Graham M Treece

University of Cambridge, Cambridge, England, United Kingdom

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Publications (129)202.34 Total impact

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    ABSTRACT: MicroabstractThe aim of this study was to examine the effects of denosumab versus placebo on cortical bone using clinical CT. We used cortical bone mapping to study the hips of women with osteoporosis treated during the FREEDOM clinical trial. We found that cortical mass surface density and thickness increased rapidly during denosumab therapy, particularly in the hip trochanteric region.Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis, to investigate the timing and precise location of denosumab versus placebo effects in the hips.We analysed clinical CT scans from 80 female participants in FREEDOM, a randomised trial, wherein half of the study participants received subcutaneous denosumab 60mg twice-yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24 and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualised and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control, and display the results on a 3D average femur model.Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over three years. One third of the increase came from increasing cortical density, and two thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12%, at key locations such as the lateral femoral trochanter, versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months.Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures seen in denosumab treated women at increased risk of fracture. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2015; 30(1). DOI:10.1002/jbmr.2325 · 6.59 Impact Factor
  • A.H. Gee · G M Treece · C J Tonkin · D M Black · K E S Poole
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    ABSTRACT: Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk. Copyright © 2015. Published by Elsevier Inc.
    Bone 07/2015; 81. DOI:10.1016/j.bone.2015.06.024 · 4.46 Impact Factor
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    ABSTRACT: Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual energy X-ray (DXA)-based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have sub-divided fracture into types, since this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The osteoporotic fractures in men (MrOS) study is a predictive case-cohort study of men over 65: we analyse 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5,994. To our knowledge, this is the largest QCT-based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We demonstrate that both cortical mass surface density, and endocortical trabecular BMD, show significant difference in fracture cases vs. cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA-based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave-one-out cross-validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 (trochanteric fractures) and 0.76 to 0.82 (femoral neck fractures). In contrast, adding DXA-based BMD to a CBM-based predictive model does not result in any significant improvement. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2015; DOI:10.1002/jbmr.2552 · 6.59 Impact Factor
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    ABSTRACT: Regular exercisers have lower fracture risk, despite modest effects of exercise on BMC. Exercise may produce localised cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical computed tomography (CT). Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localised cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualised and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional ROIs, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whilst femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; P < 0.001), with larger changes (>6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; P < 0.001), with localised changes of >12% at the anterior femoral neck, trochanter and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localised rather than being evenly distributed across the proximal femur. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2015; DOI:10.1002/jbmr.2499 · 6.59 Impact Factor
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    ABSTRACT: Combining anti-resorptive and anabolic drugs for osteoporosis may be a useful strategy to prevent hip fractures. Previous studies comparing the effects of alendronate and teriparatide alone, combined or sequentially using Quantitative Computed Tomography (QCT) in postmenopausal women have not distinguished cortical bone mineral density (CBMD) from cortical thickness (CTh) effects, nor assessed the distribution and extent of more localised changes. In this study a validated bone mapping technique was used to examine the cortical and endocortical trabecular changes in the proximal femur resulting from an 18 month course of alendronate or teriparatide. Using QCT data from a different clinical trial, the global and localised changes seen following a switch to teriparatide after an 18 month alendronate treatment or adding teriparatide to the alendronate treatment were compared.CTh increased (4.8%, p < 0.01) and CBMD decreased (-4.5%, p < 0.01) in the teriparatide group compared to no significant change in the alendronate group. A large CTh increase could be seen for the switch group (2.8%, p < 0.01) compared to a significantly smaller increase for the add group (1.5%, p < 0.01). CBMD decreased significantly for the switch group (-3.9%, p < 0.01) and was significantly different from no significant change in the add group. CTh increases were shown to be significantly greater for the switch group compared to the add group at the load bearing regions.This study provides new insights into the effects of alendronate and teriparatide combination therapies on the cortex of the proximal femur and supports the hypothesis of an increased bone remodelling by teriparatide being mitigated by alendronate. This article is protected by copyright. All rights reserved
