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Background: Magnetic resonance-guided radiotherapy with an MR-guided LINAC represents potential clinical benefits in abdominal treatments due to the superior soft-tissue contrast compared to kV-based images in conventional treatment units. However, due to the high cost associated with this technology, only a few centers have access to it. As an alternative, synthetic 4D MRI generation based on artificial intelligence methods could be implemented. Nevertheless, appropriate MRI texture generation from CT images might be challenging and prone to hallucinations, compromising motion accuracy., Purpose: To evaluate the feasibility of on-board synthetic motion-resolved 4D MRI generation from prior 4D MRI, on-board 4D cone beam CT (CBCT) images, motion modeling information, and deep learning models using the digital anthropomorphic phantom XCAT., Methods: The synthetic 4D MRI corresponds to phases from on-board 4D CBCT. Each synthetic MRI volume in the 4D MRI was generated by warping a reference 3D MRI (MRI ref , end of expiration phase from a prior 4D MRI) with a deformation field map (DFM) determined by (I) the eigenvectors from the principal component analysis (PCA) motion-modeling of the prior 4D MRI, and (II) the corresponding eigenvalues predicted by a convolutional neural network (CNN) model using the on-board 4D CBCT images as input. The CNN was trained with 1000 deformations of one reference CT (CT ref , same conditions as MRI ref ) generated by applying 1000 DFMs computed by randomly sampling the original eigenvalues from the prior 4D MRI PCA model. The evaluation metrics for the CNN model were root-mean-square error (RMSE) and mean absolute error (MAE). Finally, different on-board 4D-MRI generation scenarios were assessed by changing the respiratory period, the amplitude of the diaphragm, and the chest wall motion of the 4D CBCT using normalized root-mean-square error (nRMSE) and structural similarity index measure (SSIM) for image-based evaluation, and volume dice coefficient (VDC), volume percent difference (VPD), and center-of-mass shift (COMS) for contour-based evaluation of liver and target volumes., Results: The RMSE and MAE values of the CNN model reported 0.012 ± 0.001 and 0.010 ± 0.001, respectively for the first eigenvalue predictions. SSIM and nRMSE were 0.96 ± 0.06 and 0.22 ± 0.08, respectively. VDC, VPD, and COMS were 0.92 ± 0.06, 3.08 ± 3.73 %, and 2.3 ± 2.1 mm, respectively, for the target volume. The more challenging synthetic 4D-MRI generation scenario was for one 4D-CBCT with increased chest wall motion amplitude, reporting SSIM and nRMSE of 0.82 and 0.51, respectively., Conclusions: On-board synthetic 4D-MRI generation based on predicting actual treatment deformation from on-board 4D-CBCT represents a method that can potentially improve the treatment-setup localization in abdominal radiotherapy treatments with a conventional kV-based LINAC., (© 2024 American Association of Physicists in Medicine.)

Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study., Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity., Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6-2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity., Conclusions: Bronchoscopically implanted electromagnetic transponder-guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder-antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning.

