE‐MRE in a phantom study showing excellent agreement between measured displacement fields. In addition, unipolar MRE yields significantly increased octahedral shear strain‐SNR relative to conventional GRE‐MRE and allows for the recovery of high stiffness inclusions, where conventional GRE‐MRE fails.     

Ultrasound elastic tensor imaging: comparison with MR diffusion tensor imaging in the myocardium

We have previously proven the feasibility of ultrasound-based shear wave imaging (SWI) to non-invasively characterize myocardial fiber orientation in both in vitro porcine and in vivo ovine hearts. The SWI-estimated results were in good correlation with histology. In this study, we proposed a new and robust fiber angle estimation method through a tensor-based approach for SWI, coined together as elastic tensor imaging (ETI), and compared it with magnetic resonance diffusion tensor imaging (DTI), a current gold standard and extensively reported non-invasive imaging technique for mapping fiber architecture. Fresh porcine (n = 5) and ovine (n = 5) myocardial samples (20?×?20?×?30?mm(3)) were studied. ETI was firstly performed to generate shear waves and to acquire the wave events at ultrafast frame rate (8000 fps). A 2.8?MHz phased array probe (pitch = 0.28?mm), connected to a prototype ultrasound scanner, was mounted on a customized MRI-compatible rotation device, which allowed both the rotation of the probe from?-90° to 90° at 5° increments and co-registration between two imaging modalities. Transmural shear wave speed at all propagation directions realized was firstly estimated. The fiber angles were determined from the shear wave speed map using the least-squares method and eigen decomposition. The test myocardial sample together with the rotation device was then placed inside a 7T MRI scanner. Diffusion was encoded in six directions. A total of 270 diffusion-weighted images (b = 1000?s mm(-2), FOV = 30?mm, matrix size = 60?×?64, TR = 6?s, TE = 19?ms, 24 averages) and 45 B(0)?images were acquired in 14?h 30 min. The fiber structure was analyzed by the fiber-tracking module in software, MedINRIA. The fiber orientation in the overlapped myocardial region which both ETI and DTI accessed was therefore compared, thanks to the co-registered imaging system. Results from all ten samples showed good correlation (r(2)?= 0.81, p < 0.0001) and good agreement (3.05° bias) between ETI and DTI fiber angle estimates. The average ETI-estimated fractional anisotropy (FA) values decreased from subendocardium to subepicardium (p < 0.05, unpaired, one-tailed t-test, N = 10) by 33%, whereas the corresponding DTI-estimated FA values presented a change of?-10% (p > 0.05, unpaired, one-tailed t-test, N = 10). In conclusion, we have demonstrated that the fiber orientation estimated by ETI, which assesses the shear wave speed (and thus the stiffness), was comparable to that measured by DTI, which evaluates the preferred direction of water diffusion, and have validated this concept within the myocardium. Moreover, ETI was shown capable of mapping the transmural fiber angles with as few as seven shear wave propagation directions.