Contextual predictors of self-management and independence trajectories in adolescents and young adults with spina bifida.

AIM: To examine socioeconomic, condition-related, and neuropsychological predictors of self-management trajectories in adolescents and young adults with spina bifida. METHOD: In this longitudinal study, participants completed the Adolescent/Young Adult Self-Management and Independence Scale interview. Socioeconomic status (SES), shunt status, lesion level, and executive functioning were assessed. Growth in self-management was estimated using linear mixed-effects models. RESULTS: Participants (n = 99) were aged 18 to 27 years. Approximately half (52.5%) were female and White; 15.2% were Black; and 32.3% Hispanic or Latino. Although none of the predictors were associated with growth in self-management from ages 18 to 27 years (p > 0.05), several factors were associated with the intercept at age 18 years for total self-management. Higher SES at baseline predicted a higher total self-management score at age 18 years (b = 0.03, standard error [SE] = 0.01; p < 0.001). On average, participants at age 18 years with a shunt scored lower than those without a shunt (b = -0.90, SE = 0.32; p = 0.01); those with a thoracic lesion scored lower than those with lower lesion levels (lumbar: b = -1.22, SE = 0.34; sacral: b = -1.20, SE = 0.36; p = 0.001 for both). Better parent-reported and teacher-reported executive functions predicted higher total self-management (metacognitive: b = -0.03, SE = 0.01; behavioral regulation: b = -0.04, SE = 0.01; p < 0.05 for both). INTERPRETATION: On average, all participants improved in self-management over time. Additionally, baseline superiority in self-management for adolescents and young adults without a shunt, less severe lesions, better executive functions, and higher SES persisted over time.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain.

OBJECTIVE: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. METHODS: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. RESULTS: Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. CONCLUSIONS: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

REhabilitation Approaches in CHildren with cerebellar mutism syndrome (REACH): An international cross-disciplinary survey study.

PURPOSE: Pediatric cerebellar mutism syndrome (pCMS) can occur following resection of a posterior fossa tumor and, although some symptoms are transient, many result in long-lasting neurological deficits. A multi-disciplinary rehabilitation approach is often used in cases of pCMS; however, there have been no clinical trials to determine gold standards in rehabilitation practice in this population, which remains a research priority. The purpose of this study was to identify and compare intervention practices used in pCMS throughout the disciplines of occupational and physical therapy, speech-language pathology, and neuropsychology across geographic regions. METHODS: A 55-question e-survey was created by an international multidisciplinary research group made up of members of the Posterior Fossa Society and sent to rehabilitation professionals in pediatric neuro-oncology centers in the US, Canada, and Europe. RESULTS: Although some differences in the type of intervention used in pCMS were identified within each discipline, many of the targeted interventions including dose, frequency, and intensity were similar within disciplines across geographic regions. In addition, there were common themes identified across disciplines regarding challenges in the rehabilitation of this population. CONCLUSION: These results provide a foundation of current practices on which to build future intervention-based clinical trials.

Evaluation of acoustic-thermal simulations of in vivo magnetic resonance guided focused ultrasound ablative therapy.

PURPOSE: To evaluate numerical simulations of focused ultrasound (FUS) with a rabbit model, comparing simulated heating characteristics with magnetic resonance temperature imaging (MRTI) data collected during in vivo treatment. METHODS: A rabbit model was treated with FUS sonications in the biceps femoris with 3D MRTI collected. Acoustic and thermal properties of the rabbit muscle were determined experimentally. Numerical models of the rabbits were created, and tissue-type-specific properties were assigned. FUS simulations were performed using both the hybrid angular spectrum (HAS) method and k-Wave. Simulated power deposition patterns were converted to temperature maps using a Pennes' bioheat equation-based thermal solver. Agreement of pressure between the simulation techniques and temperature between the simulation and experimental heating was evaluated. Contributions of scattering and absorption attenuation were considered. RESULTS: Simulated peak pressures derived using the HAS method exceeded the simulated peak pressures from k-Wave by 1.6 ± 2.7%. The location and FWHM of the peak pressure calculated from HAS and k-Wave showed good agreement. When muscle acoustic absorption value in the simulations was adjusted to approximately 54% of the measured attenuation, the average root-mean-squared error between simulated and experimental spatial-average temperature profiles was 0.046 ± 0.019 °C/W. Mean distance between simulated and experimental COTMs was 3.25 ± 1.37 mm. Transverse FWHMs of simulated sonications were smaller than in in vivo sonications. Longitudinal FWHMs were similar. CONCLUSIONS: Presented results demonstrate agreement between HAS and k-Wave simulations and that FUS simulations can accurately predict focal position and heating for in vivo applications in soft tissue.

