Physics in Medicine and Biology (Phys Med Biol )

Publisher: Institute of Physics (Great Britain)


Subject coverage. The application of theoretical and practical physics to medicine, physiology and biology. Papers on physics with no obvious medical or biological applications, or papers which are almost entirely clinical or biological in their approach are not acceptable.

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    Physics in Medicine and Biology website
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    Physics in medicine & biology (Online), Physics in medicine and biology
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    Document, Periodical, Internet resource
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    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Parametric imaging in thoracic and abdominal PET can provide additional parameters more relevant to the pathophysiology of the system under study. However, dynamic data in the body are noisy due to the limiting counting statistics leading to suboptimal kinetic parameter estimates. Direct 4D image reconstruction algorithms can potentially improve kinetic parameter precision and accuracy in dynamic PET body imaging. However, construction of a common kinetic model is not always feasible and in contrast to post-reconstruction kinetic analysis, errors in poorly modelled regions may spatially propagate to regions which are well modelled. To reduce error propagation from erroneous model fits, we implement and evaluate a new approach to direct parameter estimation by incorporating a recently proposed kinetic modelling strategy within a direct 4D image reconstruction framework. The algorithm uses a secondary more general model to allow a less constrained model fit in regions where the kinetic model does not accurately describe the underlying kinetics. A portion of the residuals then is adaptively included back into the image whilst preserving the primary model characteristics in other well modelled regions using a penalty term that trades off the models. Using fully 4D simulations based on dynamic [15O]H2O datasets, we demonstrate reduction in propagation-related bias for all kinetic parameters. Under noisy conditions, reductions in bias due to propagation are obtained at the cost of increased noise, which in turn results in increased bias and variance of the kinetic parameters. This trade-off reflects the challenge of separating the residuals arising from poor kinetic modelling fits from the residuals arising purely from noise. Nonetheless, the overall root mean square error is reduced in most regions and parameters. Using the adaptive 4D image reconstruction improved model fits can be obtained in poorly modelled regions, leading to reduced errors potentially propagating to regions of interest which the primary biologic model accurately describes. The proposed methodology, however, depends on the secondary model and choosing an optimal model on the residual space is critical in improving model fits.
    Physics in Medicine and Biology 08/2014;
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    ABSTRACT: Accurate and robust estimation of motion fields in respiration-correlated CT (4D CT) images, usually performed by non-linear registration of the temporal CT frames, is a precondition for the analysis of patient-specific breathing dynamics and subsequent image-supported diagnostics and treatment planning.In this work, we present a comprehensive comparison and evaluation study of non-linear registration variants applied to the task of lung motion estimation in thoracic 4D CT data. In contrast to existing multi-institutional comparison studies (e.g. MIDRAS and EMPIRE10), we focus on the specific but common class of variational intensity-based non-parametric registration and analyze the impact of the different main building blocks of the underlying optimization problem: the distance measure to be minimized, the regularization approach and the transformation space considered during optimization. In total, 90 different combinations of building block instances are compared.Evaluated on proprietary and publicly accessible 4D CT images, landmark-based registration errors (TRE) between 1.14 and 1.20 mm for the most accurate registration variants demonstrate competitive performance of the applied general registration framework compared to other state-of-the-art approaches for lung CT registration. Although some specific trends can be observed, effects of interchanging individual instances of the building blocks on the TRE are in general rather small (no single outstanding registration variant existing); the same level of accuracy is, however, associated with significantly different degrees of motion field smoothness and computational demands. Consequently, the building block combination of choice will depend on application-specific requirements on motion field characteristics.
    Physics in Medicine and Biology 07/2014; 59(15):4247-4260.
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    ABSTRACT: The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a ‘virtual lesion’ in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V cm − 1 and exceeded 1.0 V cm − 1 in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter–white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.
    Physics in Medicine and Biology 07/2014;
  • Physics in Medicine and Biology 06/2014;
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    ABSTRACT: In vivo fluorescence imaging has been a popular functional imaging modality in preclinical imaging. Near infrared probes used in fluorescence molecular tomography (FMT) are designed to localize in the targeted tissues, hence sparse solution to the FMT image reconstruction problem is preferred. Nonconvex regularization methods are reported to enhance sparsity in the fields of statistical learning, compressed sensing etc. We investigated such regularization methods in FMT for small animal imaging with numerical simulations and phantom experiments. We adopted a majorization-minimization algorithm for the iterative reconstruction process and compared the reconstructed images using our proposed nonconvex regularizations with those using the well known L(1) regularization. We found that the proposed nonconvex methods outperform L(1) regularization in accurately recovering sparse targets in FMT.