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2015; 30(7). DOI:10.1002/jbmr.2454 · 6.59 Impact Factor
  • G M Treece · A.H. Gee
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    ABSTRACT: The local structure of the proximal femoral cortex is of interest since both fracture risk, and the effects of various interventions aimed at reducing that risk, are associated with cortical properties focused in particular regions rather than dispersed over the whole bone. Much of the femoral cortex is less than 3mm thick, appearing so blurred in clinical CT that its actual density is not apparent in the data, and neither thresholding nor full-width half-maximum techniques are capable of determining its width. Our previous work on cortical bone mapping showed how to produce more accurate estimates of cortical thickness by assuming a fixed value of the cortical density for each hip. However, although cortical density varies much less over the proximal femur than thickness, what little variation there is leads to errors in thickness measurement. In this paper, we develop the cortical bone mapping technique by exploiting local estimates of imaging blur to correct the global density estimate, thus providing a local density estimate as well as more accurate estimates of thickness. We also consider measurement of cortical mass surface density and the density of trabecular bone immediately adjacent to the cortex. Performance is assessed with ex vivo clinical QCT scans of proximal femurs, with true values derived from high resolution HRpQCT scans of the same bones. We demonstrate superior estimation of thickness than is possible with alternative techniques (accuracy 0.12±0.39mm for cortices in the range 1-3mm), and that local cortical density estimation is feasible for densities >800mg/cm(3). Copyright © 2014 Elsevier B.V. All rights reserved.
    Medical Image Analysis 12/2014; 20(1). DOI:10.1016/j.media.2014.11.012 · 3.68 Impact Factor
  • Andrew H Gee · Graham M Treece
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    ABSTRACT: Spatial normalisation is a key element of statistical parametric mapping and related techniques for analysing cohort statistics on voxel arrays and surfaces. The normalisation process involves aligning each individual specimen to a template using some sort of registration algorithm. Any misregistration will result in data being mapped onto the template at the wrong location. At best, this will introduce spatial imprecision into the subsequent statistical analysis. At worst, when the misregistration varies systematically with a covariate of interest, it may lead to false statistical inference. Since misregistration generally depends on the specimen's shape, we investigate here the effect of allowing for shape as a confound in the statistical analysis, with shape represented by the dominant modes of variation observed in the cohort. In a series of experiments on synthetic surface data, we demonstrate how allowing for shape can reveal true effects that were previously masked by systematic misregistration, and also guard against misinterpreting systematic misregistration as a true effect. We introduce some heuristics for disentangling misregistration effects from true effects, and demonstrate the approach's practical utility in a case study of the cortical bone distribution in 268 human femurs.
    Medical image analysis 02/2014; 18(2):385-393. DOI:10.1016/j.media.2013.12.007 · 3.68 Impact Factor
  • Journal of Clinical Densitometry 07/2013; 16(3):266-267. DOI:10.1016/j.jocd.2013.05.017 · 1.60 Impact Factor
  • K Poole · G Treece · A Gee · J P Brown · M R McClung · A Wang · C Libanati
    05/2013; DOI:10.1530/boneabs.1.PP433
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    T.D. Turmezei · G.M. Treece · A.H. Gee · K.E. Poole
    Osteoarthritis and Cartilage 04/2013; 21:S194. DOI:10.1016/j.joca.2013.02.408 · 4.66 Impact Factor
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    ABSTRACT: An ultrasound image is created from backscattered echoes originating from both diffuse and directional scattering. It is potentially useful to separate these two components for the purpose of tissue characterization. This article presents several models for visualization of scattering fields on 3-dimensional (3D) ultrasound imaging. By scanning the same anatomy from multiple directions, we can observe the variation of specular intensity as a function of the viewing angle. This article considers two models for estimating the diffuse and specular components of the backscattered intensity: a modification of the well-known Phong reflection model and an existing exponential model. We examine 2-dimensional implementations and also propose novel 3D extensions of these models in which the probe is not constrained to rotate within a plane. Both simulation and experimental results show that improved performance can be achieved with 3D models.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 04/2013; 32(4):699-714. DOI:10.7863/ultra.32.4.699 · 1.53 Impact Factor