Purpose: The American Association of Physicists in Medicine (AAPM) shares the results, conclusions, and recommendations from the initial Equity, Diversity, and Inclusion Climate Survey conducted in 2021., Methods and Materials: The climate survey targeted medical physicists who are full members of the AAPM and included demographic inquiries and questions intended to assess the working environmental climate in terms of a sense of belonging and inclusion, experiences of discrimination and harassment, and obstacles to participation within the AAPM. The survey invitation was sent to 5,500 members. Responses were collected from 1385 members (response rate of 25%) between January and February 2021., Results: Overall, the medical physics workplace climate was positive. However, some demographic and professional subgroups reported lower levels of agreement with positive characteristics of their workplace climates. Compared with men, women ranked lower 7 of 8 categories that characterized the workplace climate. Other subgroups that also ranked the workplace climate descriptors lower included individuals not originally from the United States and Canada (3/8). Most respondents strongly agreed/agreed that the climate within the AAPM was welcoming. However, 17% of respondents reported personally experiencing or witnessing microaggressions within the AAPM. Overall, medical physicists reported low levels of agreement that opportunities within the AAPM were available to them, from 34% to 60% among 8 categories, including opportunities to volunteer, join committees, and compete for leadership positions within the AAPM. Several subgroups reported even lower levels of agreement that these opportunities are available. Asian and Asian American respondents (3/8) and physicists with origins in countries outside the United States and Canada (7/8) reported fewer opportunities to participate in the AAPM. Medical physicists reported their experiences of discrimination and sexual harassment in their workplaces and within the AAPM. For those who reported personal experiences of sexual harassment, only 24% (15/63) felt comfortable reporting when it occurred within their workplaces, and 35% (9/26) felt comfortable reporting when it occurred within the AAPM., Conclusions: The report concludes with several recommendations for action., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To engage critical care end-users (survivors and caregivers) to describe their emotions and experiences across their recovery trajectory, and elicit their ideas and solutions for health service improvements to improve the ICU recovery experience., Design: End-user engagement as part of a qualitative design using the Framework Analysis method., Setting: The Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups)., Subjects: Patients and caregivers following critical illness and identified through the collaboratives., Interventions: None., Measurements and Main Results: Eighty-six interviews were conducted. The following themes were identified: 1) Emotions and experiences of patients-"Loss of former self; Experiences of disability and adaptation"; 2) Emotions and experiences of caregivers-"Emotional impacts, adopting new roles, and caregiver burden; Influence of gender roles; Adaptation, adjustment, recalibration"; and 3) Patient and caregiver-generated solutions to improve recovery across the arc of care-"Family-targeted education; Expectation management; Rehabilitation for patients and caregivers; Peer support groups; Reconnecting with ICU post-discharge; Access to community-based supports post-discharge; Psychological support; Education of issues of ICU survivorship for health professionals; Support across recovery trajectory." Themes were mapped to a previously published recovery framework (Timing It Right) that captures patient and caregiver experiences and their support needs across the phases of care from the event/diagnosis to adaptation post-discharge home., Conclusions: Patients and caregivers reported a range of emotions and experiences across the recovery trajectory from ICU to home. Through end-user engagement strategies many potential solutions were identified that could be implemented by health services and tested to support the delivery of higher-quality care for ICU survivors and their caregivers that extend from tertiary to primary care settings., Competing Interests: Drs. Haines’, Quasim’s, McPeake’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine (SCCM). Dr. Boehm’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI); she is funded by National Institutes of Health (NIH)/NHLBI (K12 HL137943) as is Dr. Iwashyna (K12 HL138039). Drs. Boehm and Jackson received support for article research from NIH. Dr. Hope received funding from the American Association of Critical Care Nurses. Dr. Netzer received funding from UptoDate and Springer Press. Dr. Hopkins’ institution received funding from Intermountain Research and Medical Foundation. Dr. Iwashyna disclosed government work. Dr. McPeake’s institution received funding from The University of Cambridge; she is funded by a THIS Institute Post-Doctoral Fellowship (PD-2019-02-16). Dr. Sevin received support for article research from the Department of Defense. Drs. Haines, Boehm, Quasim, McPeake, and Sevin received funding from SCCM to undertake this work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Social determinants of health (SDoH) contribute to health outcomes. We