Multi-modal co-learning with attention mechanism for head and neck tumor segmentation on 18FDG PET-CT.

PURPOSE: Effective radiation therapy requires accurate segmentation of head and neck cancer, one of the most common types of cancer. With the advancement of deep learning, people have come up with various methods that use positron emission tomography-computed tomography to get complementary information. However, these approaches are computationally expensive because of the separation of feature extraction and fusion functions and do not make use of the high sensitivity of PET. We propose a new deep learning-based approach to alleviate these challenges. METHODS: We proposed a tumor region attention module that fully exploits the high sensitivity of PET and designed a network that learns the correlation between the PET and CT features using squeeze-and-excitation normalization (SE Norm) without separating the feature extraction and fusion functions. In addition, we introduce multi-scale context fusion, which exploits contextual information from different scales. RESULTS: The HECKTOR challenge 2021 dataset was used for training and testing. The proposed model outperformed the state-of-the-art models for medical image segmentation; in particular, the dice similarity coefficient increased by 8.78% compared to U-net. CONCLUSION: The proposed network segmented the complex shape of the tumor better than the state-of-the-art medical image segmentation methods, accurately distinguishing between tumor and non-tumor regions.

Generating 3D images of VMAT plans for predictive models and activation maps associated with plan deliverability.

BACKGROUND: Intensity modulation with dynamic multi-leaf collimator (MLC) and monitor unit (MU) changes across control points (CPs) characterizes volumetric modulated arc therapy (VMAT). The increased uncertainty in plan deliverability required patient-specific quality assurance (PSQA), which remained inefficient upon Quality Assurance (QA) failure. To prevent waste before QA, plan complexity metrics (PCMs) and machine learning models with the metrics were generated, which were lack of providing CP-specific information upon QA failures. PURPOSE: By generating 3D images from digital imaging and comminications in medicine in radiation therapy (DICOM RT) plan, we proposed a predictive model that can estimate the deliverability of VMAT plans and visualize CP-specific regions associated with plan deliverability. METHODS: The patient cohort consisted of 259 and 190 cases for left- and right-breast VMAT treatments, which were split into 235 and 166 cases for training and 24 cases from each treatment for testing the networks. Three-channel 3D images generated from DICOM RT plans were fed into a DenseNet-based deep learning network. To reflect VMAT plan complexity as an image, the first two channels described MLC and MU variations between two consecutive CPs, while the last channel assigned the beam field size. The network output was defined as binary classified PSQA results, indicating deliverability. The predictive performance was assessed by accuracy, sensitivity, specificity, F1-score, and area under the curve (AUC). The gradient-weighted class activation map (Grad-CAM) highlighted the regions of CPs in VMAT plans associated with deliverability, compared against PCMs by Spearman correlation. RESULTS: The DenseNet-based predictive model yielded AUCs of 92.2% and 93.8%, F1-scores of 97.0% and 93.8% and accuracies of 95.8% and 91.7% for the left- and right-breast VMAT cases. Additionally, the specificity of 87.5% for both cases indicated that the predictive model accurately detected QA failing cases. The activation maps significantly differentiated QA failing-labeled from passing-labeled classes for the non-deliverable cases. The PCM with the highest correlation to the Grad-CAM varied from patient cases, implying that plan deliverability would be considered patient-specific. CONCLUSION: This work demonstrated that the deep learning-based network based on visualization of dynamic VMAT plan information successfully predicted plan deliverability, which also provided control-point specific planning parameter information associated with plan deliverability in a patient-specific manner.

Enhancing voxel-based dosimetry accuracy with an unsupervised deep learning approach for hybrid medical image registration.

