The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods.

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Anatomic thermochromic tissue-mimicking phantom of the lumbar spine for pre-clinical evaluation of MR-guided focused ultrasound (MRgFUS) ablation of the facet joint.

OBJECTIVE: To develop a thermochromic tissue-mimicking phantom (TTMP) with an embedded 3D-printed bone mimic of the lumbar spine to evaluate MRgFUS ablation of the facet joint and medial branch nerve. MATERIALS AND METHODS: Multiple 3D-printed materials were selected and characterized by measurements of speed of sound and linear acoustic attenuation coefficient using a through-transmission technique. A 3D model of the lumbar spine was segmented from a de-identified CT scan, and 3D printed. The 3D-printed spine was embedded within a TTMP with thermochromic ink color change setpoint at 60 °C. Multiple high energy sonications were targeted to the facet joints and medial branch nerve anatomical location using an ExAblate MRgFUS system connected to a 3T MR scanner. The phantom was dissected to assess sonication targets and the surrounding structures for color change as compared to the expected region of ablation on MR-thermometry. RESULTS: The measured sound attenuation coefficient and speed of sound of gypsum was 240 Np/m-MHz and 2471 m/s, which is the closest to published values for cortical bone. Following sonication, dissection of the TTMP revealed good concordance between the regions of color change within the phantom and expected areas of ablation on MR-thermometry. No heat deposition was observed in critical areas, including the spinal canal and nerve roots from either color change or MRI. CONCLUSION: Ablated regions in the TTMP correlated well with expected ablations based on MR-thermometry. These findings demonstrate the utility of an anatomic spine phantom in evaluating MRgFUS sonication for facet joint and medial branch nerve ablations.

The impact of technical parameters on ablation volume during MR-guided focused ultrasound of desmoid tumors.

PURPOSE: Desmoid tumors are benign, locally aggressive soft tissue tumors derived from fibroblasts. Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective treatment for desmoid tumors. The purpose of this study was to retrospectively review the MRgFUS treatments of desmoid tumors at our institution to determine which technical treatment parameters contributed most significantly to the accumulation of thermal dose. MATERIALS AND METHODS: The study protocol was approved by the local IRB. We retrospectively reviewed data from MRgFUS treatments performed in histologically-confirmed desmoid tumors, over a period of 18 months. Sonication parameter means were compared with ANOVA. Mixed effects and linear regression models were used to evaluate the relative contribution of different parameters to thermal dose volume. RESULTS: Nine-hundred thirty-six sonications were reviewed in 13 treatments. Accumulated dose per sonication was greatest for elongated sonications (0.96 cc ± 0.90) compared to short (0.88 ± 0.93 cc) and nominal (0.55 ± 0.70 cc) sonications, p < .001. 65.2% of short sonications resulted in high percentage ablations, compared to 46.0% of nominal and 35.1% of elongated sonications. Standardized beta coefficients (anticipated increased volume in cc per unit) for power, duration, energy and average temperature were 0.006, 0.057, 0.00035 and 0.03, p < .001. Regarding dose efficacy, dose area contributed the greatest to this variability - 50.7% (45.5-54.8%), followed by distance - 16.6% (12.9-20.0%). CONCLUSIONS: A variety of sonication parameters significantly contributed to thermal ablation volume following MRgFUS of desmoid tumors, in reproducible patterns. This work can serve as the basis for future models working toward improved planning for MRgFUS treatments.

T2 mapping as a predictor of nonperfused volume in MRgFUS treatment of desmoid tumors.

Objective: The objective of this study was to develop an alternative method of non-contrast monitoring of tissue ablation during focused ultrasound treatment. Desmoid tumors are benign but locally aggressive soft tissue tumors that arise from fibroblast cells. Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as an alternative to conventional therapies, showing promising results in reduction of tumor volume without significant side effects. The gold-standard assessment of the reduction of viable tumor volume post-treatment is non-perfused volume (NPV) and evaluation of NPV is typically performed with post-treatment gadolinium enhanced MR imaging. However, as gadolinium cannot be repeatedly administered during treatments, there is a need for alternative non-contrast monitoring of the tissue to prevent over and under treatment. Methods: Double-echo and multi-echo images were acquired before, during and after the MRgFUS treatment. T2 maps were generated with an exponential fit and T2 maps were compared to post-treatment post-contrast images.Results: In all five MRgFUS treatment sessions, T2 mapping showed excellent qualitative agreement with the post-contrast NPV.Conclusions: T2 mapping may be used to visualize the extent of ablation with focused ultrasound and can be used as a predictor of NPV prior to the administration of contrast during the post-treatment assessment.