identified SDoH that were modified by critical illness, and the effect of such modifications on recovery from critical illness., Design: In-depth semistructured interviews following hospital discharge. Interview transcripts were mapped against a pre-existing social policy framework: money and work; skills and education; housing, transport and neighbourhoods; and family, friends and social connections., Setting: 14 hospital sites in the USA, UK and Australia., Participants: Patients and caregivers, who had been admitted to critical care from three continents., Results: 86 interviews were analysed (66 patients and 20 caregivers). SDoH, both financial and non-financial in nature, could be negatively influenced by exposure to critical illness, with a direct impact on health-related outcomes at an individual level. Financial modifications included changes to employment status due to critical illness-related disability, alongside changes to income and insurance status. Negative health impacts included the inability to access essential healthcare and an increase in mental health problems., Conclusions: Critical illness appears to modify SDoH for survivors and their family members, potentially impacting recovery and health. Our findings suggest that increased attention to issues such as one's social network, economic security and access to healthcare is required following discharge from critical care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the efficacy of using bronchoscopically implanted anchored electromagnetic transponders (EMTs) as surrogates for 1) tumor position and 2) repeatability of lung inflation during deep-inspiration breath-hold (DIBH) lung radiotherapy., Methods: Forty-one patients treated with either hypofractionated (HF) or conventional (CF) lung radiotherapy on an IRB-approved prospective protocol using coached DIBH were evaluated for this study. Three anchored EMTs were bronchoscopically implanted into small airways near or within the tumor. DIBH treatment was gated by tracking the EMT positions. Breath-hold cone-beam-CTs (CBCTs) were acquired prior to every HF treatment or weekly for CF patients. Retrospectively, rigid registrations between each CBCT and the breath-hold planning CT were performed to match to 1) spine, 2) EMTs and 3) tumor. Absolute differences in registration between EMTs and spine were analyzed to determine surrogacy of EMTs for lung inflation. Differences in registration between EMTs and the tumor were analyzed to determine surrogacy of EMTs for tumor position. The stability of the EMTs was evaluated by analyzing the difference between inter-EMT displacements recorded at treatment from that of the plan for the CF patients, as well as the geometric residual (GR) recorded at the time of treatment., Results: A total of 219 CBCTs were analyzed. The average differences between EMT centroid and spine registration among all CBCTs were 0.45±0.42 cm, 0.29±0.28 cm, and 0.18±0.15 cm in superior-inferior (SI), anterior-posterior (AP) and lateral directions, respectively. Only 59% of CBCTs had differences in registration < 0.5 cm for EMT centroid compared to spine, indicating that lung inflation is not reproducible from simulation to treatment. The average differences between EMT centroid and tumor registration among all CBCTs were 0.13±0.13 cm, 0.14±0.13 cm and 0.12±0.12 cm in SI, AP and lateral directions, respectively. Ninety-five percent of CBCTs resulted in a < 0.5 cm change between EMT centroid and tumor registration, indicating that EMT positions correspond well with tumor position during treatments. Six out of the seven recorded CF patients had average differences in inter-EMT displacements ≤0.26 cm and average GR ≤0.22 cm, indicating that the EMTs are stable throughout treatment., Conclusions: Bronchoscopically implanted anchored EMTs are good surrogates for tumor position and are reliable for maintaining tumor position when tracked during DIBH treatment, as long as the tumor size and shape are stable. Large differences in registration between EMTs and spine for many treatments suggest that lung inflation achieved at simulation is often not reproduced., (© 2022 American Association of Physicists in Medicine.)

Purpose: To develop a novel multi-contrast four-dimensional magnetic resonance imaging (MC-4D-MRI) technique that expands single image contrast 4D-MRI to a spectrum of native and synthetic image contrasts and to evaluate its feasibility in liver tumor patients., Methods and Materials: The MC-4D-MRI technique integrates multi-parametric MRI fusion, 4D-MRI, and deformable image registration (DIR) techniques. The fusion technique consists of native MRI as input, image pre-processing, fusion algorithm, adaptation, and fused multi-contrast MRI as output. Four-dimensional deformation vector fields (4D-DVF) were generated from an original T2/T1-w 4D-MRI by deforming end-of-inhalation (EOI) to nine other phase volumes via DIR. The 4D-DVF were applied to multi-contrast MRI to generate a spectrum of 4D-MRI in different image contrasts. The MC-4D-MRI technique was evaluated in five liver tumor patients on tumor contrast-to-noise ratio (CNR), internal target volume (ITV) contouring consistency, diaphragm motion range, and tumor motion trajectory; and in digital anthropomorphic phantoms on 4D-DIR introduced errors in tumor motion range, centroid location, extent, and volume., Results: MC-4D-MRI consisting of 4D-MRIs in native image contrasts (T1-w, T2-w, and T2/T1-w) and synthetic image contrasts, such as tumor-enhanced contrast (TEC) were generated in five liver tumor patients. Patient tumor CNR increased from 2.6 ± 1.8 in the T2/T1-w MRI, to -4.4 ± 2.4, 6.6 ± 3.0, and 9.6 ± 3.9 in the T1-w, T2-w, and TEC MRI, respectively. Patient ITV inter-observer mean Dice similarity coefficient (mDSC) increased from 0.65 ± 0.10 in the original T2/T1-w 4D-MRI, to 0.76 ± 0.14, 0.77 ± 0.12, and 0.86 ± 0.05 in the T1-w, T2-w, and TEC 4D-MRI, respectively. Patient diaphragm motion range absolute differences between the three new 4D-MRIs and original T2/T1-w 4D-MRI were 1.2 ± 1.3, 0.3 ± 0.7, and 0.5 ± 0.5 mm, respectively. Patient tumor displacement phase-averaged absolute differences between the three 4D-MRIs and the original 4D-MRI were 0.72 ± 0.33, 0.62 ± 0.54, and 0.74 ± 0.43 mm in the superior-inferior (SI) direction, and 0.59 ± 0.36, 0.51 ± 0.30, and 0.50 ± 0.24 mm in the anterior-posterior (AP) direction, respectively. In the digital phantoms, phase-averaged absolute tumor centroid shift caused by the 4D-DIR were at or below 0.5 mm in SI, AP, and left-right (LR) directions., Conclusion: We developed an MC-4D-MRI technique capable of expanding single image contrast 4D-MRI along a new dimension of image contrast. Initial evaluations in liver tumor patients showed enhancements in image contrast variety, tumor contrast, and ITV contouring consistencies using MC-4D-MRI. The technique might offer new perspectives on the image contrast of MRI and 4D-MRI in MR-guided radiotherapy., (© 2021 American Association of Physicists in Medicine.)

Objectives: Investigate the challenges experienced by survivors of critical illness and their caregivers across the transitions of care from intensive care to community, and the potential problem-solving strategies used to navigate these challenges., Design: Qualitative design-data generation via interviews and data analysis via the framework analysis method., Setting: Patients and caregivers from three continents, identified through the Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups)., Subjects: Patients and caregivers following critical illness., Interventions: Nil., Measurements and Main Results: From 86 interviews (66 patients, 20 caregivers), we identified the following major themes: 1) Challenges for patients-interacting with the health system and gaps in care; managing others' expectations of illness and recovery. 2) Challenges for caregivers-health system shortfalls and inadequate communication; lack of support for caregivers. 3) Patient and caregiver-driven problem solving across the transitions of care-personal attributes, resources, and initiative; receiving support and helping others; and acceptance., Conclusions: Survivors and caregivers experienced a range of challenges across the transitions of care. There were distinct and contrasting themes related to the caregiver experience. Survivors and caregivers used comparable problem-solving strategies to navigate the challenges encountered across the transitions of care., Competing Interests: Drs. Haines’, Boehm’s, Quasim’s, McPeake’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine. Drs. Haines, Boehm, Quasim, McPeake, and Sevin received funding from the Society of Critical Care Medicine to undertake this work. Dr. Boehm is funded by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (K12 HL137943) as is Dr. Iwashyna (K12 HL138039). Drs. Boehm’s and Hope’s institutions received funding from the NHLBI. Dr. Boehm’s institution received funding from the American Association of Critical Care Nurses (AACN). Drs. Boehm and Hope received support for article research from the NIH and the AACN Impact Grant. Dr. Hope’s institution received funding from the NIH; he received funding from the AACN. Dr. Netzer received funding from UptoDate. Dr. Hopkins’ institution received funding from the Intermountain Research and Medical Foundation. Dr. Iwashyna received support for article research from the government. Dr. McPeake is funded by a THIS.Institute Post-Doctoral Fellowship (PD-2019-02-16). Dr. McPeake’s institution received funding from the THIS Institute, University of Cambridge. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: After critical illness, patients are often left with impairments in physical, social, emotional, and cognitive functioning. Peer support interventions have been implemented internationally to ameliorate these issues., Objective: To explore what patients believed to be the key mechanisms of effectiveness of peer support programs implemented during critical care recovery., Methods: In a secondary analysis of an international qualitative data set, 66 telephone interviews with patients were undertaken across 14 sites in Australia, the United Kingdom, and the United States to understand the effect of peer support during recovery from critical illness. Prevalent themes were documented with framework analysis., Results: Most patients who had been involved in peer support programs reported benefit. Patients described 3 primary mechanisms: (1) sharing experiences, (2) care debriefing, and (3) altruism., Conclusion: Peer support is a relatively simple intervention that could be implemented to support patients during recovery from critical illness. However, more research is required into how these programs can be implemented in a safe and sustainable way in clinical practice., (©2021 American Association of Critical-Care Nurses.)