BACKGROUND: Deformable registration is required to generate a time-integrated activity (TIA) map which is essential for voxel-based dosimetry. The conventional iterative registration algorithm using anatomical images (e.g., computed tomography (CT)) could result in registration errors in functional images (e.g., single photon emission computed tomography (SPECT) or positron emission tomography (PET)). Various deep learning-based registration tools have been proposed, but studies specifically focused on the registration of serial hybrid images were not found. PURPOSE: In this study, we introduce CoRX-NET, a novel unsupervised deep learning network designed for deformable registration of hybrid medical images. The CoRX-NET structure is based on the Swin-transformer (ST), allowing for the representation of complex spatial connections in images. Its self-attention mechanism aids in the effective exchange and integration of information across diverse image regions. To augment the amalgamation of SPECT and CT features, cross-stitch layers have been integrated into the network. METHODS: Two different 177 Lu DOTATATE SPECT/CT datasets were acquired at different medical centers. 22 sets from Seoul National University and 14 sets from Sunway Medical Centre are used for training/internal validation and external validation respectively. The CoRX-NET architecture builds upon the ST, enabling the modeling of intricate spatial relationships within images. To further enhance the fusion of SPECT and CT features, cross-stitch layers have been incorporated within the network. The network takes a pair of SPECT/CT images (e.g., fixed and moving images) and generates a deformed SPECT/CT image. The performance of the network was compared with Elastix and TransMorph using L1 loss and structural similarity index measure (SSIM) of CT, SSIM of normalized SPECT, and local normalized cross correlation (LNCC) of SPECT as metrics. The voxel-wise root mean square errors (RMSE) of TIA were compared among the different methods. RESULTS: The ablation study revealed that cross-stitch layers improved SPECT/CT registration performance. The cross-stitch layers notably enhance SSIM (internal validation: 0.9614 vs. 0.9653, external validation: 0.9159 vs. 0.9189) and LNCC of normalized SPECT images (internal validation: 0.7512 vs. 0.7670, external validation: 0.8027 vs. 0.8027). CoRX-NET with the cross-stitch layer achieved superior performance metrics compared to Elastix and TransMorph, except for CT SSIM in the external dataset. When qualitatively analyzed for both internal and external validation cases, CoRX-NET consistently demonstrated superior SPECT registration results. In addition, CoRX-NET accomplished SPECT/CT image registration in less than 6 s, whereas Elastix required approximately 50 s using the same PC's CPU. When employing CoRX-NET, it was observed that the voxel-wise RMSE values for TIA were approximately 27% lower for the kidney and 33% lower for the tumor, compared to when Elastix was used. CONCLUSION: This study represents a major advancement in achieving precise SPECT/CT registration using an unsupervised deep learning network. It outperforms conventional methods like Elastix and TransMorph, reducing uncertainties in TIA maps for more accurate dose assessments.

Incidence and predictors of dorsal comminution in older adults with low-energy distal radius fracture.

PURPOSE: To identify the incidence of dorsal comminution using computed tomography (CT) images and identify predictors of this phenomenon in older adults with low-energy distal radius fractures (DRFs). METHODS: A total of 150 patients aged > 50 years with fall-induced dorsally angulated DRFs were enrolled in this study. Patients were divided into two groups based on the presence of dorsal comminution, defined as a metaphyseal void of greater than one-third of the maximum posterior to anterior depth of the bone on at least three cuts in the sagittal plane on post-reduction CT images. Data on participants' basic demographics, including age, sex, body mass index (BMI), and AO classification of DRFs, were collected. Bone mineral density (BMD) was assessed using T-scores of the femoral neck, and cortical thickness of the distal radius was determined from plain post-reduction radiographs. Radiological parameters and combined ulnar fractures were measured on plain pre-reduction radiographs. RESULTS: Among study participants, 91 (61%) had dorsal comminution, whereas 59 (39%) had no dorsal comminution on CT images. Both patient groups were compared based on presence of dorsal comminution, and showed no significant differences in age, sex, BMI, BMD, or cortical thickness on radiographs. However, all radiological parameters were better in the no dorsal comminution group than in the dorsal comminution group, and the proportion of patients with combined ulnar fractures was higher in the dorsal comminution group. In the multivariate analysis, the presence of combined ulnar fractures was the only significant predictor of dorsal comminution (p = 0.029, odds ratio = 2.267, 95% confidence interval: 1.085-4.736). CONCLUSION: The incidence of dorsal comminution is relatively high in patients with low-energy DRFs aged > 50 years. In particular, the presence of combined ulnar fractures is closely associated with dorsal comminution of DRFs. Thus, surgeons should exercise caution when evaluating this phenomenon.

Subperiosteal delivery of transforming growth factor beta 1 and human growth hormone from mineralized PCL films.

The ability to locally deliver bioactive molecules to distinct regions of the skeleton may provide a novel means by which to improve fracture healing, treat neoplasms or infections, or modulate growth. In this study, we constructed single-sided mineral-coated poly-ε-caprolactone membranes capable of binding and releasing transforming growth factor beta 1 (TGF-ß1) and human growth hormone (hGH). After demonstrating biological activity in vitro and characterization of their release, these thin bioabsorbable membranes were surgically implanted using an immature rabbit model. Membranes were circumferentially wrapped under the periosteum, thus placed in direct contact with the proximal metaphysis to assess its bioactivity in vivo. The direct effects on the metaphyseal bone, bone marrow, and overlying periosteum were assessed using radiography and histology. Effects of membrane placement at the tibial growth plate were assessed via physeal heights, tibial growth rates (pulsed fluorochrome labeling), and tibial lengths. Subperiosteal placement of the mineralized membranes induced greater local chondrogenesis in the plain mineral and TGF-ß1 samples than the hGH. More exuberant and circumferential ossification was seen in the TGF-ß1 treated tibiae. The TGF-ß1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups. While the proximal tibial growth plates were taller in the hGH treated than TGF-ß1, no differences in growth rates or overall tibial lengths were found. In conclusion, these data demonstrate the feasibility of using bioabsorbable mineral coated membranes to deliver biologically active compounds subperiosteally in a sustained fashion to affect cells at the insertion site, bone marrow, and even growth plate.

Simplified image-based dosimetry using planar images and patient-specific S-values.