Thermal diffusivity and perfusion constants from in vivo MR-guided focussed ultrasound treatments: a feasibility study.

PURPOSE: This study investigates the feasibility of non-invasively determining thermal diffusivity (α) and the Pennes perfusion parameter (w) from pre-clinical and clinical magnetic resonance-guided focussed ultrasound (MRgFUS) temperature data. MATERIALS AND METHODS: Pre-clinical MRgFUS experiments were performed in rabbit muscle (N = 3, 28 sonications) using three-dimensional MR thermometry. Eight sonications were made in a clinical QA phantom with two-dimensional thermometry. Retrospective property determination was performed on clinical uterine fibroid (N = 8, 9 sonications) and desmoid tumour (N = 4, 7 sonications) data. The property determination method fits an analytical solution to MRgFUS temperatures in the coronal MR plane, including all temperatures acquired during heating and one cooling image. When possible, additional cooling data were acquired for property determination. RESULTS: Rabbit α and w from Heating Data (α = 0.164 mm2s-1, w = 7.9 kg m-3 s-1) and Heating and Cooling Data (α = 0.146 mm2s-1, w = 3.3 kg m-3 s-1) were within the range of gold-standard invasive measurements, with >50% reduction in variability by including cooling data. QA phantom property determination with cooling data yielded properties within 3% of expected values (α = 0.144 mm2s-1, w = 0.0 kg m-3 s-1), a difference that was not statistically significant (p = 0.053). Uterine fibroid (Heating Data: α = 0.212 mm2s-1, w = 11.0 kg m-3 s-1) and desmoid tumour (Heating & Cooling Data: α = 0.245 mm2s-1, w = 4.7 kg m-3 s-1) properties are feasible but lack independent verification. CONCLUSIONS: Thermal diffusivity and the Pennes perfusion parameter can be obtained from in vivo data and with clinical MRgFUS protocols. Property values are consistently improved by including cooling data. The utility of this property determination method will increase as clinical protocols implement improved temperature imaging.

Effect of Sonication Duration and Power on Ablation Depth During MR-Guided Focused Ultrasound of Bone.

PURPOSE: To evaluate the effect of differences in sonication duration and power on the size of postcontrast ablation zone following magnetic resonance-guided focused ultrasound (MRgFUS) of bone in a swine femoral bone model. MATERIALS AND METHODS: Experimental procedures received approval from the Institutional Committee on Animal Research. MRgFUS was used to create two thermal lesions in the left femur of six pigs. Each target was subjected to six sonications. 400J of energy was used for each sonication. However, the distal target received the standard sonication duration of 20 seconds (20W), while the proximal target received a longer sonication duration of 40 seconds (10W). MRgFUS lesions were imaged with fat-saturated spoiled gradient echo sequence at 3.0T MRI 10 minutes following the administration of contrast. Maximum three-plane dimensions of the hypoenhanced ablation area were measured. RESULTS: Postcontrast MR images demonstrated ovoid regions of hypoenhancement at each target. The average depth of ablation was significantly greater for the shorter high-power sonications (7.3 mm), compared to the longer lower-power sonications (4.5 mm), P = 0.026. The craniocaudal dimension was also greater for the shorter ablations 26.7 mm compared to the longer sonications 21.0 mm, P = 0.006. CONCLUSION: Contrary to anecdotal clinical experience, this preclinical model suggests that during MRgFUS of bone, standard duration, higher-power sonications resulted in deeper ablation volumes compared to long duration, lower-power sonications. These results suggest that to achieve deeper ablations, if longer sonications are used, then the power should be relatively maintained, for a net energy increase. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1418-1422.

Bone remodeling after MR imaging-guided high-intensity focused ultrasound ablation: evaluation with MR imaging, CT, Na(18)F-PET, and histopathologic examination in a swine model.

