Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of 'development' and 'validation' cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

High-resolution entry and exit surface dosimetry in a 1.5 T MR-linac.

The magnetic field of a transverse MR-linac alters electron trajectories as the photon beam transits through materials, causing lower doses at flat entry surfaces and increased doses at flat beam-exiting surfaces. This study investigated the response of a MOSFET detector, known as the MOSkin™, for high-resolution surface and near-surface percentage depth dose measurements on an Elekta Unity. Simulations with Geant4 and the Monaco treatment planning system (TPS), and EBT-3 film measurements, were also performed for comparison. Measured MOSkin™ entry surface doses, relative to Dmax, were (9.9 ± 0.2)%, (10.1 ± 0.3)%, (11.3 ± 0.6)%, (12.9 ± 1.0)%, and (13.4 ± 1.0)% for 1 × 1 cm2, 3 × 3 cm2, 5 × 5 cm2, 10 × 10 cm2, and 22 × 22 cm2 fields, respectively. For the investigated fields, the maximum percent differences of Geant4, TPS, and film doses extrapolated and interpolated to a depth suitable for skin dose assessment at the beam entry, relative to MOSkin™ measurements at an equivalent depth were 1.0%, 2.8%, and 14.3%, respectively, and at a WED of 199.67 mm at the beam exit, 3.2%, 3.7% and 5.7%, respectively. The largest measured increase in exit dose, due to the electron return effect, was 15.4% for the 10 × 10 cm2 field size using the MOSkin™ and 17.9% for the 22 × 22 cm2 field size, using Geant4 calculations. The results presented in the study validate the suitability of the MOSkin™ detector for transverse MR-linac surface dosimetry.

Pelvic organ motion and dosimetric implications during horizontal patient rotation for prostate radiation therapy.

PURPOSE: Gantry-free radiation therapy systems utilizing patient rotation would be simpler and more cost effective than the conventional gantry-based systems. Such a system could enable the expansion of radiation therapy to meet global demand and reduce capital costs. Recent advances in adaptive radiation therapy could potentially be applied to correct for gravitational deformation during horizontal patient rotation. This study aims to quantify the pelvic organ motion and the dosimetric implications of horizontal rotation for prostate intensity-modulated radiation therapy (IMRT) treatments. METHODS: Eight human participants who previously received prostate radiation therapy were imaged in a clinical magnetic resonance imaging (MRI) scanner using a bespoke patient rotation system (PRS). The patients were imaged every 45 degrees during a full roll rotation (0-360 degrees). Whole pelvic bone, prostate, rectum, and bladder motion were compared to the supine position using dice similarity coefficient (DSC) and mean absolute surface distance (MASD). Prostate centroid motion was compared in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) direction prior to and following pelvic bone-guided rigid registration. Seven-field prostate IMRT treatment plans were generated for each patient rotation angles under three adaption scenarios: No plan adaption, rigid planning target volume (PTV)-guided alignment to the prostate, and plan re-optimization. Prostate, rectum, and bladder doses were compared for each adaption scenario. RESULTS: Pelvic bone motion within the PRS of up to 53 mm relative to the supine position was observed for some participants. Internal organ motion was greatest at the 180-degree PRS couch angle (prone), with prostate centroid motion range < 2 mm LR, 0 mm to 14 mm SI, and -11 mm to 4 mm AP. Rotation with no adaption of the treatment plan resulted in an underdose to the PTV -- in some instances up to 75% (D95%: 78 ± 0.3 Gy at supine to 20 ± 15.0 Gy at the 225-degree PRS couch angle). Bladder dose was reduced during the rotation by up to 98% (V60 Gy: 15.0 ± 9.4% supine to 0.3 ± 0.5% at the 225-degree PRS couch angle). In some instances, the rectum dose increased during rotation (V60Gy: 20.0 ± 4.5% supine to 25.0 ± 15.0% at the 135-degree PRS couch angle). Rigid PTV-guided alignment resulted in PTV coverage which, though statistically lower (P < 0.05 for all D95% values), was within 1 Gy of the supine plans. Plan re-optimization resulted in a statistically equivalent PTV coverage compared to the supine plans (P > 0.05 for all D95% metrics and all within ±0.4 Gy). For both rigid PTV-guided alignment and plan re-optimization, rectum dose volume metrics were reduced compared to the supine position between the 90- and 225-degree PRS couch angles (P < 0.05). Bladder dose volume metrics were not impacted by rotation. CONCLUSION: Pelvic bone and internal organ motion are present during patient rotation. Rigid PTV-guided alignment to the prostate will be a requirement if prostate IMRT is to be safely delivered using patient rotation. Plan re-optimization for each PRS couch angle to account for anatomical deformations further improves the PTV coverage.