BACKGROUND: Single time point measurement approach and hybrid dosimetry were proposed to simplify the dosimetry process. It is anticipated that utilizing patient-specific S-value would enable more accurate dosimetry assessment based on imaging compared to using the conventional MIRD S-values. PURPOSE: We performed planar image-based dosimetry scaled with a single SPECT image for the entire treatment cycle using patient-specific S-values (PSS dosimetry) of organs. PSS dosimetry could further simplify the dosimetry procedure compared with a conventional 2D planar/3D SPECT hybrid dosimetry, as PSS dosimetry requires only one SPECT/CT image for the treatment of the entire cycle, whereas the conventional hybrid dosimetry requires a SPECT/CT image for each treatment cycle. METHODS: 177Lu-DOTATATE SPECT/CT and planar image datasets acquired from Seoul National University Hospital (SNUH, Seoul, Republic of Korea) were utilized for the evaluation. Images were acquired 4, 24, 48, and 120 h after patients' intravenous injection of 177Lu-DOTATATE. Dose estimations based on a Monte Carlo (MC) simulation using the Geant4 Application for Emission Tomography (GATE) (v.8.2) were considered as the reference. Planar image-based dosimetry scaled with a single SPECT image was performed using the patient-specific S-value (PSS). Briefly, the CT image was considered as the patient's anatomical reference and PSSs were quantified using the multiple voxel S-value (VSV) method. Then, PSS dosimetry was performed by obtaining activity information from sequential planar images and a scaling factor derived from a single SPECT/planar image pair. Hybrid dosimetry using sequential planar images and a single SPECT image was performed for comparison. The absorbed doses of the kidneys, bone marrow (BM) in the lumbar spine, liver, and spleen calculated using the PSS and hybrid dosimetries were compared with the reference MC results. RESULTS: The mean differences (MDs) of the self-absorption S-values between S-value of OLINDA/EXM and PSS for the kidneys, liver, and spleen were -0.04%, -2.39%, and -2.62%, respectively. However, the differences in the self-absorption S-values were significantly higher for the BM (84.99%) and the remainder of the body (ROB) (280.84%). The absorbed doses estimated by the PSS and hybrid dosimetries showed relatively high errors compared with MC simulation result, regardless of the organ. In contrast, the PSS and hybrid dosimetries produced similar dose estimates. For the entire cycles of the treatment, the MDs of absorbed doses between PSS and hybrid dosimetries were -3.31%, -6.04%, 3.37%, and -2.17% for the kidneys, BM, liver, and spleen, respectively. Through a correlation analysis and the Wilcoxon signed-rank test, we concluded that there was no significant difference between the results obtained by the two dosimetry methods. CONCLUSIONS: As the PSS was derived using CT images with actual anatomical information and organ-specific volume of interest (VOI), PSS dosimetry provided reliable results. PSS dosimetry was robust in estimating the absorbed dose for the later treatment cycles. Therefore, PSS dosimetry outperformed hybrid dosimetry in terms of dose estimation for a greater number of treatment cycles.

Magnetic resonance imaging analysis of the distribution of cartilage damage in scaphoid nonunion.

This study aimed to evaluate the distribution and severity of cartilage damage using magnetic resonance imaging in patients with scaphoid nonunion without advanced wrist arthritis. We retrospectively analysed MRI of patients who underwent osteosynthesis for scaphoid nonunion. Cartilage damage was assessed in eight wrist regions using a modified Whole-Organ Magnetic Resonance Imaging Score. The frequencies of regions affected by any cartilage damage (Score ≥2.5) depicted on MRI were analysed. The study included 32 patients (31 men and one woman), with a mean age of 32 years (SD 11). The distal radioscaphoid (29/32), scaphotrapeziotrapezoid (STT) (22/32), proximal radioscaphoid (14/32) and scaphocapitate (11/32) joints were most commonly affected by degenerative cartilage damage. The STT and proximal radioscaphoid joint were especially likely to be involved in early-stage scaphoid nonunion advanced collapse. We recommend that surgeons should investigate the cartilage status of these joints during decision-making for scaphoid nonunion surgery.Level of evidence: III.

Empowering Vision Transformer by Network Hyper-Parameter Selection for Whole Pelvis Prostate Planning Target Volume Auto-Segmentation.

U-Net, based on a deep convolutional network (CNN), has been clinically used to auto-segment normal organs, while still being limited to the planning target volume (PTV) segmentation. This work aims to address the problems in two aspects: 1) apply one of the newest network architectures such as vision transformers other than the CNN-based networks, and 2) find an appropriate combination of network hyper-parameters with reference to recently proposed nnU-Net ("no-new-Net"). VT U-Net was adopted for auto-segmenting the whole pelvis prostate PTV as it consisted of fully transformer architecture. The upgraded version (v.2) applied the nnU-Net-like hyper-parameter optimizations, which did not fully cover the transformer-oriented hyper-parameters. Thus, we tried to find a suitable combination of two key hyper-parameters (patch size and embedded dimension) for 140 CT scans throughout 4-fold cross validation. The VT U-Net v.2 with hyper-parameter tuning yielded the highest dice similarity coefficient (DSC) of 82.5 and the lowest 95% Haussdorff distance (HD95) of 3.5 on average among the seven recently proposed deep learning networks. Importantly, the nnU-Net with hyper-parameter optimization achieved competitive performance, although this was based on the convolution layers. The network hyper-parameter tuning was demonstrated to be necessary even for the newly developed architecture of vision transformers.