PURPOSE: To serially monitor bone remodeling in the swine femur after magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) ablation with MR imaging, computed tomography (CT), sodium fluorine 18 (Na(18)F)-positron emission tomography (PET), and histopathologic examination, as a function of sonication energy. MATERIALS AND METHODS: Experimental procedures received approval from the local institutional animal care and use committee. MR imaging-guided HIFU was used to create distal and proximal ablations in the right femurs of eight pigs. The energy used at the distal target was higher (mean, 419 J; range, 390-440 J) than that used at the proximal target (mean, 324 J; range, 300-360 J). Imaging was performed before and after ablation with 3.0-T MR imaging and 64-section CT. Animals were reevaluated at 3 and 6 weeks with MR imaging (n = 8), CT (n = 8), Na(18)F-PET (n = 4), and histopathologic examination (n = 4). Three-dimensional ablation lengths were measured on contrast material-enhanced MR images, and bone remodeling in the cortex was measured on CT images. RESULTS: Ablation sizes at MR imaging 3 and 6 weeks after MR imaging-guided HIFU ablation were similar between proximal (low-energy) and distal (high-energy) lesions (average, 8.7 × 21.9 × 16.4 mm). However, distal ablation lesions (n = 8) demonstrated evidence of subperiosteal new bone formation at CT, with a subtle focus of new ossification at 3 weeks and a larger focus of ossification at 6 weeks. New bone formation was associated with increased uptake at Na(18)F-PET in three of four animals; this was confirmed at histopathologic examination in four of four animals. CONCLUSION: MR imaging-guided HIFU ablation of bone may result in progressive remodeling, with both subcortical necrosis and subperiosteal new bone formation. This may be related to the use of high energies. MR imaging, CT, and PET are suitable noninvasive techniques to monitor bone remodeling after MR imaging-guided HIFU ablation.

Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI.

PURPOSE: To demonstrate the feasibility of using ultrashort echo-time MRI to quantify T1 changes in cortical bone due to heating. METHODS: Variable flip-angle T1 mapping combined with 3D ultrashort echo-time imaging was used to measure T1 in cortical bone. A calibration experiment was performed to detect T1 changes with temperature in ex vivo cortical bone samples from a bovine femur. Ultrasound heating experiments were performed using an interstitial applicator in ex vivo bovine femur specimens, and heat-induced T1 changes were quantified. RESULTS: The calibration experiment demonstrated that T1 increases with temperature in cortical bone. We observed a linear relationship between temperature and T1 with a linear coefficient between 0.67 and 0.84 ms/°C over a range of 25-70°C. The ultrasound heating experiments showed increased T1 changes in the heated regions, and the relationship between the temperature changes and T1 changes was similar to that of the calibration. CONCLUSION: We demonstrated a temperature dependence of T1 in ex vivo cortical bone using a variable flip-angle ultrashort echo-time T1 mapping method.

International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions.

Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

MRI-guided high-intensity focused ultrasound ablation of bone: evaluation of acute findings with MR and CT imaging in a swine model.

PURPOSE: To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and computed tomography (CT) imaging following MR-guided high-intensity focused ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and energy. MATERIALS AND METHODS: Experimental procedures received approval from the local Institutional Animal Care and Use Committee. MRgHIFU was used to create distal and proximal ablations in the right femur of eight pigs. Each target was dosed with four or six sonications within similar volumes. The energy dosed to the distal target was higher (419 ± 19 J) than the proximal target (324 ± 17 J). The targeted femur and contralateral control were imaged before and after ablation using MR at 3T. Qualitative changes in signal on T1-weighted, T2-weighted, and T1-weighted postcontrast images were assessed. Ablation dimensions were calculated from postcontrast MRI. The 64-slice CT images were also obtained before and after ablation and qualitative changes were assessed. RESULTS: MRgHIFU bone ablation size measured on average 8.5 × 21.1 × 16.2 mm (transverse × craniocaudal × anteroposterior). Interestingly, within similar prescribed volumes, increasing the number of sonications from 4 to 6 increased the depth of the intramedullary hypoenhanced zone from 2.9 mm to 6.5 mm (P < 0.001). There was no difference in the appearance of low versus high energy ablations. CT imaging did not show structural abnormalities. CONCLUSION: The number of MRgHIFU focal sonications can be used to increase the depth of treatment within the targeted bone. Unlike CT, T2-weighted and contrast-enhanced MR demonstrated the hyperacute structural changes in the femur and surrounding soft tissue.