Anatomical deformation due to horizontal rotation: towards gantry-free radiation therapy.

Gantry-free radiation therapy systems may be simpler and more cost effective, particularly for MRI-guided photon or hadron therapy. This study aims to understand and quantify anatomical deformations caused by horizontal rotation with scan sequences sufficiently short to facilitate integration into an MRI-guided workflow. Rigid and non-rigid pelvic deformations due to horizontal rotation were quantified for a cohort of 8 healthy volunteers using a bespoke patient rotation system and a clinical MRI scanner. For each volunteer a reference scan was acquired at 0° followed by sequential faster scans in 45° increments through to 360°. All fast scans were registered to the 0° image via a three-step process: first, images were aligned using MR visible couch markers. Second, the scans were pre-processed then rigidly registered to the 0° image. Third, the rigidly registered scans were non-rigidly registered to the 0° image to assess soft tissue deformation. The residual differences after rigid and non-rigid registration were determined from the transformation matrix and the deformation vector field, respectively. The rigid registration yielded mean rotations of ⩽2.5° in all cases. The average 3D translational magnitudes range was 5.8 ± 2.9 mm-30.0 ± 11.0 mm. Translations were most significant in the left-right (LR) direction. Smaller translations were observed in the anterior-posterior (AP) and superior-inferior (SI) directions. The maximum deformation magnitudes range was: 10.0 ± 0.9 mm-28.0 ± 2.8 mm and average deformation magnitudes range: 2.3 ± 0.6 mm-7.5 ± 1.0 mm. Average non-rigid deformation magnitude was correlated with BMI (correlation coefficient 0.84, p  = 0.01). Rigid pelvic deformations were most significant in the LR direction but could be accounted for with on-line adjustments. Non-rigid deformations can be significant and will need to be accounted for in order to facilitate the delivery of gantry-free therapy with an automated patient rotation system.

Mesenchymal stem cell therapy inhibited inflammatory and profibrotic pathways induced by partial bladder outlet obstruction and prevented high-pressure urine storage.

BACKGROUND: Partial bladder outlet obstruction (pBOO) is characterized by an initial inflammatory response that progresses to smooth muscle hypertrophy and fibrosis. Current treatment modalities carry high risk of morbidity. Mesenchymal stem cells (MSCs) are undifferentiated adult cells with reparative, immunomodulatory, and anti-inflammatory capacities. The ability of MSCs to inhibit inflammatory and profibrotic pathways in bladder cells has been recently reported. OBJECTIVES: This study aimed to investigate the therapeutic effects of MSCs on pBOO-induced inflammatory, profibrotic signaling pathways and end-organ physiology. MATERIALS AND METHODS: Twenty Sprague Dawley rats were randomly assigned to 5 groups: unobstructed controls, pBOO for 2 and 4 weeks, pBOO+MSCs for 2 and 4 weeks. Partial bladder outlet obstruction was surgically induced followed by intravenous injection of MSCs. Endpoint urodynamics was performed, and bladder tissue harvested for analysis. Reverse transcription real time polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to study gene and protein expression of major inflammatory and profibrotic markers. RESULTS: Partial bladder outlet obstruction resulted in an upregulation of transforming growth factor beta (TGFß1), mothers against decapentaplegic homolog 2/3 (SMAD2/3), hypoxia inducible factor 1 alpha (HIF1α), hypoxia inducible factor 3 alpha (HIF3α), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNFα), mechanistic target of rapamycin (mTOR), p70 ribosomal S6 protein kinase (p70 S6K), collagen 1 (COL1), and collagen 3 (COL3) expression in a time-dependent manner. This was coupled with a downregulation of interleukin (IL)-10 expression. Increase of bladder fibrosis was directly related to the duration of pBOO and associated with high urine storage pressure. Injected MSCs were identified in the bladder 4 weeks after therapy. The immunomodulatory effect of MSCs(defined by reduced TNFα and increased IL-10 and VEGF) was most predominant 2 weeks after therapy. Significant downregulation of profibrotic genes occurred 4 weeks after therapy. End filling pressure, hypertrophy, and fibrosis were significantly reduced after MSC therapy (P < 0.05). DISCUSSION: Mesenchymal stem cell therapy led to a profound systematic improvement of the obstructed bladder. This included an initial anti-inflammatory response and a subsequent antifibrotic reaction. Essentially, both phases were associated with a reduction of urine storage pressure. The intravenously injected MSCs were tracked in the bladder. However, their presence in non-target organs such as the lungs, spleen, and liver was not tracked. CONCLUSIONS: Partial bladder outlet obstruction induced significant upregulation of hypoxic, inflammatory, and profibrotic markers. Mesenchymal stem cell therapy potently inhibited these pathways and improved bladder function.

