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.

Detection of maturity and ligament injury using magic angle directional imaging.

PURPOSE: To investigate whether magnetic field-related anisotropies of collagen may be correlated with postmortem findings in animal models. METHODS: Optimized scan planning and new MRI data-processing methods were proposed and analyzed using Monte Carlo simulations. Six caprine and 10 canine knees were scanned at various orientations to the main magnetic field. Image intensities in segmented voxels were used to compute the orientation vectors of the collagen fibers. Vector field and tractography plots were computed. The Alignment Index was defined as a measure of orientation distribution. The knees were subsequently assessed by a specialist orthopedic veterinarian, who gave a pathological diagnosis after having dissected and photographed the joints. RESULTS: Using 50% less scans than reported previously can lead to robust calculation of fiber orientations in the presence of noise, with much higher accuracy. The 6 caprine knees were found to range from very immature (< 3 months) to very mature (> 3 years). Mature specimens exhibited significantly more aligned collagen fibers in their patella tendons compared with the immature ones. In 2 of the 10 canine knees scanned, partial cranial caudal ligament tears were identified from MRI and subsequently confirmed with encouragingly high consistency of tractography, Alignment Index, and dissection results. CONCLUSION: This method can be used to detect injury such as partial ligament tears, and to visualize maturity-related changes in the collagen structure of tendons. It can provide the basis for new, noninvasive diagnostic tools in combination with new scanner configurations that allow less-restricted field orientations.

Focused ultrasound induced hyperthermia accelerates and increases the uptake of anti-HER-2 antibodies in a xenograft model.

Image guided drug delivery has gained significant attention during the last few years. Labelling nanoparticles or macromolecules and monitoring their fate in the body provides information that can be used to modulate their biodistribution and improve their pharmacokinetics. In this study we label antibodies and monitor their distribution in the tumours post intravenous injection. Using Focused Ultrasound (FUS, a non-invasive method of hyperthermia) we increase the tumour temperature to 42°C for a short period of time (3-5min) and we observe an increased accumulation of labelled antibody. Repetition of focused ultrasound induced hyperthermic treatment increased still further the accumulation of the antibodies in the tumour. This treatment also augmented the accumulation of other macromolecules non-specific to the tumour, such as IgG and albumin. These effects may be used to enhance the therapeutic efficiency of antibodies and/or targeted nanoparticles.

Thermosensitive, near-infrared-labeled nanoparticles for topotecan delivery to tumors.

Liposomal nanoparticles have proven to be versatile systems for drug delivery. However, the progress in clinic has been slower and less efficient than expected. This suggests a need for further development using carefully designed chemical components to improve usefulness under clinical conditions and maximize therapeutic effect. For cancer chemotherapy, PEGylated liposomes were the first nanomedicine to reach the market and have been used clinically for several years. Approaches toward targeted drug delivery using next generation "thermally triggered" nanoparticles are now in clinical trials. However, clinically tested thermosensitive liposomes (TSLs) lack the markers that allow tumor labeling and improved imaging for tissue specific applied hyperthermia. Here we describe the development of optically labeled TSLs for image guidance drug delivery and proof-of-concept results for their application in the treatment of murine xenograft tumors using the anticancer drug topotecan. These labeled TSLs also allow the simultaneous, real-time diagnostic imaging of nanoparticle biodistribution using a near-infrared (NIR; 750-950 nm) fluorophore coupled to a lipidic component of the lipid bilayer. When combined with multispectral fluorescence analysis, this allows for specific and high sensitivity tracking of the nanoparticles in vivo. The application of NIR fluorescence-labeled TSLs could have a transformative effect on future cancer chemotherapy.

Thermal ablative treatment of uterine fibroids.

In addition to surgical methods of treating uterine fibroids, numerous non-invasive treatments have been developed. Many of these involve the use of hyperthermia, the heating of tissue by a variety of methods. These include the use of lasers, radiofrequency, microwave energy and high intensity focused ultrasound, guided by both ultrasound and magnetic resonance imaging. In this review we examine the technology behind these treatment modalities and review the current evidence for their use.

The evolution of ventral intermediate nucleus targeting in MRI-guided focused ultrasound thalamotomy for essential tremor: an international multi-center evaluation.