MR-Guided Focused Ultrasound Thalamotomy in the Setting of Aneurysm Clip.

We report on a 75-year-old woman with a history of right MCA aneurysm clipping and medically refractive right-hand tremor. We successfully performed focused ultrasound thalamotomy of the left ventral intermediate nucleus under MR imaging-guidance at 3T. A thorough pretreatment evaluation of MR thermometry was critical to ensure that adequate precision could be achieved at the intended target. The tremor showed a 75% decrease at 24 hours postprocedure and a 50% decrease at a 3-month follow-up. There were no immediate adverse events.

Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain.

PURPOSE: To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS). MATERIALS AND METHODS: Four different temperature reconstruction methods were compared in volunteers (without heating) and patients undergoing transcranial MRgFUS: single baseline subtraction, multibaseline subtraction, hybrid single baseline/referenceless reconstruction, and hybrid multibaseline/referenceless reconstruction. Absolute temperature error and temporal temperature uncertainty of the different reconstruction methods were analyzed and compared. RESULTS: Absolute temperature errors and temporal temperature uncertainty were highest with single baseline subtraction and lowest with hybrid multibaseline/referenceless reconstruction in all areas of the brain. Pulsation of the brain and susceptibility changes from tongue motion or swallowing caused substantial temperature errors when single or multibaseline subtraction was used, which were much reduced when the referenceless component was added to the reconstruction. CONCLUSION: Hybrid multibaseline/referenceless thermometry accurately measures temperature changes in the brain with fewer artifacts and errors due to motion than pure baseline subtraction methods.

Approaches for modelling interstitial ultrasound ablation of tumours within or adjacent to bone: theoretical and experimental evaluations.

PURPOSE: The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumours within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. METHODS: 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7-MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or magnetic resonance temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. RESULTS: High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models. CONCLUSIONS: Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumours near and within bone, with applications toward treatment planning.

Influence of cerebrospinal fluid on power absorption during transcranial magnetic resonance-guided focused ultrasound treatment.

BACKGROUND: Ultrasound beam aberration correction is vital when focusing ultrasound through the skull bone in transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) applications. Current methods make transducer element phase adjustments to compensate for the variation in skull properties (shape, thickness, and acoustic properties), but do not account for variations in the internal brain anatomy. PURPOSE: Our objective is to investigate the effect of cerebrospinal fluid (CSF) and brain anatomy on beam focusing in tcMRgFUS treatments. METHODS: Simulations were conducted with imaging data from 20 patients previously treated with focused ultrasound for disabling tremor. The Hybrid Angular Spectrum (HAS) method was used to test the effect of including cerebral spinal fluid (CSF) and brain anatomy in determining the element phases used for aberration correction and beam focusing. Computer tomography (CT) and magnetic resonance imaging (MRI) images from patient treatments were used to construct a segmented model of each patient's head. The segmented model for treatment simulation consisted of water, skin, fat, brain, CSF, diploë, and cortical bone. Transducer element phases used for treatment simulation were determined using time reversal from the desired focus, generating a set of phases assuming a homogeneous brain in the intracranial volume, and a second set of phases assigning CSF acoustic properties to regions of CSF. In addition, for three patients, the relative effect of separately including CSF speed of sound values compared to CSF attenuation values was found. RESULTS: We found that including CSF acoustic properties (speed of sound and attenuation) during phase planning compared to phase correction without considering CSF increased the absorbed ultrasound power density ratios at the focus over a range of 1.06 to 1.29 (mean of 17% ± 6%) for 20 patients. Separately considering the CSF speed of sound and CSF attenuation showed that the increase was due almost entirely to including the CSF speed of sound; considering only the CSF attenuation had a negligible effect. CONCLUSIONS: Based on HAS simulations, treatment planning phase determination using morphologically realistic CSF and brain anatomy yielded an increase of up to 29% in the ultrasound focal absorbed power density. Future work will be required to validate the CSF simulations.

Non-invasive central nervous system assessment of a porcine model of neuropathic pain demonstrates increased latency of somatosensory-evoked potentials.

