Referenceless MR thermometry during canine prostate ablation

The single reference variable flip angle sequence with a multi-echo stack of stars acquisition (SR-VFA-SoS) simultaneously measures temperature change using proton resonance frequency (PRF) shift and T1-based thermometry methods. This work evaluates SR-VFA-SoS thermometry in MR-guided focused ultrasound in an in vivo rabbit model. Simultaneous PRF shift thermometry and T1-based thermometry were obtained in a New Zealand white rabbit model (n = 7) during MR-guided focused ultrasound surgery using the SR-VFA-SoS sequence at 3 T. Distinct locations in muscle (n = 16), fat (n = 12), or the interface of both tissues (n = 23) were heated. The T1-temperature coefficient of fat was determined using least-squares fitting of inversion recovery-based T1 maps of untreated fat harvested from the animal and was applied to the in vivo measured heat-induced T1 changes to create temperature maps. Using k-space weighted image contrast reconstruction, temporal resolution of 1.71 s was achieved for simultaneous thermometry at 1.5 × 1.5 × 2 mm voxel resolution. PRF shift thermometry was not sensitive to heating in fat. T1 changes were observed in fat at the ultrasound focus. The mean T1-temperature coefficient for fat was determined to be 1.9%/°C ± 0.2%/°C. Precision was 0.76°C ± 0.18°C for PRF shift thermometry in muscle and 1.93°C ± 0.60°C for T1-based thermometry in fat. Sonications in muscle showed an increase in T1 of 2.4%/°C ± 0.9%/°C. The SR-VFA-SoS sequence was shown to simultaneously measure temperature change using PRF shift and T1-based methods in an in vivo model, providing thermometry for both aqueous and fat tissues.

Referenceless proton resonance frequency (PRF) shift thermometry is robust to B 0 drift and inter-scan tissue displacement in temperature change measurement during minimally invasive thermotherapy procedures such as High Intensity Focused Ultrasound (HIFU). In this method, the baseline phase of the heated region is extrapolated from unheated region by a polynomial model. The procedure would involve the time-consuming phase unwrapping procedure necessary for polynomial modeling. We propose here a novel method for referenceless PRF without the need for phase unwrapping. The method fits the spatial derivative of phase image to the polynomial model to avoid phase unwrapping. The baseline phase of heated region is then numerically integrated from the predicted phase derivative image based on the polynomial model. Our experiment demonstrated that the new method improved computational efficiency by 2 to 4 times with slightly better accuracy to the original referenceless thermometry. The speed improvement would facilitate the application of the technique to multi-slice and 3D near-real-time MR thermometry.

The purpose of this study is to demonstrate the first work of T 1-based magnetic resonance thermometry using magnetic resonance fingerprinting (dubbed MRFT). We compared temperature estimation of MRFT with proton resonance frequency shift (PRFS) thermometry on ex vivo bovine muscle. We demonstrated MRFT’s feasibility in predicting temperature on ex vivo bovine muscles with deep brain stimulation (DBS) lead. B 0 maps generated from MRFT were compared with gold standard B 0 maps near the DBS lead. MRFT and PRFS estimated temperatures were compared in the presence of motion. All experiments were performed on a 3 Tesla whole-body GE Premier system with a 21-channel receive head coil (GE Healthcare, Milwaukee, WI). Four fluoroptic probes were used to measure the temperature at the center of a cold muscle (probe 1), the room temperature water bottle (probe 2), and the center and periphery of the heated muscle (probes 3 and 4). We selected regions of interest (ROIs) around the location of the probes and used simple linear regression to generate the temperature sensitivity calibration equations that convert T 1 maps and Δs maps to temperature maps. We then repeated the same setup and compared MRFT and PRFS thermometry temperature estimation with gold standard probe measurements. For the MRFT experiment on DBS lead, we taped the probe to the tip of the DBS lead and used a turbo spin echo sequence to induce heating near the lead. We selected ROIs around the tip of the lead to compare MRFT temperature estimation with probe measurements and compared with PRFS temperature estimation. Vendor-supplied B 0 mapping sequence was acquired to compare with MRFT-generated B 0 maps. We found strong linear relationships (R 2 > 0.958) between T 1 and temperature and Δs and temperatures in our temperature sensitivity calibration experiment. MRFT and PRFS thermometry both accurately predict temperature (RMSE < 1.55 °C) compared to probe measurements. MRFT estimated temperature near DBS lead has a similar trend as the probe temperature. Both B 0 maps show inhomogeneities around the lead. MRFT estimated temperature is less sensitive to motion.

