MR Thermometry Research Articles

PRF thermometry during MR-guided focused ultrasound ablation in a preclinical thiel model

Proton Resonance Frequency (PRF) MR Thermometry is a useful method for treatment planning with MR-guided Focused Ultrasound (MRgFUS), as it provides accurate, real-time temperature maps. Thiel is an embalming medium that retains physical properties and life-like characteristics of human and animal tissue. The aim of the present study was to determine the accuracy of PRF Thermometry during MRgFUS and to estimate the value of PRF coefficient of pre-clinical Thiel embalmed human and animal tissue, and compare to fresh tissue and gel phantom.

The importance of phase drift correction for accurate MR thermometry in long duration MR-HIFU exposures

In MRI-guided high-intensity focused ultrasound (MR-HIFU) therapy, temperature-dependent proton resonance frequency (PRF) shift is a key factor to quantify and visualize the spatial heating pattern in treated and surrounding tissue. However, during treatment, multiple scanner-related changes can impact the accuracy of the temperature measurements obtained with the PRF shift method and cause an over/under estimation of temperature, which can be a major safety issue for treatments involving real-time temperature control. Hence, it is necessary to apply corrections to ensure accurate temperature measurements during heating. Prior to image acquisition, the central MR frequency F0 can be measured to adjust the F0 of next image acquisition. After acquisition, corrections can be applied to the acquired images to remove scanner-related influences, most importantly phase drift. Different phase drift correction algorithms such as conventional and polynomial adaptive drift correction estimate the background phase by fitting a linear or polynomial to the image phase outside the treatment area and perform the correction accordingly. The goal of this study was to understand the performance of these algorithms for long heating durations as would be experienced during hyperthermia or transurethral HIFU (>20 minutes).

MR bone imaging

Bone is highly relevant to focused ultrasound therapy, both as a potential treatment target and because it interferes with treatment of other organs such as the brain. It is challenging to image cortical bone using MRI, however, due to low water density and fast signal decay in bony tissues. Ultrashort echo time (UTE) imaging is a specialized MR technique that allows the weak, short-lived signal from cortical bone to be imaged despite these limitations. Potential applications of UTE bone imaging in MR-guided focused ultrasound include direct MR thermometry of bone heating, which is not possible using standard proton resonance shift (PRFS) techniques, and in situ skull imaging during brain treatment procedures, which could replace the separate CT scan currently required for transcranial focused ultrasound.

Performance analysis of a dedicated breast MR-HIFU system during ablation of breast tumors in patients

correction method was used to correct on-line for respiration-induced magnetic field fluctuations.[2] The performance of the correction method was assessed in absence of HIFU heating. The temporal standard deviation (SD) in temperature maps calculated before and after applying the correction method and the number of dynamics needed before switching to the intervention phase were used as a measure of performance. The targeting accuracy and precision of the system was assessed using MR thermometry data. For each sonication the trajectory of the center of mass of the heating pattern in the focal area over time was calculated. The standard deviation of the distribution of the distances between the center of mass in time and the mean center of mass was defined as precision. The distance between the mean center of mass and the planned treatment position was defined as accuracy.

MR-guided focused ultrasound for painful bone metastases: safety when combined with chemotherapy

Magnetic Resonance guided Focused Ultrasound (MRgFUS) is a non-invasive, non-ionizing treatment producing thermal ablation using high intensity focused ultrasound and MR thermometry to denervate pain from bone metastases. A recent phase III study comparing MRgFUS to sham treatment for a painful bone metastasis allowed patients to be treated with concurrent chemotherapy as long as the regimen was stable for at least 4 weeks. We performed a retrospective analysis of the safety of combination MRgFUS with active systemic chemotherapy in patients treated on this study.

MRI-guided transurethral ultrasound prostate ablation: midterm outcomes of a phase I clinical trial

MRI-guided transurethral ultrasound ablation (TULSA) is a new minimally-invasive modality for the treatment of prostate cancer, which aims to provide local disease control with low morbidity. A transurethral ultrasound device generates a continuous volume of thermal coagulation that is shaped precisely to the prostate using real-time MR thermometry and active temperature feedback control. The aim of this multi-center, prospective Phase I clinical study is to determine the safety and feasibility of MRI-guided TULSA, and to assess initial efficacy for treatment of localized prostate cancer.