BACKGROUND: The study of chronic pain and its treatments requires a robust animal model with objective and quantifiable metrics. Porcine neuropathic pain models have been assessed with peripheral pain recordings and behavioral responses, but thus far central nervous system electrophysiology has not been investigated. This work aimed to record non-invasive, somatosensory-evoked potentials (SEPs) via electroencephalography in order to quantitatively assess chronic neuropathic pain induced in a porcine model. NEW METHOD: Peripheral neuritis trauma (PNT) was induced unilaterally in the common peroneal nerve of domestic farm pigs, with the contralateral leg serving as the control for each animal. SEPs were generated by stimulation of the peripheral nerves distal to the PNT and were recorded non-invasively using transcranial electroencephalography (EEG). The P30 wave of the SEP was analyzed for latency changes. RESULTS: P30 SEPs were successfully recorded with non-invasive EEG. PNT resulted in significantly longer P30 SEP latencies (p < 0.01 [n = 8]) with a median latency increase of 14.3 [IQR 5.0 - 17.5] ms. Histological results confirmed perineural inflammatory response and nerve damage around the PNT nerves. COMPARISON WITH EXISTING METHOD(S): Control P30 SEPs were similar in latency and amplitude to those previously recorded invasively in healthy pigs. Non-invasive recordings have numerous advantages over invasive measures. CONCLUSIONS: P30 SEP latency can serve as a quantifiable neurological measure that reflects central nervous system processing in a porcine model of chronic pain. Advancing the development of a porcine chronic pain model will facilitate the translation of experimental therapies into human clinical trials.

Feasibility of non-invasive recording of somatosensory evoked potential in pigs.

BACKGROUND: Non-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality. RESULTS: Pigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21-47] mcg/kg of dexmedetomidine, 0.3 [0.2-0.3] mg/kg of midazolam, and 0.3 [0.3-0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11-12]; median score at 30 min: 11.5 [10.5-12]). Heart rate (median [range]) (55 [49-71] beats per minute), respiratory rate (24 [21-30] breaths per minute), and hemoglobin oxygen saturation (99 [98-100]%) and body temperature (37.7 [37.4-37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents. CONCLUSIONS: In this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.

Real-time MR thermometry for monitoring HIFU ablations of the liver.

A high-resolution and high-speed pulse sequence is presented for monitoring high-intensity focused ultrasound ablations in the liver in the presence of motion. The sequence utilizes polynomial-order phase saturation bands to perform outer volume suppression, followed by spatial-spectral excitation and three readout segmented echo-planar imaging interleaves. Images are processed with referenceless thermometry to create temperature-rise images every frame. The sequence and reconstruction were implemented in RTHawk and used to image stationary and moving sonications in a polyacrylamide gel phantom (62.4 acoustic W, 50 sec, 550 kHz). Temperature-rise images were compared between moving and stationary experiments. Heating spots and corresponding temperature-rise plots matched very well. The stationary sonication had a temperature standard deviation of 0.15 degrees C compared to values of 0.28 degrees C and 0.43 degrees C measured for two manually moved sonications at different velocities. Moving the phantom (while not heating) with respect to the transducer did not cause false temperature rises, despite susceptibility changes. The system was tested on nonheated livers of five normal volunteers. The mean temperature rise was -0.05 degrees C, with a standard deviation of 1.48 degrees C. This standard deviation is acceptable for monitoring high-intensity focused ultrasound ablations, suggesting real-time imaging of moving high-intensity focused ultrasound sonications can be clinically possible.

Reweighted ℓ1 referenceless PRF shift thermometry.

Temperature estimation in proton resonance frequency (PRF) shift MR thermometry requires a reference, or pretreatment, phase image that is subtracted from image phase during thermal treatment to yield a phase difference image proportional to temperature change. Referenceless thermometry methods derive a reference phase image from the treatment image itself by assuming that in the absence of a hot spot, the image phase can be accurately represented in a smooth (usually low order polynomial) basis. By masking the hot spot out of a least squares (ℓ(2)) regression, the reference phase image's coefficients on the polynomial basis are estimated and a reference image is derived by evaluating the polynomial inside the hot spot area. Referenceless methods are therefore insensitive to motion and bulk main field shifts, however, currently these methods require user interaction or sophisticated tracking to ensure that the hot spot is masked out of the polynomial regression. This article introduces an approach to reference PRF shift thermometry that uses reweighted ℓ(1) regression, a form of robust regression, to obtain background phase coefficients without hot spot tracking and masking. The method is compared to conventional referenceless thermometry, and demonstrated experimentally in monitoring HIFU heating in a phantom and canine prostate, as well as in a healthy human liver.

