Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation.

High doses of radiation to the hippocampus have been correlated with increased cognitive decline following radiation therapy for brain metastases. To mitigate these effects, a variety of hippocampal sparing techniques have been implemented for both whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). The goal of this review article is to provide a practical resource for the clinical implementation of hippocampal-sparing radiation therapy, starting with a brief background on the function and delineation of the hippocampal structure, as well as radiation effects on the hippocampus and the most widely recommended dose constraints. Considerations for treatment simulation are discussed, including options for cranial immobilization and optional head tilt. Hippocampal sparing has been demonstrated for WBRT using helical TomoTherapy, static intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) with a variety of patient setup positions, beam arrangements, and planning parameters. Tomotherapy has been shown to achieve slightly greater hippocampal sparing in some studies, while VMAT enables the most efficient treatment delivery. Hippocampal sparing has also been evaluated in a wide range of studies for both GammaKnife and linear accelerator (LINAC)-based SRS, with the proximity of metastases to the hippocampus being the most significant predictor of hippocampal dose. The methods and resulting hippocampal doses from these studies on both WBRT and SRS are discussed, as well as the role of automation in hippocampal sparing radiation therapy.

Automatic segmentation of high-risk clinical target volume for tandem-and-ovoids brachytherapy patients using an asymmetric dual-path convolutional neural network.

PURPOSES: Preimplant diagnostic magnetic resonance imaging is the gold standard for image-guided tandem-and-ovoids (T&O) brachytherapy for cervical cancer. However, high dose rate brachytherapy planning is typically done on postimplant CT-based high-risk clinical target volume (HR-CTVCT ) because the transfer of preimplant Magnetic resonance (MR)-based HR-CTV (HR-CTVMR ) to the postimplant planning CT is difficult due to anatomical changes caused by applicator insertion, vaginal packing, and the filling status of the bladder and rectum. This study aims to train a dual-path convolutional neural network (CNN) for automatic segmentation of HR-CTVCT on postimplant planning CT with guidance from preimplant diagnostic MR. METHODS: Preimplant T2-weighted MR and postimplant CT images for 65 (48 for training, eight for validation, and nine for testing) patients were retrospectively solicited from our institutional database. MR was aligned to the corresponding CT using rigid registration. HR-CTVCT and HR-CTVMR were manually contoured on CT and MR by an experienced radiation oncologist. All images were then resampled to a spatial resolution of 0.5 × 0.5 × 1.25 mm. A dual-path 3D asymmetric CNN architecture with two encoding paths was built to extract CT and MR image features. The MR was masked by HR-CTVMR contour while the entire CT volume was included. The network put an asymmetric weighting of 18:6 for CT: MR. Voxel-based dice similarity coefficient (DSCV ), sensitivity, precision, and 95% Hausdorff distance (95-HD) were used to evaluate model performance. Cross-validation was performed to assess model stability. The study cohort was divided into a small tumor group (<20 cc), medium tumor group (20-40 cc), and large tumor group (>40 cc) based on the HR-CTVCT for model evaluation. Single-path CNN models were trained with the same parameters as those in dual-path models. RESULTS: For this patient cohort, the dual-path CNN model improved each of our objective findings, including DSCV , sensitivity, and precision, with an average improvement of 8%, 7%, and 12%, respectively. The 95-HD was improved by an average of 1.65 mm compared to the single-path model with only CT images as input. In addition, the area under the curve for different networks was 0.86 (dual-path with CT and MR) and 0.80 (single-path with CT), respectively. The dual-path CNN model with asymmetric weighting achieved the best performance with DSCV of 0.65 ± 0.03 (0.61-0.70), 0.79 ± 0.02 (0.74-0.85), and 0.75 ± 0.04 (0.68-0.79) for small, medium, and large group. 95-HD were 7.34 (5.35-10.45) mm, 5.48 (3.21-8.43) mm, and 6.21 (5.34-9.32) mm for the three size groups, respectively. CONCLUSIONS: An asymmetric CNN model with two encoding paths from preimplant MR (masked by HR-CTVMR ) and postimplant CT images was successfully developed for automatic segmentation of HR-CTVCT for T&O brachytherapy patients.

