Benjamin F. Cox

Wireless MR tracking of interventional devices using phase-field dithering and projection reconstruction

PURPOSE Device tracking is crucial for interventional MRI (iMRI) because conventional device materials do not contribute to the MR signal, may cause susceptibility artifacts and are generally invisible if moved out of the scan plane. A robust method for wireless tracking and dynamic guidance of interventional devices equipped with wirelessly connected resonant circuits (wRC) is presented. METHODS The proposed method uses weak spatially-selective excitation pulses with very low flip angle (0.3°), a Hadamard multiplexed tracking scheme and employs phase-field dithering to obtain the 3D position of a wRC. RF induced heating experiments (ASTM protocol) and balloon angioplasties of the iliac artery were conducted in a perfused vascular phantom and three Thiel soft-embalmed human cadavers. RESULTS Device tip tracking was interleaved with various user-selectable fast pulse sequences receiving a geometry update from the tracking kernel in less than 30ms. Integrating phase-field dithering significantly improved our tracking robustness for catheters with small diameters (4-6 French). The volume root mean square distance error was 2.81mm (standard deviation: 1.31mm). No significant RF induced heating (<0.6°C) was detected during heating experiments. CONCLUSION This tip tracking approach provides flexible, fast and robust feedback loop, intuitive iMRI scanner interaction, does not constrain the physician and delivers very low specific absorption rates. Devices with wRC can be exchanged during a procedure without modifications to the iMRI setup or the pulse sequence. A drawback of our current implementation is that position information is available for a single tracking coil only. This was satisfactory for balloon angioplasties of the iliac artery, but further studies are required for complex navigation and catheter shapes before animal trials and clinical application.

Microultrasound characterisation of ex vivo porcine tissue for ultrasound capsule endoscopy

Gastrointestinal (GI) disease development and progression is often characterised by cellular and tissue architectural changes within the mucosa and sub-mucosa layers. Current clinical capsule endoscopy and other approaches are heavily reliant on optical techniques which cannot detect disease progression below the surface layer of the tissue. To enhance the ability of clinicians to detect cellular changes earlier and more confidently, both quantitative and qualitative microultrasound (μUS) techniques are investigated in healthy ex vivo porcine GI tissue. This work is based on the use of single-element, focussed μUS transducers made with micromoulded piezocomposite operating at around 48 MHz. To explore the possibility that μUS can detect Crohns disease and other inflammatory bowel diseases, ex vivo porcine small bowel tissue samples were cannulised and perfused with phosphate-buffered saline followed by various dilutions of polystyrene microspheres. Comparison with fluorescent imaging showed that the microspheres had infiltrated the microvasculature of the samples and that μUS was able to successfully detect this as a mimic of inflammation. Samples without microspheres were analysed using quantitative ultrasound to assess mechanical properties. Attenuation coefficients of 1.78 ± 0.66 dB/mm and 1.92 ± 0.77 dB/mm were obtained from reference samples which were surgically separated from the muscle layer. Six intact samples were segmented using a software algorithm and the acoustic impedance, Z, for varying tissue thicknesses, and backscattering coefficient, BSC, were calculated using the reference attenuation values and tabulated.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.

Progress towards a multi-modal capsule endoscopy device featuring microultrasound imaging

Current clinical standards for endoscopy in the gastrointestinal (GI) tract combine high definition optics and ultrasound imaging to view the lumen superficially and through its thickness. However, these instruments are limited to the length of an endoscope and the only clinically available, autonomous devices able to travel the full length of the GI tract easily offer only video capsule endoscopy (VCE). Our work seeks to overcome this limitation with a device (“Sonopill”) for multimodal capsule endoscopy, providing optical and microultrasound (μUS) imaging and supporting sensors1.μUS transducers have been developed with multiple piezoelectric materials operating across a range of centre frequencies to study viability in the GI tract. Because of the combined constraints of μUS imaging and the low power / heat tolerance of autonomous devices, a hybrid approach has been taken to the transducer design, with separate transmit and receive arrays allowing multiple manufacturing approaches to maximise system efficiency. To explore these approaches fully, prototype devices have been developed with PVDF, high-frequency PZT and PMN-PT composites, and piezoelectric micromachined ultrasonic transducer arrays. Test capsules have been developed using 3D printing to investigate issues including power consumption, heat generation / dissipation, acoustic coupling, signal strength and capsule integrity. Because of the high functional density of the electronics in our proposed system, application specific integrated circuits (ASICs) have been developed to realise the ultrasound transmit and receive circuitry along with white-light and autofluorescence imaging with singlephoton avalanche detectors (SPADs). The ultrasound ASIC has been developed and the SPAD electronics and optical subsystem have been validated experimentally. The functionality of various transducer materials.

