Inadequate Rates of BRCA Testing with its Negative Consequences for Women with Epithelial Ovarian Cancer and their Families: an Overview of the Literature.

Fifteen per cent of women with epithelial ovarian cancer possess inherited mutations in the BRCA genes. Knowledge of her BRCA status is important to her and her family. Poly(ADP-ribose) polymerase (PARP) inhibitors provide a new therapeutic option for her. For her family it provides the opportunity for the prevention of what otherwise is often a lethal disease. To access these opportunities, the mandatory first step is testing the woman with the cancer. However, referral rates for genetic counselling and subsequent BRCA testing are low, in the of 10-30% range. The current paradigm needs the patient to be referred to genetics, be counselled and then undergo testing. Such an ad hoc process will never be 100% successful. Removing the human element by using reflex tumour testing as part of the routine pathological analysis is an obvious solution. Now 100% of women carrying mutations will be identified. Subsequent testing within the family would identify all the carriers, who would then be eligible for risk-reducing surgery. The current process for this is also flawed, with significant drop off at each stage, as it involves the woman with epithelial ovarian carcinoma and a mutation providing the information to her family who then in turn need to be referred or make an appointment for genetic counselling/testing and then, finally, if carrying the mutation, make a decision about risk-reducing surgery. Process improvements and education can help to diminish these roadblocks. The relevant available literature has been reviewed in order to provide an extensive overview of this broad topic with actual rates of counselling/testing at each step, the uptake of risk-reducing surgery and some solutions to make the process more effective. The value of PARP inhibitors and surgical prevention are also discussed, but in a more condensed format.

Finite element analysis to investigate variability of MR elastography in the human thigh.

PURPOSE: To develop finite element analysis (FEA) of magnetic resonance elastography (MRE) in the human thigh and investigate inter-individual variability of measurement of muscle mechanical properties. METHODS: Segmentation was performed on MRI datasets of the human thigh from 5 individuals and FEA models consisting of 12 muscles and surrounding tissue created. The same material properties were applied to each tissue type and a previously developed transient FEA method of simulating MRE using Abaqus was performed at 4 frequencies. Synthetic noise was applied to the simulated data at various levels before inversion was performed using the Elastography Software Pipeline. Maps of material properties were created and visually assessed to determine key features. The coefficient of variation (CoV) was used to assess the variability of measurements in each individual muscle and in the groups of muscles across the subjects. Mean measurements for the set of muscles were ranked in size order and compared with the expected ranking. RESULTS: At noise levels of 2% the CoV in measurements of |G*| ranged from 5.3 to 21.9% and from 7.1 to 36.1% for measurements of ϕ in the individual muscles. A positive correlation (R2 value 0.80) was attained when the expected and measured |G*| ranking were compared, whilst a negative correlation (R2 value 0.43) was found for ϕ. CONCLUSIONS: Created elastograms demonstrated good definition of muscle structure and were robust to noise. Variability of measurements across the 5 subjects was dramatically lower for |G*| than it was for ϕ. This large variability in ϕ measurements was attributed to artefacts.

The simulation of magnetic resonance elastography through atherosclerosis.

The clinical diagnosis of atherosclerosis via the measurement of stenosis size is widely acknowledged as an imperfect criterion. The vulnerability of an atherosclerotic plaque to rupture is associated with its mechanical properties. The potential to image these mechanical properties using magnetic resonance elastography (MRE) was investigated through synthetic datasets. An image of the steady state wave propagation, equivalent to the first harmonic, can be extracted directly from finite element analysis. Inversion of this displacement data yields a map of the shear modulus, known as an elastogram. The variation of plaque composition, stenosis size, Gaussian noise, filter thresholds and excitation frequency were explored. A decreasing mean shear modulus with an increasing lipid composition was identified through all stenosis sizes. However the inversion algorithm showed sensitivity to parameter variation leading to artefacts which disrupted both the elastograms and quantitative trends. As noise was increased up to a realistic level, the contrast was maintained between the fully fibrous and lipid plaques but lost between the interim compositions. Although incorporating a Butterworth filter improved the performance of the algorithm, restrictive filter thresholds resulted in a reduction of the sensitivity of the algorithm to composition and noise variation. Increasing the excitation frequency improved the techniques ability to image the magnitude of the shear modulus and identify a contrast between compositions. In conclusion, whilst the technique has the potential to image the shear modulus of atherosclerotic plaques, future research will require the integration of a heterogeneous inversion algorithm.

