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Background: Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T 1 mapping of hypoxia biomarkers show promise, T 1 -to-noise ratio (T 1 NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T 1 -weighted contrast images with simultaneous T 1 mapping., Purpose: To optimize MP2RAGE for low-field T 1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T 1 mapping in healthy volunteers., Methods: The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T 1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T 1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T 1 values (400-850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T 1 maps. Mean (± SD) T 1 relative error, T 1 NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T 1 maps were generated. Mean (± SD) T 1 values for WM and GM were determined. Whole-brain T 1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T 1 difference maps were generated to evaluate 3D spatial variation., Results: Low-field MP2RAGE optimization resulted in parameters: MP2RAGE TR of 3250 ms, inversion times (TI 1 /TI 2 ) of 500/1200 ms, and flip angles (α 1 /α 2 ) of 7/5°. Eurospin T 1 maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, T 1 NR of 20.13 ± 5.31, and CV of 2.22% ± 0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (± SD) T 1 values: 435.36 ± 10.01 ms for WM and 623.29 ± 14.64 ms for GM across subjects, showing excellent concordance with literature. Whole-brain T 1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T 1 values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel-by-voxel T 1 difference maps show a normal 3D spatial distribution of noise in WM and GM., Conclusions: Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T 1 maps with high T 1 NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T 1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers., (© 2024 American Association of Physicists in Medicine.)

High dose-rate brachytherapy is a treatment technique for gynecologic cancers where intracavitary applicators are placed within the patient's pelvic cavity. To ensure accurate radiation delivery, localization of the applicator at the time of insertion is vital. This study proposes a novel method for acquiring, registering, and fusing three-dimensional (3D) trans-abdominal and 3D trans-rectal ultrasound (US) images for visualization of the pelvic anatomy and applicators during gynecologic brachytherapy. The workflow was validated using custom multi-modal pelvic phantoms and demonstrated during two patient procedures. Experiments were performed for three types of intracavitary applicators: ring-and-tandem, ring-and-tandem with interstitial needles, and tandem-and-ovoids. Fused 3D US images were registered to magnetic resonance (MR) and computed tomography (CT) images for validation. The target registration error (TRE) and fiducial localization error (FLE) were calculated to quantify the accuracy of our fusion technique. For both phantom and patient images, TRE and FLE across all modality registrations (3D US versus MR or CT) resulted in mean ± standard deviation of 4.01 ± 1.01 mm and 0.43 ± 0.24 mm, respectively. This work indicates proof of concept for conducting further clinical studies leveraging 3D US imaging as an accurate, accessible alternative to advanced modalities for localizing brachytherapy applicators., (© 2024. The Author(s).)

Breast cancer screening has substantially reduced mortality across screening populations. However, a clinical need persists for more accessible, cost-effective, and robust approaches for increased-risk and diverse patient populations, especially those with dense breasts where screening mammography is suboptimal. We developed and validated a cost-effective, portable, patient-dedicated three-dimensional (3D) automated breast ultrasound (ABUS) system for point-of-care breast cancer screening. The 3D ABUS system contains a wearable, rapid-prototype 3D-printed dam assembly, a compression assembly, and a computer-driven 3DUS scanner, adaptable to any commercially available US machine and transducer. Acquisition is operator-agnostic, involves a 40-second scan time, and provides multiplanar 3D visualization for whole-breast assessment. Geometric reconstruction accuracy was evaluated with a 3D grid phantom and tissue-mimicking breast phantoms, demonstrating linear measurement and volumetric reconstruction errors < 0.2 mm and < 3%, respectively. The system's capability was demonstrated in a healthy male volunteer and two healthy female volunteers, representing diverse patient geometries and breast sizes. The system enables comfortable ultrasonic coupling and tissue stabilization, with adjustable compression to improve image quality while alleviating discomfort. Moreover, the system effectively mitigates breathing and motion, since its assembly affixes directly onto the patient. While future studies are still required to evaluate the impact on current clinical practices and workflow, the 3D ABUS system shows potential for adoption as an alternative, cost-effective, dedicated point-of-care breast cancer screening approach for increased-risk populations and limited-resource settings., (© 2023. Springer Nature Limited.)

