Ultrasound-guided trans-rectal high-intensity focused ultrasound (HIFU) for advanced cervical cancer ablation is feasible: a case report.

High-intensity focused ultrasound (HIFU) is an ablative treatment undergoing assessment for the treatment of benign and malignant disease. We describe the first reported intracavitary HIFU ablation for recurrent, unresectable and symptomatic cervical cancer.A 38 year old woman receiving palliative chemotherapy for metastatic cervical adenocarcinoma was offered ablative treatment from an intracavitary trans-rectal HIFU device (Sonablate® 500). Pre-treatment symptoms included vaginal bleeding and discharge that were sufficient to impede her quality of life. No peri-procedural adverse events occurred. Symptoms resolved completely immediately post-procedure, reappeared at 7 days, increasing to pre-procedural levels by day 30.This first time experience of intracavitary cervical HIFU suggests that it is feasible for palliation of advanced cervical cancer, with no early evidence of unexpected toxicity. Ethical approval had also been granted for the use of per-vaginal access if appropriate. This route, alone or in combination with the rectal route, may provide increased accessibility in future patients with a redesigned device more suited to trans-vaginal ablations.Intracavitary HIFU is a potentially safe procedure for the treatment of cervical cancer and able to provide symptomatic improvement in the palliative setting

Heterogeneity in the non-planarity and arterial curvature of arteriovenous fistulae in vivo

Objective: Native arteriovenous fistulae (AVF) for haemodialysis are susceptible to non-maturation. Adverse features of local blood flow have been implicated in the formation of peri-anastomotic neointimal hyperplasia which may underpin non-maturation. While computational fluid dynamic simulations of idealised models highlight the importance of geometry on fluid and vessel wall interactions, little is known in vivo about AVF geometry and its role in adverse clinical outcomes. This study set out to examine the three-dimensional geometry of native AVF and the geometric correlates of AVF failure. Methods: As part of an observational study between 2013 and 2016, patients underwent creation of an upper limb AVF according to current surgical best practice. Phase-contrast MRI was performed on the day of surgery to obtain luminal geometry along with ultrasound measurements of flow. MRI datasets were segmented and reconstructed for quantitative and qualitative analysis of local geometry. Clinical maturation was evaluated at six weeks. Results: 60 patients were successfully imaged on the day of surgery. Radiocephalic (n=17), brachiocephalic (n=40) and brachiobasilic (n=3) fistulae were all included in the study. Centrelines extracted from segmented vessel lumen exhibited significant heterogeneity in arterial non-planarity and curvature. Furthermore, these features are more marked in brachiocephalic as compared to radiocephalic fistulae. Across the cohort, the projected bifurcation angle was was 73° (±16°) mean (±sd). Geometry was preserved at two weeks in 20 patients who underwent repeat imaging. A greater degree of arterial non-planarity (log odds ratio (logOR) 0.95 per 0.1/vessel diameter (95% CI 0.22 to 1.90, P= .03)) along with a larger bifurcation angle (logOR 0.05 per degree (95% CI 0.01 to 0.09, P= .02)) are associated with a great rate of maturation, as is fistula location (upper vs lower arm) logOR -1.9 (95% CI -3.2 to 0.7, P = .002) . Conclusions: There is significant heterogeneity in the three-dimensional geometry of arteriovenous fistulae, in particular, arterial non-planarity and curvature. In this largest cohort of AVF geometry to date, the effect of individual geometric correlates on maturation is uncertain but supports the premise that future modelling studies will need to acknowledge the complex geometry of AVF

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up

Background MR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined. Objective To assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET. Methods 14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24-month data. Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores. Results The mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p < 0.001) whilst BFS-NTA worsened by 8.8% (p < 0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p < 0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p < 0.001) reduction from post anterior-VIM/VOP to post-PSA ablation. Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p < 0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p = 0.001) and non-treated arm (UETTS-NTA) 30.5% (p = 0.003). At 24 months residual adverse effects were slight unsteadiness (n = 1) and mild hemi-chorea (n = 1). Conclusion Unilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile

Ethnicity and prediction of cardiovascular disease: performance of QRISK2 and Framingham scores in a U.K. tri-ethnic prospective cohort study (SABRE--Southall And Brent REvisited).

OBJECTIVE: To evaluate QRISK2 and Framingham cardiovascular disease (CVD) risk scores in a tri-ethnic U.K. population. DESIGN: Cohort study. SETTING: West London. PARTICIPANTS: Randomly selected from primary care lists. Follow-up data were available for 87% of traced participants, comprising 1866 white Europeans, 1377 South Asians, and 578 African Caribbeans, aged 40-69 years at baseline (1998-1991). MAIN OUTCOME MEASURES: First CVD events: myocardial infarction, coronary revascularisation, angina, transient ischaemic attack or stroke reported by participant, primary care or hospital records or death certificate. RESULTS: During follow-up, 387 CVD events occurred in men (14%) and 78 in women (8%). Both scores underestimated risk in European and South Asian women (ratio of predicted to observed risk: European women: QRISK2: 0.73, Framingham: 0.73; South Asian women: QRISK2: 0.52, Framingham: 0.43). In African Caribbeans, Framingham over-predicted in men and women and QRISK2 over-predicted in women. Framingham classified 28% of participants as high risk, predicting 54% of all such events. QRISK2 classified 19% as high risk, predicting 42% of all such events. Both scores performed poorly in identifying high risk African Caribbeans; QRISK2 and Framingham identified as high risk only 10% and 24% of those who experienced events. CONCLUSIONS: Neither score performed consistently well in all ethnic groups. Further validation of QRISK2 in other multi-ethnic datasets, and better methods for identifying high risk African Caribbeans and South Asian women, are required

The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images

Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery

Towards a multiphysics modelling framework for thermosensitive liposomal drug delivery to solid tumour combined with ultrasound hyperthermia

Systemic toxicity and insufficient drug accumulation at the tumour site are main barriers in chemotherapy. Thermosensitive liposomes (TSL) combined with high intensity focused ultrasound (HIFU) has emerged as a potential solution to overcome these barriers through targeted drug delivery and localised release. Owing to the multiple physical and biochemical processes involved in this combination therapy, mathematical modelling becomes an indispensable tool for detailed analysis of the transport processes and prediction of tumour drug uptake. To this end, a multiphysics model has been developed to simulate the transport of chemotherapy drugs delivered through a combined HIFU-TSL system. All key delivery processes are considered in the model; these include interstitial fluid flow, HIFU acoustics, bioheat transfer, drug release and transport, as well as tumour drug uptake. The capability of the model is demonstrated through its application to a 2-D prostate tumour model reconstructed from magnetic resonance images. Our results not only demonstrate the feasibility of the model to simulate this combination therapy, but also confirm the advantage of HIFU-TSL drug delivery system with enhancement of drug accumulation in tumour regions and reduction of drug availability in normal tissue. This multiphysics modelling framework can serve as a useful tool to assist in the design of HIFU-TSL drug delivery systems and treatment regimen for improved anticancer efficacy