Background: The ventral intermediate nucleus (VIM) is the premiere target in magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for tremor; however, there is no consensus on the optimal coordinates for ablation. This study aims to ascertain the various international VIM targeting approaches (VIM-TA) and any evolution in practice. Methods: International MRgFUS centers were invited to share VIM-TAs in 2019 and 2021. Analyses of any modification in practice and of anatomical markers and/or tractography in use were carried out. Each VIM-TA was mapped in relation to the mid-commissural point onto a 3D thalamic nucleus model created from the Schaltenbrand-Wahren atlas. Results: Of the 39 centers invited, 30 participated across the study period, providing VIM-TAs from 26 centers in 2019 and 23 in 2021. The results are reported as percentages of the number of participating centers in that year. In 2019 and 2021, respectively, 96.2% (n = 25) and 95.7% (n = 22) of centers based their targeting on anatomical landmarks rather than tractography. Increased adoption of tractography in clinical practice and/or for research was noted, changing from 34.6% to 78.3%. There was a statistically significant change in VIM-TAs in the superior-inferior plane across the study period; the percentage of VIM-TAs positioned 2 mm above the intercommissural line (ICL) increased from 16.0% in 2019 to 40.9% in 2021 (WRST, p < 0.05). This position is mapped at the center of VIM on the 3D thalamic model created based on the Schaltenbrand-Wahren atlas. In contrast, the VIM-TA medial-lateral and anterior-posterior positions remained stable. In 2022, 63.3% of participating centers provided the rationale for their VIM-TAs and key demographics. The centers were more likely to target 2 mm above the ICL if they had increased experience (more than 100 treatments) and/or if they were North American. Conclusion: Across the study period, FUS centers have evolved their VIM targeting superiorly to target the center of the VIM (2 mm above the ICL) and increased the adoption of tractography to aid VIM localization. This phenomenon is observed across autonomous international centers, suggesting that it is a more optimal site for FUS thalamotomy in tremors.

'Am I fixed, am I better now?': undergoing MR-guided focused ultrasound for essential tremor: an interpretative phenomenological analysis.

Introduction: Essential tremor (ET) is characterised by postural and intentional tremor typically affecting the upper limbs, which can negatively impact functionality and quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a novel and promising non-invasive treatment for ET which offers instantaneous results. Methods: Using interpretative phenomenological analysis we explored the experience of undergoing MRgFUS in six ET patients as well as their experiences pre- and post-procedure. Results: One-time, retrospective semi-structured interviews were conducted and six themes emerged: Life pre-treatment: "It's everyday tasks that get you down" and "Most people who understand, they are okay. Some people aren't"; MRgFUS: Treatment day: "Going into the unknown" and "There's no way I was going to press that button"; and Life post-treatment: "One is good. Two is better" and "Am I fixed, am I better now?." Discussion: The findings point to a significant period of adjustment associated with living with ET and the effects of undergoing ET MRgFUS treatment. As ET progressed, participants struggled to cope with increasing symptoms and had to develop coping strategies to manage life with ET. The procedure itself was perceived as strange and extraordinary and despite some immediate adverse effects participants were determined to go through with it. Post procedure, all participants reported tremor suppression which was life changing. While some participants still felt burdened by ET, others expressed it took them a while to psychologically adjust to what essentially was their new body. This study has highlighted the need for patients to be supported at all stages of their ET journey.

Quantifying hepatic steatosis - more than meets the eye.

AIMS: The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is the histological tool used to assess disease severity based on steatosis, inflammation and hepatocyte ballooning. As steatosis contributes up to three of a potential eight points to NAS, it is important to quantify steatosis accurately. We sought to determine the optimum histological technique for identifying fat in tissue. METHODS AND RESULTS: Using tissue from a mouse model of NAFLD, with validation in human liver biopsies, the percentage steatosis and fat droplet size were assessed in haematoxylin and eosin (H&E)- and Oil Red-O (ORO)-stained sections by light microscopy and digital image analysis (DIA). Results were compared to biochemical tissue triglyceride content and MRI assessment of hepatic lipid content. H&E steatosis assessment correlated poorly with tissue triglyceride concentration. However, ORO DIA exhibited much higher sensitivity and specificity for steatosis and correlated very well with triglyceride concentration in mouse and human liver (R = 0.706, P = 0.001 and R = 0.894, P =0.041, respectively). MRI-based assessment of steatosis was inaccurate. CONCLUSIONS: ORO DIA is the most accurate method for detecting and quantifying steatosis. Although H&E-based NAS remains clinically valid in both clinical research and experimental situations, ORO DIA is a more robust technique to assess liver steatosis accurately for NAS scoring.

MRI-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis low back pain--case series of an innovative new technique.