Comparative study on gamma-ray detectors for in-situ ocean radiation monitoring system.

Large-sized crystals and state-of-the-art photosensors are desirable to cope with low environmental radioactivity (e.g., 1-2 Bq∙m-3137Cs in surface seawater) for homeland security purposes. We compared the performances of two different gamma-ray detector assemblies, GAGG crystal + silicon photomultiplier (SiPM) and NaI(Tl) crystal + photomultiplier tube, for our mobile in-situ ocean radiation monitoring system. We performed energy calibration, followed by water tank experiments with varying the depth of a137Cs point source. Experimental energy spectra were compared with MCNP-simulated spectra with identical setup and the consistency was validated. We finally assessed the detection efficiency and minimum detectable activity (MDA) of the detectors. Both GAGG and NaI detectors exhibited favorable energy resolutions (7.98 ± 0.13% and 7.01 ± 0.58% at 662 keV, respectively) and MDAs (33.1 ± 0.0645 and 13.5 ± 0.0327 Bq∙m-3 for 24-h 137Cs measurement, respectively). Matching the geometry of the GAGG crystal with that of the NaI crystal, the GAGG detector outperformed the NaI detector. The results demonstrated that the GAGG detector is potentially advantageous over the NaI detector in detection efficiency and compactness.

How Does the Addition of Dexamethasone to a Brachial Plexus Block Change Pain Patterns After Surgery for Distal Radius Fractures? A Randomized, Double-blind Study.

BACKGROUND: Although brachial plexus block in volar plating surgery for distal radius fractures is reportedly associated with lower postoperative pain scores, rebound pain has been reported to occur after the initial block wears off. Dexamethasone can be used in multimodal strategies for antiemesis and to control pain postoperatively. Although prior studies have suggested that anesthesia can be prolonged by adding dexamethasone to regional blocks, no randomized trials we are aware of have ascertained whether doing so will make a clinically important difference in pain after surgery for distal radius fractures. QUESTIONS/PURPOSES: Do patients who receive supplemental dexamethasone in a brachial plexus block for volar plating of unstable distal radius fractures have (1) better pain scores at 4, 8, 24, and 48 hours postoperatively than patients who have not received dexamethasone, and (2) lower fentanyl consumption and administration of antiemetic drugs without change in serum blood glucose, as well as a longer analgesic duration from the block after surgery than patients who have not received dexamethasone? METHODS: This randomized, double-blind trial included 69 patients undergoing surgery for distal radius fractures under ultrasound-guided supraclavicular brachial plexus blocks who were randomly allocated into two groups: a nondexamethasone group receiving a brachial plexus block with 0.5% ropivacaine and a dexamethasone group receiving 0.5% ropivacaine and 5 mg of dexamethasone. Thirty-four patients were allocated to the dexamethasone group and 35 were allocated to the nondexamethasone group. Nine patients (four in the dexamethasone group and five in the nondexamethasone group) were excluded after randomization because local anesthetics were used during their surgical procedures owing to an incomplete block or they requested patient-controlled analgesia after surgery. The treatment groups did not differ in any important ways, including age, gender, BMI, hand dominance, and AO/Orthopaedic Trauma Association classification. All patients received the same surgical procedure and perioperative care protocol, except for the injected agents during their brachial plexus block. The primary outcome was postoperative pain, evaluated using a 10-mm VAS at 4, 8, 12, 24, and 48 hours after surgery. The minimum clinically important difference for the VAS score was 2 of 10 points. Secondary outcome variables included fentanyl administration as a rescue analgesic, the number of patients receiving antiemetic medications because of fentanyl administration, and the duration of brachial plexus block. Serum blood glucose was measured 1 day before, immediately after, and 24 hours after surgery. Patients, surgeons, and outcome assessors were blinded to treatment allocation. RESULTS: The only clinically important between-group difference in VAS pain scores was at 8 hours, favoring the group that received dexamethasone over the group that did not (1.9 ± 1.6 versus 4.7 ± 2.7; mean difference -2.8 [95% CI -3.9 to -1.6]; p < 0.001). After brachial plexus block, the most severe pain score in both groups was reported at 12 hours postoperatively and gradually diminished over time. There was no between-group difference in fentanyl use between those who received dexamethasone and those who did not (21 ± 38 mcg versus 31 ± 29 mcg; mean difference -10 [95% CI -27.4 to 7.4]; p = 0.26). Furthermore, the use of antiemetics did not differ between the groups (27% [eight of 30] versus 37% [11 of 30]; odds ratio 1.6 [95% CI 0.5 to 4.8]; p = 0.41). Baseline and 24-hour postoperative serum blood glucose level did not differ between the groups. However, the immediately postoperative serum blood glucose level was higher in the dexamethasone group than in the nondexamethasone group (121 ± 29 versus 104 ± 20; mean difference 16 [95% CI 3.3 to 28.8]; p = 0.02). The brachial plexus block duration was 3 hours longer (95% CI 0.8 to 5.2 hours) in the dexamethasone group than that in the nondexamethasone group (11 ± 5 hours versus 8 ± 3 hours; p = 0.01). CONCLUSION: The postoperative pain level in patients who received supplemental dexamethasone in a regional block was not clinically different from that of patients who received conventional brachial plexus block anesthesia when undergoing volar plating for distal radius fractures. However, patients who received a brachial plexus block with dexamethasone experienced slight prolongation of their block and decrease in pain 8 hours after surgery. LEVEL OF EVIDENCE: Level I, therapeutic study.

