Transient Extensive Edema as a Rare Complication of MRgFUS Thalamotomy.

The Effect of Contouring Variability on Dosimetric Parameters for Brain Metastases Treated With Stereotactic Radiosurgery

Objective To quantitatively assess the plan quality of conventional fractionated volumetric modulated arc therapy (VMAT) plans for liver cancer treatments using flattening filter-free (FFF) and flattening filter (FF) modes based on plan quality metric (PQM). Methods A total of ten patients with liver tumor were selected. The patients were planned in FF and FFF mode of 6 MV X-ray respectively. The dose distribution of the planning target volume (PTV) and the organ at risk (OAR) were evaluated, and the monitor units (MUs) and the beam on time (BoT) were compared. According to the clinical requirements, a PQM with 16 submetrics was defined to evaluate the plan quality of the two modes. Results The maximal dose of FFF plan was less than that of FF plan (t=3.828, P<0.05). The normalized volume of 5 Gy (V5) and mean dose (Dmean) of the normal liver of FFF plan were lower than those of the FF plan (t=2.716, 3.007, P<0.05). The average MU of FFF plan [(574±130) MU] was higher than that of FF plan [(518±81) MU](t=-2.782, P<0.05), while the average BoT of FFF plan [(108±36)s] was significantly lower than that of FF plan [(160±29) s](t=6.767, P<0.05). The score of FFF plan was higher than that of FF plan (t=-2.746, P<0.05). Conclusions FFF mode can better protect the OAR at low dose levels. The MU of FFF mode plan were higher, but the beam on time was significantly lower than FF mode plan. With reference to the PQM evaluation criteria, the overall plan quality of the FFF mode was slightly higher. Key words: Plan quality metric; Flattening filter-free; Liver cancer; Volumetric modulated arc therapy; Dosimetry

A retrospective study to establish recommendations for plan quality metrics in Lung SBRT.

Implementation of automation routines leveraging deep learning (DL) methods has been a growing topic of interest. The focus of this work is on the Gamma Knife (GK) workflow, specifically the approximation of dose distributions from GK plan parameters and the prediction of dose distributions using DL. These works contribute towards the larger goal of treatment plan prediction and are seen as intermediate steps towards that end. The approximation of dose distributions was motivated by the closed nature of the GK system, which causes complications with the evaluation of the predictions made by the DL models. The approximation utilizes a superposition method, accumulating dose from a basis set of dose distributions which correspond to specific sector activations of the GK system. The approximation method was compared to the original dose distributions calculated by the GK treatment planning system (TPS), Leksell GammaPlan, for 30 patients using the similarity metrics of Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) as well as the plan quality metrics of coverage, selectivity, and gradient index. In the range of clinical planning significance, the metrics reported strong agreement to the original calculation (DSC > 0.85, HD < 2.5mm, coverage difference = 0.014 ± 0.035, selectivity difference = 0.008 ± 0.037, and gradient index difference = 0.118 ± 0.192). The second focus of this work was to improve the performance of DL models used to predict dose distributions from target contour information. This was accomplished by applying transforms to the binary target contour volumes, resulting in alternate model input channels that encode the distance of each voxel to the boundary of the nearest contour, both within and outside of the contours. Training and evaluation were performed with a standard UNet and HD-UNet architecture for large and small targets separately. DSC and Predictions resulting from these encodings resulted in significantly better predictions (p < 0.05) than their binary target counterparts at all (excluding 90% isodose for the HD-Unet) threshold levels for small targets. The large target trainings were significantly (p < 0.05) improved in the mid-to-high dose ranges.