First application of the Automated QUantitative Analysis (AQUA) technique to quantify PTEN protein expression in ovarian cancer: A correlative study of NCIC CTG OV.16.

BACKGROUND: Platinum resistance is a dominant cause of poor outcomes in advanced ovarian cancer (OC). A mechanism of platinum resistance is the inhibition of apoptosis through phosphatidylinositol 3 kinase (PI3K) pathway activation. The role of phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, as a tumor biomarker is unclear. Quantitative analysis of PTEN expression as an alternative to immunohistochemistry has not been considered. PATIENTS AND METHODS: In 238 patient tumors from the NCIC-CTG trial OV.16, PTEN protein expression was quantified by Automated QUantitative Analysis (AQUA). Cox model was used to study the association between PTEN expression and clinical outcomes using a minimum p-value approach in univariate analysis. Multivariate analysis was used to adjust for clinical and pathological parameters. RESULTS: PTEN scores (range 13.9-192.3) of the 202 samples that passed quality control were analyzed. In univariate analysis, there was a trend suggesting an association between PTEN expression by AQUA as a binary variable (low ≤61 vs high >61) and progression free survival (HR=0.77, p=0.083), and in multivariate analysis, this association approached significance (HR=0.74, p=0.059). The relationship between quantitative PTEN expression and PFS differed (p=0.01 for interaction) by the extent of surgical debulking (residual disease (RD) <1cm or ≥1cm), with a numerically superior PFS in patients with high PTEN (23.5 vs 14.9m) only when RD<1cm (p=0.19). There was no association between PTEN levels and overall survival. CONCLUSIONS: AQUA is a novel method to measure PTEN expression. Further study of PTEN as a biomarker in OC is warranted.

Outcome of patients with primary refractory diffuse large B cell lymphoma after R-CHOP treatment.

Primary refractory diffuse large B cell lymphoma (DLBCL) following R-CHOP chemotherapy is a major concern. We identified 1126 patients with DLBCL treated with R-CHOP from 2000 to 2009, of whom 166 (15 %) had primary refractory disease. Of the 75/166 (45 %) who were age <70 years and had been planned for stage-directed curative therapy, 43 (57 %) were primary nonresponders and 32 (43 %) relapsed within 3 months of completing R-CHOP. Thirty of 75 (40 %) patients had serious comorbidity and organ dysfunction precluding intensive treatment and had palliative treatment only. Twelve of 45 (27 %) patients responded to second-line treatment and underwent ASCT. The median overall survival for the 75 patients was 10 months with only seven patients alive without evidence of disease at follow-up ranging from 14 to 106 months. Primary refractory DLBCL after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach.

Recent developments in vascular ultrasound technology.

This article describes four technologies relevant to vascular ultrasound which are available commercially in 2015, and traces their origin back through the research literature. The technologies are 3D ultrasound and its use in plaque volume estimation (first described in 1994), colour vector Doppler for flow visualisation (1994), wall motion for estimation of arterial stiffness (1968), and shear wave elastography imaging of the arterial wall (2010). Overall these technologies have contributed to the understanding of vascular disease but have had little impact on clinical practice. The basic toolkit for vascular ultrasound has for the last 25 years been real-time B-mode, colour flow and spectral Doppler. What has changed over this time is improvement in image quality. Looking ahead it is noted that 2D array transducers and high frame rate imaging continue to spread through the commercial vascular ultrasound sector and both have the potential to impact on clinical practice.