    Physics in Medicine and Biology 05/2014; 59(12):2901-2912.
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    ABSTRACT: Physics in Medicine and Biology (PMB) awards its 'Citations Prize' to the authors of the original research paper that has received the most citations in the preceding five years (according to the Institute for Scientific Information (ISI)). The lead author of the winning paper is presented with the Rotblat Medal (named in honour of Professor Sir Joseph Rotblat, a Nobel Prize winner who also was the second-and longest serving-Editor of PMB, from 1961-1972). The winner of the 2013 Citations Prize for the paper which has received the most citations in the previous five years (2008-2012) is [Formula: see text] Figure. Four of the prize winning authors. From left to right: Thomas Istel (Philips), Jens-Peter Schlomka (with medal, MorphoDetection), Ewald Roessl (Philips), and Gerhard Martens (Philips). Title: Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography Authors: Jens Peter Schlomka(1), Ewald Roessl(1), Ralf Dorscheid(2), Stefan Dill(2), Gerhard Martens(1), Thomas Istel(1), Christian Bäumer(3), Christoph Herrmann(3), Roger Steadman(3), Günter Zeitler(3), Amir Livne(4) and Roland Proksa(1) Institutions: (1) Philips Research Europe, Sector Medical Imaging Systems, Hamburg, Germany (2) Philips Research Europe, Engineering & Technology, Aachen, Germany (3) Philips Research Europe, Sector Medical Imaging Systems, Aachen, Germany (4) Philips Healthcare, Global Research and Advanced Development, Haifa, Israel Reference: Schlomka et al 2008 Phys. Med. Biol. 53 4031-47 This paper becomes the first to win both this citations prize and also the PMB best paper prize (The Roberts Prize), which it won for the year 2008. Discussion of the significance of the winning paper can be found in this medicalphysicsweb article from the time of the Roberts Prize win ( The author's enthusiasm for their prototype spectral CT system has certainly been reflected in the large number of citations the paper subsequently has received. Our warm congratulations go to the winning authors.
    Physics in Medicine and Biology 05/2014; 59(12):2861-2862.
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    ABSTRACT: We are developing a computerized system for bladder segmentation on CT urography (CTU), as a critical component for computer-aided detection of bladder cancer. The presence of regions filled with intravenous contrast and without contrast presents a challenge for bladder segmentation. Previously, we proposed a conjoint level set analysis and segmentation system (CLASS). In case the bladder is partially filled with contrast, CLASS segments the non-contrast (NC) region and the contrast-filled (C) region separately and automatically conjoins the NC and C region contours; however, inaccuracies in the NC and C region contours may cause the conjoint contour to exclude portions of the bladder. To alleviate this problem, we implemented a local contour refinement (LCR) method that exploits model-guided refinement (MGR) and energy-driven wavefront propagation (EDWP). MGR propagates the C region contours if the level set propagation in the C region stops prematurely due to substantial non-uniformity of the contrast. EDWP with regularized energies further propagates the conjoint contours to the correct bladder boundary. EDWP uses changes in energies, smoothness criteria of the contour, and previous slice contour to determine when to stop the propagation, following decision rules derived from training. A data set of 173 cases was collected for this study: 81 cases in the training set (42 lesions, 21 wall thickenings, 18 normal bladders) and 92 cases in the test set (43 lesions, 36 wall thickenings, 13 normal bladders). For all cases, 3D hand segmented contours were obtained as reference standard and used for the evaluation of the computerized segmentation accuracy. For CLASS with LCR, the average volume intersection ratio, average volume error, absolute average volume error, average minimum distance and Jaccard index were 84.2 ± 11.4%, 8.2 ± 17.4%, 13.0 ± 14.1%, 3.5 ± 1.9 mm, 78.8 ± 11.6%, respectively, for the training set and 78.0 ± 14.7%, 16.4 ± 16.9%, 18.2 ± 15.0%, 3.8 ± 2.3 mm, 73.8 ± 13.4% respectively, for the test set. With CLASS only, the corresponding values were 75.1 ± 13.2%, 18.7 ± 19.5%, 22.5 ± 14.9%, 4.3 ± 2.2 mm, 71.0 ± 12.6%, respectively, for the training set and 67.3 ± 14.3%, 29.3 ± 15.9%, 29.4 ± 15.6%, 4.9 ± 2.6 mm, 65.0 ± 13.3%, respectively, for the test set. The differences between the two methods for all five measures were statistically significant (p < 0.001) for both the training and test sets. The results demonstrate the potential of CLASS with LCR for segmentation of the bladder.