Testing the effectiveness of interactive training on sexual harassment and assault in field science.

Fieldwork is a critical tool for scientific research, particularly in applied disciplines. Yet fieldwork is often unsafe, especially for members of historically marginalized groups and people whose presence in scientific spaces threatens traditional hierarchies of power, authority, and legitimacy. Research is needed to identify interventions that prevent sexual harassment and assault from occurring in the first place. We conducted a quasi-experiment assessing the impacts of a 90-min interactive training on field-based staff in a United States state government agency. We hypothesized that the knowledge-based interventions, social modeling, and mastery experiences included in the training would increase participants' sexual harassment and assault prevention knowledge, self-efficacy, behavioural intention, and behaviour after the training compared to a control group of their peers. Treatment-control and pre-post training survey data indicate that the training increased participants' sexual harassment and assault prevention knowledge and prevention self-efficacy, and, to a lesser extent, behavioural intention. These increases persisted several months after the training for knowledge and self-efficacy. While we did not detect differences in the effect of the training for different groups, interestingly, post-hoc tests indicated that women and members of underrepresented racial groups generally scored lower compared to male and white respondents, suggesting that these groups self-assess their own capabilities differently. Finally, participants' likelihood to report incidents increased after the training but institutional reports remained low, emphasizing the importance of efforts to transform reporting systems and develop better methods to measure bystander actions. These results support the utility of a peer-led interactive intervention for improving workplace culture and safety in scientific fieldwork settings. PROTOCOL REGISTRATION: "The stage 1 protocol for this Registered Report was accepted in principle on August 24, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.21770165 .

A Non-Contrast Multi-Parametric MRI Biomarker for Assessment of MR-Guided Focused Ultrasound Thermal Therapies.

OBJECTIVE: We present the development of a non-contrast multi-parametric magnetic resonance (MPMR) imaging biomarker to assess treatment outcomes for magnetic resonance-guided focused ultrasound (MRgFUS) ablations of localized tumors. Images obtained immediately following MRgFUS ablation were inputs for voxel-wise supervised learning classifiers, trained using registered histology as a label for thermal necrosis. METHODS: VX2 tumors in New Zealand white rabbits quadriceps were thermally ablated using an MRgFUS system under 3 T MRI guidance. Animals were re-imaged three days post-ablation and euthanized. Histological necrosis labels were created by 3D registration between MR images and digitized H&E segmentations of thermal necrosis to enable voxel-wise classification of necrosis. Supervised MPMR classifier inputs included maximum temperature rise, cumulative thermal dose (CTD), post-FUS differences in T2-weighted images, and apparent diffusion coefficient, or ADC, maps. A logistic regression, support vector machine, and random forest classifier were trained in red a leave-one-out strategy in test data from four subjects. RESULTS: In the validation dataset, the MPMR classifiers achieved higher recall and Dice than a clinically adopted 240 cumulative equivalent minutes at 43 °C (CEM 43) threshold (0.43) in all subjects. The average Dice scores of overlap with the registered histological label for the logistic regression (0.63) and support vector machine (0.63) MPMR classifiers were within 6% of the acute contrast-enhanced non-perfused volume (0.67). CONCLUSIONS: Voxel-wise registration of MPMR data to histological outcomes facilitated supervised learning of an accurate non-contrast MR biomarker for MRgFUS ablations in a rabbit VX2 tumor model.

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain.

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. Methods: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. Results: Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

Simultaneous proton resonance frequency T1 - MR shear wave elastography for MR-guided focused ultrasound multiparametric treatment monitoring.

