Sonication methods and motion compensation for magnetic resonance guided high-intensity focused ultrasound

High-intensity focused ultrasound (HIFU) is an efficient noninvasive therapeutic technique for localized heating of tissues deep within the human body through intact skin. Magnetic resonance imaging (MRI) can provide excellent soft-tissue contrast and can be used for both treatment planning and post-treatment assessment of the induced tissue damage. MRI can also provide temperature sensitive in vivo images via proton resonance frequency shift thermometry. Combined, the use of MRI and HIFU (MR-HIFU) ablation make for a promising therapeutic modality for controlled and noninvasive selective tissue destruction. Sonication strategies, MR thermometry methods, feedback control, and motion compensation for MR-HIFU were developed and evaluated in this thesis. The primary aim of the thesis was to develop a safe and efficient strategy for clinical MR-HIFU ablation. An efficient volumetric method of ablation was achieved by utilizing the phased-array capabilities of the transducer and the inherent heat diffusion of already deposited heat. The induced temperature rise was monitored with rapid multiplane MR thermometry with a volumetric coverage of the heated region. Acquisition and display of temperature images during sonication improved the safety of the therapy. The therapeutic procedure was evaluated in a large animal model and proved to provide a substantial improvement in efficiency as compared to existing methods without compromising safety. The second aim was to improve the reliability of the proposed volumetric sonication strategy. This was achieved with a simple and robust binary feedback algorithm that adjusted the sonication duration of each part of the sonication trajectory based on the temperature rise as obtained by volumetric MR thermometry. The feedback algorithm was evaluated in a large animal model, and was found to reduce the variability in thermal lesion size by approximately 70%. The third aim was to develop a through-plane motion correction method for real-time MR thermometry without disturbing thermometry. This was achieved with a fat-selective navigator. This navigator outperformed the conventional navigator for direct tracking of the kidney under free breathing. The navigator also provided accurate indexing of the look-up-table used to correct the reference phase for MR thermometry of mobile organs. Finally, the combination of through-plane motion correction provided by the fat-selective navigator with existing methods of in-plane motion correction and reference phase correction, allowed for an accurate 3D motion compensation of both MR thermometry and MR-HIFU sonication

Generation of treatment plans for Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) in the liver

In this thesis, the self-scanning method is proposed to handle organ motion. It takes advantage of the perpetual respiratory motion to passively scan the tumor. In other words, we are placing the static focal point of the HIFU into the tumor. The motion caused by breathing shifts the tumor through this focal point. We anticipate at which time point tumor tissue is located under the focal spot and modulate the HIFU intensity based on this information. Once the tumor has been ablated along the self-scanned trajectory, the focal spot is relocated to a different but static position within the body. With this method, we combine the advantages of the gating and the tracking method: a HIFU device with a fixed focus can be used and a high duty cycle is achieved. Moreover, since with the self-scanning approach no lateral steering of the focal spot is required, fewer secondary lobes are generated and position-dependent decay of the focal spot intensity during lateral steering is avoided. However, this comes at the cost of an increased complexity at the planning stage

Design and development of magnetic resonance imaging (MRI) compatible tissue mimicking phantoms for evaluating focused ultrasound thermal protocols