    Physics in Medicine and Biology 05/2014; 59(11):2767-2785.
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    ABSTRACT: Today, quantitative analysis of three-dimensional (3D) dynamics of the left ventricle (LV) cannot be performed directly in the catheter lab using a current angiographic C-arm system, which is the workhorse imaging modality for cardiac interventions. Therefore, myocardial wall analysis is completely based on the 2D angiographic images or pre-interventional 3D/4D imaging. In this paper, we present a complete framework to study the ventricular wall motion in 4D (3D+t) directly in the catheter lab. From the acquired 2D projection images, a dynamic 3D surface model of the LV is generated, which is then used to detect ventricular dyssynchrony. Different quantitative features to evaluate LV dynamics known from other modalities (ultrasound, magnetic resonance imaging) are transferred to the C-arm CT data. We use the ejection fraction, the systolic dyssynchrony index a 3D fractional shortening and the phase to maximal contraction (ϕi, max) to determine an indicator of LV dyssynchrony and to discriminate regionally pathological from normal myocardium. The proposed analysis tool was evaluated on simulated phantom LV data with and without pathological wall dysfunctions. The LV data used is publicly available online at In addition, the presented framework was tested on eight clinical patient data sets. The first clinical results demonstrate promising performance of the proposed analysis tool and encourage the application of the presented framework to a larger study in clinical practice.
    Physics in Medicine and Biology 05/2014; 59(9):2265-84.
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    ABSTRACT: We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas-tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research.
    Physics in Medicine and Biology 05/2014; 59(11):2801-2811.
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    ABSTRACT: We are developing a 1 mm resolution small animal positron emission tomography (PET) system using 3D positioning cadmium zinc telluride photon detectors comprising 40 mm × 40 mm × 5 mm crystals metalized with a cross-strip electrode pattern with a 1 mm anode strip pitch. We optimized the electrode pattern design for intrinsic sensitivity and spatial, energy and time resolution performance using a test detector comprising cathode and steering electrode strips of varying dimensions. The study found 3 and 5 mm width cathode strips locate charge-shared photon interactions near cathode strip boundaries with equal precision. 3 mm width cathode strips exhibited large time resolution variability as a function of photon interaction location between the anode and cathode planes (∼26 to ∼127.5 ns full width at half maximum (FWHM) for 0.5 mm and 4.2 mm depths, respectively). 5 mm width cathode strips by contrast exhibited more stable time resolution for the same interaction locations (∼34 to ∼83 ns FWHM), provided more linear spatial positioning in the direction orthogonal to the electrode planes, and as much as 68.4% improvement in photon sensitivity over the 3 mm wide cathode strips. The results were understood by analyzing the cathode strips' weighting functions, which indicated a stronger 'small pixel' effect in the 3 mm wide cathode strips. Photon sensitivity and anode energy resolution were seen to improve with decreasing steering electrode bias from 0 to -80 V w.r.t. the anode potential. A slight improvement in energy resolution was seen for wider steering electrode strips (400 versus 100 µm) for charge-shared photon interactions. Although this study successfully focused on electrode pattern features for PET performance, the results are generally applicable to semiconductor photon detectors employing cross-trip electrode patterns.
    Physics in Medicine and Biology 05/2014; 59(11):2599-2621.