An instrumented bone/soft tissue phantom designed to mimic HIFU treatments of bone

Clinically, HIFU exposures of bone are used to palliate pain from primary or secondary bone tumours. Such tumours weaken bone structure and render the patient susceptible to bone fracture. Ultrasound metrology for bone exposures is extremely challenging. The ultrasound beam is strongly reflected at the bone surface, with rapid surface absorption of sound entering the cortex. Pain relief is obtained when the HIFU induced temperature increase ablates the peri-osteal nerves. Standard PRF based MR thermometry, used for treatment monitoring, is inappropriate for bone. Thus, a method of determining the temperature distribution in a clinical environment is needed.

Optical measurement of skin temperature in MR-HIFU

MR-guided high-intensity focused ultrasound (MR-HIFU) treatments may cause skin heating in the vicinity of the treatment site. Current MR thermometry methods do not provide reliable measurements of skin temperature either during the sonication or during the cool-down periods between sonications. These technical challenges require additional pauses to decrease the likelihood of skin burns, thus impacting treatment duration. Therefore, quantitative, accurate, and rapid techniques are needed to measure surface skin temperature during HIFU treatment. This study aims to develop an optical method that detects temperature changes at the skin surface to maintain a safe skin temperature during treatment and to reduce pauses between sonications.

Assessing temperature dependence of T1 in cortical bone using ultrashort echo-time MRI

MR-guided high-intensity focused ultrasound (HIFU) ablation is a promising, noninvasive method for treatment of bone tumors and palliation of pain. During thermal therapy, temperature mapping is necessary to ensure proper heat deposition in targeted tumors as well as to prevent undesired heating in healthy tissues. However, conventional proton resonance frequency-based MR thermometry cannot be applied in cortical bone due to its short T2* relaxation time. Recently, it was shown that ultrashort echo-time MRI can be used to assess T1 change in cortical bone due to temperature change (Han M, ISMRM 2014, P262). This work focused on characterization of temperature dependence of T1 in cortical bone by performing a calibration experiment.

MR temperature imaging using PRF phase difference and a geometric model-based fat suppression method.

Because protons in fat do not exhibit a temperature-dependent frequency shift, proton resonance frequency shift (PRFS)-based MR thermometry always suffers from disturbances due to the presence of fats or lipids. A new fat suppression method for PRFS-based MR thermometry is proposed to obtain accurate variation of phase angle. Similar to the approach of separating fat and water with the two-point Dixon technique, we first scan a complex MR image for reference and then scan another complex image varying with temperature at the same TE point. Based on the conventional PRFS method, we use geometric relationships to remove the effect of fat on the variation of the phase angle. Two phantoms with different water-to-fat ratios are involved in the temperature mapping test. Experimental results show that the temperature images of two phantoms are approximated under the same conditions. The proposed fat suppression method is simple and effective for PRFS-based MR thermometry.

Evaluation of radiofrequency safety by high temperature resolution MR thermometry using a paramagnetic lanthanide complex.

The current practice of calculating the specific absorption rate (SAR) relies on local temperature measurements made using temperature probes. For an accurate SAR measurement, a temperature imaging method that provides high temperature sensitivity is desirable, because acceptable levels of SAR produce small temperature changes. MR thermometry using paramagnetic lanthanide complexes can be used to obtain absolute temperature measurements with sub-degree temperature and sub-millimeter spatial resolution. The aim of this study was to develop and evaluate a high temperature resolution MR technique to determine SAR. MR thermometry using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonate) (TmDOTP(5-)), which has an almost 10(2) times stronger chemical shift temperature dependence than water, was used to develop a novel method for SAR measurement. Three-dimensional temperature and SAR images were calculated using MR images acquired with a conventional gradient recalled echo sequence and SAR-intensive T1ρ sequence. Effects of the presence of conducting wire and increasing T1ρ spin-lock pulse duration were also examined. SAR distribution could be visualized clearly and surges associated with conducting wires and increasing pulse duration were identified clearly in the computed high spatial resolution SAR images. A novel method with high temperature sensitivity is proposed as a tool to evaluate radiofrequency safety in MRI.