  • N. Tsaousis · A. H. Gee · G. M. Treece · K. E. S. Poole
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    ABSTRACT: Hip fracture is the leading cause of acute orthopaedic hospital admission amongst the elderly, with around a third of patients not surviving one year post-fracture. Although various preventative therapies are available, patient selection is difficult. The current state-of-the-art risk assessment tool (FRAX) ignores focal structural defects, such as cortical bone thinning, a critical component in characterizing hip fragility. Cortical thickness can be measured using CT, but this is expensive and involves a significant radiation dose. Instead, Dual-Energy X-ray Absorptiometry (DXA) is currently the preferred imaging modality for assessing hip fracture risk and is used routinely in clinical practice. Our ambition is to develop a tool to measure cortical thickness using multi-view DXA instead of CT. In this initial study, we work with digitally reconstructed radiographs (DRRs) derived from CT data as a surrogate for DXA scans: this enables us to compare directly the thickness estimates with the gold standard CT results. Our approach involves a model-based femoral shape reconstruction followed by a data-driven algorithm to extract numerous cortical thickness point estimates. In a series of experiments on the shaft and trochanteric regions of 48 proximal femurs, we validated our algorithm and established its performance limits using 20 views in the range 0°-171°: estimation errors were 0:19 +/- 0:53mm (mean +/- one standard deviation). In a more clinically viable protocol using four views in the range 0°-51°, where no other bony structures obstruct the projection of the femur, measurement errors were -0:07 +/- 0:79 mm.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2013; DOI:10.1117/12.2006389 · 0.20 Impact Factor
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    R James Housden · Andrew H Gee · Graham M Treece · Richard W Prager
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    ABSTRACT: Most quasi-static ultrasound elastography methods image only the axial strain, derived from displacements measured in the direction of ultrasound propagation. In other directions, the beam lacks high resolution phase information and displacement estimation is therefore less precise. However, these estimates can be improved by steering the ultrasound beam through multiple angles and combining displacements measured along the different beam directions. Previously, beamsteering has only considered the 2D case to improve the lateral displacement estimates. In this paper, we extend this to 3D using a simulated 2D array to steer both laterally and elevationally in order to estimate the full 3D displacement vector over a volume. The method is tested on simulated and phantom data using a simulated 6-10MHz array, and the precision of displacement estimation is measured with and without beamsteering. In simulations, we found a statistically significant improvement in the precision of lateral and elevational displacement estimates: lateral precision 35.69μm unsteered, 3.70μm steered; elevational precision 38.67μm unsteered, 3.64μm steered. Similar results were found in the phantom data: lateral precision 26.51μm unsteered, 5.78μm steered; elevational precision 28.92μm unsteered, 11.87μm steered. We conclude that volumetric 3D beamsteering improves the precision of lateral and elevational displacement estimates.
    Ultrasonics 11/2012; 53(2). DOI:10.1016/j.ultras.2012.10.010 · 1.81 Impact Factor
  • E Dyer · U. Zeeshan Ijaz · R Housden · R Prager · A Gee · G Treece
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    ABSTRACT: Objective This work is concerned with the creation of three-dimensional (3D) extended-field-of-view ultrasound from a set of volumes acquired using a mechanically swept 3D probe. 3D volumes of ultrasound data can be registered by attaching a position sensor to the probe; this can be an inconvenience in a clinical setting. A position sensor can also cause some misalignment due to patient movement and respiratory motion. We propose a combination of three-degrees-of-freedom image registration and an unobtrusively integrated inertial sensor for measuring orientation. The aim of this research is to produce a reliable and portable ultrasound system that is able to register 3D volumes quickly, making it suitable for clinical use. Method As part of a feasibility study we recruited 28 pregnant females attending for routine obstetric scans to undergo 3D extended-field-of-view ultrasound. A total of 49 data sets were recorded. Each registered data set was assessed for correct alignment of each volume by two independent observers. Results In 77-83% of the data sets more than four consecutive volumes registered. The successful registration relies on good overlap between volumes and is adversely affected by advancing gestational age and foetal movement. Conclusion The development of reliable 3D extended-field-of-view ultrasound may help ultrasound practitioners to demonstrate the anatomical relation of pathology and provide a convenient way to store data.