Independent assessment of MRI-induced temperature change and SAR distributions in phantoms

The T1 and T2 temperature dependence of female breast adipose tissue was investigated at 1.5 T in order to evaluate the applicability of relaxation-based MR thermometry in fat for the monitoring of thermal therapies in the breast. Relaxation times T1 , T2 and T2TSE (the apparent T2 measured using a turbo spin echo readout sequence) were measured in seven fresh adipose breast samples for temperatures from 25 to 65 °C. Spectral water suppression was used to reduce the influence of the residual water signal. The temperature dependence of the relaxation times was characterized. The expected maximum temperature measurement errors based on average calibration lines were calculated. In addition, the heating-cooling reversibility was investigated for two samples. The T1 and T2TSE temperature (T) dependence could be fitted well with an exponential function of 1/T. A linear relationship between T2 and temperature was found. The temperature coefficients (mean ± inter-sample standard deviation) of T1 and T2TSE increased from 25 °C (dT1/dT = 5.35 ± 0.08 ms/°C, dT2TSE/dT = 3.82 ± 0.06 ms/°C) to 65 °C (dT1 /dT = 9.50 ± 0.16 ms/°C, dT2TSE/dT = 7.99 ± 0.38 ms/°C). The temperature coefficient of T2 was 0.90 ± 0.03 ms/°C. The temperature-induced changes in the relaxation times were found to be reversible after heating to 65 °C. Given the small inter-sample variation of the temperature coefficients, relaxation-based MR thermometry appears to be feasible in breast adipose tissue, and may be used as an adjunct to proton resonance frequency shift (PRFS) thermometry in aqueous tissue (glandular + tumor).

To present a three-dimensional (3D) segmented echoplanar imaging (EPI) pulse sequence implementation that provides simultaneously the proton resonance frequency shift temperature of aqueous tissue and the longitudinal relaxation time (T1 ) of fat during thermal ablation. The hybrid sequence was implemented by combining a 3D segmented flyback EPI sequence, the extended two-point Dixon fat and water separation, and the double flip angle T1 mapping techniques. High-intensity focused ultrasound (HIFU) heating experiments were performed at three different acoustic powers on excised human breast fat embedded in ex vivo porcine muscle. Furthermore, T1 calibrations with temperature in four different excised breast fat samples were performed, yielding an estimate of the average and variation of dT1 /dT across subjects. The water only images were used to mask the complex original data before computing the proton resonance frequency shift. T1 values were calculated from the fat-only images. The relative temperature coefficients were found in five fat tissue samples from different patients and ranged from 1.2% to 2.6%/°C. The results demonstrate the capability of real-time simultaneous temperature mapping in aqueous tissue and T1 mapping in fat during HIFU ablation, providing a potential tool for treatment monitoring in organs with large fat content, such as the breast.

The paper describes measuring equipment for sensitive measurement of temperature changes of the order of 10−3‡C which, compared with the method used hitherto for experimental investigation of magnetothermal phenomena, has the advantage that the preparation of the sample is simple and, as a consequence of using thermistors, the reaction to temperature changes is quick.

To evaluate the precision of in vivo temperature measurements in adipose and glandular breast tissue using a multi-echo hybrid PRF/T1 pulse sequence. A high-bandwidth, multi-echo hybrid PRF/T1 sequence was developed for monitoring temperature changes simultaneously in fat- and water-based tissues. The multiple echoes were combined with the optimal weightings for magnitude and phase images, allowing for precise measurement of both T1 and the proton resonance frequency (PRF) shift. The sequence was tested during in vivo imaging of 10 healthy volunteers in a breast-specific MR-guided focused ultrasound system and also during focused ultrasound heating of excised breast adipose tissue. The in vivo results indicated that the sequence can measure PRF temperatures with 1.25 × 1.25 × 3.5 mm resolution, 1.9 s temporal resolution, and 1.0°C temperature precision, and can measure T1 values with 3.75 × 3.75 × 3.5 mm resolution, 3.8 s temporal resolution, and 2.5%-4.8% precision. The excised tissue heating experiments demonstrate the sequence's ability to monitor temperature changes simultaneously in water- and fat-based tissues. The addition of a high-bandwidth, multi-echo readout to the hybrid PRF/T1 sequence improves the precision of each measurement, providing a sequence that will be beneficial to several MR-guided thermal therapies.