Background: Multiparametric MRI (mpMRI) is an effective tool for detecting and staging prostate cancer (PCa), guiding interventional therapy, and monitoring PCa treatment outcomes. MRI-guided focal laser ablation (FLA) therapy is an alternative, minimally invasive treatment method to conventional therapies, which has been demonstrated to control low-grade, localized PCa while preserving patient quality of life. The therapeutic success of FLA depends on the accurate placement of needles for adequate delivery of ablative energy to the target lesion. We previously developed an MR-compatible mechatronic system for prostate FLA needle guidance and validated its performance in open-air and clinical 3T in-bore experiments using virtual targets., Purpose: To develop a robust MRI-to-mechatronic system registration method and evaluate its in-bore MR-guided needle delivery accuracy in tissue-mimicking prostate phantoms., Methods: The improved registration multifiducial assembly houses thirty-six aqueous gadolinium-filled spheres distributed over a 7.3 × 7.3 × 5.2 cm volume. MRI-guided needle guidance accuracy was quantified in agar-based tissue-mimicking prostate phantoms on trajectories (N = 44) to virtual targets covering the mechatronic system's range of motion. 3T gradient-echo recalled (GRE) MRI images were acquired after needle insertions to each target, and the air-filled needle tracks were segmented. Needle guidance error was measured as the shortest Euclidean distance between the target point and the segmented needle trajectory, and angular error was measured as the angle between the targeted trajectory and the segmented needle trajectory. These measurements were made using both the previously designed four-sphere registration fiducial assembly on trajectories (N = 7) and compared with the improved multifiducial assembly using a Mann-Whitney U test., Results: The median needle guidance error of the system using the improved registration fiducial assembly at a depth of 10 cm was 1.02 mm with an interquartile range (IQR) of 0.42-2.94 mm. The upper limit of the one-sided 95% prediction interval of needle guidance error was 4.13 mm. The median (IQR) angular error was 0.0097 rad (0.0057-0.015 rad) with a one-sided 95% prediction interval upper limit of 0.022 rad. The median (IQR) positioning error using the previous four-sphere registration fiducial assembly was 1.87 mm (1.77-2.14 mm). This was found to be significantly different (p = 0.0012) from the median (IQR) positioning error of 0.28 mm (0.14-0.95 mm) using the new registration fiducial assembly on the same trajectories. No significant difference was detected between the medians of the angular errors (p = 0.26)., Conclusion: This is the first study presenting an improved registration method and validation in tissue-mimicking phantoms of our remotely actuated MR-compatible mechatronic system for delivery of prostate FLA needles. Accounting for the effects of needle deflection, the system was demonstrated to be capable of needle delivery with an error of 4.13 mm or less in 95% of cases under ideal conditions, which is a statistically significant improvement over the previous method. The system will next be validated in a clinical setting., (© 2022 American Association of Physicists in Medicine.)

Background: Mammographic screening has reduced mortality in women through the early detection of breast cancer. However, the sensitivity for breast cancer detection is significantly reduced in women with dense breasts, in addition to being an independent risk factor. Ultrasound (US) has been proven effective in detecting small, early-stage, and invasive cancers in women with dense breasts., Purpose: To develop an alternative, versatile, and cost-effective spatially tracked three-dimensional (3D) US system for whole-breast imaging. This paper describes the design, development, and validation of the spatially tracked 3DUS system, including its components for spatial tracking, multi-image registration and fusion, feasibility for whole-breast 3DUS imaging and multi-planar visualization in tissue-mimicking phantoms, and a proof-of-concept healthy volunteer study., Methods: The spatially tracked 3DUS system contains (a) a six-axis manipulator and counterbalanced stabilizer, (b) an in-house quick-release 3DUS scanner, adaptable to any commercially available US system, and removable, allowing for handheld 3DUS acquisition and two-dimensional US imaging, and (c) custom software for 3D tracking, 3DUS reconstruction, visualization, and spatial-based multi-image registration and fusion of 3DUS images for whole-breast imaging. Spatial tracking of the 3D position and orientation of the system and its joints (J 1-6 ) were evaluated in a clinically accessible workspace for bedside point-of-care (POC) imaging. Multi-image registration and fusion of acquired 3DUS images were assessed