Animal models are often used to test the efficacy and safety of clinical applications employing focused ultrasound that range in various stages of research, development and commercialization. The animals are usually subjected to conditions that cause pain, distress and euthanasia. Access to cadaveric models is not easy and affordable for all research institutions, whereas conservation and changes of their physical properties over time can be a delimiting factor for translational research. The above set the motivation for this project, which its primary objective is to design and develop appropriate tissue mimicking phantoms using a simplistic and cost effective methodology. These phantoms are expected to contribute in reducing the need for animal testing and allow researchers to get hands experience with tools that will promote and accelerate testing in focused ultrasound thermal protocols. The main requirements for these phantoms are to be geometrically accurate, compatible with magnetic resonance imaging (MRI) and to be composed of materials that approximate the acoustic and thermal properties of the replicated tissues. Throughout the duration of the project three ultrasonic composite phantoms (head, femur bone-muscle and breast-rib) were developed. The acoustic properties of candidate materials were assessed using pulse-echo immersion and through transmission techniques. The thermal properties were estimated by observing the rate of heat diffusion following a sonication in the soft tissue parts with MR thermometry. Acrylonitrile butadiene styrene (ABS) was used to replicate bone tissue, where its acoustic attenuation coefficient was found to be 16.01 ± 6.18 dB/cm at 1 MHz and the speed of sound at 2048 ± 79 m/s. Soft tissue parts consisted out of agar-based gels doped with varying concentrations of additives that controlled the relative contribution of acoustic absorption (evaporated milk) and scatter (silica dioxide) to total attenuation independently. Brain tissue phantom (2 % w/v agar - 1.2 % w/v SiO2 - 25 % v/v evaporated milk) matched an attenuation coefficient of 0.59 ± 0.05 dB/cm-MHz whereas muscle and breast mimicking phantom (2 % w/v agar - 2 % w/v SiO2 - 40 % v/v evaporated milk) were estimated of inducing an attenuation coefficient of the order of 0.99 ±0.08 dB/cm-MHz. The speed of sound for the brain and muscle/breast recipe were estimated at 1485 ± 12 m/s and 1529 ± 13 m/s respectively. The thermal conductivity of the brain phantom was estimated to be 0.52 ± 0.06 W/mº-C and 0.57 ± 0.10 W/mº-C for the muscle/breast phantom. The acoustic and thermal properties of candidate materials were within range of the replicated tissues extracted from literature, except the speed of sound in ABS compared which was lower compared to bone (~3000 m/s). Three dimensional models of bone parts (skull, femur, rib) were reconstructed in Standard Tessellation Language (STL) format by segmenting bony tissue of interest from adult human computed tomography (CT) images. The STL bone models were 3D printed in ABS using a fused deposition modelling (FDM) machine. The final composite phantoms were fabricated by molding the agar based soft tissue phantoms inside/around the ABS bone phantoms. The functionality of all three composite phantoms was assessed with focused ultrasound sonications applied by a 1 MHz single element transducer while temperature was monitored with 1.5 Tesla MRI scanner. A spoiled gradient recalled (SPGR) pulse sequence was used to produce phase images that were analyzed using a custom coded software developed in Matlab that employed proton-resonance frequency shift (PRFS) thermometry

A Framework for Temperature Imaging using the Change in Backscattered Ultrasonic Signals

Hyperthermia is a cancer treatment that elevates tissue temperature to 40 to 43oC. It would benefit from a non-invasive, safe, inexpensive and convenient thermometry to monitor heating patterns. Ultrasound is a modality that meets these requirements. In our initial work, using both prediction and experimental data, we showed that the change in the backscattered energy: CBE) is a potential parameter for TI. CBE, however, was computed in a straightforward yet ad hoc manner. In this work, we developed and exploited a mathematical representation for our approach to TI to optimize temperature accuracy. Non-thermal effects of noise and motion confound the use of CBE. Assuming additive white Gaussian noise, we applied signal averaging and thresholding to reduce noise effects. Our motion compensation algorithms were also applied to images with known motion to evaluate factors affecting the compensation performance. In the framework development, temperature imaging was modeled as a problem of estimating temperature from the random processes resulting from thermal changes in signals. CBE computation was formalized as a ratio between two random variables. Mutual information: MI) was studied as an example of possible parameters for temperature imaging based on the joint distributions. Furthermore, a maximum likelihood estimator: MLE) was developed. Both simulations and experimental results showed that noise effects were reduced by signal averaging. The motion compensation algorithms proved to be able to compensate for motion in images and were improved by choosing appropriate interpolation methods and sample rates. For images of uniformly distributed scatterers, CBE and MI can be computed independent of SNR to improve the temperature accuracy. The application of the MLE also showed improvements in temperature accuracy compared to the energy ratio from the signal mean in simulations. The application of the framework to experimental data requires more work to implement noise reduction approaches in 3D heating experiments. The framework identified ways in which we were able to reduce the effects of both noise and motion. The framework formalized our approaches to temperature imaging, improved temperature accuracy in simulations, and can be applied to experimental data if the noise reduction approaches can be implemented for 3D experiments