Complications, Recovery, and Early Functional Outcomes and Oncologic Control Following In-bore Focal Laser Ablation of Prostate Cancer

From April 2013 to July 2014, 25 consecutive men participated in a longitudinal outcomes study following in-bore magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) of prostate cancer (PCa). Eligibility criteria were clinical stage T1c and T2a disease; prostate-specific antigen (PSA) <10 ng/ml; Gleason score <8; and cancer-suspicious regions (CSRs) on multiparametric MRI harboring PCa. CSRs harboring PCa were ablated using a Visualase cooled laser applicator system. Tissue temperature was monitored throughout the ablation cycle by proton resonance frequency shift magnetic resonance thermometry from phase-sensitive images. There were no significant differences between baseline and 3-mo mean American Urological Association Symptom Score or Sexual Health Inventory in Men scores. No man required pads at any time. Overall, the mean PSA decrease between baseline and 3 mo was 2.3 ng/ml (44.2%). Of 28 sites subjected to target biopsy after FLA, 26 (96%) showed no evidence of PCa. Our study provides encouraging evidence that excellent early oncologic control of significant PCa can be achieved following FLA, with virtually no complications or adverse impact on quality of life. Longer follow-up is required to show that oncologic control is durable. Patient summaryEarly results for focal laser ablation of prostate cancer are very encouraging. Until long-term oncologic control is demonstrated, focal laser ablation must be considered an investigational treatment option.

TU‐EF‐210‐05: A Fast and Efficient Method for Determining Coagulation Temperatures of Tissue‐Mimicking Thermal Therapy Gel Phantoms: Validated by Magnetic Resonance Thermometry

Purpose:To develop a simple and efficient method for determining coagulation temperatures of transparent thermal therapy gel phantoms. Tissue‐mimicking thermal therapy phantoms (TMTTPs) that coagulate at specific temperatures are valuable tools for developing and evaluating treatment strategies related to therapy using focused ultrasound, laser, microwave or radiofrequency ablation. The specific formula for a TMTTP will depend on the application and as such finding the coagulation temperature for a specific TMTTP is crucial.Methods:We used a previously published TMTTP formula with 2% (w/v) of bovine serum albumin as the temperature sensitive protein. Using the programmable heating settings of a polymerase chain reaction (PCR) machine we heated 50 µl gel samples to various temperatures for 3 min and imaged them to determine the coagulation temperature by quantifying the resulting opacity. These measured coagulation temperatures were then validated using high‐intensity focused ultrasound (HIFU) heating and magnetic resonance thermometry and T2 mapping using a clinical MR‐HIFU system.Results:The PCR heating method produced consistent and reproducible coagulation of the gel samples, and the coagulation temperature was determined by a 7.5% increase in opacity compared to non‐coagulated gel samples. The resulting coagulation temperatures for TMTTPs of increasing pH levels were found to be 43.6 ± 0.4 °C, 53.1 ± 0.8 °C and 60.1 ± 1.0 °C for a pH of 4.25, 4.50 and 4.75, respectively. The corresponding coagulation temperatures determined by MR thermometry were within the range of 50 to 55 °C for pH 4.50 and within 58 to 66 °C for pH 4.75.Conclusion:The PCR heating method provides a fast and reproducible measurement of the coagulation temperature of transparent TMTTPs. The temperatures determined using this method were well within the range of coagulation temperatures determined using the MR‐thermometry validation.Dr. Ari Partanen is a paid employee of Philips Healthcare

WE‐EF‐BRA‐12: Magnetic Resonance‐ Guided High‐Intensity Focused Ultrasound for Localized Ablation of Head and Neck Tissue Structures: A Feasibility Study in An Animal Model

Purpose:High‐intensity focused ultrasound (HIFU) ablation is feasible in the head and neck [1]. This study aims to expand upon these findings to assess the feasibility of treatment planning and monitoring via magnetic resonance imaging (MRI) guidance using a clinical MR‐guided HIFU platform.Methods:Two 31 kg pigs were anaesthetized, shaved, and positioned prone on the HIFU table (Sonalleve, Philips Healthcare, Vantaa, Finland). The necks were acoustically coupled to the integrated transducer using gel pads and degassed water. MR imaging verified acoustic coupling and facilitated target selection in the thyroid and thymus. Targets were thermally ablated with 130–200 W of acoustic power over a period of 16 s at a frequency of 1.2 MHz while being monitored through real‐time, multi‐planar MR‐thermometry. Contrast‐enhanced MR imaging was used to assess treatment efficacy. Post‐treatment, animals were euthanized and sonicated tissues were harvested for histology assessment.Results:MR‐thermometry, post‐contrast‐imaging, and gross pathology demonstrated that the system was capable of causing localized thermal ablation in both the thyroid and the thymus without damaging the aerodigestive tract. In one animal, superficial bruising was observed in the ultrasound beam path. Otherwise, there were no adverse events. Analysis of the tissue histology found regions of damage consistent with acute thermal injury at the targeted locations.Conclusion:It is feasible to use a clinical MR‐guided HIFU platform for extracorporeal ablation of porcine head and neck tissues. MR guidance and thermometry are sufficient to target and monitor treatment in the thyroid region, despite the presence of the inhomogeneous aerodigestive tract. Further study is necessary to assess efficacy and survival using a tumor model, and to examine what modifications should be made to the transducer positioning system and associated patient positioning aids to adapt it for clinical head and neck targets.Reference:[1] Esnault et al. (2011). Thyroid, 21(9), 965– 973.Funding support provided by Philips Healthcare. Ari Partanen is a paid employee of Philips Healthcare.