The Radixact Synchrony system allows for target motion correction when tracking either fiducials in/around the target or a dense lesion in the lung. As such evaluation testing and quality assurance (QA) tests are required. To allow for QA procedures to be performed with a range of available phantoms evaluation of the dosimetric delivery accuracy was performed for a range of motions, phantoms, and motion platforms. A Computerized Imaging Reference Systems, Incorporated (CIRS) 1D motion platform and Accuray Tomotherapy "Cheese" phantom was utilized to perform absolute dose and GafChromic EBT3 film measurements. A HexaMotion platform and Delta4 phantom were utilized to quantify the effects of 1D and 3D motions. Inter-device comparison was performed with the ArcCHECK and Delta4 phantoms and GafChromic EBT3 film, five patient plans were delivered to each phantom when static and with two different motion types both with and without Synchrony motion correction. A range of QA tests are described. A phantom was designed to allow for daily verification of system functionality. This test allows for the detection of either fiducials or a dense silicone target with a stationary phantom. Monthly testing procedures are described that allow the user to verify the dosimetric improvement when utilizing synchrony delivery motion compensation versus uncorrected motions. These can be performed utilizing a 1D motion stage with an ion-chamber and GafChromic EBT3 film to allow for a 2D dosimetric validation. Alternatively, a 3D motion platform can be utilized where available. Monthly and annual imaging tests are described. Finally, annual test procedures designed to verify the coincidence of the imaging system and treatment isocenter are described. The evaluation of the Synchrony system using a range of QA devices shows consistently high dosimetric accuracy with similar trends in passing criteria found with GafChromic EBT3 film, ArcCHECK, and Delta4 phantoms for density-based respiratory model compensation. These results highlight the large improvements in the dose distribution when motion is accounted for with the Synchrony system as measured with a range of phantoms and motion platforms that the majority of users will have available. The testing methods and QA procedures described provide guidance for new users of the Radixact Synchrony system as they implement their own QA programs for this system, until such time as an AAPM task group report is made available. QA procedures including Kilovolts (kV) imaging quality metrics and imaging dose parameters, dose deposition accuracy, target detection coincidence, and target position detection accuracy are described.

Fine-tuning the normal tissue objective in eclipse for lung stereotactic body radiation therapy

In this prospective study we investigated the absolute accuracy of the conventional simulation in head and skull base tumors. 41 isocenters in 40 consecutive patients with tumors of the head and skull base were included. In all cases a rigid stereotactic mask system was used for non-invasive fixation. The stereotactic ("calculated") coordinates of the isocenter were defined by the treatment planning computer. Each patient underwent a physical simulation using exclusively anatomical reference points to define the "preliminary" isocenter. The displacement between its coordinates and those of the stereotactic target point was recorded in X-, Y- and Z-direction with help of the targeting device, and the spatial error was calculated. Additionally, the patients were stratified by basal or calvarial tumor site to estimate the importance of the basal bone structures in the simulation accuracy. The influence of the learning effect on simulation accuracy was also determined. The results showed an accuracy of set-up at the linac within 1 mm in all three directions as calculated from orthogonal portal films. Mean shift of the isocenter coordinates obtained from physical simulation compared to the calculated stereotactic coordinates was 2.15 mm, 2.54 mm, and 2.69 mm for X-, Y-, and Z-direction, respectively. Mean spatial displacement amounted 5.06 mm, and the median was 4.50 mm. No significant difference could be noted between basal and calvarial location of the isocenter. A significant "learning effect" was observed with a decrease in spatial shift with increasing patient numbers. This effect was stronger in basal lesions, whereas calvarial lesions showed only a minor, insignificant effect. In conclusion, a physical simulation requires a safety margin of 5 mm in PTV definition in addition to other factors, e.g. organ movement.

The object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C-54°C. Seventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors' institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = -0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance-induced spatial-shifting artifacts. Mean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C-54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor. In transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.

Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes. The authors queried the MarketScan database (2007-2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs. The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non-CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6-13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2-44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7-5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5-4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001). The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.

Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose &lt; 6 CEM43&deg;C and T &lt; 45&deg;C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose &gt; 240 CEM43&deg;C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