with a quadrants-based protocol in tissue-mimicking phantoms and the target registration error (TRE) was quantified. Whole-breast 3DUS imaging and multi-planar visualization were evaluated with a tissue-mimicking breast phantom. Feasibility for spatially tracked whole-breast 3DUS imaging was assessed in a proof-of-concept healthy male and female volunteer study., Results: Mean tracking errors were 0.87 ± 0.52, 0.70 ± 0.46, 0.53 ± 0.48, 0.34 ± 0.32, 0.43 ± 0.28, and 0.78 ± 0.54 mm for joints J 1-6 , respectively. Lookup table (LUT) corrections minimized the error in joints J 1 , J 2 , and J 5 . Compound motions exercising all joints simultaneously resulted in a mean tracking error of 1.08 ± 0.88 mm (N = 20) within the overall workspace for bedside 3DUS imaging. Multi-image registration and fusion of two acquired 3DUS images resulted in a mean TRE of 1.28 ± 0.10 mm. Whole-breast 3DUS imaging and multi-planar visualization in axial, sagittal, and coronal views were demonstrated with the tissue-mimicking breast phantom. The feasibility of the whole-breast 3DUS approach was demonstrated in healthy male and female volunteers. In the male volunteer, the high-resolution whole-breast 3DUS acquisition protocol was optimized without the added complexities of curvature and tissue deformations. With small post-acquisition corrections for motion, whole-breast 3DUS imaging was performed on the healthy female volunteer showing relevant anatomical structures and details., Conclusions: Our spatially tracked 3DUS system shows potential utility as an alternative, accurate, and feasible whole-breast approach with the capability for bedside POC imaging. Future work is focused on reducing misregistration errors due to motion and tissue deformations, to develop a robust spatially tracked whole-breast 3DUS acquisition protocol, then exploring its clinical utility for screening high-risk women with dense breasts., (© 2022 American Association of Physicists in Medicine.)

Purpose: Prostate cancer is the most common non-cutaneous cancer among men in the United States and is the second leading cause of cancer death in American men. (Siegel et al. [2019] CA: A Cancer J Clin.69(1):7-34.) Focal laser ablation (FLA) has the potential to control small tumors while preserving urinary and erectile function by leaving the neurovascular bundles and urethral sphincters intact. Accurate needle guidance is critical to the success of FLA. Multiparametric magnetic resonance images (mpMRI) can be used to identify targets, guide needles, and assess treatment outcomes. The purpose of this work was to design and evaluate the accuracy of an MR-compatible mechatronic system for in-bore transperineal guidance of FLA ablation needles to localized lesions in the prostate., Methods: The mechatronic system was constructed entirely of non-ferromagnetic materials, with actuation controlled by piezoelectric motors and optical encoders. The needle guide hangs between independent front and rear two-link arms, which allows for horizontal and vertical translation as well as pitch and yaw rotation of the guide with a 6.0 cm range of motion in each direction. Needles are inserted manually through a chosen hole in the guide, which has been aligned with the target in the prostate. Open-air positioning error was evaluated using an optical tracking system (0.25 mm RMS accuracy) to measure 125 trajectories in free space. Correction of systematic bias in the system was performed using 85 of the trajectories, and the remaining 40 were used to estimate the residual error. The error was calculated as the horizontal and vertical displacement between the axis of the desired and measured trajectories at a typical needle insertion depth of 10 cm. MR-compatibility was evaluated using a grid phantom to assess image degradation due to the presence of the system, and induced force, heating, and electrical interference in the system were assessed qualitatively. In-bore positioning error was evaluated on 25 trajectories., Results: Open-air mean positioning error at the needle tip was 0.80 ± 0.36 mm with a one-sided 95% confidence interval of 1.40 mm. The mean deviation of needle trajectories from the planned direction was 0.14 ± 0.06 ∘ . In the MR bore, the mean positioning error at the needle tip was 2.11 ± 1.05 mm with a one-sided 95% prediction interval of 3.84 mm. The mean angular error was 0.49 ± 0.26 ∘ . The system was found to be compatible with the MR environment under the specified gradient-echo sequence parameters used in this study., Conclusion: A complete system for delivering needles to localized prostate tumors was developed and described in this work, and its compatibility with the MR environment was demonstrated. In-bore MRI positioning error was sufficiently small for targeting small localized prostate tumors., (© 2021 American Association of Physicists in Medicine.)