CT-free quantitative SPECT for automatic evaluation of %thyroid uptake based on deep-learning.

PURPOSE: Quantitative thyroid single-photon emission computed tomography/computed tomography (SPECT/CT) requires computed tomography (CT)-based attenuation correction and manual thyroid segmentation on CT for %thyroid uptake measurements. Here, we aimed to develop a deep-learning-based CT-free quantitative thyroid SPECT that can generate an attenuation map (µ-map) and automatically segment the thyroid. METHODS: Quantitative thyroid SPECT/CT data (n = 650) were retrospectively analyzed. Typical 3D U-Nets were used for the µ-map generation and automatic thyroid segmentation. Primary emission and scattering SPECTs were inputted to generate a µ-map, and the original µ-map from CT was labeled (268 and 30 for training and validation, respectively). The generated µ-map and primary emission SPECT were inputted for the automatic thyroid segmentation, and the manual thyroid segmentation was labeled (280 and 36 for training and validation, respectively). Other thyroid SPECT/CT (n = 36) and salivary SPECT/CT (n = 29) were employed for verification. RESULTS: The synthetic µ-map demonstrated a strong correlation (R2 = 0.972) and minimum error (mean square error = 0.936 × 10-4, %normalized mean absolute error = 0.999%) of attenuation coefficients when compared to the ground truth (n = 30). Compared to manual segmentation, the automatic thyroid segmentation was excellent with a Dice similarity coefficient of 0.767, minimal thyroid volume difference of - 0.72 mL, and a short 95% Hausdorff distance of 9.416 mm (n = 36). Additionally, %thyroid uptake by synthetic µ-map and automatic thyroid segmentation (CT-free SPECT) was similar to that by the original µ-map and manual thyroid segmentation (SPECT/CT) (3.772 ± 5.735% vs. 3.682 ± 5.516%, p = 0.1090) (n = 36). Furthermore, the synthetic µ-map generation and automatic thyroid segmentation were successfully performed in the salivary SPECT/CT using the deep-learning algorithms trained by thyroid SPECT/CT (n = 29). CONCLUSION: CT-free quantitative SPECT for automatic evaluation of %thyroid uptake can be realized by deep-learning.

Voxel-Based Internal Dosimetry for 177Lu-Labeled Radiopharmaceutical Therapy Using Deep Residual Learning.

Purpose: In this study, we propose a deep learning (DL)-based voxel-based dosimetry method in which dose maps acquired using the multiple voxel S-value (VSV) approach were used for residual learning. Methods: Twenty-two SPECT/CT datasets from seven patients who underwent 177Lu-DOTATATE treatment were used in this study. The dose maps generated from Monte Carlo (MC) simulations were used as the reference approach and target images for network training. The multiple VSV approach was used for residual learning and compared with dose maps generated from deep learning. The conventional 3D U-Net network was modified for residual learning. The absorbed doses in the organs were calculated as the mass-weighted average of the volume of interest (VOI). Results: The DL approach provided a slightly more accurate estimation than the multiple-VSV approach, but the results were not statistically significant. The single-VSV approach yielded a relatively inaccurate estimation. No significant difference was noted between the multiple VSV and DL approach on the dose maps. However, this difference was prominent in the error maps. The multiple VSV and DL approach showed a similar correlation. In contrast, the multiple VSV approach underestimated doses in the low-dose range, but it accounted for the underestimation when the DL approach was applied. Conclusion: Dose estimation using the deep learning-based approach was approximately equal to that in the MC simulation. Accordingly, the proposed deep learning network is useful for accurate and fast dosimetry after radiation therapy using 177Lu-labeled radiopharmaceuticals.

Automatic Lung Cancer Segmentation in [18F]FDG PET/CT Using a Two-Stage Deep Learning Approach.

