Imaging biochemistry: applications to breast cancer.

The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour biochemistry in vivo is reviewed. To this end, results obtained both from patients in vivo and from tumour extracts and model systems are discussed. An association has been observed between transformation and an increase in phosphomonoesters (PMEs) detected in the 31P MRS spectrum, as well as an increase in choline-containing metabolites detected in the 1H spectrum. A decrease in PME content after treatment is associated with response to treatment as assessed by tumour volume. Experiments in model systems aimed at understanding the underlying biochemical processes are presented, as well as data indicating the usefulness of MRS in monitoring the uptake and metabolism of some chemotherapeutic agents

High electron mobility in nearly lattice-matched AlInN∕AlN∕GaN heterostructure field effect transistors

High electron mobility was achieved in Al1−xInxN∕AlN∕GaN (x=0.20–0.12)heterostructurefield effect transistors(HFETs) grown by metal-organic chemical vapor deposition. Reduction of In composition from 20% to 12% increased the room temperature equivalent two-dimensional-electron-gas density from 0.90×1013to1.64×1013cm−2 with corresponding electron mobilities of 1600 and 1410cm2/Vs, respectively. The 10Kmobility reached 17600cm2/Vs for the nearly lattice-matched Al0.82In0.18N∕AlN∕GaNheterostructure with a sheet carrier density of 9.6×1012cm−2. For comparison, the AlInN∕GaNheterostructure without the AlN spacer exhibited a high sheet carrier density(2.42×1013cm−2) with low mobility(120cm2/Vs) at room temperature. The high mobility in our samples is in part attributed to ∼1nm AlN spacer which significantly reduces the alloy scattering as well as provides a smooth interface. The HFETs having gate dimensions of 1.5×40μm2 and a 5μm source-drain separation exhibited a maximum transconductance of ∼200mS∕mm with good pinch-off characteristics and over 10GHz current gain cutoff frequency

A computerized volumetric segmentation method applicable to multi-centre MRI data to support computer-aided breast tissue analysis, density assessment and lesion localization.

Density assessment and lesion localization in breast MRI require accurate segmentation of breast tissues. A fast, computerized algorithm for volumetric breast segmentation, suitable for multi-centre data, has been developed, employing 3D bias-corrected fuzzy c-means clustering and morphological operations. The full breast extent is determined on T1-weighted images without prior information concerning breast anatomy. Left and right breasts are identified separately using automatic detection of the midsternum. Statistical analysis of breast volumes from eighty-two women scanned in a UK multi-centre study of MRI screening shows that the segmentation algorithm performs well when compared with manually corrected segmentation, with high relative overlap (RO), high true-positive volume fraction (TPVF) and low false-positive volume fraction (FPVF), and has an overall performance of RO 0.94 ± 0.05, TPVF 0.97 ± 0.03 and FPVF 0.04 ± 0.06, respectively (training: 0.93 ± 0.05, 0.97 ± 0.03 and 0.04 ± 0.06; test: 0.94 ± 0.05, 0.98 ± 0.02 and 0.05 ± 0.07)

Magnetic Resonance Imaging-Based Assessment of Breast Cancer-Related Lymphoedema Tissue Composition.

OBJECTIVES: The aim of this study was to propose a magnetic resonance imaging acquisition and analysis protocol that uses image segmentation to measure and depict fluid, fat, and muscle volumes in breast cancer-related lymphoedema (BCRL). This study also aims to compare affected and control (unaffected) arms of patients with diagnosed BCRL, providing an analysis of both the volume and the distribution of the different tissue components. MATERIALS AND METHODS: The entire arm was imaged with a fluid-sensitive STIR and a 2-point 3-dimensional T1W gradient-echo-based Dixon sequences, acquired in sagittal orientation and covering the same imaging volume. An automated image postprocessing procedure was developed to simultaneously (1) contour the external volume of the arm and the muscle fascia, allowing separation of the epifacial and subfascial volumes; and to (2) separate the voxels belonging to the muscle, fat, and fluid components. The total, subfascial, epifascial, muscle (subfascial), fluid (epifascial), and fat (epifascial) volumes were measured in 13 patients with unilateral BCRL. Affected versus unaffected volumes were compared using a 2-tailed paired t test; a value of P < 0.05 was considered to be significant. Pearson correlation was used to investigate the linear relationship between fat and fluid excess volumes. The distribution of fluid, fat, and epifascial excess volumes (affected minus unaffected) along the arm was also evaluated using dedicated tissue composition maps. RESULTS: Total arm, epifascial, epifascial fluid, and epifascial fat volumes were significantly different (P < 0.0005), with greater volume in the affected arms. The increase in epifascial volume (globally, 94% of the excess volume) constituted the bulk of the lymphoedematous swelling, with fat comprising the main component. The total fat excess volume summed over all patients was 2.1 times that of fluid. Furthermore, fat and fluid excess volumes were linearly correlated (Pearson r = 0.75), with the fat excess volume being greater than the fluid in 11 subjects. Differences in muscle compartment volume between affected and unaffected arms were not statistically significant, and contributed only 6% to the total excess volume. Considering the distribution of the different tissue excess volumes, fluid accumulated prevalently around the elbow, with substantial involvement of the upper arm in only 3 cases. Fat excess volume was generally greater in the upper arm; however, the relative increase in epifascial volume, which considers the total swelling relative to the original size of the arm, was in 9 cases maximal within the forearm. CONCLUSIONS: Our measurements indicate that excess of fat within the epifascial layer was the main contributor to the swelling, even when a substantial accumulation of fluid was present. The proposed approach could be used to monitor how the internal components of BCRL evolve after presentation, to stratify patients for treatment, and to objectively assess treatment response. This methodology provides quantitative metrics not currently available during the standard clinical assessment of BCRL and shows potential for implementation in clinical practice

Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma.

31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi) using the chemical shift difference between pH-dependent inorganic phosphate (Pi) and a pH-independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct Pi–PCr method was best for those spectra with a very well-defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the Pi–αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water-based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the Pi–αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment-related changes of the order of 0.1 pH units should be detectable

The Morphology of the Thermal Sunyaev-Zel'dovich Sky

At high angular frequencies the thermal Sunyaev-Zel'dovich (tSZ) effect constitutes the dominant signal in the CMB sky. The tSZ effect is caused by large scale pressure fluctuations in the baryonic distribution in the Universe so its statistical properties provide estimates of corresponding properties of the projected 3D pressure fluctuations. It's power spectrum is a sensitive probe of the density fluctuations, and the bispectrum can be used to separate the bias associated with pressure. The bispectrum is often probed with a one-point real-space analogue, the skewness. In addition to the skewness the morphological properties, as probed by the well known Minkowski Functionals (MFs), also require the generalized one-point statistics, which at the lowest order are identical to the skewness parameters. The concept of generalized skewness parameters can be extended to define a set of three associated generalized skew-spectra. We use these skew-spectra to probe the morphology of the tSZ sky or the y-sky. We show how these power spectra can be recovered from the data in the presence of arbitrary mask and noise templates using the well known Pseudo-Cl (PCL) approach for arbitrary beam shape. We also employ an approach based on the halo model to compute the tSZ bispectrum. The bispectrum from each of these models is then used to construct the generalized skew-spectra. We consider the performance of an all-sky survey with Planck-type noise and compare the results against a noise-free ideal experiment using a range of smoothing angles. We find that the skew-spectra can be estimated with very high signal-to-noise ratio from future frequency cleaned tSZ maps that will be available from experiments such as Planck. This will allow their mode by mode estimation for a wide range of angular frequencies and will help us to differentiate them from various other sources of non-Gaussianity.Comment: 18 pages, 10 figures, submitted to MNRA

A novel approach to evaluate spatial resolution of MRI clinical images for optimization and standardization of breast screening protocols.

Purpose Stringent quality assurance is required in MRI breast screening to ensure that different scanners and imaging protocols reach similar diagnostic performance. The authors propose a methodology, based on power spectrum analysis (PSA), to evaluate spatial resolution in clinical images. To demonstrate this approach, the authors have retrospectively compared two MRI sequences commonly employed in breast screening.Methods In a novel approach to PSA, spatial frequency response curves (SFRCs) were extracted from the images. The SFRC characterizes spatial resolution describing the spatial frequency content of an image over a range of frequencies. Verification of the SFRCs was performed on MRI images of Eurospin agarose gel tubes acquired with different resolution settings. SFRCs of volunteer and patient images obtained with two clinical MRI sequences were then compared. The two sequences differed primarily in k-space coverage pattern, which was either radial (RAD) or linear (LIN).Results The computed SFRCs were able to demonstrate the differences between RAD and LIN sequences in relatively small groups of subjects. The curves showed a similar pattern of decay in both volunteer and patient images, indicating that the spatial frequency response is mainly determined by the imaging protocol and not by intersubject anatomical differences. The LIN protocol produced images with increased sharpness; this was reflected in the corresponding SFRCs, which showed a higher content of spatial frequencies associated with image details.Conclusions The SFRC can provide an objective assessment of the presence of spatial details in the image and represent a useful quality assurance tool in the evaluation of different breast screening protocols. With a reference image, a comparative analysis of the SFRCs could ensure that equivalent image quality is achieved across different scanners and sites

Noise-Corrected, Exponentially Weighted, Diffusion-Weighted MRI (niceDWI) Improves Image Signal Uniformity in Whole-Body Imaging of Metastatic Prostate Cancer.