2D monolithic silicon-diode array detectors in megavoltage photon beams: does the fabrication technology matter? A medical physicist's perspective.

A family of prototype 2D monolithic silicon-diode array detectors (MP512, Duo, Octa) has been proposed by the Centre for Medical Radiation Physics, University of Wollongong (Australia) for relative dosimetry in small megavoltage photon beams. These detectors, which differ in the topology of their 512 sensitive volumes, were originally fabricated on bulk p-type substrates. More recently, they have also been fabricated on epitaxial p-type substrates. In the literature, their performance has been individually characterized for quality assurance (QA) applications. The present study directly assessed and compared that of a MP512-bulk and that of a MP512-epitaxial in terms of radiation hardness, long-term stability, response linearity with dose, dose per pulse and angular dependence. Their measurements of output factors, off-axis ratios and percentage depth doses in square radiation fields collimated by the jaws and produced by 6 MV and 10 MV flattened photon beams were then benchmarked against those by commercially available detectors. The present investigation was aimed at establishing, from a medical physicist's perspective, how the bulk and epitaxial fabrication technologies would affect the implementation of the MP512s into a QA protocol. Based on results, the MP512-epitaxial would offer superior radiation hardness, long-term stability and achievable uniformity and reproducibility of the response across the 2D active area.

A prospective study of weekly intensity modulated radiation therapy plan adaptation for head and neck cancer: improved target coverage and organ at risk sparing.

This prospective study of weekly CT scanning and plan adaption during H&N IMRT reports on the frequency of plan adaptations based on dosimetric differences between original and re-optimised IMRT plans. The volumetric and geometric change occurring in target volumes and salivary glands is also described. Ten H&N cancer patients underwent weekly planning CT imaging and re-optimisation of the IMRT plan if PTV or OAR coverage was unacceptable. Comparisons of PTV and parotid gland dosimetry between the original and adaptive plans were made. Parotid and submandibular gland volume changes and shift were calculated. Eight of ten patients required one or more plan adaptations, with 41% of adaptations occurring by fraction ten. Salivary glands reduced in volume, with a medial shift of the lateral border of the parotid gland and a superior shift of the submandibular gland. Change in PTV coverage did not correlate with weight loss or nutritional score. Inadequate PTV coverage, requiring plan adaptation, occurs early in the course of IMRT. A weekly Adaptive RT (ART) protocol results in significant improvement of PTV coverage. Implementation of a clinical ART protocol should include imaging and dose calculation within the first ten fractions.

A simple model for transit dosimetry based on a water equivalent EPID.

PURPOSE: The aim of this study was to demonstrate a new model for implementing a transit dosimetry system as a means of in vivo dose verification with a water equivalent electronic portal imaging device (WE-EPID) and a conventional treatment planning system (TPS). METHOD AND MATERIALS: A standard amorphous silicon (a-Si) EPID was modified to a WE-EPID configuration by replacing the metal-plate/phosphor screen situated above the photodiode detector with a 3 cm thick water equivalent plastic x ray converter material. A clinical TPS was used to calculate dose to the WE-EPID in its conventional EPID position behind the phantom/patient. The "extended phantom" concept was used to facilitate dose calculation at the EPID position, which is outside the CT field of view (FOV). The CT images were manipulated from 512 × 512 into 1024 × 1024 and padded pixels were assigned the density of air before importing to the TPS. The virtual WE-EPID was added as an RT structure of water density at the EPID plane. The accuracy of TPS dose calculations at the EPID plane in transit geometry was first evaluated for different field sizes and thickness of object in the beam by comparison with the dose measured using a 2D ion chamber array (ICA) and the WE-EPID. Following basic dose response tests, clinical fields including direct single fields (open and wedged) and modulated fields (integrated or control point by control point doses for VMAT) were measured for 6 MV photons with varying of solid water thickness or an anthropomorphic phantom present in beam. The EPID images were corrected for dark signal and pixel sensitivity and converted to dose using a single dose calibration factor. The 2D dose evaluation was conducted using 3%/3 and 2%/2 mm gamma-index criteria. RESULTS: The measured dose-response with the ICA and WE-EPID for all basic dose-response tests agreed with TPS dose calculations to within 1.5%. The maximum difference in dose profiles for the largest measured field size of 25 × 25 cm2 was 2.5%. Gamma evaluation showed at least 94% (3%/3 mm criteria) and 90% (2%/2 mm) agreement in both integrated and control-point doses for all clinical fields acquired by the WE-EPID and ICA when compared with TPS-calculated portal dose images. CONCLUSION: A new approach to transit dose verification has been demonstrated utilizing a water equivalent EPID and a commercial TPS. The accuracy of dose calculations at the EPID plane using a commercial TPS beam model was experimentally confirmed. The model proposed in this study provides an accurate method to directly verify doses delivered during treatment without the additional uncertainties inherent in modelling the complex dose-response of standard EPIDs.