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions: an iliac angioplasty exemplar case study

PurposeA methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics.MethodsThree clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages’ durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated.ResultsSignificant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries.ConclusionsThis work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education.

Luminally expressed gastrointestinal biomarkers

ABSTRACT Introduction: A biomarker is a measurable indicator of normal biologic processes, pathogenic processes or pharmacological responses. The identification of a useful biomarker is challenging, with several hurdles to overcome before clinical adoption. This review gives a general overview of a range of biomarkers associated with inflammatory bowel disease or colorectal cancer along the gastrointestinal tract. Areas covered: These markers include those that are already clinically accepted, such as inflammatory markers such as faecal calprotectin, S100A12 (Calgranulin C), Fatty Acid Binding Proteins (FABP), malignancy markers such as Faecal Occult Blood, Mucins, Stool DNA, Faecal microRNA (miRNA), other markers such as Faecal Elastase, Faecal alpha-1-antitrypsin, Alpha2-macroglobulin and possible future markers such as microbiota, volatile organic compounds and pH. Expert commentary: There are currently a few biomarkers that have been sufficiently validated for routine clinical use at present such as FC. However, many of these biomarkers continue to be limited in sensitivity and specificity for various GI diseases. Emerging biomarkers have the potential to improve diagnosis and monitoring but further study is required to determine efficacy and validate clinical utility.

Ultrasound capsule endoscopy: sounding out the future

Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently.

Ultrasound facilitated marking of gastrointestinal tissue with fluorescent material

The epithelial lining of the gastrointestinal (GI) mucosal layer is an effective barrier to the contents of the gut lumen. Selective channels and tight junctions prevent contamination of the sterile internal environment of the body. Conversely, the gut barrier also prevents desired agents from entering the GI tissue. This hinders marking of tissue for further clinical follow-up. Focused ultrasound (US) may provide a potential means of overcoming the gut barrier and allowing penetration of material beyond it which was explored in a series of tests. Experiments were carried out on 14 individual postmortem-obtained murine small bowel samples for a total of 23 sonication/control paired tests. A favourable result of 80% indicated that focused US can pass a nanoscale fluorescent agent through the gut barrier. Further work is required to elucidate where the agent resides, intercellular or intracellular, post-sonication.

Preclinical feasibility of a technology framework for MRI-guided iliac angioplasty

PurposeInterventional MRI has significant potential for image guidance of iliac angioplasty and related vascular procedures. A technology framework with in-room image display, control, communication and MRI-guided intervention techniques was designed and tested for its potential to provide safe, fast and efficient MRI-guided angioplasty of the iliac arteries.MethodsA 1.5-T MRI scanner was adapted for interactive imaging during endovascular procedures using new or modified interventional devices such as guidewires and catheters. A perfused vascular phantom was used for testing. Pre-, intra- and post-procedural visualization and measurement of vascular morphology and flow was implemented. A detailed analysis of X-ray fluoroscopic angiography workflow was conducted and applied. Two interventional radiologists and one physician in training performed 39 procedures. All procedures were timed and analyzed.ResultsMRI-guided iliac angioplasty procedures were successfully performed with progressive adaptation of techniques and workflow. The workflow, setup and protocol enabled a reduction in table time for a dedicated MRI-guided procedure to 6 min 33 s with a mean procedure time of 9 min 2 s, comparable to the mean procedure time of 8 min 42 s for the standard X-ray-guided procedure.ConclusionsMRI-guided iliac vascular interventions were found to be feasible and practical using this framework and optimized workflow. In particular, the real-time flow analysis was found to be helpful for pre- and post-interventional assessments. Design optimization of the catheters and in vivo experiments are required before clinical evaluation.

Ex vivo ovine liver model simulating respiratory motion and blood perfusion for validating image-guided HIFU systems.

The effect of moving organs and blood perfusion on image guided procedures such as focused ultrasound is challenging therefore we have developed ex vivo ovine liver phantoms to simulate respiratory motion and blood perfusion. The simulator was used to validate ultrasound image-guided HIFU treatment when the target tissue was moving.