Hybrid referenceless and multibaseline subtraction MR thermometry for monitoring thermal therapies in moving organs.

PURPOSE: Magnetic resonance thermometry using the proton resonance frequency (PRF) shift is a promising technique for guiding thermal ablation. For temperature monitoring in moving organs, such as the liver and the heart, problems with motion must be addressed. Multi-baseline subtraction techniques have been proposed, which use a library of baseline images covering the respiratory and cardiac cycle. However, main field shifts due to lung and diaphragm motion can cause large inaccuracies in multi-baseline subtraction. Referenceless thermometry methods based on polynomial phase regression are immune to motion and susceptibility shifts. While referenceless methods can accurately estimate temperature within the organ, in general, the background phase at organ/tissue interfaces requires large polynomial orders to fit, leading to increased danger that the heated region itself will be fitted by the polynomial and thermal dose will be underestimated. In this paper, a hybrid method for PRF thermometry in moving organs is presented that combines the strengths of referenceless and multi-baseline thermometry. METHODS: The hybrid image model assumes that three sources contribute to image phase during thermal treatment: Background anatomical phase, spatially smooth phase deviations, and focal, heat-induced phase shifts. The new model and temperature estimation algorithm were tested in the heart and liver of normal volunteers, in a moving phantom HIFU heating experiment, and in numerical simulations of thermal ablation. The results were compared to multi-baseline and referenceless methods alone. RESULTS: The hybrid method allows for in vivo temperature estimation in the liver and the heart with lower temperature uncertainty compared to multi-baseline and referenceless methods. The moving phantom HIFU experiment showed that the method accurately estimates temperature during motion in the presence of smooth main field shifts. Numerical simulations illustrated the method's sensitivity to algorithm parameters and hot spot features. CONCLUSIONS: This new hybrid method for MR thermometry in moving organs combines the strengths of both multi-baseline subtraction and referenceless thermometry and overcomes their fundamental weaknesses.

MR imaging-guided percutaneous cryoablation of the prostate in an animal model: in vivo imaging of cryoablation-induced tissue necrosis with immediate histopathologic correlation.

PURPOSE: To evaluate the feasibility of magnetic resonance (MR) imaging-guided percutaneous cryoablation of normal canine prostates and to identify MR imaging features that accurately predict the area of tissue damage at a microscopic level. MATERIALS AND METHODS: Six adult male mixed-breed dogs were anesthetized, intubated, and placed in a 0.5-T open MR imaging system. A receive-only endorectal coil was placed, and prostate location and depth were determined on T1-weighted fast spin-echo (FSE) MR imaging. After placement of cryoprobes and temperature sensors, three freezing protocols were used to ablate prostate tissue. Ice ball formation was monitored with T1-weighted FSE imaging. Tissue necrosis area was assessed with contrast-enhanced weighted MR imaging and compared with histopathologic findings. RESULTS: A total of 12 cryolesions (mean size, 1.2 cm) were bilaterally created in six prostates. Ice ball formation was oval and signal-free on T1-weighted FSE sequences in all cases. Postprocedural contrast-enhanced MR imaging typically showed a nonenhancing area of low signal intensity centrally located within the frozen area, surrounded by a bright enhancing rim in all cases. On histopathologic examination, two distinct zones were identified within cryolesions. Centrally, a necrotic zone with complete cellular destruction and hemorrhage was found. Between this necrotic zone and normal glandular tissue, a zone of fragmented and intact glands, interstitial edema, and rare acute inflammatory cells was seen. Correlation between nonenhancement on contrast-enhanced weighted MR images and tissue necrosis on pathologic examination was consistent within all six dogs. CONCLUSIONS: MR imaging-guided cryoablation of the prostate is technically feasible. The nonenhancing area on postablation contrast-enhanced weighted MR imaging accurately predicts the area of cryoablation-induced tissue necrosis on pathologic analysis.