Short and long time MR signal behavior of randomly distributed water and fat-numerical simulations.

The MR time-signal behavior of water has been reported to be different on short and long time scales for systems of randomly distributed perturbers in water in the static dephasing regime. Up to now, the signal of the perturbers in such systems has not been taken into consideration. Water-fat emulsions are macroscopically homogeneous systems and can be considered as microscopically randomly distributed perturbing fat spheres embedded in water. In such water-fat systems, the signal of the perturber, fat, cannot be ignored. Since water and fat are within the same system, the fat signal behavior may show similarities with water, with differences in short and long time scales. This could complicate fat-referenced MR thermometry (MRT) methods such as multi-gradient echo-based (MGE) MRT. Simulations were performed using a numerical phantom comprising spherical fat objects embedded in a spherical water medium. To characterize the fat signal, the theoretical signal description of water was fitted to the simulated fat signal. The simulated signals were sampled as an MGE signal and MGE MRT was used to calculate temperatures. The sampling was done with and without delay, to investigate the effect on the temperature error of the time ranges in which the signal was sampled. It was confirmed that the fat signal behavior was similar to that of water and consisted of two regimes. The separation between the short and long time scales was approximately at 55 ms for fat, as compared with 8.9 ms for water. Without delayed signal sampling, the MGE MRT temperature error was about 2.5°C. With delayed sampling such that both the water and the fat signals were either in the short or in the long time scale the error was reduced to 0.2°C.

DCE-MRI and IVIM-MRI of rabbit Vx2 tumors treated with MR-HIFU-induced mild hyperthermia.

BACKGROUND: The purpose of this study is to investigate whether changes could be detected in dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR parameters upon MR-guided high-intensity focused ultrasound (MR-HIFU)-induced hyperthermia in a rabbit Vx2 tumor model. METHODS: Five Vx2 tumor-bearing New Zealand white rabbits were treated with hyperthermia using a clinical MR-HIFU system. Data were acquired before and after hyperthermia. For the DCE analysis, the extended Tofts model was used. For the IVIM analysis, a Bayesian approach was used. Maps were reconstructed of the DCE parameters (K (trans), k ep, and v p ) and IVIM parameters (D t , f p , and D p ). Individual parameter histograms and two-dimensional cross-correlation histograms were constructed to analyze changes in the parameters after hyperthermia. Changes in median values were tested for statistical significance with the Mann-Whitney U test. RESULTS: The MR temperature measurements confirmed that mild hyperthermia (40 to 42 °C) was successfully achieved in all rabbits. One rabbit died during treatment and was excluded from the analysis. In the remaining four rabbits, an increase in D t was observed. In three rabbits, an increase in K (trans) was observed, while in the other rabbits, all three DCE parameter values decreased. Mixed changes were seen for v p and f p . CONCLUSIONS: Changes in DCE and IVIM parameters were detected after hyperthermia and were variable between the rabbits. DCE- and IVIM-MRI may be promising tools to assess tumor responses to hyperthermia. Further research in a larger number of subjects is necessary in order to assess their value for treatment response monitoring.

Multi-gradient echo MR thermometry for monitoring of the near-field area during MR-guided high intensity focused ultrasound heating.

The multi-gradient echo MR thermometry (MGE MRT) method is proposed to use at the interface of the muscle and fat layers found in the abdominal wall, to monitor MR-HIFU heating. As MGE MRT uses fat as a reference, it is field-drift corrected. Relative temperature maps were reconstructed by subtracting absolute temperature maps. Because the absolute temperature maps are reconstructed of individual scans, MGE MRT provides the flexibility of interleaved mapping of temperature changes between two arbitrary time points. The method's performance was assessed in an ex vivo water bath experiment. An ex vivo HIFU experiment was performed to show the method's ability to monitor heating of consecutive HIFU sonications and to estimate cooling time constants, in the presence of field drift. The interleaved use between scans of a clinical protocol was demonstrated in vivo in a patient during a clinical uterine fibroid treatment. The relative temperature measurements were accurate (mean absolute error 0.3 °C) and provided excellent visualization of the heating of consecutive HIFU sonications. Maps were reconstructed of estimated cooling time constants and mean ROI values could be well explained by the applied heating pattern. Heating upon HIFU sonication and subsequent cooling could be observed in the in vivo demonstration.

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

BACKGROUND: Magnetic 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. METHODS: Analyses 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). RESULTS: The 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. CONCLUSIONS: In 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.

Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases.

BACKGROUND: Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently emerged as an effective treatment option for painful bone metastases. We describe here the first experience with volumetric MR-HIFU for palliative treatment of painful bone metastases and evaluate the technique on three levels: technical feasibility, safety, and initial effectiveness. METHODS: In this observational cohort study, 11 consecutive patients (7 male and 4 female; median age, 60 years; age range, 53-86 years) underwent 13 treatments for 12 bone metastases. All patients exhibited persistent metastatic bone pain refractory to the standard of care. Patients were asked to rate their worst pain on an 11-point pain scale before treatment, 3 days after treatment, and 1 month after treatment. Complications were monitored. All data were prospectively recorded in the context of routine clinical care. Response was defined as a ≥2-point decrease in pain at the treated site without increase in analgesic intake. Baseline pain scores were compared to pain scores at 3 days and 1 month using the Wilcoxon signed-rank test. For reporting, the STROBE guidelines were followed. RESULTS: No treatment-related major adverse events were observed. At 3 days after volumetric MR-HIFU ablation, pain scores decreased significantly (p = 0.045) and response was observed in a 6/11 (55%) patients. At 1-month follow-up, which was available for nine patients, pain scores decreased significantly compared to baseline (p = 0.028) and 6/9 patients obtained pain response (overall response rate 67% (95% confidence interval (CI) 35%-88%)). CONCLUSIONS: This is the first study reporting on the volumetric MR-HIFU ablation for painful bone metastases. No major treatment-related adverse events were observed during follow-up. The results of our study showed that volumetric MR-HIFU ablation for painful bone metastases is technically feasible and can induce pain relief in patients with metastatic bone pain refractory to the standard of care. Future research should be aimed at standardization of the treatment procedures and treatment of larger numbers of patients to assess treatment effectiveness and comparison to the standard of care.