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

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.

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

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).

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

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.

Measurement of proton resonance frequency shift coefficient during MR-guided focused ultrasound on Thiel embalmed tissue.

PURPOSE: To estimate the value of proton resonance frequency (PRF) shift coefficient of explanted Thiel embalmed animal and human tissue used as a preclinical model for treatment with MR-guided focused ultrasound (FUS). METHODS: Thiel embalmed human liver, ovine liver, and porcine muscle were heated using two methods: bulk heating and FUS-induced heating. Phase-referenced PRF thermometry was applied during cooling of the tissue to obtain a series of phase difference, ΔΦ, maps. A fiber-optic thermocouple was inserted in the tissue to measure the temperature difference, ΔT. The PRF shift coefficient was calculated from the measured ΔΦ, ΔT. RESULTS: In the case of bulk heating, the mean values (±SD) of the PRF coefficient for Thiel embalmed ovine liver, porcine muscle, and human liver were: 0.017 (5 × 10-4 ) ppm/°C, 0.015 (6 × 10-4 ) ppm/°C, and 0.012 (6 × 10-4 ) ppm/°C, respectively. Similar values were found in tissues heated with FUS. CONCLUSION: The values of PRF coefficient measured for the Thiel embalmed tissue were higher than the values for fresh tissue, suggesting that embalming a tissue with Thiel fluid can affect PRF thermometry. The chemical composition of the Thiel fluid and the electrical conductivity may explain these results. Magn Reson Med 74:260-265, 2015. © 2014 Wiley Periodicals, Inc.

An integrated model-based software for FUS in moving abdominal organs.

Focused ultrasound surgery (FUS) is a non-invasive method for tissue ablation that has the potential for complete and controlled local tumour destruction with minimal side effects. The treatment of abdominal organs such as the liver, however, requires particular technological support in order to enable a safe, efficient and effective treatment. As FUS is applied from outside the patient's body, suitable imaging methods, such as magnetic resonance imaging or diagnostic ultrasound, are needed to guide and track the procedure. To facilitate an efficient FUS procedure in the liver, the organ motion during breathing and the partial occlusion by the rib cage need to be taken into account in real time, demanding a continuous patient-specific adaptation of the treatment configuration. Modelling the patient's respiratory motion and combining this with tracking data improves the accuracy of motion predictions. Modelling and simulation of the FUS effects within the body allows the use of treatment planning and has the potential to be used within therapy to increase knowledge about the patient status. This article describes integrated model-based software for patient-specific modelling and prediction for FUS treatments of moving abdominal organs.

Thermometry during MR-guided focused ultrasound in a preclinical model based on Thiel embalmed tissue.

BACKGROUND: The purpose of this work was to determine the accuracy of Proton Resonance Frequency (PRF) thermometry during MR-guided Focused Ultrasound (MRgFUS) ablation on explanted Thiel embalmed human and animal liver, fresh animal liver, and compared to gel phantom. MATERIAL AND METHODS: PRF thermometry during MRgFUS was conducted using a 1.5T MRI system. The phantom and the organs were sonicated with the following energies: 300J, 600J, 1000J and 1400J. The temperature increase which was measured using PRF thermometry during sonication was compared to actual temperature rise in the same conditions measured by fibre optic thermocouple. RESULTS: Sonication of fresh animal liver showed temperature differences varying between 0.27°C and 0.40°C, whereas the phantom results showed temperature differences from 0.23°C to 0.40°C. For the Thiel embalmed organs, the temperature difference varied from 1.17 °C to 3.13°C for the ovine liver, and from 1.3°C to 3.10°C for the human liver. CONCLUSION: The temperature differences measured in the fresh liver were small and similar to those found for the gel phantom. However, the temperature differences calculated for the Thiel embalmed organs were higher compared to the fresh organ. This indicates that the PRF-based temperature calibration of the Focused Ultrasound machine for Thiel embalmed tissue is necessary.

Lymphoma Severity and Type Are Associated With Aortic FDG Uptake by 18F-FDG PET/CT Imaging.

BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Characterization of functionally significant coronary artery disease by a coronary computed tomography angiography-based index: a comparison with positron emission tomography.

AIMS: To test the hypothesis that virtual functional assessment index (vFAI) is related with regional flow parameters derived by quantitative positron emission tomography (PET) and can be used to assess abnormal vasodilating capability in coronary vessels with stenotic lesions at coronary computed tomography angiography (CCTA). METHODS AND RESULTS: vFAI, stress myocardial blood flow (MBF), and myocardial flow reserve (MFR) were assessed in 78 patients (mean age 62.2 ± 7.7 years) with intermediate pre-test likelihood of coronary artery disease (CAD). Coronary stenoses ≥50% were considered angiographically significant. PET was considered positive for significant CAD, when more than one contiguous segments showed stress MBF ≤2.3 mL/g/min for 15O-water or <1.79 mL/g/min for 13N-ammonia. MFR thresholds were ≤2.5 and ≤2.0, respectively. vFAI was lower in vessels with abnormal stress MBF (0.76 ± 0.10 vs. 0.89 ± 0.07, P < 0.001) or MFR (0.80 ± 0.10 vs. 0.89 ± 0.07, P < 0.001). vFAI had an accuracy of 78.6% and 75% in unmasking abnormal stress MBF and MFR in 15O-water and 82.7% and 71.2% in 13N-ammonia studies, respectively. Addition of vFAI to anatomical CCTA data increased the ability for predicting abnormal stress MBF and MFR in 15O-water studies [AUCccta + vfai = 0.866, 95% confidence interval (CI) 0.783-0.949; P = 0.013 and AUCccta + vfai = 0.737, 95% CI 0.648-0.825; P = 0.007, respectively]. An incremental value was also demonstrated for prediction of stress MBF (AUCccta + vfai = 0.887, 95% CI 0.799-0.974; P = 0.001) in 13N-ammonia studies. A similar trend was recorded for MFR (AUCccta + vfai = 0.780, 95% CI 0.632-0.929; P = 0.13). CONCLUSION: vFAI identifies accurately the presence of impaired vasodilating capability. In combination with anatomical data, vFAI enhances the diagnostic performance of CCTA.

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation.

BACKGROUND AND OBJECTIVE: Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for liver tumour ablation is a challenging task due to motion caused by breathing and occlusion due the ribcage between the transducer and the tumour. To overcome these challenges, a novel system for liver tumour ablation during free breathing has been designed. METHODS: The novel TRANS-FUSIMO Treatment System (TTS, EUFP7) interacts with a Magnetic Resonance (MR) scanner and a focused ultrasound transducer to sonicate to a moving target in liver. To meet the requirements of ISO 13485; a quality management system for medical device design, the system needs to be tested for certain process parameters. The duration of sonication and, the delay after the sonication button is activated, are among the parameters that need to be quantified for efficient and safe ablation of tumour tissue. A novel methodology is developed to quantify these process parameters. A computerised scope is programmed in LabVIEW to collect data via hydrophone; where the coordinates of fiber-optic sensor assembly was fed into the TRANS-FUSIMO treatment software via Magnetic Resonance Imaging (MRI) to sonicate to the tip of the sensor, which is synchronised with the clock of the scope, embedded in a degassed water tank via sensor assembly holder. The sonications were executed for 50 W, 100 W, 150 W for 10 s to quantify the actual sonication duration and the delay after the emergency stop by two independent operators for thirty times. The deviation of the system from the predefined specs was calculated. Student's-T test was used to investigate the user dependency. RESULTS: The duration of sonication and the delay after the sonication were quantified successfully with the developed method. TTS can sonicate with a maximum deviation of 0.16 s (Std 0.32) from the planned duration and with a delay of 14 ms (Std 0.14) for the emergency stop. Student's T tests indicate that the results do not depend on operators (p > .05). CONCLUSION: The evidence obtained via this protocol is crucial for translation- of-research into the clinics for safe application of MRgFUS. The developed protocol could be used for system maintenance in compliance with quality systems in clinics for daily quality assurance routines.