    The British journal of radiology 10/2012; 85(1018):e919-24. DOI:10.1259/bjr/46007369 · 2.02 Impact Factor
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    ABSTRACT: Individuals with osteoporosis are predisposed to hip fracture during trips, stumbles or falls, but half of all hip fractures occur in those without generalised osteoporosis. By analysing ordinary clinical CT scans using a novel cortical thickness mapping technique, we discovered patches of markedly thinner bone at fracture-prone regions in the femurs of women with acute hip fracture compared with controls. We analysed CT scans from 75 female volunteers with acute fracture and 75 age- and sex-matched controls. We classified the fracture location as femoral neck or trochanteric before creating bone thickness maps of the outer 'cortical' shell of the intact contra-lateral hip. After registration of each bone to an average femur shape and statistical parametric mapping, we were able to visualise and quantify statistically significant foci of thinner cortical bone associated with each fracture type, assuming good symmetry of bone structure between the intact and fractured hip. The technique allowed us to pinpoint systematic differences and display the results on a 3D average femur shape model. The cortex was generally thinner in femoral neck fracture cases than controls. More striking were several discrete patches of statistically significant thinner bone of up to 30%, which coincided with common sites of fracture initiation (femoral neck or trochanteric). Femoral neck fracture patients had a thumbnail-sized patch of focal osteoporosis at the upper head-neck junction. This region coincided with a weak part of the femur, prone to both spontaneous 'tensile' fractures of the femoral neck, and as a site of crack initiation when falling sideways. Current hip fracture prevention strategies are based on case finding: they involve clinical risk factor estimation to determine the need for single-plane bone density measurement within a standard region of interest (ROI) of the femoral neck. The precise sites of focal osteoporosis that we have identified are overlooked by current 2D bone densitometry methods.
    PLoS ONE 06/2012; 7(6):e38466. DOI:10.1371/journal.pone.0038466 · 3.23 Impact Factor
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    G M Treece · K E S Poole · A.H. Gee
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    ABSTRACT: There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.
    Medical image analysis 02/2012; 16(5):952-65. DOI:10.1016/j.media.2012.02.008 · 3.68 Impact Factor
  • U. Z. Ijaz · R. J. Housden · G. M. Treece · R. W. Prager · A. H. Gee · Umer Zeeshan Ijaz · R. James Housden · Graham M. Treece · Richard W. Prager · Andrew H. Gee
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    ABSTRACT: An ultrasound image is created from back-scattered echoes originating both from diffuse and directional scattering. It is potentially useful to separate these two components for the purpose of tissue characterization. This paper presents several models for visualization of scattering fields in 3D ultrasound. By scanning the same anatomy from multiple directions, we can observe the variation of specular intensity as a function of viewing angle. This paper considers two models for estimating the diffuse and specular components of the backscattered intensity: a modification of the well-known Phong reflection model and an existing exponential model. We examine 2D implementations and also propose novel 3D extensions of these models in which the probe is not constrained to rotate within a plane. Both simulation and experimental results show that improved performance can be achieved with 3D models. 1
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    E. L. Neale · R. Housden · G. Treece · A. Gee · R. Prager
    Ultrasound in Obstetrics and Gynecology 10/2011; 38(S1). DOI:10.1002/uog.9992 · 3.14 Impact Factor
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    ABSTRACT: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.
    Clinical Radiology 08/2011; 66(11):1064-71. DOI:10.1016/j.crad.2011.05.015 · 1.66 Impact Factor
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    ABSTRACT: Ultrasound elastography is a technique used for clinical imaging of tissue stiffness with a conventional ultrasound machine. It was first proposed two decades ago, but active research continues in this area to the present day. Numerous clinical applications have been investigated, mostly related to cancer imaging, and though these have yet to prove conclusive, the technique has seen increasing commercial and clinical interest. This paper presents a review of the most widely adopted, non-quantitative, techniques focusing on technical innovations rather than clinical applications. The review is not intended to be exhaustive, concentrating instead on placing the various techniques in context according to the authors' perspective of the field.
    Interface focus: a theme supplement of Journal of the Royal Society interface 08/2011; 1(4):540-52. DOI:10.1098/rsfs.2011.0011 · 3.12 Impact Factor

Publication Stats

2k Citations
202.34 Total Impact Points

Institutions

  • 1999–2015
    • University of Cambridge
      • • Department of Engineering
      • • Department of Radiology
      Cambridge, England, United Kingdom
  • 2013
    • University of Glasgow
      • School of Engineering
      Glasgow, SCT, United Kingdom