Automatic detection and segmentation of multiple brain metastases on magnetic resonance image using asymmetric UNet architecture.

Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSCv), sensitivity (S v), precision (P v), BM-based sensitivity (S BM), and false detection rate (F BM) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSCv of 0.84 and lowest F BM of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.

Technical Note: Characterization of x-ray beam profiles for a fluoroscopic system incorporating copper filtration.

PURPOSE: The goal of this study was to investigate x-ray beam profiles at various water depths to characterize the two-dimensional x-ray dose distribution, allowing for off-axis and out-of-field radiation dose estimation for a wide range of x-ray beam spectra commonly encountered in fluoroscopically guided interventional procedures. METHODS: A Siemens Artis interventional fluoroscope was operated in a service mode to generate a continuous x-ray beam at fixed x-ray beam spectra, defined by their kVp and the thickness of additional copper filtration. A PTW scanning water tank with a diode detector was used to measure the x-ray beam profiles at several depths in water at various fields of view and x-ray beam spectra, both parallel and perpendicular to the anode-cathode axis direction. RESULTS: X-ray beam profiles, including out-of-field tails, were characterized for a wide range of beam qualities. The anode heel effect was pronounced even at depth, resulting in large dose variations across the x-ray field; this effect was even more definite at large fields of view, at higher kVps, and in the absence of additional copper filtration. CONCLUSIONS: This study investigated and characterized 2D radiation dose deposition in water from x-ray beam spectra commonly used by modern fluoroscopes in interventional procedures. This knowledge can be applied to manual dosimetry calculations or can be used to refine the accuracy of automated dose mapping tools or Monte Carlo simulations of the radiation dose to soft tissue within the x-ray field and to tissue adjacent to the primary beam. Additionally, this study illustrates a substantial reduction of the anode heel effect by using moderate amounts of additional copper filtration to harden the x-ray beam spectrum.

Volumetric-based image guidance is superior to marker-based alignments for stereotactic body radiotherapy of prostate cancer.

PURPOSES: The aim of this study was to evaluate a dual marker-based and soft-tissue based image guidance for inter-fractional corrections in stereotactic body radiotherapy (SBRT) of prostate cancer. METHODS/MATERIALS: We reviewed 18 patients treated with SBRT for prostate cancer. An endorectal balloon was inserted at simulation and each treatment. Planning margins were 3 mm/0 mm posteriorly. Prior to each treatment, a dual image guidance protocol was applied to align three makers using stereoscopic x ray images and then to the soft tissue using kilo-voltage cone beam CT (kV-CBCT). After treatment, prostate (CTV), rectal wall, and bladder were delineated on each kV-CBCT, and delivered dose was recalculated. Dosimetric endpoints were analyzed, including V36.25 Gy for prostate, and D0.03 cc for bladder and rectal wall. RESULTS: Following initial marker alignment, additional translational shifts were applied to 22 of 84 fractions after kV-CBCT. Among the 22 fractions, ten fractions exceeded 3 mm shifts in any direction, including one in the left-right direction, four in the superior-inferior direction, and five in the anterior-posterior direction. With and without the additional kV-CBCT shifts, the average V36.25 Gy of the prostate for the 22 fractions was 97.6 ± 2.6% with the kV x ray image alone, and was 98.1 ± 2.4% after applying the additional kV-CBCT shifts. The improvement was borderline statistical significance using Wilcoxon signed-rank test (P = 0.007). D0.03 cc was 45.8 ± 6.3 Gy vs. 45.1 ± 4.9 Gy for the rectal wall; and 49.5 ± 8.6 Gy vs. 49.3 ± 7.9 Gy for the bladder before and after applying kV-CBCT shifts. CONCLUSIONS: Marker-based alignment alone is not sufficient. Additional adjustments are needed for some patients based kV-CBCT.

Percent depth doses and X-ray beam characterizations of a fluoroscopic system incorporating copper filtration.