Purpose: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy., Methods and Materials: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and D mean . These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values., Results: The multivariate analysis showed V40Gy and D mean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%., Conclusions: In addition to V20Gy and D mean , the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy., (© 2020 The Authors.)

To understand from the perspective of patients who did, and did not attend ICU recovery programs, what were the most important components of successful programs and how should they be organized., Design: International, qualitative study., Setting: Fourteen hospitals in the United States, United Kingdom, and Australia., Patients: We conducted 66 semi-structured interviews with a diverse group of patients, 52 of whom had used an ICU recovery program and 14 whom had not., Interventions: None., Measurements and Main Results: Using content analysis, prevalent themes were documented to understand what improved their outcomes. Contrasting quotes from patients who had not received certain aspects of care were used to identify perceived differential effectiveness. Successful ICU recovery programs had five key components: 1) Continuity of care; 2) Improving symptom status; 3) Normalization and expectation management; 4) Internal and external validation of progress; and 5) Reducing feelings of guilt and helplessness. The delivery of care which achieved these goals was facilitated by early involvement (even before hospital discharge), direct involvement of ICU staff, and a focus on integration across traditional disease, symptom, and social welfare needs., Conclusions: In this multicenter study, conducted across three continents, patients identified specific and reproducible modes of benefit derived from ICU recovery programs, which could be the target of future intervention refinement., Competing Interests: Drs. McPeake’s, Boehm’s, Hibbert’s, Bastin’s, Johnson’s, Montgomery-Yates’s, Quasim’s, Haines’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine. Dr. McPeake’s, Dr. Quasim’s, and Mrs. MacTavish’s institutions received funding from the Health Foundation (United Kingdom). Drs. Boehm’s (K12 HL137943) and Hope’s institutions received funding from the American Association of Critical-Care Nurses and the National Heart, Lung, and Blood Institute. Drs. Boehm, Hope, and Jackson received support for article research from the National Institutes of Health. Dr. Iwashyna disclosed government work (K12 HL138039). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The purpose of this study is to improve on-board volumetric cine magnetic resonance imaging (VC-MRI) using multi-slice undersampled cine images reconstructed using spatio-temporal k-space data, patient prior 4D-MRI, motion modeling (MM) and free-form deformation (FD) for real-time 3D target verification of liver and lung radiotherapy., Methods: A previous method was developed to generate on-board VC-MRI by deforming prior MRI images based on a MM and a single-slice on-board 2D-cine image. The two major improvements over the previous method are: (I) FD was introduced to estimate VC-MRI to correct for inaccuracies in the MM; (II) multi-slice undersampled 2D-cine images reconstructed by a k-t SLR reconstruction method were used for FD-based estimation to maintain the temporal resolution while improving the accuracy of VC-MRI. The method was evaluated using XCAT lung simulation and four liver patients' data., Results: For XCAT, VC-MRI estimated using ten undersampled sagittal 2D-cine MRIs resulted in volume percent difference/volume dice coefficient/center-of-mass shift of 9.77%±3.71%/0.95±0.02/0.75±0.26 mm among all scenarios based on estimation with MM and FD. Adding FD optimization improved VC-MRI accuracy substantially for scenarios with anatomical changes. For patient data, the mean tumor tracking errors were 0.64±0.51, 0.62±0.47 and 0.24±0.24 mm along the superior-inferior (SI), anterior-posterior (AP) and lateral directions, respectively, across all liver patients., Conclusions: It is feasible to improve VC-MRI accuracy while maintaining high temporal resolution using FD and multi-slice undersampled 2D cine images for real-time 3D target verification., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