PURPOSE: To develop an efficient MRI pulse sequence to simultaneously measure multiple parameters that have been shown to correlate with tissue nonviability following thermal therapies. METHODS: A 3D segmented EPI pulse sequence was used to simultaneously measure proton resonance frequency shift (PRFS) MR thermometry (MRT), T1 relaxation time, and shear wave velocity induced by focused ultrasound (FUS) push pulses. Experiments were performed in tissue mimicking gelatin phantoms and ex vivo bovine liver. Using a carefully designed FUS triggering scheme, a heating duty cycle of approximately 65% was achieved by interleaving FUS ablation pulses with FUS push pulses to induce shear waves in the tissue. RESULTS: In phantom studies, temperature increases measured with PRFS MRT and increases in T1 correlated with decreased shear wave velocity, consistent with material softening with increasing temperature. During ablation in ex vivo liver, temperature increase measured with PRFS MRT initially correlated with increasing T1 and decreasing shear wave velocity, and after tissue coagulation with decreasing T1 and increasing shear wave velocity. This is consistent with a previously described hysteresis in T1 versus PRFS curves and increased tissue stiffness with tissue coagulation. CONCLUSION: An efficient approach for simultaneous and dynamic measurements of PRSF, T1 , and shear wave velocity during treatment is presented. This approach holds promise for providing co-registered dynamic measures of multiple parameters, which correlates to tissue nonviability during and following thermal therapies, such as FUS.

Validation of a drift-corrected 3D MR temperature imaging sequence for breast MR-guided focused ultrasound treatments.

Real-time temperature monitoring is critical to the success of thermally ablative therapies. This work validates a 3D thermometry sequence with k-space field drift correction designed for use in magnetic resonance-guided focused ultrasound treatments for breast cancer. Fiberoptic probes were embedded in tissue-mimicking phantoms, and temperature change measurements from the probes were compared with the magnetic resonance temperature imaging measurements following heating with focused ultrasound. Precision and accuracy of measurements were also evaluated in free-breathing healthy volunteers (N = 3) under a non-heating condition. MR temperature measurements agreed closely with those of fiberoptic probes, with a 95% confidence interval of measurement difference from -2.0 °C to 1.4 °C. Field drift-corrected measurements in vivo had a precision of 1.1 ± 0.7 °C and were accurate within 1.3 ± 0.9 °C across the three volunteers. The field drift correction method improved precision and accuracy by an average of 46 and 42%, respectively, when compared to the uncorrected data. This temperature imaging sequence can provide accurate measurements of temperature change in aqueous tissues in the breast and support the use of this sequence in clinical investigations of focused ultrasound treatments for breast cancer.

Consensus on an implicit bias and health disparities curriculum in neonatal medicine: a Delphi study.

OBJECTIVE: Despite longstanding and recurrent calls for effective implicit bias (IB) education in health professions education as one mechanism to reduce ongoing racism and health disparities, such curricula for neonatal-perinatal medicine (NPM) are limited. We aim to determine the key curricular elements for educating NPM fellows, advanced practice providers, and attending physicians in the critical topics of IB and health disparities. STUDY DESIGN: A modified Delphi study was performed with content experts in IB and health disparities who had educational relationships to those working and training in the neonatal intensive care unit. RESULT: Three Delphi rounds were conducted from May to November 2021. Experts reached consensus on a variety of items for inclusion in the curriculum, including educational goals, learning objectives, teaching strategies, and educator principles. CONCLUSION: Essential curricular components of an IB and health disparities curriculum for neonatal medicine were defined using rigorous consensus building methodology.

Flipping the Teachers: Impact of a Standardized Physiology Curriculum on Neonatology Medical Educators.

