Senay Mihcin

Feasibility study of pre-clinical Thiel embalmed human cadaver for MR-guided focused ultrasound of the spine

Abstract Background Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive treatment option based on high acoustic absorption and minimal thermal conductivity of the bone to destroy nerves and reduce pain. There is lack of a preclinical validation tool with correct human anatomy. This work introduces usage of an ex-vivo Thiel embalmed human tissue model for preclinical verification of MRgFUS on intervertebral discs or bone metastases within the spinal body. Material and methods Thiel embalmed human cadaver was subjected to FUS sonication of the vertebra (with energies 250J, 420J, 600J) and the intervertebral disc (with energies 310J, 610J, 950J) of the lumbar spine for 20s of sonication under MR guidance. Results For the vertebra, maximum temperatures were recorded as 38 °C, 58.3 °C, 69 °C. The intervertebral disc reached maximum temperatures of 23.7 °C, 54 °C, 83 °C. The temperature measurements showed that the spinal canal and adjacent organs were not heated > 0.1 °C. Conclusions A heating pattern that can induce thermal ablation was achieved in the vertebral body and the intervertebral disc. Adjacent structures and nerves were not heated in lethal levels. Thus, the Thiel embalmed human cadaver can be a safe and efficient model for preclinical study of application of MRgFUS on the upper lumbar spine.

A focused ultrasound treatment system for moving targets (part I): generic system design and in-silico first-stage evaluation

BackgroundFocused ultrasound (FUS) is entering clinical routine as a treatment option. Currently, no clinically available FUS treatment system features automated respiratory motion compensation. The required quality standards make developing such a system challenging.MethodsA novel FUS treatment system with motion compensation is described, developed with the goal of clinical use. The system comprises a clinically available MR device and FUS transducer system. The controller is very generic and could use any suitable MR or FUS device. MR image sequences (echo planar imaging) are acquired for both motion observation and thermometry. Based on anatomical feature tracking, motion predictions are estimated to compensate for processing delays. FUS control parameters are computed repeatedly and sent to the hardware to steer the focus to the (estimated) target position. All involved calculations produce individually known errors, yet their impact on therapy outcome is unclear. This is solved by defining an intuitive quality measure that compares the achieved temperature to the static scenario, resulting in an overall efficiency with respect to temperature rise. To allow for extensive testing of the system over wide ranges of parameters and algorithmic choices, we replace the actual MR and FUS devices by a virtual system. It emulates the hardware and, using numerical simulations of FUS during motion, predicts the local temperature rise in the tissue resulting from the controls it receives.ResultsWith a clinically available monitoring image rate of 6.67 Hz and 20 FUS control updates per second, normal respiratory motion is estimated to be compensable with an estimated efficiency of 80%. This reduces to about 70% for motion scaled by 1.5. Extensive testing (6347 simulated sonications) over wide ranges of parameters shows that the main source of error is the temporal motion prediction. A history-based motion prediction method performs better than a simple linear extrapolator.ConclusionsThe estimated efficiency of the new treatment system is already suited for clinical applications. The simulation-based in-silico testing as a first-stage validation reduces the efforts of real-world testing. Due to the extensible modular design, the described approach might lead to faster translations from research to clinical practice.

Evidence-based cross validation for acoustic power transmission for a novel treatment system

Abstract Introduction: The novel Trans-Fusimo Treatment System (TTS) is designed to control Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy to ablate liver tumours under respiratory motion. It is crucial to deliver the acoustic power within tolerance limits for effective liver tumour treatment via MRgFUS. Before application in a clinical setting, evidence of reproducibility and reliability is a must for safe practice. Materials and methods: The TTS software delivers the acoustic power via ExAblate-2100 Conformal Bone System (CBS) transducer. A built-in quality assurance application was developed to measure the force values, using a novel protocol to measure the efficiency for the electrical power values of 100 and 150W for 6s of sonication. This procedure was repeated 30 times by two independent users against the clinically approved ExAblate-2100 CBS for cross-validation. Results: Both systems proved to deliver the power within the accepted efficiency levels (70–90%). Two sample t-tests were used to assess the differences in force values between the ExAblate-2100 CBS and the TTS (p > 0.05). Bland-Altman plots were used to demonstrate the limits of agreement between the two systems falling within the 10% limits of agreement. Two sample t-tests indicated that TTS does not have user dependency (p > 0.05). Conclusions: The TTS software proved to deliver the acoustic power without exceeding the safety levels. Results provide evidence as a part of ISO13485 regulations for CE marking purposes. The developed methodology could be utilised as a part of quality assurance system in clinical settings; when the TTS is used in clinical practice.