Long-term follow-up after traditional versus modified perineal approach in the management of female epispadias.

OBJECTIVE: Isolated female epispadias (IFE) is a rare congenital anomaly. The defect extends to the bladder neck, which is usually incompetent. The traditional surgical approach includes urethral and genital reconstruction in the first year, followed by bladder neck reconstruction (Young-Dees-Leadbetter cervicoplasty (YDL)) at the age of social continence. An alternative single-stage technique includes urethral, bladder neck and clitoris repair by a perineal approach. The aim of the present study was to describe long-term follow-up of patients who underwent the traditional vs alternative approach. MATERIALS AND METHODS: A retrospective review was performed of all female epispadias cases managed between 2000 and 2013. The YDL procedure (Group 1) vs single-stage perineal approach (Group 2) cases were followed and compared. Collected variables included: patients' demographics, age at diagnosis and surgery, presence of associated anomalies, clinical presentation, presence of vesicoureteral reflux (VUR), and pre-operative and postoperative continence. RESULTS: A total of 12 cases of female epispadias were managed and followed between 2000 and 2013. No major complications occurred in either group. Urinary continence evaluated in seven children showed that none (0/3) and 4/7 (57%) were continent following the initial procedure in Group 1 and Group 2, respectively. All patients in Group 1 failed to achieve continence and required re-intervention. CONCLUSIONS: Female epispadias could be successfully repaired using a single-stage modified perineal approach that achieved good continence with volitional voiding, good cosmetic results and compared favorably with the ones repaired with the YDL technique. The additional step of performing bladder neck tailoring to achieve a funneling configuration seemed to be useful in improving continence.

Defining and assessing an anisotropic delineation margin for modern radiotherapy.

PURPOSE: Uncertainty in target volume delineation for modern radiotherapy impacts dosimetry and patient outcomes. Delineation uncertainty is generally overlooked in practice as a source of error, potentially since historically, other uncertainties have been the main focus. This work defined and assessed an anisotropic delineation margin in both polar and spherical coordinate systems in order to account for the spatially varying nature of this uncertainty using a whole breast radiotherapy cohort as a proof of concept. METHODS: A cohort of 21 whole breast radiotherapy patient datasets with clinical target volumes delineated by eight independent observers was utilized. Patients were divided into categories based on target volume and laterality. An anisotropic delineation margin for each category was determined by multiplying the average standard deviation in observer contours in each category by a factor of two. Standard deviation was determined in both polar and spherical coordinates at angular increments. This anisotropic approach was compared to a conventional clinical approach, where the delineation margin was applied in the cardinal directions only. The assessment of the delineation margin was undertaken by comparing the encompassment of the observer volumes by the target volume with added margin. The extra, presumed healthy tissue included in the margin and the malignant tissue missed by the margin were determined. RESULTS: The proposed delineation margin is effective at accounting for inter-observer variation, producing >95% coverage of all CTVs for polar, spherical, and Cartesian margins in 82%, 79%, and 92% of cases, respectively. Additionally, <1% malignant tissue was missed for 65%, 70%, and 91% of cases and <37% healthy tissue was included in 95%, 89%, and 97% of cases. A conventional delineation margin approach is most appropriate for small and gold standard target volumes. However, for large target volumes, an anisotropic margin is necessary, producing significantly greater coverage of CTVs, including significantly less presumed healthy tissue and missing significantly less malignant tissue. CONCLUSIONS: All delineation margin methods that account for target volume and laterality proved to be adequate, with appropriate encompassment of interobserver variation and minimal inclusion of extra excess healthy tissue and exclusion of possible malignant tissue. The anisotropic approach was found to be superior to a conventional approach for target volumes >1400 cm3 only with significantly greater encompassment of interobserver variation, less missed malignant tissue and less included healthy tissue. This methodology has been validated for a whole breast radiotherapy cohort as a proof of concept, however could be applied to other anatomical sites.