OBJECTIVE: To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis pain. METHODS: Patients with a positive response to facet joint interventions were recruited from Pain and Spinal Clinics. Treatments were performed at the levels of pain according to symptomatology, previous invasive treatment and MRI grading of facet joint osteoarthritis. Both safety and efficacy data were collected. Pain palliation was evaluated using a validated pain numerical rating scale (NRS), Oswestry disability questionnaire (ODQ), Brief Pain Inventory (BPI) and the EuroQol (EQ-5D) health state score RESULTS: Eighteen patients were treated. There were no major adverse events. At 6/12 we found a reduction in both the NRS (average/worst) pain scores (60.2 %/51.2 %). This was associated with 45.9 % improvement in the ODQ score and 61.9 % reduction in the BPI interference score. We observed an improvement in the EuroQol (EQ-5D) health state score based on UK coefficients of +0.379 (0.317 to 0.696). CONCLUSIONS: Our phase I observational pilot study has evaluated an innovative new technique that is both non-invasive and radiation free. It is the first description of this procedure in the literature. In all patients the technique was safe, free of complications, effective and well tolerated. KEY POINTS: Magnetic resonance-guided focused ultrasound offers non-invasive therapy for facet joint pain. MRgFUS appears to be an effective and safe thermal ablation technique for facet joint pain. Real-time image control and thermal feedback minimise complications. MRgFUS allows outpatient management of facet joint osteoarthritic low back pain.

Tissue specific considerations in implementing high intensity focussed ultrasound under magnetic resonance imaging guidance.

High-intensity focused ultrasound can ablate a target permanently, leaving tissues through which it passes thermally unaffected. When delivered under magnetic resonance (MR) imaging guidance, the change in tissue relaxivity on heating is used to monitor the temperatures achieved. Different tissue types in the pre-focal beam path result in energy loss defined by their individual attenuation coefficients. Furthermore, at interfaces with different acoustic impedances the beam will be both reflected and refracted, changing the position of the focus. For complex interfaces this effect is exacerbated. Moreover, blood vessels proximal to the focal region can dissipate heat, altering the expected region of damage. In the target volume, the temperature distribution depends on the thermal conductivity (or diffusivity) of the tissue and its heat capacity. These are different for vascular tissues, water and fat containing tissues and bone. Therefore, documenting the characteristics of the pre-focal and target tissues is critical for effective delivery of HIFU. MR imaging provides excellent anatomic detail and characterization of soft tissue components. It is an ideal modality for real-time planning and monitoring of HIFU ablation, and provides non-invasive temperature maps. Clinical applications involve soft-tissue (abdomino-pelvic applications) or bone (brain applications) pre-focally and at the target (soft-tissue tumors and bone metastases respectively). This article addresses the technical difficulties of delivering HIFU effectively when vascular tissues, densely cellular tissues, fat or bone are traversed pre-focally, and the clinical applications that target these tissues. The strengths and limitations of MR techniques used for monitoring ablation in these tissues are also discussed.

The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

Screening for encapsulating peritoneal sclerosis in patients on peritoneal dialysis: role of CT scanning.

BACKGROUND: We previously validated a scoring system for abdominal/pelvic CT scans in patients with symptomatic encapsulating peritoneal sclerosis (EPS). CT scans of patients with symptomatic EPS were significantly different from control peritoneal dialysis (PD) or haemodialysis patient scans; scans performed before EPS was clinically evident were near normal in 9 of 13 patients. We have now investigated CT scanning as a screening modality in a larger group of patients on long-term PD. METHODS: Pre-diagnostic CT scans performed in 20 patients for routine screening or other indications at least 3 months before EPS developed, and later diagnostic scans when EPS was clinically evident, were scored by three radiologists. The control group included CT scans of 20 PD patients who had not developed EPS (median follow-up 2.25 years). Analysis was by non-parametric tests. CT scores ranged from 0 to 22; > 2.5 was considered abnormal. RESULTS: Clinical EPS only developed after transplantation or transfer to HD. Diagnostic scans scored significantly higher than pre-diagnostic or control scans (median scores 9, 2 and 1; P < 0.001), confirming previous work. The pre-EPS diagnosis of 12 asymptomatic patients had a median CT score = 1.75, similar to the control group. Eight patients had had a limited episode of abdominal symptoms (seven required hospitalization), but did not have the clinical picture of EPS; their median CT score was 4.5 (P = 0.0016 cf control group). The time from pre-diagnostic scan to clinical EPS (median 0.82 years) and duration of PD at time of pre-diagnostic scan (median 7.1 years) did not differ significantly between the symptomatic and asymptomatic groups. CONCLUSIONS: CT screening of asymptomatic PD patients is not indicated; EPS may occur within a year or less of a normal CT scan. Abdominal symptoms in long-term PD patients can be associated with CT scan abnormalities; these patients are at increased risk of EPS after stopping PD.