Purpose: Since accurate lung cancer segmentation is required to determine the functional volume of a tumor in [18F]FDG PET/CT, we propose a two-stage U-Net architecture to enhance the performance of lung cancer segmentation using [18F]FDG PET/CT. Methods: The whole-body [18F]FDG PET/CT scan data of 887 patients with lung cancer were retrospectively used for network training and evaluation. The ground-truth tumor volume of interest was drawn using the LifeX software. The dataset was randomly partitioned into training, validation, and test sets. Among the 887 PET/CT and VOI datasets, 730 were used to train the proposed models, 81 were used as the validation set, and the remaining 76 were used to evaluate the model. In Stage 1, the global U-net receives 3D PET/CT volume as input and extracts the preliminary tumor area, generating a 3D binary volume as output. In Stage 2, the regional U-net receives eight consecutive PET/CT slices around the slice selected by the Global U-net in Stage 1 and generates a 2D binary image as the output. Results: The proposed two-stage U-Net architecture outperformed the conventional one-stage 3D U-Net in primary lung cancer segmentation. The two-stage U-Net model successfully predicted the detailed margin of the tumors, which was determined by manually drawing spherical VOIs and applying an adaptive threshold. Quantitative analysis using the Dice similarity coefficient confirmed the advantages of the two-stage U-Net. Conclusion: The proposed method will be useful for reducing the time and effort required for accurate lung cancer segmentation in [18F]FDG PET/CT.

Risk factors for hardware-related complications after extra-articular distal humerus fracture fixation using an anatomical locking plate.

PURPOSE: We aimed to identify the incidence and risk factors of hardware-related complications in patients treated with anatomical locking plate fixation for extra-articular distal humerus fractures. METHODS: From 2013 to 2020, patients with extra-articular distal humerus fractures who underwent open reduction and internal fixation with an extra-articular distal humerus locking plate (EADHP) were retrospectively reviewed and categorized according to the presence/absence of hardware-related complications. Hardware-related complications were defined as the occurrence of skin prominence on the plate and discomfort in activities of daily living. Patient demographics, the lateral condylar angle, lateral body length, shaft-condylar angle of the humerus, and plate length were analyzed. RESULTS: Of the 29 patients, 10 (34%) did not develop hardware-related complications (group A), whereas 19 (66%) did (group B). Patient demographics did not differ between the groups. However, the number of patients who underwent hardware removal was significantly greater in group B (16/19) than in group A (4/10; p = 0.032). Radiologic assessment revealed no significant difference in the lateral condylar or shaft-condylar angle. However, the lateral body length was greater in group A than in group B (44.5 ± 4.8 vs. 39.5 ± 3.7, p = 0.007). The plate length significantly differed between the groups. Twelve of 19 (63%) patients in group B received short-hole plates (six holes), while nine of ten (90%) patients in group A received long-hole plates (eight holes). In the multivariable analysis, the lateral body length of the distal humerus (p = 0.047, odds ratio = 0.734, 95% confidence interval: 0.542-0.996) and plate length (p = 0.036, odds ratio = 0.076, 95% confidence interval: 0.542-0.996) were associated with hardware-related complications. CONCLUSIONS: Most patients developed hardware-related complications, particularly with short plates, mainly because of the narrow lateral body length of the distal humerus. Surgeons should be careful to secure EADHP in the appropriate position, especially when short plates are used in patients with narrow lateral body length.

Outcomes of Primary Volar Locking Plate Fixation of Open Distal Radius Fractures.

Background: Few studies have reported the outcomes of primary volar locking plate fixation in Gustilo and Anderson type II and IIIA open distal radius fractures. We report the outcomes of treatment of Gustilo and Anderson type II and IIIA open distal radius fractures using primary volar locking plate fixation. Methods: We retrospectively reviewed 24 patients with open distal radius fractures who were treated using primary volar locking plate fixation. The range of motion (ROM) and modified Mayo wrist scores were measured to assess functional outcomes. Radiological outcomes included the bone union period, radial inclination, volar tilt, radial length and ulnar variance. Results: Functional outcomes, including mean ROM in flexion (39.1°) and extension (52.5°), improved following primary volar locking plate treatment. Radiological outcomes were as follows. Mean bone union period, radial length and ulnar variance were 7.8 months, 10.4 and 0.7 mm, respectively. Two patients had superficial wound infection 2 weeks after surgery and one patient had non-union of the radius that required implant removal, autologous iliac crest bone graft and plate re-fixation. Conclusions: Primary volar locking plate fixation is a safe and reliable treatment option for Gustilo and Anderson type II and IIIA open distal radius fractures. By providing firm stabilisation and allowing early ROM exercise, primary volar locking plate fixation resulted in good functional and radiological outcomes. Level of Evidence: Level IV (Therapeutic).

Ultra-low-dose intraoperative X-ray imager for minimally invasive surgery: a pilot imaging study.