In vivo skin dose measurement using MOSkin detectors in tangential breast radiotherapy.

The purpose of this study is to measure patient skin dose in tangential breast radiotherapy. Treatment planning dose calculation algorithm such as Pencil Beam Convolution (PBC) and in vivo dosimetry techniques such as radiochromic film can be used to accurately monitor radiation doses at tissue depths, but they are inaccurate for skin dose measurement. A MOSFET-based (MOSkin) detector was used to measure skin dose in this study. Tangential breast radiotherapies ("bolus" and "no bolus") were simulated on an anthropomorphic phantom and the skin doses were measured. Skin doses were also measured in 13 patients undergoing each of the techniques. In the patient study, the EBT2 measurements and PBC calculation tended to over-estimate the skin dose compared with the MOSkin detector (p<0.05) in the "no bolus radiotherapy". No significant differences were observed in the "bolus radiotherapy" (p>0.05). The results from patients were similar to that of the phantom study. This shows that the EBT2 measurement and PBC calculation, while able to predict accurate doses at tissue depths, are inaccurate in predicting doses at build-up regions. The clinical application of the MOSkin detectors showed that the average total skin doses received by patients were 1662±129cGy (medial) and 1893±199cGy (lateral) during "no bolus radiotherapy". The average total skin doses were 4030±72cGy (medial) and 4004±91cGy (lateral) for "bolus radiotherapy". In some cases, patient skin doses were shown to exceed the dose toxicity level for skin erythema. Hence, a suitable device for in vivo dosimetry is necessary to accurately determine skin dose.

Technical Note: Experimental results from a prototype high-field inline MRI-linac.

PURPOSE: The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid magnetic resonance imaging (MRI)-treatment systems, high field and low field, and inline and perpendicular configurations. As part of a new MRI-linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-linac system. This work describes results from a prototype experimental system to demonstrate the feasibility of a high field inline MR-linac. METHODS: The magnet is a 1.5 T MRI system (Sonata, Siemens Healthcare) was located in a purpose built radiofrequency (RF) cage enabling shielding from and close proximity to a linear accelerator with inline (and future perpendicular) orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multileaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-linac experiments was performed to investigate (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array; and (3) electron contamination effects measured using Gafchromic film and an electronic portal imaging device (EPID). RESULTS: (1) Image quality was unaffected by the radiation beam with the macropodine phantom image with the beam on being almost identical to the image with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background intensity when the radiation beam was on. (3) Film and EPID measurements demonstrated electron focusing occurring along the centerline of the magnet axis. CONCLUSIONS: A proof-of-concept high-field MRI-linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field inline MRI-linac and study a number of the technical challenges and solutions.

Dose enhancement in radiotherapy of small lung tumors using inline magnetic fields: A Monte Carlo based planning study.

PURPOSE: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6 MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. METHODS: A total of eight clinical lung tumor cases were recalculated using Monte Carlo methods, and external magnetic fields of 0.5, 1.0, and 3 T were included to observe the impact on dose to the planning target volume (PTV) and gross tumor volume (GTV). Three plans were 6 MV 3D-CRT plans while 6 were 6 MV IMRT. The GTV's ranged from 0.8 to 16 cm(3), while the PTV's ranged from 1 to 59 cm(3). In addition, the dose changes in a 30 cm diameter cylindrical water phantom were investigated for small beams. The central 20 cm of this phantom contained either water or lung density insert. RESULTS: For single beams, an inline magnetic field of 1 T has a small impact in lung dose distributions by reducing the lateral scatter of secondary electrons, resulting in a small dose increase along the beam. Superposition of multiple small beams leads to significant dose enhancements. Clinically, this process occurs in the lung tissue typically surrounding the GTV, resulting in increases to the D98% (PTV). Two isolated tumors with very small PTVs (3 and 6 cm(3)) showed increases in D98% of 23% and 22%. Larger PTVs of 13, 26, and 59 cm(3) had increases of 9%, 6%, and 4%, describing a natural fall-off in enhancement with increasing PTV size. However, three PTVs bounded to the lung wall showed no significant increase, due to lack of dose enhancement in the denser PTV volume. In general, at 0.5 T, the GTV mean dose enhancement is around 60% lower than that at 1 T, while at 3 T, it is 5%-60% higher than 1 T. CONCLUSIONS: Monte Carlo methods have described significant and predictable dose enhancement effects in small lung tumor plans for 6 MV radiotherapy when an external inline magnetic field is included. Results of this study indicate that future clinical inline MRI-guided radiotherapy systems will be able to deliver a dosimetrically superior treatment to small (PTV < 15 cm(3)), isolated lung tumors over non-MRI-Linac systems. This increased efficacy coincides with the reimbursement in the United States of lung CT screening and the likely rapid growth in the number of patients with small lung tumors to be treated with radiotherapy.