A Protocol for Improved Measurement of Arterial Flow Rate in Preclinical Ultrasound.

PURPOSE: To describe a protocol for the measurement of blood flow rate in small animals and to compare flow rate measurements against measurements made using a transit time flowmeter. MATERIALS AND METHODS: Measurements were made in rat and mice using a Visualsonics Vevo 770 scanner. The flow rate in carotid and femoral arteries was calculated from the time-average maximum velocity and vessel diameter. A correction factor was applied to correct for the overestimation of velocity arising from geometric spectral broadening. Invasive flow rate measurements were made using a Transonics system. RESULTS: Measurements were achieved in rat carotid and femoral arteries and in mouse carotid arteries. Image quality in the mouse femoral artery was too poor to obtain diameter measurements. The applied correction factor in practice was 0.71-0.77. The diameter varied by 6-18% during the cardiac cycle. There was no overall difference in the flow rate measured using ultrasound and using transit-time flowmeters. The flow rates were comparable with those previously reported in the literature. There was wide variation in flow rates in the same artery in individual animals. Transit-time measurements were associated with changes of a factor of 10 during the typical 40 min measurement period, associated with probe movement, vessel spasm, vessel kinking and other effects. CONCLUSION: A protocol for the measurement of flow rate in arteries in small animals has been described and successfully used in rat carotid and femoral arteries and in mouse carotid arteries. The availability of a noninvasive procedure for flow rate measurement avoids the problems with changes in flow associated with an invasive procedure.

Dose-dense paclitaxel in advanced ovarian cancer.

Carboplatin and paclitaxel, delivered on a 3-weekly basis, is the historical standard for the management of advanced epithelial ovarian cancers (EOC). Increased dose intensity, the inclusion of additional active cytotoxic agents and lengthening treatment duration have failed to improve the outcomes seen with standard doses of carboplatin and paclitaxel in the treatment of EOC. Dose-dense (i.e. weekly) delivery of paclitaxel may exploit anticancer mechanisms such as anti-angiogenesis and the induction of apoptosis. Tumour regrowth may be more effectively impaired by the dose-dense delivery of paclitaxel. Non-randomised studies of dose-dense chemotherapy in EOC have been promising, particularly in heavily pretreated and platinum-resistant disease, with reported response rates as high as 60%. Dose-dense paclitaxel also seems to be well tolerated. These observations led to a number of comparative trials of dose-dense paclitaxel chemotherapy, three have been reported and four are ongoing. This review explores the rationale behind dose-dense delivery of paclitaxel and evaluates the results of completed phase III trials.

A phase II study single agent of aflibercept (VEGF Trap) in patients with recurrent or metastatic gynecologic carcinosarcomas and uterine leiomyosarcoma. A trial of the Princess Margaret Hospital, Chicago and California Cancer Phase II Consortia.

OBJECTIVE: The aim of this multi-institutional non randomized phase II trial was to determine the efficacy and safety of single agent aflibercept (VEGF Trap), a recombinant fusion protein that blocks multiple vascular endothelial growth factor isoforms, in women with gynecologic soft tissue sarcoma. METHODS: Patients were enrolled in two cohorts each with Simon two stage designs: uterine leiomyosarcoma and carcinosarcoma of endometrial, ovarian or fallopian tube origin. Eligibility criteria included ≤2 prior lines of chemotherapy for metastatic disease and ECOG performance status of ≤2. Aflibercept 4mg/kg was administered intravenously on day 1 of a 14 day cycle. Primary endpoints were objective response and disease stabilization (Progression Free Survival (PFS) at 6 months). RESULTS: 41 patients with uterine leiomyosarcoma and 22 patients with carcinosarcoma (19 uterine, 3 ovarian) were enrolled on study. In the leiomyosarcoma cohort, eleven (27%) patients had stable disease (SD), 4 with SD lasting at least 24 weeks. The 6 month PFS was 17%, with median time to progression (TTP) of 1.8 (95% CI:1.6-2.1) months. In the carcinosarcoma cohort, two (9%) patients had SD, one lasting >24 weeks, median TTP was 1.6 months (95%CI: 1.1-1.7) No partial responses were observed in patients from either cohort. Grade 3 or more aflibercept related toxicity was uncommon and included hypertension, fatigue, headache and abdominal pain. CONCLUSIONS: Single agent aflibercept has modest activity in patients with uterine leiomyosarcoma and minimal activity in women with carcinosarcoma.

Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective.

Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival (os) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival (pfs) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to evaluate the relevance of pfs as a valid endpoint in ovarian cancer;reach a Canadian consensus on the relevance of pfs in ovarian cancer; andtry to address how pfs translates into clinical benefit in ovarian cancer.Overall, the findings and the group consensus posit that future studies should ensure that trials are designed to evaluate pfs, os, and other clinically relevant endpoints such as disease-related symptoms or quality of life;incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active;stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified, clinically relevant endpoint such as os or symptom relief; anddiscourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention.

Exploring palliative treatment outcomes in women with advanced or recurrent ovarian clear cell carcinoma.

OBJECTIVE: Clear cell carcinoma (CCC) of the ovary is increasingly recognized as responding poorly to chemotherapy (CT). This review examines the outcomes achieved with a variety of CT regimens, looking for evidence of activity that might guide the development of more effective treatments. METHODS: A retrospective chart review of all cases of CCC referred to the BC Cancer Agency (BCCA) between 2000 and 2008 was conducted. Data were collected from those with primarily advanced disease and from those who recurred after adjuvant treatment. Outcomes were measured using broad definitions of treatment benefit (any objective or subjective evidence of disease control) in order to reflect the real-life use of palliative therapy. RESULTS: There were 158 women with pure CCC. First-line therapy for advanced disease was delivered to 33 patients. Second- and third-line treatment was delivered to 47 and 25 patients, respectively. The total number of treatment courses was 105: 88 CT-alone courses, 14 radiation therapy (RT)-alone and 3 combined modality. Treatment benefit was recorded in 24% of patients receiving CT, 64% of patients receiving RT, and each who received combined modality treatment. There was no CT drug class identified as obviously efficacious. CONCLUSION: Most patients with advanced or recurrent CCC have a low benefit-to-failure ratio from palliative CT. The role of RT and targeted agents must be explored to improve clinical outcomes for such patients.

Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study.

BACKGROUND: Breast cancer 1 (BRCA1) protein inactivation in sporadic ovarian carcinoma (OC) is common and low BRCA1 expression is linked with platinum sensitivity. The clinical validation of BRCA1 as a prognostic marker in OC remains unresolved. PATIENTS AND METHODS: In 251 patient samples from the NCIC CTG clinical trial, OV.16, BRCA1 protein expression was determined by immunohistochemistry. RESULTS: For all patients, when BRCA1 score was analyzed as a continuous variable, there was no significant correlation between BRCA1 protein expression and progression-free survival (PFS) [adjusted hazard ratio (HR) = 1.15 (0.96-1.37), P = 0.12] or response rate [HR = 0.89 (0.70-1.12), P = 0.32]. In the 116 patients with minimal residual disease (RD), higher BRCA1 expression correlated significantly with worse PFS [HR = 1.40 (1.04-1.89), P = 0.03]. Subgroup analysis divided patients with minimal RD into low (BRCA1 ≤2.5) and high (BRCA1 >2.5) expression groups. Patients with low BRCA1 expression had a more favorable outcome [median PFS was 24.7 and 16.6 months in patients with low and high BRCA1, respectively; HR = 0.56 (0.35-0.89), P = 0.01]. CONCLUSIONS: This study suggests that BRCA1 protein is a prognostic marker in sporadic OC patients with minimal RD. Further research is needed to evaluate BRCA1 as a predictive biomarker and to target BRCA1 expression to enhance chemotherapeutic sensitivity.