PURPOSE: In this investigation, we sought to characterize X-ray beam qualities and quantitate percent depth dose (PDD) curves for fluoroscopic X-ray beams incorporating added copper (Cu) filtration, such as those commonly used in fluoroscopically guided interventions (FGI). The intended application of this research is for dosimetry in soft tissue from FGI procedures using these data. METHODS: All measurements in this study were acquired on a Siemens (Erlangen, Germany) Artis zeego fluoroscope. X-ray beam characteristics of first half-value layer (HVL), second HVL, homogeneity coefficients (HCs), backscatter factors (BSFs) and kVp accuracy and precision were determined to characterize the X-ray beams used for the PDD measurements. A scanning water tank was used to measure PDD curves for 60, 80, 100, and 120 kVp X-ray beams with Cu filtration thicknesses of 0.0, 0.1, 0.3, 0.6, and 0.9 mm at 11 cm, 22 cm, and 42 cm nominal fields of view, in water depths of 0 to 150 mm. RESULTS: X-ray beam characteristics of first HVLs and HCs differed from previous published research of fluoroscopic X-ray beam qualities without Cu filtration. PDDs for 60, 80, 100, and 120 kVp with 0 mm of Cu filtration were comparable to previous published research, accounting for differences in fluoroscopes, geometric orientation, type of ionization chamber, X-ray beam quality, and the water tank used for data collection. PDDs and X-ray beam characteristics for beam qualities with Cu filtration are presented, which have not been previously reported. CONCLUSIONS: The data sets of X-ray beam characteristics and PDDs presented in this study can be used to estimate organ or soft tissue doses at depth involving similar beam qualities or to compare with mathematical models.

Dosimetric impact of orthopedic metal artifact reduction (O-MAR) on Spine SBRT patients.

The dosimetric impact of orthopedic metal artifact reduction (O-MAR) on spine SBRT patients has not been comprehensively studied, particularly with spinal prostheses in high-dose gradient regions. Using both phantom and patient datasets, we investigated dosimetric effects of O-MAR in combination of various metal locations and dose calculation algorithms. A physical phantom, with and without a titanium insert, was scanned. A clinical patient plan was applied to the artifact-free reference, non-O-MAR, and O-MAR phantom images with the titanium located either inside or outside of the tumor. Subsequently, five clinical patient plans were calculated with pencil beam and Monte Carlo (iPlan) on non-O-MAR and O-MAR patient images using an extended CT-density table. The dose differences for phantom plans and patient plans were analyzed using dose distributions, dose-volume histograms (DVHs), gamma index, and selected dosimetric endpoints. From both phantom plans and patient plans, O-MAR did not affect dose distributions and DVHs while minimizing metal artifacts. Among patient plans, we found that, when the same dose calculation method was used, the difference in the dosimetric endpoints between non-O-MAR and O-MAR datasets were small. In conclusion, for spine SBRT patients with spinal prostheses, O-MAR image reconstruction does not affect dose calculation accuracy while minimizing metal artifacts. Therefore, O-MAR images can be safely used for clinical spine SBRT treatment planning.

In vivo study of transverse carpal ligament stiffness using acoustic radiation force impulse (ARFI) imaging.

The transverse carpal ligament (TCL) forms the volar boundary of the carpal tunnel and may provide mechanical constraint to the median nerve, leading to carpal tunnel syndrome. Therefore, the mechanical properties of the TCL are essential to better understand the etiology of carpal tunnel syndrome. The purpose of this study was to investigate the in vivo TCL stiffness using acoustic radiation force impulse (ARFI) imaging. The shear wave velocity (SWV) of the TCL was measured using Virtual Touch IQ(TM) software in 15 healthy, male subjects. The skin and the thenar muscles were also examined as reference tissues. In addition, the effects of measurement location and ultrasound transducer compression on the SWV were studied. The SWV of the TCL was dependent on the tissue location, with greater SWV values within the muscle-attached region than those outside of the muscle-attached region. The SWV of the TCL was significantly smaller without compression (5.21 ± 1.08 m/s) than with compression (6.62 ± 1.18 m/s). The SWV measurements of the skin and the thenar muscles were also affected by transducer compression, but to different extents than the SWV of the TCL. Therefore to standardize the ARFI imaging procedure, it is recommended that a layer of ultrasound gel be maintained to minimize the effects of tissue compression. This study demonstrated the feasibility of ARFI imaging for assessing the stiffness characteristics of the TCL in vivo, which has the potential to identify pathomechanical changes of the tissue.