MagicPlate-512: A 2D silicon detector array for quality assurance of stereotactic motion adaptive radiotherapy.

PURPOSE: Spatial and temporal resolutions are two of the most important features for quality assurance instrumentation of motion adaptive radiotherapy modalities. The goal of this work is to characterize the performance of the 2D high spatial resolution monolithic silicon diode array named "MagicPlate-512" for quality assurance of stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) combined with a dynamic multileaf collimator (MLC) tracking technique for motion compensation. METHODS: MagicPlate-512 is used in combination with the movable platform HexaMotion and a research version of radiofrequency tracking system Calypso driving MLC tracking software. The authors reconstruct 2D dose distributions of small field square beams in three modalities: in static conditions, mimicking the temporal movement pattern of a lung tumor and tracking the moving target while the MLC compensates almost instantaneously for the tumor displacement. Use of Calypso in combination with MagicPlate-512 requires a proper radiofrequency interference shielding. Impact of the shielding on dosimetry has been simulated by (GEANT)4 and verified experimentally. Temporal and spatial resolutions of the dosimetry system allow also for accurate verification of segments of complex stereotactic radiotherapy plans with identification of the instant and location where a certain dose is delivered. This feature allows for retrospective temporal reconstruction of the delivery process and easy identification of error in the tracking or the multileaf collimator driving systems. A sliding MLC wedge combined with the lung motion pattern has been measured. The ability of the MagicPlate-512 (MP512) in 2D dose mapping in all three modes of operation was benchmarked by EBT3 film. RESULTS: Full width at half maximum and penumbra of the moving and stationary dose profiles measured by EBT3 film and MagicPlate-512 confirm that motion has a significant impact on the dose distribution. Motion, no motion, and motion with MLC tracking profiles agreed within 1 and 0.4 mm, respectively, for all field sizes tested. Use of electromagnetic tracking system generates a fluctuation of the detector baseline up to 10% of the full scale signal requiring a proper shielding strategy. MagicPlate-512 is also able to reconstruct the dose variation pulse-by-pulse in each pixel of the detector. An analysis of the dose transients with motion and motion with tracking shows that the tracking feedback algorithm used for this experiment can compensate effectively only the effect of the slower transient components. The fast changing components of the organ motion can contribute only to discrepancy of the order of 15% in penumbral region while the slower components can change the dose profile up to 75% of the expected dose. CONCLUSIONS: MagicPlate-512 is shown to be, potentially, a valid alternative to film or 2D ionizing chambers for quality assurance dosimetry in SRS or SBRT. Its high spatial and temporal resolutions allow for accurate reconstruction of the profile in any conditions with motion and with tracking of the motion. It shows excellent performance to reconstruct the dose deposition in real time or retrospectively as a function of time for detailed analysis of the effect of motion in a specific pixel or area of interest.

Proton beam deflection in MRI fields: Implications for MRI-guided proton therapy.