OBJECTIVE: Academic physicians must teach elements in an Accreditation Council for Graduate Medical Education (ACGME)-mandated curriculum while balancing career development and clinical workload. Exploring educator perceptions on the learning environment and comparing two instructional methods (traditional didactics [TD] vs. flipped classroom [FC]) in one pediatric subspecialty may elucidate current challenges, barriers, and strategies to optimize learning and educator satisfaction. STUDY DESIGN: A randomized trial comparing effectiveness and learner preference for FC versus TD physiology teaching was conducted in ACGME-accredited neonatal-perinatal medicine (NPM) fellowship programs in 2018 to 2019. Educator preferences were elicited through online surveys pre- and postintervention. Free-text comments were provided for questions exploring strengths, challenges, and opportunities in fellowship education. Statistical analysis included comparisons of demographics and pre-post-intervention educator responses between groups. Thematic analysis of text responses was conducted to identify common subthemes. RESULTS: From 61 participating programs, 114 FC educators and 130 TD educators completed surveys. At baseline, all educators experienced professional satisfaction from teaching fellows, but noted challenges with time available to create and/or deliver educational content, limited content expertise amongst faculty, colleagues' limited enthusiasm toward educating fellows, and lack of perceived value of education by institutions given limited protected time or credit toward promotion. Postintervention, educators in both groups noted a preference to teach physiology using FC due to interactivity, learner enthusiasm, and learner-centeredness. FC educators had a 17% increase in preference to teach using FC (p = 0.001). Challenges with FC included ensuring adequate trainee preparation, protecting educational time, and providing educators with opportunities to develop facilitation skills. CONCLUSION: Overall, NPM educators in a trial evaluating a standardized, peer-reviewed curriculum report professional satisfaction from teaching, but described logistical challenges with developing/delivering content. Educators preferred instruction using FC, but identified challenges with learner preparedness and ensuring adequate educator time and skill. Future efforts should be dedicated to addressing these barriers. KEY POINTS: · Many challenges exist for educators teaching neonatal-perinatal medicine fellows, including time, support, and recognition.. · Many educators preferred using flipped classroom methodology with a standardized curriculum due to interactivity and learner-centeredness.. · Benefits of a standardized, peer-reviewed curriculum include reduced preparation time, adaptability of content, and learning environment enhancement..

Comparison of knowledge acquisition and retention following traditional didactic vs. flipped classroom education utilizing a standardized national curriculum: a randomized controlled trial.

OBJECTIVE: Measure the effectiveness of and preference for a standardized, national curriculum utilizing flipped classrooms (FC) in neonatal-perinatal medicine (NPM) fellowships. STUDY DESIGN: Multicentered equivalence, cluster randomized controlled trial of NPM fellowship programs randomized to receive standardized physiology education as in-class lectures (traditional didactic, TD arm) or as pre-class online videos followed by in-class discussions (FC arm). Four multiple-choice question quizzes and three surveys were administered to measure knowledge acquisition, retention, and educational preferences. RESULTS: 530 fellows from 61 NPM fellowships participated. Quiz performance was comparable between groups at all time points (p = NS, TD vs FC at 4 time points). Post intervention, more fellows in both groups preferred group discussions (pre/post FC 42% vs. 58%, P = 0.002; pre/post TD 43% vs. 60%, P = < 0.001). FC fellows were more likely to rate classroom effectiveness positively (FC/TD, 70% vs. 36%, P < 0.001). CONCLUSIONS: FCs promote knowledge acquisition and retention equivalent to TD and FC modalities are preferred by fellows.

A k-space-based method to measure and correct for temporal B0 field variations in MR temperature imaging.

PURPOSE: Present a method to use change in phase in repeated Cartesian k-space measurements to monitor the change in magnetic field for dynamic MR temperature imaging. METHODS: The method is applied to focused ultrasound heating experiments in a gelatin phantom and an ex vivo salt pork sample, without and with simulated respiratory motion. RESULTS: In each experiment, phase variations due to B0 field drift and respiration were readily apparent in the measured phase difference. With correction, the SD of the temperature over time was reduced from 0.18°C to 0.14°C (no breathing) and from 0.81°C to 0.22°C (with breathing) for the gelatin phantom, and from 0.68°C to 0.13°C (no breathing) and from 1.06°C to 0.17°C (with breathing) for the pork sample. The accuracy in nonheated regions, assessed as the RMS error deviation from 0°C, improved from 1.70°C to 1.11°C (no breathing) and from 4.73°C to 1.47°C (with breathing) for the gelatin phantom, and from 5.95°C to 0.88°C (no breathing) and from 13.40°C to 1.73°C (with breathing) for the pork sample. The correction did not affect the temperature measurement accuracy in the heated regions. CONCLUSION: This work demonstrates that phase changes resulting from variations in B0 due to drift and respiration, commonly seen in MR thermometry applications, can be measured directly from 3D Cartesian acquisition methods. The correction of temporal field variations using the presented technique improved temperature accuracy, reduced variability in nonheated regions, and did not reduce accuracy in heated regions.