Renal artery stenosis: comparative assessment by unenhanced renal artery MRA versus contrast-enhanced MRA.

OBJECTIVES: To evaluate steady-state free precession (SSFP) non-contrast-enhanced MR angiography (Unenhanced-MRA) versus conventional contrast-enhanced MR angiography (CE-MRA) in the detection of renal artery stenosis (RAS). METHODS: Retrospective analysis of 70 consecutive patients referred for suspected RAS, examined by SSFP Unenhanced-MRA and CE-MRA. Image quality, quality of visible renal arterial segments, presence and grade of RAS were evaluated. The Unenhanced-MRA were compared against reference standard CE-MRA results. RESULTS: 149 renal arteries were assessed with 21 haemodynamically significant stenoses (≥ 50% stenosis) demonstrated by CE-MRA. Combined sensitivity and specificity for RAS detection by Unenhanced-MRA was 72.8% and 97.8% respectively. There is substantial correlation for RAS detection between Unenhanced-MRA and CE-MRA with kappa values of between 0.64 and 0.74. There was excellent inter-observer correlation for RAS on Unenhanced-MRA (kappa values 0.82-1.0). CONCLUSIONS: Our study has shown Unenhanced-MRA to be a viable alternative to CE-MRA, yielding images equal in quality without the requirement for gadolinium contrast agents. The sensitivity and specificity for the detection of haemodynamically significant stenoses are comparable to CE-MRA. Potentially, Unenhanced-MRA could be used as an initial investigation to avoid performing CE-MRA in patients with normal renal arteries, however we suggest that its real value will lie in being complementary to CE-MRA.

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor.

Introduction: Magnetic Resonance guided Focused UltraSound (MRgFUS) is an emerging technique that utilizes multiple high-energy low-frequency ultrasound beams generated from a multi-element transducer focused onto a single site to cause thermal ablation of the target tissue. The ExAblate Neuro 4000 system is the leading MRgFUS brain system, performing targeted thermal ablation on specific nuclei in the brain. Its precision targeting opens up new and exciting possibilities for future treatments of a wide range of neurological diseases.  Areas covered: This article aims to introduce the non-expert reader (clinician and non-clinicians) to the role of the ExAblate Neuro 4000 System in brain MRgFUS. The current clinical uses of the ExAblate system in the brain are explored with a particular focus on Essential Tremor, where internationally there is most experience, this includes reference to current literature. The safety and efficacy of MRgFUS treatments are explored and the challenges the ExAblate system must overcome to balance these juxtaposed outcomes.Expert opinion: We describe the hopes for future clinical uses of the ExAblate Neuro 4000 system to treat neurological disease and consider further advancements in MRgFUS transducer technology that may open up new exciting frontiers within the brain.

Image-guided thermosensitive liposomes for focused ultrasound enhanced co-delivery of carboplatin and SN-38 against triple negative breast cancer in mice.

Triggerable nanocarriers have the potential to significantly improve the therapeutic index of existing anticancer agents. They allow for highly localised delivery and release of therapeutic cargos, reducing off-target toxicity and increasing anti-tumour activity. Liposomes may be engineered to respond to an externally applied stimulus such as focused ultrasound (FUS). Here, we report the first co-delivery of SN-38 (irinotecan's super-active metabolite) and carboplatin, using an MRI-visible thermosensitive liposome (iTSL). MR contrast enhancement was achieved by the incorporation of a gadolinium lipid conjugate in the liposome bilayer along with a dye-labelled lipid for near infrared fluorescence bioimaging. The resulting iTSL were successfully loaded with SN-38 in the lipid bilayer and carboplatin in the aqueous core - allowing co-delivery of both. The iTSL demonstrated both thermosensitivity and MR-imageability. In addition, they showed effective local targeted co-delivery of carboplatin and SN-38 after triggered release with brief FUS treatments. A single dosage induced significant improvement of anti-tumour activity (over either the free drugs or the iTSL without FUS-activation) in triple negative breast cancer xenografts tumours in mice.

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice.

Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels for spatial mapping and tissue uptake tracking, providing key location and timing information for the application of an external stimulus to trigger drug release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach for treating small tissue volumes and is particularly effective at inducing drug release from thermosensitive nanocarriers. Here, we present a novel MR-imageable thermosensitive liposome (iTSL) for drug delivery to triple-negative breast cancers (TNBC). Methods: A macrocyclic gadolinium-based Magnetic Resonance Imaging (MRI) contrast agent was covalently linked to a lipid. This was incorporated at 30 mol% into the lipid bilayer of a thermosensitive liposome that was also encapsulating doxorubicin. The resulting iTSL-DOX formulation was assessed for physical and chemical properties, storage stability, leakage of gadolinium or doxorubicin, and thermal- or FUS-induced drug release. Its effect on MRI relaxation time was tested in phantoms. Mice with tumours were used for studies to assess both tumour distribution and contrast enhancement over time. A lipid-conjugated near-infrared fluorescence (NIRF) probe was also included in the liposome to facilitate the real time monitoring of iTSL distribution and drug release in tumours by NIRF bioimaging. TNBC (MDA-MB-231) tumour-bearing mice were then used to demonstrate the efficacy at retarding tumour growth and increasing survival. Results: iTSL-DOX provided rapid FUS-induced drug release that was dependent on the acoustic power applied. It was otherwise found to be stable, with minimum leakage of drug and gadolinium into buffers or under challenging conditions. In contrast to the usually suggested longer FUS treatment we identified that brief (~3 min) FUS significantly enhanced iTSL-DOX uptake to a targeted tumour and triggered near-total release of encapsulated doxorubicin, causing significant growth inhibition in the TNBC mouse model. A distinct reduction in the tumours' average T1 relaxation times was attributed to the iTSL accumulation. Conclusions: We demonstrate that tracking iTSL in tumours using MRI assists the application of FUS for precise drug release and therapy.

ADPKD-what the radiologist should know.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disorder and a leading cause of end stage renal failure (ESRF) affecting over 12 million people worldwide. Whilst the mainstay of diagnosis has historically favoured the imaging domain, the progression of disease was until very recently thought to be best monitored via biochemical analysis, i.e. measurement of estimated glomerular filtration rate. Imaging modalities such as sonography, CT and MRI have more recently proven to be key in monitoring disease progression. As much as half of the renal parenchyma can be lost with no real derangement in renal function. Tolvaptan, a vasopressin antagonist has been shown to slow disease progression and preserve renal function. Here we discuss at length the pathogenesis of ADPKD, the various diagnostic challenges surrounding its evaluation, new treatment options and monitoring of disease progression via serial imaging. We also propose monitoring of the efficacy of Tolvaptan at slowing the rate of deterioration in renal function in patients with ADPKD through MRI guided volumetric analysis of the kidneys.

Thermosensitive Liposome-Mediated Drug Delivery in Chemotherapy: Mathematical Modelling for Spatio-temporal Drug Distribution and Model-Based Optimisation.

Thermosensitive liposome-mediated drug delivery has shown promising results in terms of improved therapeutic efficacy and reduced side effects compared to conventional chemotherapeutics. In order to facilitate our understanding of the transport mechanisms and their complex interplays in the drug delivery process, computational models have been developed to simulate the multiple steps involved in liposomal drug delivery to solid tumours. In this study we employ a multicompartmental model for drug-loaded thermosensitive liposomes, with an aim to identify the key transport parameters in determining therapeutic dosing and outcomes. The computational model allows us to not only examine the temporal and spatial variations of drug concentrations in the different compartments by utilising the tumour cord concept, but also assess the therapeutic efficacy and toxicity. In addition, the influences of key factors on systemic plasma concentration and intracellular concentration of the active drug are investigated; these include different chemotherapy drugs, release rate constants and heating duration. Our results show complex relationships between these factors and the predicted therapeutic outcome, making it difficult to identify the "best" parameter set. To overcome this challenge, a model-based optimisation method is proposed in an attempt to find a set of release rate constants and heating duration that can maximise intracellular drug concentration while minimising systemic drug concentration. Optimisation results reveal that under the operating conditions and ranges examined, the best outcome would be achieved with a low drug release rate at physiological temperature, combined with a moderate to high release rate at mild hyperthermia and 1 h heating after injection.

Laser ablation of hepatocellular carcinoma--a review.

A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term outcome and complication rates of laser ablation is included and comparison with RFA made. The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.