Purpose: For lung and liver tumors requiring radiotherapy, motion artifacts are common in 4D-CT images due to the small axial field-of-view (aFOV) of conventional CT scanners. This may negatively impact contouring and dose calculation accuracy and could lead to a geographic miss during treatment. Recent advancements in volumetric CT (vCT) enable an aFOV up to 160 mm in a single rotation, which may reduce motion artifacts. However, the impact of large aFOV on CT number required for dose calculation needs to be evaluated before clinical implementation. The objective of this study was to determine the utility of a 256-slice vCT scanner for 4D-CT simulation by evaluating image quality and generating relative electron density (RED) curves., Methods: Images were acquired on a 256-slice GE Revolution CT scanner with 40 mm, 80 mm, 120 mm, 140 mm, and 160 mm aFOV. Image quality was assessed by evaluating CT number linearity, uniformity, noise, and low-contrast resolution. The relationship between each quality metric and aFOV was assessed., Results: CT number linearity, uniformity, noise, and low-contrast resolution were within the expected range for each image set, except CT number in Teflon and Delrin, which were underestimated. Spearman correlation coefficient (ρ) showed that the CT number for Teflon (ρ = 1.0, p = 0.02), Delrin (ρ = 1.0, p = 0.02), and air (ρ = 1.0, p = 0.02) was significantly related to aFOV, while all other measurements were not. The measured deviations from expected values were not clinically significant., Conclusion: These results suggest that vCT can be used for CT simulation for radiation treatment planning., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Image-guided needle biopsy of small, detectable lesions is crucial for early-stage diagnosis, treatment planning, and management of breast cancer. High-resolution positron emission mammography (PEM) is a dedicated functional imaging modality that can detect breast cancer independent of breast tissue density, but anatomical context and real-time needle visualization are not yet available to guide biopsy. We propose a mechatronic guidance system integrating an ultrasound (US)-guided core-needle biopsy (CNB) with high-resolution PEM localization to improve the spatial sampling of breast lesions. This paper presents the benchtop testing and phantom studies to evaluate the accuracy of the system and its constituent components for targeted PEM-US-guided biopsy under simulated high-resolution PEM localization., Methods: A mechatronic guidance system was developed to operate with the Radialis PEM system and a conventional US system. The system includes a user-operated guidance arm and end-effector biopsy device, integrating a US transducer and CNB gun, with its needle focused on a remote center of motion (RCM). Custom software modules were developed to track, display, and guide the end-effector biopsy device. Registration of the mechatronic guidance system to a simulated PEM detector plate was performed using a landmark-based method. Testing was performed with fiducials positioned in the peripheral and central regions of the simulated detector plate and registration error was quantified. Breast phantom experiments were performed under ideal detection and localization to evaluate for bias in the end-effector biopsy device. The accuracy of the complete mechatronic guidance system to perform targeted breast biopsy was assessed using breast phantoms with simulated lesions. Three-dimensional positioning error was quantified, and principal component analysis assessed for directional trends in 3D space within 95% prediction intervals. Targeted breast biopsies with test phantoms were performed and an overall in-plane needle targeting error was quantified., Results: The mean registration errors were 0.63 mm (N = 44) and 0.73 mm (N = 72) in the peripheral and central regions of the simulated PEM detector plate, respectively. A 3D 95% prediction ellipsoid shows an error volume <2.0 mm in diameter, centered on the mean registration error. Under ideal detection and localization, targets <1.0 mm in diameter can be sampled with 95% confidence. The complete mechatronic guidance system was able to successfully spatially sample simulated breast lesions, 4 mm and 6 mm in diameter and height (N = 20) in known 3D positions in the PEM image coordinate space. The 3D positioning error was 0.85 mm (N = 20) with 0.64 mm in-plane and 0.44 mm cross-plane component errors. Targeted breast biopsies resulted in a mean in-plane needle targeting error of 1.08 mm (N = 15) allowing for targets 1.32 mm in radius to be sampled with 95% confidence., Conclusions: We demonstrated the utility of our mechatronic guidance system for targeted breast biopsy under high-resolution PEM localization. Breast phantom studies showed the ability to accurately guide, position, and target breast lesions with the accuracy to spatially sample targets <3.0 mm in diameter with 95% confidence. Future work will integrate the developed system with the Radialis PEM system toward combined PEM-US-guided breast biopsy., (© 2021 American Association of Physicists in Medicine.)