Essentials of neonatal-perinatal medicine fellowship: innovations in medical education.

Due to the changing complex healthcare environment, educational innovation is essential to meet the needs of current and future neonatal-perinatal medicine (NPM) leaders. Greater clinical demands, decreased academic funding, and expanded graduate medical education program requirements have negatively impacted time for teaching and educational scholarship potentially limiting innovation in the field. By focusing on adult learning principles, embracing technology, and promoting collaboration, today's educators are preparing the next generation of neonatologists. Current innovations include regionalizing simulation boot camps, leveraging virtual learning to increase accessibility, developing niche training opportunities, and incorporating population health principles within existing quality initiatives. Areas in need of additional innovation include faculty and fellow development for teaching skills, expansion of educational networks, and dissemination and financial support of educational scholarship. These efforts and future innovations will require medical institutions and national NPM organizations to further invest in the medical educator as part of their missions.

DNA methylation in former extremely low birth weight newborns: association with cardiovascular and endocrine function.

BACKGROUND: There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations. METHODS: School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element. RESULTS: We observed a modest correlation between log AUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor (GR in term-born infants. There was an association between LINE1 methylation and cortisol response to awakening and a negative correlation between LINE1 and systolic blood pressure at 6-7 years. Methylation of the GR promoter region showed a positive association with systolic blood pressure at 6-7 years of age. CONCLUSIONS: These results show that extremely preterm birth, followed by complex patterns of endocrine, cardiovascular, and metabolic exposures during early postnatal life, is associated with lasting changes in DNA methylation patterns in genes involved in hypothalamic pituitary adrenal axis function, adrenal hormonal regulation, and cardiometabolic risk. IMPACT: Preterm infants have significant environmental and physiological exposures during early life that may have lasting impact on later function. Alterations in hypothalamic pituitary adrenal axis (HPA) function have been associated with these exposures. We examined the associated changes in DNA methylation of important genes involved in HPA function, metabolism, and global DNA methylation. The changes we saw in DNA methylation may help to explain associated cardiovascular, metabolic, and growth disturbance in these children in later life.

Experimental validation of acoustic and thermal modeling in heterogeneous phantoms using the hybrid angular spectrum method.

PURPOSE: The aim was to quantitatively validate the hybrid angular spectrum (HAS) algorithm, a rapid wave propagation technique for heterogeneous media, with both pressure and temperature measurements. METHODS: Heterogeneous tissue-mimicking phantoms were used to evaluate the accuracy of the HAS acoustic modeling algorithm in predicting pressure and thermal patterns. Acoustic properties of the phantom components were measured by a through-transmission technique while thermal properties were measured with a commercial probe. Numerical models of each heterogeneous phantom were segmented from 3D MR images. Cylindrical phantoms 30-mm thick were placed in the pre-focal field of a focused ultrasound beam and 2D pressure measurements obtained with a scanning hydrophone. Peak pressure, full width at half maximum, and normalized root mean squared difference (RMSDn) between the measured and simulated patterns were compared. MR-guided sonications were performed on 150-mm phantoms to obtain MR temperature measurements. Using HAS-predicted power density patterns, temperature simulations were performed. Experimental and simulated temperature patterns were directly compared using peak and mean temperature plots, RMSDn metrics, and accuracy of heating localization. RESULTS: The average difference between simulated and hydrophone-measured peak pressures was 9.0% with an RMSDn of 11.4%. Comparison of the experimental MRI-derived and simulated temperature patterns showed RMSDn values of 10.2% and 11.1% and distance differences between the centers of thermal mass of 2.0 and 2.2 mm. CONCLUSIONS: These results show that the computationally rapid hybrid angular spectrum method can predict pressure and temperature patterns in heterogeneous models, including uncertainties in property values and other parameters, to within approximately 10%.

Histology to 3D in vivo MR registration for volumetric evaluation of MRgFUS treatment assessment biomarkers.