CA 125 normalization with chemotherapy is independently predictive of survival in advanced endometrial cancer.

OBJECTIVE: Changes in CA 125 with chemotherapy predict outcome for epithelial ovarian cancer. There is no such data for advanced endometrial cancer. METHOD: Retrospective review of all women receiving carboplatin and paclitaxel for advanced endometrial cancer at any of the institutions of the British Columbia Cancer Agency between September 1995 and September 2006. RESULTS: 185 newly diagnosed women were treated. Univariable analysis for progression-free survival identified as adverse predictors: grade 3, positive residual, age > 60, deep myometrial invasion, increasing stage/substage, papillary serous subtype, presence of cervical involvement, ECOG 1 or greater, CA 125 above 35 either preoperatively or at start of cycle 1 and CA 125 greater than 24 at the start of cycle 3. Upon multivariate analysis, CA 125 above 24 at cycle 3, grade 3 and positive residual remained as independent predictors. The single most important factor identified by decision tree analysis was CA 125 level at cycle 3. CONCLUSION: As with epithelial ovarian cancer, changes in CA 125 are highly predictive of outcome for advanced, chemotherapy treated endometrial cancer.

Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers.

BACKGROUND: To explore the influence of ovarian cancer histotype on the effectiveness of adjuvant radiotherapy (RT). METHODS: A review of a population-based experience included all referred women with no reported macroscopic residuum following primary surgery who underwent adjuvant platin-based chemotherapy (CT), with or without sequential RT, and for whom it was possible to assign histotype according to the contemporary criteria. RESULTS: Seven hundred and three subjects were eligible, of these 351 received RT. For those with apparent stage I and II tumors, the cohort with clear cell (C), endometrioid (E), and mucinous (M) disease who additionally received RT exhibited a 40% reduction in disease-specific mortality and a 43% reduction in overall mortality. CONCLUSIONS: The curability of those with stage I and II C-, E-, and M-type ovarian carcinomas was enhanced by RT-containing adjuvant therapy. This benefit did not extend to those with stage III or serous tumors. These findings necessitate reassessments of the role of RT and of the nonselective surgical and CT approaches that have characterized ovarian cancer care.

Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

BACKGROUND: Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. METHODS: Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. RESULTS: A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) CONCLUSIONS: Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.

Haemodynamics and blood flow measured using ultrasound imaging.

Visualization of, and measurements related to, haemodynamic phenomena in arteries may be made using ultrasound systems. Most ultrasound technology relies on simple measurements of blood velocity taken from a single site, such as the peak systolic velocity for assessment of the degree of lumen reduction caused by an arterial stenosis. Real-time two-dimensional (2D) flow field visualization is possible using several methods, such as colour flow, blood flow imaging, and echo particle image velocimetry; these have applications in the examination of the flow field in diseased arteries and in heart chambers. Three-dimensional (3D) and four-dimensional ultrasound systems have been described. These have been used to provide 2D velocity profile data for the estimation of volumetric flow. However, they are limited for haemodynamic evaluation in that they provide only one component of the velocity. The provision of all seven components (three space, three velocity, and one time) is possible using image-guided modelling, in which 3D ultrasound is combined with computational fluid dynamics. This method also allows estimation of turbulence data and of relevant quantities such as the wall shear stress.

Fluid-structure interaction in axially symmetric models of abdominal aortic aneurysms.