PURPOSE: This paper investigates, via magnetic modeling and Monte Carlo simulation, the ability to deliver proton beams to the treatment zone inside a split-bore MRI-guided proton therapy system. METHODS: Field maps from a split-bore 1 T MRI-Linac system are used as input to geant4 Monte Carlo simulations which model the trajectory of proton beams during their paths to the isocenter of the treatment area. Both inline (along the MRI bore) and perpendicular (through the split-bore gap) orientations are simulated. Monoenergetic parallel and diverging beams of energy 90, 195, and 300 MeV starting from 1.5 and 5 m above isocenter are modeled. A phase space file detailing a 2D calibration pattern is used to set the particle starting positions, and their spatial location as they cross isocenter is recorded. No beam scattering, collimation, or modulation of the proton beams is modeled. RESULTS: In the inline orientation, the radial symmetry of the solenoidal style fringe field acts to rotate the protons around the beam's central axis. For protons starting at 1.5 m from isocenter, this rotation is 19° (90 MeV) and 9.8° (300 MeV). A minor focusing toward the beam's central axis is also seen, but only significant, i.e., 2 mm shift at 150 mm off-axis, for 90 MeV protons. For the perpendicular orientation, the main MRI field and near fringe field act as the strongest to deflect the protons in a consistent direction. When starting from 1.5 m above isocenter shifts of 135 mm (90 MeV) and 65 mm (300 MeV) were observed. Further to this, off-axis protons are slightly deflected toward or away from the central axis in the direction perpendicular to the main deflection direction. This leads to a distortion of the phase space pattern, not just a shift. This distortion increases from zero at the central axis to 10 mm (90 MeV) and 5 mm (300 MeV) for a proton 150 mm off-axis. In both orientations, there is a small but subtle difference in the deflection and distortion pattern between protons fired parallel to the beam axis and those fired from a point source. This is indicative of the 3D spatially variant nature of the MRI fringe field. CONCLUSIONS: For the first time, accurate magnetic and Monte Carlo modeling have been used to assess the transport of generic proton beams toward a 1 T split-bore MRI. Significant rotation is observed in the inline orientation, while more complex deflection and distortion are seen in the perpendicular orientation. The results of this study suggest that due to the complexity and energy-dependent nature of the magnetic deflection and distortion, the pencil beam scanning method will be the only choice for delivering a therapeutic proton beam inside a potential MRI-guided proton therapy system in either the inline or perpendicular orientation. Further to this, significant correction strategies will be required to account for the MRI fringe fields.

A two dimensional silicon detectors array for quality assurance in stereotactic radiotherapy: MagicPlate-512.

PURPOSE: Silicon diode arrays are commonly implemented in radiation therapy quality assurance applications as they have a number of advantages including: real time operation (compared to the film) and high spatial resolution, large dynamic range and small size (compared to ionizing chambers). Most diode arrays have detector pitch that is too coarse for routine use in small field applications. The goal of this work is to characterize the two-dimensional monolithic silicon diode array named "MagicPlate-512" (MP512) designed for QA in stereotactic body radiation therapy (SBRT) and stereotactic radio surgery (SRS). METHODS: MP512 is a silicon monolithic detector manufactured on ap-type substrate. An array contains of 512 pixels with size 0.5×0.5 mm2 and pitch 2 mm with an overall dimension of 52×52 mm2. The MP512 monolithic detector is wire bonded on a printed circuit board 0.5 mm thick and covered by a thin layer of raisin to preserve the silicon detector from moisture and chemical contamination and to protect the bonding wires. Characterization of the silicon monolithic diode array response was performed, and included pixels response uniformity, dose linearity, percent depth dose, output factor, and beam profiling for beam sizes relevant to SBRT and SRS and depth dose response in comparison with ionization chamber. RESULTS: MP512 shows a good dose linearity (R2=0.998) and repeatability within 0.2%. The measured depth dose response for field size of 10×10 cm2 agreed to within 1.3%, when compared to a CC13 ionization chamber for depths in PMMA up to 30 cm. The output factor of a 6 MV Varian 2100EX medical linac beam measured by MP512 at the isocenter agrees to within 2% when compared to PTW diamond, Scanditronix point EDD-2 diode and MOSkin detectors for field sizes down to 1×1 cm2. An over response of 4% was observed for square beam size smaller than 1 cm when compared to EBT3 films, while the beam profiles (FWHM) of MP512 match to within 2% the data measured by radiochromic film. CONCLUSIONS: The response of the 2D detector array, MP512, has been evaluated. The properties of the array demonstrated suitability for use as in phantom dosimeter for QA in SRS and SBRT. Although MP512 matches film measurements down to 1×1 cm2 well, it showed a discrepancy of 4% in the determination of output factors of beams smaller than 0.5×0.5 cm2 due to the field perturbation generated by the large amount of silicon surrounding the central diode. MP512 is highly capable of measuring beam size (FWHM) and has a discrepancy of less than 1.3% when compared to EBT3 film. A reduction in the detector pitch to less than 2 mm would improve the penumbra reconstruction accuracy at the cost readout electronics complexity.

Electron contamination modeling and reduction in a 1 T open bore inline MRI-linac system.