To predict real-time 3D deformation field maps (DFMs) using Volumetric Cine MRI (VC-MRI) and adaptive boosting and multi-layer perceptron neural network (ADMLP-NN) for 4D target tracking. One phase of a prior 4D-MRI is set as the prior phase, MRI prior . Principal component analysis (PCA) is used to extract three major respiratory deformation modes from the DFMs generated between the prior and remaining phases. VC-MRI at each time-step is considered a deformation of MRI prior , where the DFM is represented as a weighted linear combination of the PCA components. The PCA weightings are solved by minimizing the differences between on-board 2D cine MRI and its corresponding VC-MRI slice. The PCA weightings solved during the initial training period are used to train an ADMLP-NN to predict PCA weightings ahead of time during the prediction period. The predicted PCA weightings are used to build predicted 3D DFM and ultimately, predicted VC-MRIs for 4D target tracking. The method was evaluated using a 4D computerized phantom (XCAT) with patient breathing curves and MRI data from a real liver cancer patient. Effects of breathing amplitude change and ADMLP-NN parameter variations were assessed. The accuracy of the PCA curve prediction was evaluated. The predicted real-time 3D tumor was evaluated against the ground-truth using volume dice coefficient (VDC), center-of-mass-shift (COMS), and target tracking errors. For the XCAT study, the average VDC and COMS for the predicted tumor were 0.92  ±  0.02 and 1.06  ±  0.40 mm, respectively, across all predicted time-steps. The correlation coefficients between predicted and actual PCA curves generated through VC-MRI estimation for the 1st/2nd principal components were 0.98/0.89 and 0.99/0.57 in the SI and AP directions, respectively. The optimal number of input neurons, hidden neurons, and MLP-NN for ADMLP-NN PCA weighting coefficient prediction were determined to be 7, 4, and 10, respectively. The optimal cost function threshold was determined to be 0.05. PCA weighting coefficient and VC-MRI accuracy was reduced for increased prediction-step size. Accurate PCA weighting coefficient prediction correlated with accurate VC-MRI prediction. For the patient study, the predicted 4D tumor tracking errors in superior-inferior, anterior-posterior and lateral directions were 0.50  ±  0.47 mm, 0.40  ±  0.55 mm, and 0.28  ±  0.12 mm, respectively. Preliminary studies demonstrated the feasibility to use VC-MRI and artificial neural networks to predict real-time 3D DFMs of the tumor for 4D target tracking.

Objectives: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism., Design: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation., Subjects and Setting: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals., Measurements and Main Results: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success., Conclusions: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.

Purpose: On-board MRI can provide superb soft tissue contrast for improving liver SBRT localization. However, the availability of on-board MRI in clinics is extremely limited. On the contrary, on-board kV imaging systems are widely available on radiotherapy machines, but its capability to localize tumors in soft tissue is limited due to its poor soft tissue contrast. This study aims to explore the feasibility of using an on-board kV imaging system and patient prior knowledge to generate on-board four-dimensional (4D)-MRI for target localization in liver SBRT., Methods: Prior 4D MRI volumes were separated into end of expiration (EOE) phase (MRI prior ) and all other phases. MRI prior was used to generate a synthetic CT at EOE phase (sCT prior ). On-board 4D MRI at each respiratory phase was considered a deformation of MRI prior . The deformation field map (DFM) was estimated by matching DRRs of the deformed sCT prior to on-board kV projections using a motion modeling and free-form deformation optimization algorithm. The on-board 4D MRI method was evaluated using both XCAT simulation and real patient data. The accuracy of the estimated on-board 4D MRI was quantitatively evaluated using Volume Percent Difference (VPD), Volume Dice Coefficient (VDC), and Center of Mass Shift (COMS). Effects of scan angle and number of projections were also evaluated., Results: In the XCAT study, VPD/VDC/COMS among all XCAT scenarios were 10.16 ± 1.31%/0.95 ± 0.01/0.88 ± 0.15 mm using orthogonal-view 30° scan angles with 102 projections. The on-board 4D MRI method was robust against the various scan angles and projection numbers evaluated. In the patient study, estimated on-board 4D MRI was generated successfully when compared to the "reference on-board 4D MRI" for the liver patient case., Conclusions: A method was developed to generate on-board 4D MRI using prior 4D MRI and on-board limited kV projections. Preliminary results demonstrated the potential for MRI-based image guidance for liver SBRT using only a kV imaging system on a conventional LINAC., (© 2018 American Association of Physicists in Medicine.)