Update on Peritoneal Dialysis: Core Curriculum 2016

The fundamental goal of ultrasound thermal therapy is to provide proper thermal lesion formations for effective tumour treatment. The quality of the therapy depends mostly on its positional precision. To date, most ultrasound thermal therapy treatments have focused on the formation of power or temperature patterns. The non-linear and time-delay effects of thermal dose formation prohibit direct control of the thermal dose distribution. In the paper, the control of thermal lesions by regulation of the temperature of a pilot point is proposed. This scheme utilises the high correlation between temperature elevation and thermal dose at the forward boundary of thermal lesions. To verify the feasibility, a 2D ultrasound phased array system was used to generate thermal lesions of various sizes, and the temperature elevation required to generate a thermal dose threshold was investigated. Results showed that the required temperature elevation was found to be a reasonably constant value of 52.5 degrees C under differing conditions when the focal area was small. When the focal area under consideration was large, the required temperature elevation became a monotonic function of blood perfusion rate, ranging from 49.2 to 52.5 degrees C. When the reference temperature of the pilot point was set at a conservative value (52.5 degrees C), the thermal lesions were controlled precisely under a wide range of blood perfusion and power pattern changes, tested by using a more realistic model that takes into account thermal-induced attenuation and blood perfusion changes. This changed the complex thermal dose control problem into a simple temperature regulation problem, which makes implementation of thermal lesion control easier, giving the scheme a high potential for application to current ultrasound thermal therapy systems.

Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 – 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, bladder, seminal vesicles) were manually segmented (Mimics, Materialise) and converted to 3D finite element meshes (3-Matic, Materialise). The chosen test cases consisted of patients with medium and large sized glands and models of bulk tissue ablation covered volumes in a single quadrant in posterior prostate, hemi-gland targets and “hockey-stick” targets (lesions in three quadrants). Ultrasound applicator placement was determined such that devices were positioned along the prostate periphery while avoiding surrounding anatomy. Transducer sector angles were chosen based on applicator location within limits of fabrication practicability. Thermal models were numerically solved using finite element methods (FEM) in COMSOL Multiphysics. Temperature and thermal dose distributions were calculated to determine treated volumes (> 240 CEM43C, >52 °C) and safety profiles (<10 CEM43C, <45 °C) for nerve, rectal and urethral sparing. Modeling studies indicated that focal targets could be ablated with single or multiple interstitial applicators placed along the prostate periphery. In the representative cases explored during this study, thermal targets could be ablated with acoustic intensity values between 11 – 19 W/cm2 within 6 – 15 min of sonication time. Unifocal ablation could be performed by a single directional applicator (210° sectors). Hemi-gland targets were ablated by two directional applicators (210° sectors). Hockey-stick ablations were performed using 3 directional applicators (2 - 210° and 1 - 150°).

The purpose of this study is to investigate the feasibility and performance of a stationary, non-focused dual-sectored tubular transurethral ultrasound applicator for thermal exposure of tissue regions adjacent to the urethra for treatment of stress urinary incontinence (SUI) through acoustic and biothermal simulations on 3D anatomical models. Parametric studies in a generalized tissue model over dual-sectored ultrasound applicator configurations (acoustic surface intensities, lateral active acoustic output sector angles, and durations) were performed. Selected configurations and delivery strategies were applied on 3D pelvic anatomical models. Temperature and thermal dose distributions on the target region and surrounding tissues were calculated. Endovaginal cooling was explored as a strategy to mitigate vaginal heating. The 75-90° dual-sectored transurethral tubular transducer (3.5mm outer diameter (OD), 14mm length, 6.5MHz, 8.8-10.2W/cm2) and 2-3-min sonication duration were selected from the parametric study for acoustic and biothermal simulations on anatomical models. The transurethral applicator with two opposing 75-90° active lateral tubular sectors can create two heated volumes for a total of up to 1.8cm3 over 60 EM43°C, with at least 10mm radial penetration depth, 1.2mm urethral sparing, and no lethal damage to the vagina and adjacent bone (< 60 EM43°C). Endovaginal cooling can be applied to further reduce the vaginal wall exposure (< 15 EM43°C). Simulations on 3D anatomical models indicate that dual-sectored transurethral ultrasound applicators can selectively heat pelvic floor tissue lateral to the mid-urethra in short treatment durations, without damaging adjacent vaginal and bone tissues, as a potential alternative treatment option for stress urinary incontinence. Graphical abstract Schema for in silico investigation of transurethral ultrasound thermal therapy applicator for minimally invasive treatment of SUI.

γ+ index: A new evaluation parameter for quantitative quality assurance