THE DETERMINATION of the VOLUMETRIC WEAR for SURGICALLY RETRIEVED HIP IMPLANTS BASED on CMM

The effects of wear mechanisms on the long-term survivorship of artificial hip implants emphasized the importance of determining the 3D volumetric wear in retrieved hip replacements. Traditional methods for determining the volumetric wear on acetabular cups require reference surface from a pre-worn model, which is not feasible for clinical retrieved implants. In this study, a methodology based on co-ordinate measuring machine (CMM) measurement is proposed to reconstruct the reference surface by applying a mathematical model on those selected unworn regions of the acetabular liners. For validation purposes, three polyethylene liners from 5-million-cycle hip simulator testing were employed, whose wear volume at different measurement points was determined by applying the developed method and the results were compared to those determined via traditional approaches. Volumetric loss estimated by the developed method was found to correlate well with the results estimated by the traditional methods (R2=0.9949). Moreover, two surgically retrieved inserts were analyzed using the developed methodology. The wear volume estimated from the two retrieved liners was also found to agree well with the observation from X-ray photograph. Results demonstrated that the proposed method is effective in determining the volumetric wear for retrieved components providing viable unworn regions on the liner.

Reference-less MR thermometry on pre-clinical thiel human cadaver for liver surgery with MRgFUS

Abstract Purpose: Reference-less MR thermometry can be a promising technique for temperature mapping during liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS), as it is more robust to breathing motion than Proton Resonance Frequency MR thermometry. However, there is a lack of a pre-clinical model for repeatable testing of reference-less thermometry. The purpose of this work was to verify the explanted Thiel embalmed human liver and whole Thiel embalmed human cadaver for application of a custom made reference-less thermometry algorithm during MRgFUS sonication. Material and methods: Phase maps were generated during sonication as an input to the algorithm. A square Region-of-Interest (ROI) was designed around the heated area. The ROI was interpolated using a two-dimensional polynomial to the surrounding phase map to calculate the background phase. Results: Using the phase information from the images, the temperature rise was measured. Validation of the methodology showed accordance of temperatures with actual temperatures. Conclusions: The explanted liver and the whole cadaver constitute a promising and feasible model to study reference-less techniques for thermometry during MRgFUS, before clinical trials.

Principles of focused ultrasound

Abstract Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by delivering a sufficiently high level of acoustic energy in situ of the human body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided (USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for monitoring purposes. The principles and technologies of FUS/HiFU are described in this paper including the basics of MR guidance techniques and MR temperature mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the treatment of various benign and few malignant lesions in the last two decades. Current technical limitations of ultrasound guided and MRI guided Focused Ultrasound, as well as adverse effects for the application of this technique are outlined including challenges of ablating moving organs (liver and kidney). An outlook to possible applications is provided; exampling clinical trials discussing future options.

Acoustic characterization of Thiel liver for magnetic resonance-guided focused ultrasound treatment

Abstract Background: The purpose of this work was to measure the essential acoustic parameters, i.e., acoustic impedance, reflection coefficient, attenuation coefficient, of Thiel embalmed human and animal liver. The Thiel embalmed tissue can be a promising, pre-clinical model to study liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Material and methods: Using a single-element transducer and the contact pulse-echo method, the acoustic parameters, i.e., acoustic impedance, reflection coefficient and attenuation coefficient of Thiel embalmed human and animal liver were measured. Results: The Thiel embalmed livers had higher impedance, similar reflection and lower attenuation compared to the fresh tissue. Conclusions: Embalming liver with Thiel fluid affects its acoustic properties. During MRgFUS sonication of a Thiel organ, more focused ultrasound (FUS) will be backscattered by the organ, and higher acoustic powers are required to reach coagulation levels (temperatures >56 °C).

Spinal curvature for the assessment of spinal stability

Posture is one of the most important factors in spinal stability. To investigate the spinal instability, a tool was developed using the Thrustline theory. A pilot postural data pool was formed from a sample population of 40 healthy males and females for this computational model by using a device called Spinal Mouse® (SM) to record the relative positions of the vertebral bodies firstly. Then, the 2D coordinates of the vertebral bodies were calculated by an in-house developed code. Students t-tests showed significance of difference between the postures was mostly higher for X coordinates with p-value of <0.01 and with p-value of <0.05 for Y coordinates. The postural differences between the genders indicated that a pilot database is required while developing a tool for assessing the spinal stability for each gender. Flow chart demonstrated the feasibility of the application. For clinical applications, combination of the developed software with electromyography (EMG) was recommended.

Ultrasound tracked motion compensated focused ultrasound system evaluated on ex vivo ovine livers

The application of FUS in abdominal organs such as the liver or the kidneys is impeded by a number of complications. One of the most challenging is organ motion due to breathing. To achieve ablation in a target within a moving organ the FUS system has to be steered to focus on the same anatomical position. We present a prototypical system that tracks the motion of an ex vivo ovine liver via diagnostic ultrasound (US) and adjusts the focal spot to a fixed anatomical position.

US-tracked steered FUS in a respiratory ex vivo ovine liver phantom

Abstract Organ motion is a major problem for Focused Ultrasound Surgery (FUS) of liver tumors. We present a liver phantom mimicking human respiratory motion (20 mm range, 3 − 7 s/cycle) and the evaluation of an ultrasound-tracked steered FUS system on that phantom. Temperature curves are recorded while sonicating in moving and static phantom. The temperature curves correlate well and show the ability of the system to compensate breathing like motion.