Nasopharyngeal method for selective brain cooling and development of a time-resolved near-infrared technique to monitor brain temperature and oxidation status during hypothermia

Mild hypothermia at 32-35oC (HT) has been shown to be neuroprotective for neurological emergencies following severe head trauma, cardiac arrest and neonatal asphyxia. However, HT has not been widely deployed in clinical settings because: firstly, cooling the whole body below 33-34°C can induce severe complications; therefore, applying HT selectively to the brain could minimize adverse effects by maintaining core body temperature at normal level. Secondly, development of an effective and easy to implement selective brain cooling (SBC) technique, which can quickly induce brain hypothermia while avoiding complications from whole body cooling, remains a challenge. In this thesis, we studied the feasibility and efficiency of selective brain cooling (SBC) through nasopharyngeal cooling. To control the cooling and rewarming rate and because core body temperature is different from brain temperature, we also developed a non-invasive technique based on time-resolved near infrared spectroscopy (TR-NIRS) to measure local brain temperature. In normal brain, cerebral blood flow (CBF) and energy metabolism as reflected by the cerebral metabolic rate of oxygen (CMRO2) is tightly coupled leading to an oxygen extraction efficiency (OEF) of around ~33%. A decoupling of the two as in ischemia signifies oxidative stress and would lead to an increase in OEF beyond the normal value of ~33%. The final goal of this thesis is to evaluate TR-NIRS methods for measurements of CBF and CMRO2 to monitor for oxidative metabolism in the brain with and without HT treatment. Chapter 2 presents investigations on the feasibility and efficiency of the nasopharyngeal SBC by blowing room temperature or humidified cooled air into the nostrils. Effective brain cooling at a median cooling rate of 5.6 ± 1.1°C/hour compared to whole body cooling rate of 3.2 ± 0.7 was demonstrated with the nasopharyngeal cooling method. Chapter 3 describes TR-NIRS experiments performed to measure brain temperature non-invasively based on the temperature-dependence of the water absorption peaks at ~740 and 840nm. The TR-NIRS method was able to measure brain temperature with a mean difference of 0.5 ± 1.6°C (R2 = 0.66) between the TR-NIRS and thermometer measurements. Chapter 4 describes the TR-NIR technique developed to measure CBF and CMRO2 in a normoxia animal model under different anesthetics at different brain temperatures achieved by whole-body cooling. Both CBF and CMRO2 decreased with decreasing brain temperature but the ratio CMRO2:CBF (OEF) remained unchanged around the normal value of ~33%. These results demonstrate that TR-NIR can be used to monitor the oxidative status of the brain in neurological emergencies and its response to HT treatment. In summary, this thesis has established a convenient method for selective brain cooling without decreasing whole body temperature to levels when adverse effects could be triggered. TR-NIRS methods are also developed for monitoring local brain temperature to guide SBC treatment and for monitoring the oxidation status of the brain as treatment progresses