Background: With advances in surgical technology, thoracic surgeons have widely adopted minimally invasive limited-resection techniques to preserve normal tissues. However, it remains difficult to achieve in situ localization of invisible pulmonary nodules during surgery. Therefore, we proposed an in situ ultra-low-dose X-ray imaging device for intraoperative pulmonary nodule localization during minimally invasive surgeries. Methods: The proposed device features a hand-held type and consists of a carbon nanotube-based X-ray source and an intraoral dental sensor. In a preclinical study, we created pseudo pulmonary nodules using ex vivo pig lungs. Subsequently, its clinical feasibility was evaluated using ex vivo lung cancer specimens from patients with cancer who had undergone minimally invasive surgery. Results: Using the proposed device, we successfully differentiated normal and abnormal tissues from X-ray images of resected lung specimens. In addition, our proposed device only yielded an average radiation dose of 90.9 nGy for a single acquisition of X-ray images and demonstrated excellent temperature stability under consecutive X-ray irradiations. The radiation exposure of our proposed device (0.1±0.0006 µSv/h) was significantly lower than that of conventional C-arm fluoroscopy (41.5±51.8 µSv/h). In both preclinical and clinical studies, the margin of nodule shadows was clearly visualized using the proposed device. Conclusions: The proposed device substantially reduced radiation exposure to staff and patients and may allow in situ localization of pulmonary nodules. Our proposed device clearly revealed the margins of lung nodules with radiocontrast injection and showed the potential to identify solid nodules without the use of radiocontrast agents.

VEGF-attenuated platelet-rich plasma improves therapeutic effect on cartilage repair.

Autologous platelet-rich plasma (PRP) has gained popularity as a less invasive treatment for various musculoskeletal tissue injuries and conditions due to its favorable safety profile, minimal manipulation and cost-effectiveness. Although PRP treatment has been clinically used for the treatment of osteoarthritis (OA) and damaged cartilage, evidence on therapeutic efficacy has been inconsistent, which calls for a methodology to achieve consistent and improved treatment outcomes. Given that PRP contains numerous proteins, we hypothesized that attenuation of a growth factor known to be detrimental to the healing tissue would enhance efficacy of PRP treatment. Considering that VEGF-mediated angiogenesis inhibits the repair of articular cartilage, we developed VEGF-attenuated PRP by sequestering VEGF in PRP using VEGF-binding microspheres. We demonstrated that VEGF attenuation in PRP did not inhibit the effect of PRP on chondrogenic differentiation of stem cells in vitro. In addition, healing of rat OA cartilage was significantly improved after treatment with VEGF-attenuated PRP when compared to the PRP treatment group or PBS control group. We expect that attenuation of unwanted biological activity using growth factor-binding microspheres could provide a new PRP customization method broadly applicable to various tissue repair processes.

Postoperative immobilization using a short-arm cast in the semisupination position is appropriate after arthroscopic triangular fibrocartilage complex foveal repair.

AIMS: The aim of this study was to assess and compare active rotation of the forearm in normal subjects after the application of a short-arm cast (SAC) in the semisupination position and a long-arm cast (LAC) in the neutral position. A clinical study was also conducted to compare the functional outcomes of using a SAC in the semisupination position with those of using a LAC in the neutral position in patients who underwent arthroscopic triangular fibrocartilage complex (TFCC) foveal repair. METHODS: A total of 40 healthy right-handed volunteers were recruited. Active pronation and supination of the forearm were measured in each subject using a goniometer. In the retrospective clinical study, 40 patients who underwent arthroscopic foveal repair were included. The wrist was immobilized postoperatively using a SAC in the semisupination position (approximately 45°) in 16 patients and a LAC in 24. Clinical outcomes were assessed using grip strength and patient-reported outcomes. The degree of disability caused by cast immobilization was also evaluated when the cast was removed. RESULTS: Supination was significantly more restricted with LACs than with SACs in the semisupination position in male and female patients (p < 0.001 for both). However, pronation was significantly more restricted with SACs in the semisupination position than with LACs in female patients (p = 0.003) and was not significantly different in male patients (p = 0.090). In the clinical study, both groups showed improvement in all parameters with significant differences in grip strength, visual analogue scale scores for pain, modified Mayo Wrist Score, the Disability of the Arm, Shoulder, and Hand (DASH) score, and the Patient-Rated Wrist Evaluation (PRWE) score. No significant postoperative differences were noted between LACs and SACs in the semisupination position. However, the disability caused by immobilization in a cast was significantly higher in patients who had a LAC on the dominant hand (p < 0.001). CONCLUSION: We found that a SAC in the semisupination position is as effective as a LAC in restricting pronation of the forearm. In addition, postoperative immobilization with a SAC in the semisupination position resulted in comparable pain scores and functional outcomes to immobilization with a LAC after TFCC foveal repair, with less restriction of daily activities. Therefore, we recommend that surgeons consider using a SAC in the semisupination position for postoperative immobilization following TFCC foveal repair for dorsal instability of the distal radioulnar joint. Cite this article: Bone Joint J 2022;104-B(2):249-256.