Abdominal aortic aneurysm disease progression is probably influenced by tissue stresses and blood flow conditions and so accurate estimation of these will increase understanding of the disease and may lead to improved clinical practice. In this work the blood flow and tissue stresses in axially symmetric aneurysms are calculated using a complete fluid-structure interaction as a benchmark for calculating the error introduced by simpler calculations: rigid walled for the blood flow, homogeneous pressure for the tissue stress, as well as one-way-coupled interactions. The error in the peak von Mises stress in a homogeneous pressure calculation compared with a fluid-structure interaction calculation was less than 3.5 per cent for aneurysm diameters up to 7 cm. The error in the mean wall shear stress, in a rigid-walled calculation compared with a fluid-structure interaction calculation, varied from 30 per cent to 60 per cent with increasing aneurysm diameter. These results suggest that incorporation of the fluid-structure interaction is unnecessary for purely mechanical modelling, with the aim of evaluating the current rupture probability. However, for more complex biological modelling, perhaps with the aim of predicting the progress of the disease, where accurate estimation of the wall shear stress is essential, some form of fluid-structure interaction is necessary.

Measurement of arterial stiffness in subjects with vascular disease: Are vessel wall changes more sensitive than increase in intima-media thickness?

BACKGROUND AND AIMS: It is widely accepted that subjects with vascular disease have increased arterial stiffness and intima-media thickness (IMT) when compared with healthy controls. The aim of this study was to investigate indices of arterial stiffness and IMT in the common carotid arteries (CCAs) of subjects with and without peripheral arterial disease (PAD), in order to look for evidence of change in wall quality and quantity to explain increased stiffness that has been found in the arteries of subjects with vascular disease. METHODS AND RESULTS: The arterial distension waveform (ADW), IMT, diameter and brachial blood pressure were measured to calculate Young's Modulus (E) and elastic modulus (Ep) in the common carotid arteries of subjects with and without PAD. 38 subjects with confirmed PAD were compared with 43 normal controls matched for age, sex, smoking and hypertension. The mean diameter (8.35mm [95% CI 7.93-8.77] vs. 6.93mm [6.65-7.20] P<0.001, increase 20%), IMT (0.99mm [0.92-1.07] vs. 0.88mm [0.82-0.93] P=0.020, increase 12.5%), Ep (315kPa [185-444] vs. 190kPa [164-216] P=0.034, increase 66%) and E (1383kPa [836-1930] vs. 744kPa [641-846] P=0.006, increase 86%) were all significantly higher in subjects with PAD. CONCLUSIONS: This study suggests that increased stiffness observed in subjects with peripheral vascular disease is a result of change in both quantity and quality of the arterial wall. Changes in indices of arterial stiffness were much higher than changes in IMT and diameter. These preliminary observations may be an indication that indices of arterial stiffness are a sensitive early marker of atherosclerosis.

Three-dimensional imaging and computational modelling for estimation of wall stresses in arteries.

The paper reviews techniques for the estimation of wall stresses in arterial disease. Wall stresses are important as arterial disease progresses through a complex interplay between local biology and local mechanical stresses. The possibility then arises of using wall stresses as new diagnostic indicators in patients with arterial disease. Estimation of wall stresses using imaging systems is problematic. Developments in the last 10 years have been aimed at providing tools for estimation of wall stresses within individual patients, using a combination of three-dimensional (3D) imaging and computational modelling. For blood flow, 3D arterial lumen information is obtained from 3D imaging. Computational fluid dynamics is then used to estimate the 3D velocity field within the lumen, from which wall shear stress may be calculated. For arterial mechanics, the 3D arterial wall geometry is integrated with solid modelling to provide estimates of the strain field and stress field within the artery wall. For intraplaque stresses, this has been achieved through the use of detailed two-dimensional (2D) intraplaque geometry from MRI. Inverse techniques have been used to provide images of Young's modulus in atherosclerotic plaque using intravascular ultrasound and solid modelling. Several research centres now have processing chains to allow this technology to be used in clinical studies. In time, possibly over the next 10 years or so, robust protocols with proven clinical utility will arise which, when combined with high-performance computing, will allow image-guided modelling to be used as an adjunct to modern radiology in the same way that image-processing tools are used today.