Ex-vivo evaluation of MR-thermometry at 0.2 and 1.5 T

Ziel der Arbeit war die Verifizierung der MR-Thermometrie mit verschiedenen MR Sequenzen für die laserinduzierte Thermotherapie mittels fluoroptischer Temperaturmessung bei 0,2 und 1,5 Tesla, bei Temperaturen bis 80 Grad Celsius. Bei ex-vivo Schweineleber und Agarose-Phantomen wurde unter MR-Bildgebung eine laserinduzierte Thermotherapie (LITT) durchgeführt. Die Messungen erfolgten pro Tomograph mit zwei verschiedenen Empfangsspulen. Die Temperaturdarstellung basierte auf der Änderung der Protonenresonanzfrequenz (PRF) und der longitudinalen Relaxationszeit (T1). Die PRF wurde mit vier verschiedenen MR-Sequenzen gemessen: zwei Gradientenecho-Sequenzen (FLASH), einer TurboFLASH- und einer Multiecho-TRUFI-Sequenz. Bei der T1-Methode wurden ebenfalls vier verschiedene MR-Sequenzen eingesetzt: eine konventionelle Gradientenecho-Sequenz (FLASH), eine TrueFISP-Sequenz (TRUFI), eine Saturation Recovery Turbo-FLASH-Sequenz (SRTF) und eine Inversion Recovery Turbo-FLASH-Sequenz (IRTF). Die Temperatur wurde mit einem faseroptischen Thermometer kontrolliert und mit der MRT-Temperatur korreliert. Es wurde eine gute lineare Korrelation zwischen der am MRT geschätzten und der faseroptisch gemessenen Temperatur erreicht. Bei 1,5 Tesla unter Einsatz einer Kopfspule erwies sich bei Messungen an der Schweineleberprobe PRF-FLASH von Siemens mit einer mittleren Temperaturabweichung von 5,09°C als optimal. Mit einem Bodyarray ergab hier IRTF die präzisesten Temperaturbestimmungen mit einer mittleren Abweichung von 8,02°C. Die Genauigkeiten und die Linearitäten von SRTF und PRF-TFL unterschieden sich davon nur geringfügig, sie können also als gleichwertig betrachtet werden. Bei 0,2 Tesla mit einer Kopfspule ergab die Messung mit SRTF mit 6,4°C die geringste mittlere Temperaturabweichung, mit einer Multipurpose-Coil erwiesen sich TRUFI und FLASH als optimal mit einer mittleren Temperaturabweichung von 15,62°C. bzw. 14,48°C. Mit den erreichten Temperaturgenauigkeiten kann der Thermoeffekt der LITT in Echtzeitnähe kontrolliert werden. Bei 1,5 T sind PRF-FLASH oder TFL aufgrund der Exaktheit und der Gewebeunabhängigkeit vorzuziehen. PRF-TRUFI mit einer Akquisitionszeit von 1,09 s ist die schnellste implementierte Sequenz. Bei 0,2 T sind die T1-Sequenzen genauer.The purpose of this work was the evaluation of thermometry with fast MR sequences for the laser induced interstitial laser therapy (LITT) and verification of the thermometric results with a fiber-optic thermometer. The methods were evaluated at 0.2 and 1.5 Tesla with two MR-coils for each scanner. In vitro experiments were performed by use of an agarose gel mixture and lobes of pig liver. Thermometry was performed by the means of longitudinal relaxation time T1 and the proton resonance frequency shift (PRF) methods under acquisition of amplitude and phase shift images. PRF was measured with four sequences: two fast spoiled GRE sequences, a TurboFLASH sequence and a multiecho TrueFisp sequence. Four different sequences were used for T1 thermometry: a gradient echo (GE), a TrueFISP (TRUFI), a Saturation Recovery Turbo-FLASH (SRTF) and a Inversion Recovery Turbo-FLASH (IRTF) sequence. Temperature was controlled using a fiber-optic Luxtron device and correlated with the MR-temperature. The temperature dependence showed a good linear relationship. The following results were achieved with porcine liver samples: At 1.5 T PRF-FLASH showed to be most accurate (deviation 5.09°C) when using the headcoil. With the body array the IRTF sequence was most accurate with a temperature deviation of 8.02°C. SRTF and PRF-TFL were very similar in accuracy. The prf-TRUFI Sequence was the fastest one with an acquisition time of 1.09 s. At 0.2 T with a headcoil the SRTF sequence was superior with a temperature deviation of 6.4°C. With a multipurpose coil accuracy was best when using the TRUFI or SRTF sequence (deviation 15.62 and 14.48°C). The accuracy and the speed of the temperature measurements are sufficient for controlling the coagulation of tumours. For 1.5 T PRF-FLASH or RPF-TFL are the methods of choice as they show the best linear correlations with fiber-optic temperature. At 0.2 T the $T_1$ sequences are to be preferred

Evaluation of acoustic noise in magnetic resonance imaging

Magnetic resonance imaging (MRI) is a technique in which strong static and dynamic magnetic fields are used to create virtual slices of the human body. The process of MR imaging is associated with several health and safety issues which may negatively affect patient and radiological health workers. Potentially hazardous are biological effects of both the static and dynamic magnetic fields, the torques of the magnetic fields acting on ferromagnetic objects, thermal effects, and the negative effects of high acoustic sound pressures. The subject of this dissertation is the evaluation and modification of acoustic noise generated during MRI