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options.

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

A T1-based correction method for proton resonance frequency shift thermometry in breast tissue.

PURPOSE: Develop and evaluate the effectiveness of a T1-based correction method for errors in proton resonant frequency shift thermometry due to non-local field effects caused by heating in fatty breast tissues. METHODS: Computational models of human breast tissue were created by segmenting MRI data from a healthy human volunteer. MR-guided focused ultrasound (MRgFUS) heating and MR thermometry measurements were simulated in several locations in the heterogeneous segmented breast models. A T1-based correction method for PRF thermometry errors was applied and the maximum positive and negative errors and the root mean squared error (RMSE) in a region around each heating location was evaluated with and without correction. The method uses T1 measurements to estimate the temperature change in fatty tissues and correct for their influence. Experimental data from a heating study in cadaver breast tissue were analyzed, and the expected PRFS error computed. RESULTS: The simulated MR thermometry had maximum single voxel errors ranging between 10% and 18% when no correction was applied. Applying the correction led to a considerable improvement, lowering the maximum error range to 2%-5%. The 5th to 95th percentile interval of the temperature error distribution was also lowered with correction, from approximately 3.5 to 1°C. This correction worked even when T1 times were uniformly raised or lowered by 5%-10%. The experimental data showed predicted errors of 15%. CONCLUSIONS: This simulation study demonstrates that the T1-based correction method reduces MR thermometry errors due to non-local effects from heating in fatty tissues, potentially improving the accuracy of thermometry measurements during MRgFUS treatments. The presented correction method is reliant on having a patient-specific 3D model of the breast, and may be limited by the accuracy of the fat temperatures which in turn may be limited by noise or bias present in the T1 measurements.

Technical Note: Quantification of blood-spinal cord barrier permeability after application of magnetic resonance-guided focused ultrasound in spinal cord injury.

PURPOSE: To demonstrate that magnetic resonance-guided focused ultrasound (MRgFUS) facilitates blood-spinal cord barrier (BSCB) permeability and develop observer-independent MRI quantification of BSCB permeability after MRgFUS for spinal cord injury (SCI). METHODS: Noninjured Sprague-Dawley rats (n = 3) underwent MRgFUS and were administered Evans blue post-MRgFUS to confirm BSCB opening. Absorbance was measured by spectrophotometry and correlated with its corresponding image intensity. Rats (n = 21) underwent T8-T10 laminectomy and extradural compression of the spinal cord (23g weighted aneurysm-type clip, 1 min). The intervention group (n = 11) was placed on a preclinical MRgFUS system, administered microbubbles (Optison, 0.2 mL/kg), and received 3 MRgFUS sonications (25 ms bursts, 1 Hz pulses for 3 min, 3 acoustic W, approximately 1.0-2.1 MPa peak pressure as measured via hydrophone). The sham group (n = 10) received equivalent procedures with no sonications. T1w MRI was obtained both pre- and post-MRgFUS BSCB opening. Spinal cords were segmented manually or semiautomatically and a Pearson correlation with P ≤ 0.001 was used to correlate the two segmentation methods. MRgFUS sonication and control regions intensity values were evaluated with a paired t-test with a P ≤ 0.01. RESULTS: Semiautomatic segmentation reduced computational time by 95% and was correlated with manual segmentation (Pearson = 0.92, P < 0.001, n = 71 regions). In the noninjured rat group, Evans blue absorbance correlated with image intensity in the MRgFUS and control regions (Pearson = 0.82, P = 0.02, n = 6). In rats that underwent the SCI procedure, an increase in signal intensity in the MRgFUS targeted region relative to control was seen in all SCI rats (10.65 ± 12.4%, range: 0.96-43.9%, n = 11, P = 0.002). SCI sham MRgFUS revealed no change (0.63 ± 0.52%, 95% CI 0.320.95, n = 10). This result was significant between both groups (P = 0.003). CONCLUSION: The implemented semiautomatic segmentation procedure improved data analysis efficiency. Quantitative methods using contrast-enhanced MRI with histological validation are sensitive for detection of blood-spinal cord barrier opening induced by magnetic resonance-guided focused ultrasound.