Purpose: To accelerate volumetric cine MRI (VC-MRI) using undersampled 2D-cine MRI to provide real-time 3D guidance for gating/target tracking in radiotherapy., Methods: 4D-MRI is acquired during patient simulation. One phase of the prior 4D-MRI is selected as the prior images, designated as MRI prior . The on-board VC-MRI at each time-step is considered a deformation of the MRI prior . The deformation field map is represented as a linear combination of the motion components extracted by principal component analysis from the prior 4D-MRI. The weighting coefficients of the motion components are solved by matching the corresponding 2D-slice of the VC-MRI with the on-board undersampled 2D-cine MRI acquired. Undersampled Cartesian and radial k-space acquisition strategies were investigated. The effects of k-space sampling percentage (SP) and distribution, tumor sizes and noise on the VC-MRI estimation were studied. The VC-MRI estimation was evaluated using XCAT simulation of lung cancer patients and data from liver cancer patients. Volume percent difference (VPD) and Center of Mass Shift (COMS) of the tumor volumes and tumor tracking errors were calculated., Results: For XCAT, VPD/COMS were 11.93  ±  2.37%/0.90  ±  0.27 mm and 11.53  ±  1.47%/0.85  ±  0.20 mm among all scenarios with Cartesian sampling (SP  =  10%) and radial sampling (21 spokes, SP  =  5.2%), respectively. When tumor size decreased, higher sampling rate achieved more accurate VC-MRI than lower sampling rate. VC-MRI was robust against noise levels up to SNR  =  20. For patient data, the tumor tracking errors in superior-inferior, anterior-posterior and lateral (LAT) directions were 0.46  ±  0.20 mm, 0.56  ±  0.17 mm and 0.23  ±  0.16 mm, respectively, for Cartesian-based sampling with SP  =  20% and 0.60  ±  0.19 mm, 0.56  ±  0.22 mm and 0.42  ±  0.15 mm, respectively, for radial-based sampling with SP  =  8% (32 spokes)., Conclusions: It is feasible to estimate VC-MRI from a single undersampled on-board 2D cine MRI. Phantom and patient studies showed that the temporal resolution of VC-MRI can potentially be improved by 5-10 times using a 2D cine image acquired with 10-20% k-space sampling.

Purpose: To investigate the feasibility of using structural-based principal component analysis (PCA) motion-modeling and weighted free-form deformation to estimate on-board 4D-CBCT using prior information and extremely limited angle projections for potential 4D target verification of lung radiotherapy., Methods: A technique for lung 4D-CBCT reconstruction has been previously developed using a deformation field map (DFM)-based strategy. In the previous method, each phase of the 4D-CBCT was generated by deforming a prior CT volume. The DFM was solved by a motion model extracted by a global PCA and free-form deformation (GMM-FD) technique, using a data fidelity constraint and deformation energy minimization. In this study, a new structural PCA method was developed to build a structural motion model (SMM) by accounting for potential relative motion pattern changes between different anatomical structures from simulation to treatment. The motion model extracted from planning 4DCT was divided into two structures: tumor and body excluding tumor, and the parameters of both structures were optimized together. Weighted free-form deformation (WFD) was employed afterwards to introduce flexibility in adjusting the weightings of different structures in the data fidelity constraint based on clinical interests. XCAT (computerized patient model) simulation with a 30 mm diameter lesion was simulated with various anatomical and respiratory changes from planning 4D-CT to on-board volume to evaluate the method. The estimation accuracy was evaluated by the volume percent difference (VPD)/center-of-mass-shift (COMS) between lesions in the estimated and "ground-truth" on-board 4D-CBCT. Different on-board projection acquisition scenarios and projection noise levels were simulated to investigate their effects on the estimation accuracy. The method was also evaluated against three lung patients., Results: The SMM-WFD method achieved substantially better accuracy than the GMM-FD method for CBCT estimation using extremely small scan angles or projections. Using orthogonal 15° scanning angles, the VPD/COMS were 3.47 ± 2.94% and 0.23 ± 0.22 mm for SMM-WFD and 25.23 ± 19.01% and 2.58 ± 2.54 mm for GMM-FD among all eight XCAT scenarios. Compared to GMM-FD, SMM-WFD was more robust against reduction of the scanning angles down to orthogonal 10° with VPD/COMS of 6.21 ± 5.61% and 0.39 ± 0.49 mm, and more robust against reduction of projection numbers down to only 8 projections in total for both orthogonal-view 30° and orthogonal-view 15° scan angles. SMM-WFD method was also more robust than the GMM-FD method against increasing levels of noise in the projection images. Additionally, the SMM-WFD technique provided better tumor estimation for all three lung patients compared to the GMM-FD technique., Conclusion: Compared to the GMM-FD technique, the SMM-WFD technique can substantially improve the 4D-CBCT estimation accuracy using extremely small scan angles and low number of projections to provide fast low dose 4D target verification., (© 2017 American Association of Physicists in Medicine.)