Comparison of voxel S-value methods for personalized voxel-based dosimetry of 177 Lu-DOTATATE.

PURPOSE: Voxel-based dosimetry is potentially accurate than organ-based dosimetry because it considers the anatomical variations in each individual and the heterogeneous radioactivity distribution in each organ. Here, voxel-based dosimetry for 177 Lu-DOTATATE therapy was performed using single and multiple voxel S-value (VSV) methods and compared with Monte Carlo simulations. To verify these methods, we adopted sequential 177 Lu-DOTATATE single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) dataset acquired from Sunway Medical Centre using the major vendor's SPECT/CT scanner (Siemens Symbia Intevo). METHODS: The administered activity of 177 Lu-DOTATATE was 7.99 ± 0.36 GBq. SPECT/CT images were acquired 0.5, 4, 24, and 48 h after injection in Sunway Medical Centre. For the multiple VSV method, VSV kernels of 177 Lu in media with various densities were generated by Geant4 Application for Emission Tomography (GATE) simulation first. The second step involved the convolution of the time-integrated activity map with each kernel to produce medium-specific dose maps. Third, each medium-specific dose map was masked using binary medium masks, which were generated from CT-based density maps. Finally, all masked dose maps were summed to generate the final dose map. VSV methods with four different VSV sets (1, 4, 10, and 20 VSVs) were compared. Voxel-wise density correction for the single VSV method was also performed. The absorbed doses in the kidneys, bone marrow, and tumors were analyzed, and the relative errors between the VSV and Monte Carlo simulation approaches were estimated. Organ-based dosimetry using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was also compared. RESULTS: The accuracy of the multiple VSV approach increased with the number of dose kernels. The average dose estimation errors of a single VSV with density correction and 20 VSVs were less than 6% in most cases, although organ-based dosimetry using OLINDA/EXM yielded an error of up to 123%. The advantages of the single VSV method with density correction and the 20 VSVs over organ-based dosimetry were most evident in bone marrow and bone-metastatic tumors with heterogeneous medium properties. CONCLUSION: The single VSV method with density correction and multiple VSV method with 20 dose kernels enabled fast and accurate radiation dose estimation. Accordingly, voxel-based dosimetry methods can be useful for managing administration activity and for investigating tumor dose responses to further increase the therapeutic efficacy of 177 Lu-DOTATATE.

The effect of leucocyte concentration of platelet-rich plasma on outcomes in patients with lateral epicondylitis: a systematic review and meta-analysis.

HYPOTHESIS: The concentration of leukocytes influences the quality of platelet-rich plasma (PRP). However, there is no consensus on which type of PRP based on the concentration of leukocytes is the best for lateral epicondylitis (LE). METHODS: We systematically searched the MEDLINE, Embase, and Cochrane Library databases until March 1, 2020. Studies involving randomized controlled trials, patients with LE, and treatment with PRP injections were included. PRP was classified into leukocyte-poor (LP) PRP and leukocyte-rich (LR) PRP. LR-PRP was defined as PRP with a white blood cell concentration exceeding that of whole blood (4.0-10.0 per µL3), whereas LP-PRP was defined as PRP with a lower white blood cell concentration than that of whole blood. The efficacy of PRP was assessed using the visual analog scale (VAS) and success rates. RESULTS: Eleven randomized controlled trials (six involving LP-PRP and five involving LR-PRP) were eligible for inclusion in this review. Eight studies were included in the meta-analysis to evaluate the VAS score. Regarding short-term follow-up, there was no difference in the VAS scores between the LP-PRP and control groups (standard mean difference [SMD], 0.01; 95% confidence interval [CI], -0.29 to 0.30; P = 0.97), with no heterogeneity (I2 = 0%). There was also no difference in the VAS scores between the LR-PRP and control groups (SMD, -0.19; 95% CI, -0.57 to 0.20; P = 0.34), with substantial heterogeneity (I2 = 56.7%). Regarding long-term follow-up, there was no difference in the VAS scores between the LP-PRP and control groups (SMD, -0.73; 95% CI, -1.69 to 0.23; P = 0.134) with substantial heterogeneity (I2 = 88.4%). The LR-PRP group had lower VAS scores than the control group (SMD, -1.06; 95% CI, -2.02 to -0.09; P = 0.032) with substantial heterogeneity (I2 = 92%). In the LP-PRP group, there was no significant difference in the success rate (odds ratio, 1.08; 95% CI, 0.07-16.47; P = 0.956) with substantial heterogeneity (I2 = 87.7%). In the LR-PRP group, however, the patients who received PRP had a higher success rate than those in the control group (odds ratio, 2.85; 95% CI, 1.67-4.85; P < 0.01) with substantial heterogeneity (I2 = 82.9%). CONCLUSION: LR-PRP may provide pain relief and successful outcomes for patients with LE compared with alternative local injections. Better results were observed with the use of LR-PRP than with the use of LP-PRP.