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    ABSTRACT: This study investigates the in vivo therapeutic capabilities of transcostal histotripsy without using aberration correction mechanisms and its thermal impact on overlying tissues. Non-invasive liver treatments were conducted in eight pigs, with four lesions generated through transcostal windows with full ribcage obstruction and four lesions created through transabdominal windows without rib coverage. Treatments were performed by a 750 kHz focused transducer using 5 cycle pulses at 200 Hz PRF, with estimated in situ peak negative pressures of 13-17 MPa. Temperatures on overlying tissues including the ribs were measured with needle thermocouples inserted superficially beneath the skin. Treatments of approximately 40 min were applied, allowing overlying tissue temperatures to reach saturation. Lesions yielded statistically comparable ablation volumes of 3.6 ± 1.7 cm(3) and 4.5 ± 2.0 cm(3) in transcostal and transabdominal treatments, respectively. The average temperature increase observed in transcostal treatments was 3.9 ± 2.1 °C, while transabdominal treatments showed an increase of 1.7 ± 1.3 °C. No damage was seen on the ribcage or other overlying tissues. These results indicate that histotripsy can achieve effective treatment through the ribcage in vivo without requiring correction mechanisms, while inducing no substantial thermal effects or damage to overlying tissues. Such capabilities could benefit several non-invasive therapy applications involving transcostal treatment windows.
    Physics in Medicine and Biology 05/2014; 59(11):2553-2568.
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    ABSTRACT: There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.
    Physics in Medicine and Biology 05/2014; 59(11):2659-2685.
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    ABSTRACT: This work continues previous research about multiple scattering of polarized light propagation in turbid media, putting emphasis on the imaginary part of the scatterers' complex refractive index. The whole angle-dependent Müller matrix is evaluated by comparing results of a polarization sensitive radiative transfer solution to Maxwell theory. Turbid media of defined scatterer concentrations are modelled in three dimensions by sphere ensembles kept inside a cubic or spherical simulation volume. This study addresses the impact of absorption on polarization characteristics for selected media from low to high absorption. Besides that, effects caused by multiple and dependent scattering are shown for increasing volume concentration. In this context some unique properties associated with multiple scattering and absorption are pointed out. Further, scattering results in two dimensions are compared for examples of infinite parallel cylinders of high absorption and perpendicularly incident plane waves.
    Physics in Medicine and Biology 05/2014; 59(11):2583-2597.
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    ABSTRACT: In this paper, we propose a robust and accurate method that segments mammograms to three distinct regions: breast tissue, pectoral muscle and background. Our approach is built around a neural, two-layer committee machine. On the first layer, individual experts, each formed by a feature vector and a classifier, vote the local class label of the mammogram. The votes are given as an input, together with a prior map, to the second layer of the committee machine, which combines the inputs by a gating network. As the first layer features, we use effective, well-known local features based on image intensity, intensity histograms, local binary patterns, and histograms of oriented gradient. As with the first-layer classifiers and the gating network, we use support vector machines. Our experiments on a database of 495 mammograms, divided into independent training, validations and test subsets, show that our method is able to segment the breast tissue without failure, and it challenges the manual expert segmentation in the level of accuracy.
    Physics in Medicine and Biology 04/2014; 59(10):2445-2456.
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    ABSTRACT: Brachytherapy, a radiotherapy technique for treating prostate cancer, involves the implantation of numerous radioactive seeds into the prostate. While the implanted seeds can be easily identified on a computed tomography image, distinguishing the prostate and surrounding soft tissues is not as straightforward. Magnetic resonance imaging (MRI) offers superior anatomical delineation, but the seeds appear as dark voids and are difficult to identify, thus creating a conundrum. Cobalt dichloride-N-acetyl-cysteine (C4) has previously been shown to be promising as an encapsulated contrast agent marker. We performed spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) measurements of C4 solutions with varying cobalt dichloride concentrations to determine the corresponding relaxivities, r1 and r2. These relaxation parameters were investigated at different field strengths, temperatures and orientations. T1 measurements obtained at 1.5 and 3.0 T, as well as at room and body temperature, showed that r1 is field-independent and temperature-independent. Conversely, the T2 values at 3.0 T were shorter than at 1.5 T, while the T2 values at body temperature were slightly higher than at room temperature. By examining the relaxivities with the C4 vials aligned in three different planes, we found no orientation-dependence. With these relaxation characteristics, we aim to develop pulse sequences that will enhance the C4 signal against prostatic stroma. Ultimately, the use of C4 as a positive contrast agent marker will encourage the use of MRI to obtain an accurate representation of the radiation dose delivered to the prostate and surrounding normal anatomical structures.
    Physics in Medicine and Biology 04/2014; 59(10):2505-2516.

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