PURPOSE: A potential side effect of inline MRI-linac systems is electron contamination focusing causing a high skin dose. In this work, the authors reexamine this prediction for an open bore 1 T MRI system being constructed for the Australian MRI-Linac Program. The efficiency of an electron contamination deflector (ECD) in purging electron contamination from the linac head is modeled, as well as the impact of a helium gas region between the deflector and phantom surface for lowering the amount of air-generated contamination. METHODS: Magnetic modeling of the 1 T MRI was used to generate 3D magnetic field maps both with and without the presence of an ECD located immediately below the MLC's. Forty-seven different ECD designs were modeled and for each the magnetic field map was imported into Geant4 Monte Carlo simulations including the linac head, ECD, and a 30 × 30 × 30 cm(3) water phantom located at isocenter. For the first generation system, the x-ray source to isocenter distance (SID) will be 160 cm, resulting in an 81.2 cm long air gap from the base of the ECD to the phantom surface. The first 71.2 cm was modeled as air or helium gas, with the latter encased between two windows of 50 µm thick high density polyethlyene. 2D skin doses (at 70 µm depth) were calculated across the phantom surface at 1 × 1 mm(2) resolution for 6 MV beams of field size of 5 × 5, 10 × 10, and 20 × 20 cm(2). RESULTS: The skin dose was predicted to be of similar magnitude as the generic systems modeled in previous work, 230% to 1400% of D(max) for 5 × 5 to 20 × 20 cm(2), respectively. Inclusion of the ECD introduced a nonuniformity to the MRI imaging field that ranged from ∼20 to ∼140 ppm while the net force acting on the ECD ranged from ∼151 N to ∼1773 N. Various ECD designs were 100% efficient at purging the electron contamination into the ECD magnet banks; however, a small percentage were scattered back into the beam and continued to the phantom surface. Replacing a large portion of the extended air-column between the ECD and phantom surface with helium gas is a key element as it significantly minimized the air-generated contamination. When using an optimal ECD and helium gas region, the 70 µm skin dose is predicted to increase moderately inside a small hot spot over that of the case with no magnetic field present for the jaw defined square beams examined here. These increases include from 12% to 40% of [Formula: see text] for 5 × 5 cm(2), 18% to 55% of D(max) for 10 × 10 cm(2), and from 23% to 65% of D(max) for 20 × 20 cm(2). CONCLUSIONS: Coupling an efficient ECD and helium gas region below the MLCs in the 160 cm isocenter MRI-linac system is predicted to ameliorate the impact electron contamination focusing has on skin dose increases. An ECD is practical as its impact on the MRI imaging distortion is correctable, and the mechanical forces acting on it manageable from an engineering point of view.

Sensitivity of assays for the detection of HPA-1a antibodies: results of an international workshop demonstrating the impact of cation chelation from integrin αIIbß3 on three widely used assays.

BACKGROUND AND OBJECTIVES: HPA-1a antibodies account for 70-80% of cases of fetal-neonatal alloimmune thrombocytopenia (FNAIT) in Caucasians. However, numerous workshops have demonstrated variability in their detection. We recently showed that exposure of αIIbß3 to ethylene diamine tetraacetic acid (EDTA) affected binding of many anti-αIIbß3 monoclonal, and HPA-1a allo-, antibodies; this adversely affected sensitivity of the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and indirect platelet immunofluorescence test (PIFT). This study presents results from an international workshop studying the impact of cation chelation on HPA-1a antibody detection in routine diagnostic laboratories. MATERIALS AND METHODS: Serum and EDTA-anticoagulated plasma samples containing anti-HPA-1a were distributed to 39 laboratories. Participants were asked to detect and identify any HPA antibodies present. RESULTS: 2/39 (5.1%) participants were able to detect and identify anti-HPA-1a in the serum, but not in the plasma sample. EDTA plasma reduced MAIPA assay sensitivity by ≥ 20% in 17/24 (70.8%) laboratories and by ≥ 50% in 9/24 (37.5%) when using HPA-1a1a platelets (mean: 27.7%, range 0-85.1%); when using HPA-1a1b platelets 3/4 (75%), participants reported ≥ 50% loss of sensitivity (mean 65.6%, range 0-96.6%). A small but significant increase in optical densities was observed in antigen capture ELISA assays when using plasma (mean difference: 0.081, P < 0.01). Insufficient PIFT data were returned to draw firm conclusions. CONCLUSION: Use of EDTA plasma significantly affects the sensitivity of the MAIPA assay and can affect detection of even potent, FNAIT-causing examples of anti-HPA-1a. These data highlight the importance of use of αIIbß3 in an appropriate conformation for the sensitive detection of anti-HPA-1a.