SU‐E‐J‐04: Integration of Interstitial High Intensity Therapeutic Ultrasound Applicators On a Clinical MRI‐Guided High Intensity Focused Ultrasound Treatment Planning Software Platform

Purpose:Interstitial high intensity therapeutic ultrasound (HITU) applicators can be used to ablate tissue percutaneously, allowing for minimally‐invasive treatment without ionizing radiation [1,2]. The purpose of this study was to evaluate the feasibility and usability of combining multielement interstitial HITU applicators with a clinical magnetic resonance imaging (MRI)‐guided focused ultrasound software platform.Methods:The Sonalleve software platform (Philips Healthcare, Vantaa, Finland) combines anatomical MRI for target selection and multi‐planar MRI thermometry to provide real‐time temperature information. The MRI‐compatible interstitial US applicators (Acoustic MedSystems, Savoy, IL, USA) had 1–4 cylindrical US elements, each 1 cm long with either 180° or 360° of active surface. Each applicator (4 Fr diameter, enclosed within a 13 Fr flexible catheter) was inserted into a tissue‐mimicking agar‐silica phantom. Degassed water was circulated around the transducers for cooling and coupling. Based on the location of the applicator, a virtual transducer overlay was added to the software to assist targeting and to allow automatic thermometry slice placement. The phantom was sonicated at 7 MHz for 5 minutes with 6–8 W of acoustic power for each element. MR thermometry data were collected during and after sonication.Results:Preliminary testing indicated that the applicator location could be identified in the planning images and the transducer locations predicted within 1 mm accuracy using the overlay. Ablation zones (thermal dose ≥ 240 CEM43) for 2 active, adjacent US elements ranged from 18 mm × 24 mm (width × length) to 25 mm × 25 mm for the 6 W and 8 W sonications, respectively.Conclusion:The combination of interstitial HITU applicators and this software platform holds promise for novel approaches in minimally‐invasive MRI‐guided therapy, especially when bony structures or air‐filled cavities may preclude extracorporeal HIFU.[1] Diederich et al. IEEE UFFFC 46.5 (1999): 1218.[2] Chopra et al. PMB 50.21 (2005): 4957.Funding support was provided by Philips Healthcare and in‐kind support from Acoustic MedSystems Inc. Ari Partanen is a paid employee of Philips Healthcare. Goutam Ghoshal and Everette Clif Burdette are paid employees of Acoustic MedSystems Inc.

High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles.

BackgroundDuring high-intensity focused ultrasound (HIFU) surgical procedures, there is a need to rapidly ablate pathological tissue while minimizing damage to healthy tissue. Current techniques are limited by relatively long procedure times and risks of off-target heating of healthy tissue. One possible solution is the use of microbubbles, which can improve the efficiency of thermal energy delivery during HIFU procedures. However, microbubbles also suffer from limitations such as low spatial selectivity and short circulation time in vivo. In this study, the use of a dual-perfluorocarbon nanodroplet that can enhance thermal ablation, yet retains high spatial selectivity and circulation half-life, was evaluated in vivo and compared to traditional microbubble agents during HIFU ablations of rat liver.MethodsHigh-intensity focused ultrasound (1.1 MHz, 4.1 MPa, 15-s continuous wave) was applied to rat liver in vivo, and heating was monitored during sonication by magnetic resonance thermometry. Thermometry data were analyzed to quantify temperature rise and ablated area, both at the target and prefocally, for HIFU applied 5, 15, or 95 min after intravenous injection of either nanodroplet or microbubble agents. Sham control experiments (no injected agents) were also performed.ResultsAt all three time points, nanodroplets significantly enhanced thermal delivery to the target, achieving temperatures 130 % higher and ablated areas 30 times larger than no-agent control sonications. Nanodroplets did not significantly enhance off-target surface heating. Microbubbles also resulted in significantly greater thermal delivery, but heating was concentrated at the proximal surface of the animal, causing skin burns. Furthermore, microbubbles resulted in lower thermal delivery to the desired target than even the control case, with the notable exception of the 95-min time point.ConclusionsResults indicate that the nanodroplet formulation studied here can substantially increase thermal delivery at the acoustic focus while avoiding prefocal heating. In contrast, microbubbles resulted in greater prefocal heating and less heating at the target. Furthermore, nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 h after injection. The use of a dual-perfluorocarbon nanodroplet formulation as described herein could substantially reduce HIFU procedure times without increasing the risk of skin burns.