Purpose: To characterize the voxel-wise uncertainties of Apparent Diffusion Coefficient (ADC) estimation from whole-body diffusion-weighted imaging (WBDWI). This enables the calculation of a new parametric map based on estimates of ADC and ADC uncertainty to improve WBDWI imaging standardization and interpretation: NoIse-Corrected Exponentially-weighted diffusion-weighted MRI (niceDWI). Methods: Three approaches to the joint modeling of voxel-wise ADC and ADC uncertainty (σADC) are evaluated: (i) direct weighted least squares (DWLS), (ii) iterative linear-weighted least-squares (IWLS), and (iii) smoothed IWLS (SIWLS). The statistical properties of these approaches in terms of ADC/σADC accuracy and precision is compared using Monte Carlo simulations. Our proposed post-processing methodology (niceDWI) is evaluated using an ice-water phantom, by comparing the contrast-to-noise ratio (CNR) with conventional exponentially-weighted DWI. We present the clinical feasibility of niceDWI in a pilot cohort of 16 patients with metastatic prostate cancer. Results: The statistical properties of ADC and σADC conformed closely to the theoretical predictions for DWLS, IWLS, and SIWLS fitting routines (a minor bias in parameter estimation is observed with DWLS). Ice-water phantom experiments demonstrated that a range of CNR could be generated using the niceDWI approach, and could improve CNR compared to conventional methods. We successfully implemented the niceDWI technique in our patient cohort, which visually improved the in-plane bias field compared with conventional WBDWI. Conclusions: Measurement of the statistical uncertainty in ADC estimation provides a practical way to standardize WBDWI across different scanners, by providing quantitative image signals that improve its reliability. Our proposed method can overcome inter-scanner and intra-scanner WBDWI signal variations that can confound image interpretation

Stress test measurements of lattice-matched InAlN/AlN/GaN HFET structures

InAlN/GaN heterostructures offer some benefits over existing AlGaN/GaN heterostructures for HFET device applications. In addition to having a larger bandgap than typical AlGaN compounds used in HFET devices (with Al < 30%), which leads to better confinement and subsequent larger power carrying capacity, InAlN can be grown lattice-matched to GaN, resulting in strain-free heterostructures. As such, lattice-matched InAlN provides a unique system wherein the reliability of the devices may exceed that of the strained AlGaN/GaN devices as a result of being able to decouple the hot electron/hot phonon effects on the reliability from the strain related issues. In this work, we subjected lattice-matched InAlN-based HFETs to electrical stress and observed the corresponding degradation in maximum drain current. We found that the degradation rates are lower only for a narrow range of moderate gate biases, corresponding to low field average 2-dimensional electron gas (2DEG) densities of 9–10 × 10 12  cm −2 . We propose that the degradation is attributable to the buildup of hot phonons since the degradation rates as a function of electron density generally follow the hot phonon lifetime versus electron density. This provides evidence that hot phonons have a significant role in device degradation and there exists an optimal 2DEG density to minimize hot phonon related degradation. We did not observe any correlation between the degradation rate and the gate leakage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77433/1/1345_ftp.pd

Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging.

The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion-weighted MRI (DWI) fails to account for differential T 2 s in the model compartments, resulting in overestimation of pseudodiffusion fraction f. An extended model, T2-IVIM, allows removal of the confounding echo-time (TE) dependence of f, and provides direct compartment T 2 estimates. Two consented healthy volunteer cohorts (n  =  5, 6) underwent DWI comprising multiple TE/b-value combinations (Protocol 1: TE  =  62-102 ms, b  =  0-250 mm-2s, 30 combinations. Protocol 2: 8 b-values 0-800 mm-2s at TE  =  62 ms, with 3 additional b-values 0-50 mm-2s at TE  =  80, 100 ms; scanned twice). Data from liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model using all data. Repeat-measures coefficients of variation were assessed for Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1) demonstrated apparent f increasing with longer TE: 22.4  ±  7% (TE  =  62 ms) to 30.7  ±  11% (TE  =  102 ms); T2-IVIM model fitting accounted for all data variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates (IVIM: 27.9  ±  6%, T2-IVIM: 18.3  ±  7%), as well as T 2  =  42.1  ±  7 ms, 77.6  ±  30 ms for true and pseudodiffusion compartments, respectively. A reduced Protocol 2 dataset yielded comparable results in a clinical time frame (11 min). The confounding dependence of IVIM f on TE can be accounted for using additional b/TE images and the extended T2-IVIM model