Biomechanical interaction between the transverse carpal ligament and the thenar muscles.

The transverse carpal ligament (TCL) serves as the origin of the thenar muscles and is integral to thenar muscle contraction anatomically and biomechanically. TCL hypertrophy has been observed in patients with carpal tunnel syndrome and is potentially caused by repetitive hand use. The purpose of this study was to investigate the biomechanical interaction between the TCL and the thenar muscles. Specifically, the morphological changes of the carpal arch, formed by the TCL, in response to thenar muscle contractions were examined during isometric tip pinch between the thumb and index finger. Ultrasound videos of the carpal tunnel were recorded from 13 healthy subjects and were synchronized with the forces measured by a pinch dynamometer. The thenar muscles' ulnar point, trapezium, and hamate were tracked by a pattern-matching program. The pinch force significantly affected the carpal arch height, width, and area (P < 0.005). As the pinch force increased from 0 to 100% maximum voluntary contraction force, the carpal arch height increased from 1.8 ± 1.0 to 2.3 ± 1.3 mm, the carpal arch width decreased from 23.9 ± 2.4 to 23.1 ± 2.4 mm, and the carpal arch area increased from 22.2 ± 13.6 to 27.3 ± 16.3 mm(2). The TCL was pulled volarly during thenar muscle contractions, providing evidence for the biomechanical interaction between the ligament and muscles. Repetitive biomechanical stimulation on the TCL from thenar muscle contractions could lead to tissue remodeling and then TCL hypertrophy. This study sheds light on the potential cause of TCL hypertrophy, which may be an etiological factor for carpal tunnel syndrome.

Pressure-morphology relationship of a released carpal tunnel.

We investigated morphological changes of a released carpal tunnel in response to variations of carpal tunnel pressure. Pressure within the carpal tunnel is known to be elevated in patients with carpal tunnel syndrome and dependent on wrist posture. Previously, increased carpal tunnel pressure was shown to affect the morphology of the carpal tunnel with an intact transverse carpal ligament (TCL). However, the pressure-morphology relationship of the carpal tunnel after release of the TCL has not been investigated. Carpal tunnel release (CTR) was performed endoscopically on cadaveric hands and the carpal tunnel pressure was dynamically increased from 10 to 120 mmHg. Simultaneously, carpal tunnel cross-sectional images were captured by an ultrasound system, and pressure measurements were recorded by a pressure transducer. Carpal tunnel pressure significantly affected carpal arch area (p < 0.001), with an increase of >62 mm(2) at 120 mmHg. Carpal arch height, length, and width also significantly changed with carpal tunnel pressure (p < 0.05). As carpal tunnel pressure increased, carpal arch height and length increased, but the carpal arch width decreased. Analyses of the pressure-morphology relationship for a released carpal tunnel revealed a nine times greater compliance than that previously reported for a carpal tunnel with an intact TCL. This change of structural properties as a result of transecting the TCL helps explain the reduction of carpal tunnel pressure and relief of symptoms for patients after CTR surgery.

A digit alignment device for kinematic analysis of the thumb and index finger.

Kinematic analysis of the digits using optical motion capture systems relies on defining accurate coordinate systems for the individual segments. Limitations of previous digit kinematic protocols include marker placement errors, marker occlusion and superimposition, and skin movement artifact. The purpose of this study was to develop a protocol utilizing a digit alignment device (DAD) and nail marker clusters to overcome these limitations. Ten subjects underwent 10 static calibration trials for validation. The orientation of the thumb distal phalange relative to the index finger distal phalange was described using Euler angles of pitch(x), yaw(y'), and roll(z''). The digit calibration protocol demonstrated high accuracy (0.5°, 1.9° and 2.2° for x, y', z'') and precision (1.4°, 2.3° and 3.1° for x, y', z''). The developed protocol provided convenient identification of transformations that determine anatomically relevant coordinate systems for the distal phalanges of the digits. The potential of utilizing this protocol as a standardized tool for digit kinematics was demonstrated using a dynamic task of precision pinching.