Fast temperature estimation from undersampled k-space with fully-sampled center for MR guided microwave ablation

This study aims to observe and estimate the temperature changes caused by the echo train lengths (ETLs) of fast-spin echo to ensure radiofrequency (RF)-related safety. RF-induced heating on ETL-stepped changes is evaluated using the proton resonance frequency shift (PRF) method and optic-fiber thermography (OFT). The increase in temperature caused by a clinical sequence was compared to that accumulated by the corresponding ETLs. The temperatures are similarly increased in ETLs from 10 to 30 (PRF: 0.109 ± 0.025 ℃, OFT: 0.079 ± 0.009 ℃), suggesting that a large number of ETLs could be utilized at practical sites. The RF-induced heating in the clinical setting (PRF: 0.775 ± 0.069 ℃, OFT: 0.510 ± 0.015 ℃) is comparable to the estimated temperature on the ETL-stepped changes (PRF: 0.780 ℃, OFT: 0.553 ℃). These enable accelerated acquisition with a large number of ETLs to be practically used and RF-induced safety to be thoroughly guaranteed.

Non-invasive detection of small temperature changes (C) is pivotal to the further advance of regional hyperthermia as a treatment modality for deep-seated tumours. Magnetic resonance (MR) thermography methods are considered to be a promising approach. Four methods exploiting temperature-dependent parameters were evaluated in phantom experiments. The investigated temperature indicators were spin-lattice relaxation time , diffusion coefficient D, shift of water proton resonance frequency (water PRF) and resonance frequency shift of the methoxy group of the praseodymium complex (Pr probe). The respective pulse sequences employed to detect temperature-dependent signal changes were the multiple readout single inversion recovery (T One by Multiple Read Out Pulses; TOMROP), the pulsed gradient spin echo (PGSE), the fast low-angle shot (FLASH) with phase difference reconstruction, and the classical chemical shift imaging (CSI). Applying these sequences, experiments were performed in two separate and consecutive steps. In the first step, calibration curves were recorded for all four methods. In the second step, applying these calibration data, maps of temperature changes were generated and verified. With the equal total acquisition time of approximately 4 min for all four methods, the uncertainties of temperature changes derived from the calibration curves were less than C (Pr probe C, water PRF C, C and C). The corresponding maps of temperature changes exhibited slightly higher errors but still in the range or less than C (C, C, C, C respectively). The calibration results indicate the Pr probe method to be most sensitive and accurate. However, this advantage could only be partially transferred to the thermographic maps because of the coarse matrix of the classical CSI sequence. Therefore, at present the water PRF method appears to be most suitable for MR monitoring of small temperature changes during hyperthermia treatment.

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).

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

To establish accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. Protocol patients with advanced extremity sarcomas were treated with external beam radiation therapy and hyperthermia. Invasive temperature measures were compared to noninvasive magnetic resonance thermal imaging (MRTI) at 1.5 T performed during hyperthermia. Volumetric temperature rise images were obtained using the proton resonance frequency shift (PRFS) technique during heating in a 140 MHz miniannular phased array applicator. MRTI temperature changes were compared to invasive measurements of temperature with a multisensor fiber optic probe inside a #15 g catheter in the tumor. Since the PRFS technique is sensitive to drifts in the primary imaging magnetic field, temperature change distributions were corrected automatically during treatment using temperature-stable reference materials to characterize field changes in 3D. The authors analyzed MRT images and compared, in evaluable treatments, MR-derived temperatures to invasive temperatures measured in extremity sarcomas. Small regions of interest (ROIs) were specified near each invasive sensor identified on MR images. Temperature changes in the interstitial sensors were compared to the corresponding ROI PRFS-based temperature changes over the entire treatment and over the steady-state period. Nonevaluable treatments (motion/imaging artifacts, noncorrectable drifts) were not included in the analysis. The mean difference between MRTI and interstitial probe measurements was 0.91 degrees C for the entire heating time and 0.85 degrees C for the time at steady state. These values were obtained from both tumor and normal tissue ROIs. When the analysis is done on just the tumor ROIs, the mean difference for the whole power on time was 0.74 degrees C and during the period of steady state was 0.62 degrees C. The data show that for evaluable treatments, excellent correlation (deltaT < 1 degrees C) of MRTI-ROI and invasive measurements can be achieved, but that motion and other artifacts are still serious challenges that must be overcome in future work.

MR-guided high-intensity focused ultrasound (HIFU) for treatment of uterine fibroids and painful bone metastases uses the proton resonant frequency shift (PRF) for temperature monitoring in water-based tissues. However, PRF fails to detect temperature changes in tissues with high lipid content, such as fat and bone marrow. Previous studies have shown a change in T2 of subcutaneous fat, red and yellow bone marrow during treatments with focused ultrasound. The lack of calibration data for 3T acquisitions, however, makes it difficult to convert T2 values into maps of tissue temperature. In this study we investigated the dependence of T2 temperature on temperature in porcine adipose tissue and bovine yellow bone marrow at thermal equilibrium at 3T.