Influence of water and fat heterogeneity on fat-referenced MR thermometry.

To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. The sphere experiment showed susceptibility-related errors of 8.4 °C and 0.2 °C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37 °C was 47.2 ± 21.6 °C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7 °C) yielded a maximum temperature error of 6.6 °C compared with 2.5 °C without fat referencing. Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors.

PO-0709: MRg-HIFU hyperthermia for recurrent rectal cancer: MR thermometry evaluation and preclinical validation

PO-0709: MRg-HIFU hyperthermia for recurrent rectal cancer: MR thermometry evaluation and preclinical validation

Quality of MR thermometry during palliative MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of bone metastases.

BackgroundMagnetic resonance (MR)-guided high-intensity focused ultrasound has emerged as a clinical option for palliative treatment of painful bone metastases, with MR thermometry (MRT) used for treatment monitoring. In this study, the general image quality of the MRT was assessed in terms of signal-to-noise ratio (SNR) and apparent temperature variation. Also, MRT artifacts were scored for their occurrence and hampering of the treatment monitoring.MethodsAnalyses were performed on 224 MRT datasets retrieved from 13 treatments. The SNR was measured per voxel over time in magnitude images, in the target lesion and surrounding muscle, and was averaged per treatment. The standard deviation over time of the measured temperature per voxel in MRT images, in the muscle outside the heated region, was defined as the apparent temperature variation and was averaged per treatment. The scored MRT artifacts originated from the following sources: respiratory and non-respiratory time-varying field inhomogeneities, arterial ghosting, and patient motion by muscle contraction and by gross body movement. Distinction was made between lesion type, location, and procedural sedation and analgesic (PSA).ResultsThe average SNR was highest in and around osteolytic lesions (21 in lesions, 27 in surrounding muscle, n = 4) and lowest in the upper body (9 in lesions, 16 in surrounding muscle, n = 4). The average apparent temperature variation was lowest in osteolytic lesions (1.2°C, n = 4) and the highest in the upper body (1.7°C, n = 4). Respiratory time-varying field inhomogeneity MRT artifacts occurred in 85% of the datasets and hampered treatment monitoring in 81%. Non-respiratory time-varying field inhomogeneities and arterial ghosting MRT artifacts were most frequent (94% and 95%) but occurred only locally. Patient motion artifacts were highly variable and occurred less in treatments of osteolytic lesions and using propofol and esketamine as PSA.ConclusionsIn this study, the general image quality of MRT was observed to be higher in osteolytic lesions and lower in the upper body. Respiratory time-varying field inhomogeneity was the most prominent MRT artifact. Patient motion occurrence varied between treatments and seemed to be related to lesion type and type of PSA. Clinicians should be aware of these observed characteristics when interpreting MRT images.Electronic supplementary materialThe online version of this article (doi:10.1186/s40349-015-0026-7) contains supplementary material, which is available to authorized users.

Radiation induced structural and magnetic transformations in nanoparticle MnxZn(1−x)Fe2O4 ferrites

Nanoparticle magnetic materials are suitable for multiple modern high end medical applications like targeted drug delivery, gene therapy, hyperthermia and MR thermometry imaging. Majority of these applications are confined to use of Mn–Zn ferrite nanoparticles. These nanoparticles are normally left in the body after their requisite application. Preparing these nanoparticles is usually a much involved job. However with the development of the simple technique MnxZn1−xFe2O4 nanoparticles could be prepared with much ease. The nanoparticles of MnxZn1−xFe2O4 with (x=1.0, 0.7, 0.5, 0.3, 0.0) were prepared and irradiated with gamma radiation of various intensities ranging between 500 R to 10,000 R, after appropriate structural and magnetic characterization. Irradiated samples were investigated for structural and magnetic properties, as well as for structural stability and cation distribution.The irradiated nanoparticles exhibited structural stability with varied cation distribution and magnetic properties, dependent on gamma radiation dose. Surprisingly samples also exhibited quenching of lattice parameter and particle size. The changes introduced in the cation distribution, lattice constant, particle size and magnetic properties were found to be irreversible with time lapse and were of permanent nature exhibiting good stability even after several months. Thus the useful properties of nanoparticles could be enhanced on modifying the cation distribution inside the nanoparticles by application of gamma radiation.