Ultrasound assessment of transverse carpal ligament thickness: a validity and reliability study.

The transverse carpal ligament (TCL) forms the palmar boundary of the carpal tunnel and plays an important role in carpal tunnel mechanics. TCL hypertrophy has been observed for individuals with carpal tunnel syndrome (CTS) and postulated as a potential etiologic factor. Ultrasound is particularly advantageous for TCL imaging because of its capability of detecting the interfaces between the TCL and other tissues. The purposes of this study were to develop an ultrasound based method to measure the TCL thickness and to test the validity and reliability of this method. Three operators conducted two sessions of ultrasound examination on eight cadaveric specimens and eight healthy volunteers. A custom script was used to calculate TCL thickness along the TCL length from the ultrasound images. The ultrasound based TCL thickness of the cadaveric specimens was compared with the dissection based TCL thickness for validation. The results showed Pearson's correlation coefficients of 0.867-0.928, intraclass correlation coefficient (ICC) values of 0.726-0.865, a standard error of measurement of 0.02-0.07 mm and a minimal detectable difference of 0.05-0.15 mm. The high correlation coefficients and small errors indicate that the ultrasound based method is valid for measuring TCL thickness. Furthermore, ultrasound measurements showed excellent intraoperator and interoperator reliability with ICC values as 0.826-0.933 and 0.840-0.882, respectively. The ultrasound based TCL thickness was in the range of 0.93-2.34 (1.54 ± 0.33) mm and agreed well with previous studies. The ultrasound method developed in this study is a valuable tool to examine morphologic properties of healthy and pathologic TCLs.

Viscoelastic properties of isolated collagen fibrils.

Understanding the viscoelastic behavior of collagenous tissues with complex hierarchical structures requires knowledge of the properties at each structural level. Whole tissues have been studied extensively, but less is known about the mechanical behavior at the submicron, fibrillar level. Using a microelectromechanical systems platform, in vitro coupled creep and stress relaxation tests were performed on collagen fibrils isolated from the sea cucumber dermis. Stress-strain-time data indicate that isolated fibrils exhibit viscoelastic behavior that could be fitted using the Maxwell-Weichert model. The fibrils showed an elastic modulus of 123 ± 46 MPa. The time-dependent behavior was well fit using the two-time-constant Maxwell-Weichert model with a fast time response of 7 ± 2 s and a slow time response of 102 ± 5 s. The fibrillar relaxation time was smaller than literature values for tissue-level relaxation time, suggesting that tissue relaxation is dominated by noncollagenous components (e.g., proteoglycans). Each specimen was tested three times, and the only statistically significant difference found was that the elastic modulus is larger in the first test than in the subsequent two tests, indicating that viscous properties of collagen fibrils are not sensitive to the history of previous tests.

In vitro fracture testing of submicron diameter collagen fibril specimens.

Mechanical testing of collagenous tissues at different length scales will provide improved understanding of the mechanical behavior of structures such as skin, tendon, and bone, and also guide the development of multiscale mechanical models. Using a microelectromechanical-systems (MEMS) platform, stress-strain response curves up to failure of type I collagen fibril specimens isolated from the dermis of sea cucumbers were obtained in vitro. A majority of the fibril specimens showed brittle fracture. Some displayed linear behavior up to failure, while others displayed some nonlinearity. The fibril specimens showed an elastic modulus of 470 ± 410 MPa, a fracture strength of 230 ± 160 MPa, and a fracture strain of 80% ± 44%. The fibril specimens displayed significantly lower elastic modulus in vitro than previously measured in air. Fracture strength/strain obtained in vitro and in air are both significantly larger than those obtained in vacuo, indicating that the difference arises from the lack of intrafibrillar water molecules produced by vacuum drying. Furthermore, fracture strength/strain of fibril specimens were different from those reported for collagenous tissues of higher hierarchical levels, indicating the importance of obtaining these properties at the fibrillar level for multiscale modeling.