Aim: During cancer radiotherapy treatment, on-board four-dimensional-cone beam computed tomography (4D-CBCT) provides important patient 4D volumetric information for tumor target verification. Reconstruction of 4D-CBCT images requires sorting of acquired projections into different respiratory phases. Traditional phase sorting methods are either based on external surrogates, which might miscorrelate with internal structures; or on 2D internal structures, which require specific organ presence or slow gantry rotations. The aim of this study is to investigate the feasibility of a 3D motion modeling-based method for markerless 4D-CBCT projection-phase sorting., Methods: Patient 4D-CT images acquired during simulation are used as prior images. Principal component analysis (PCA) is used to extract three major respiratory deformation patterns. On-board patient image volume is considered as a deformation of the prior CT at the end-expiration phase. Coefficients of the principal deformation patterns are solved for each on-board projection by matching it with the digitally reconstructed radiograph (DRR) of the deformed prior CT. The primary PCA coefficients are used for the projection-phase sorting., Results: PCA coefficients solved in nine digital phantoms (XCATs) showed the same pattern as the breathing motions in both the anteroposterior and superoinferior directions. The mean phase sorting differences were below 2% and percentages of phase difference < 10% were 100% for all the nine XCAT phantoms. Five lung cancer patient results showed mean phase difference ranging from 1.62% to 2.23%. The percentage of projections within 10% phase difference ranged from 98.4% to 100% and those within 5% phase difference ranged from 88.9% to 99.8%., Conclusion: The study demonstrated the feasibility of using PCA coefficients for 4D-CBCT projection-phase sorting. High sorting accuracy in both digital phantoms and patient cases was achieved. This method provides an accurate and robust tool for automatic 4D-CBCT projection sorting using 3D motion modeling without the need of external surrogate or internal markers., Competing Interests: Conflicts of interest There are no conflicts of interest.

Purpose: The purpose of this study was to develop a techique to generate on-board volumetric cine-magnetic resonance imaging (VC-MRI) using patient prior images, motion modeling, and on-board 2-dimensional cine MRI., Methods and Materials: One phase of a 4-dimensional MRI acquired during patient simulation is used as patient prior images. Three major respiratory deformation patterns of the patient are extracted from 4-dimensional MRI based on principal-component analysis. The on-board VC-MRI at any instant is considered as a deformation of the prior MRI. The deformation field is represented as a linear combination of the 3 major deformation patterns. The coefficients of the deformation patterns are solved by the data fidelity constraint using the acquired on-board single 2-dimensional cine MRI. The method was evaluated using both digital extended-cardiac torso (XCAT) simulation of lung cancer patients and MRI data from 4 real liver cancer patients. The accuracy of the estimated VC-MRI was quantitatively evaluated using volume-percent-difference (VPD), center-of-mass-shift (COMS), and target tracking errors. Effects of acquisition orientation, region-of-interest (ROI) selection, patient breathing pattern change, and noise on the estimation accuracy were also evaluated., Results: Image subtraction of ground-truth with estimated on-board VC-MRI shows fewer differences than image subtraction of ground-truth with prior image. Agreement between normalized profiles in the estimated and ground-truth VC-MRI was achieved with less than 6% error for both XCAT and patient data. Among all XCAT scenarios, the VPD between ground-truth and estimated lesion volumes was, on average, 8.43 ± 1.52% and the COMS was, on average, 0.93 ± 0.58 mm across all time steps for estimation based on the ROI region in the sagittal cine images. Matching to ROI in the sagittal view achieved better accuracy when there was substantial breathing pattern change. The technique was robust against noise levels up to SNR = 20. For patient data, average tracking errors were less than 2 mm in all directions for all patients., Conclusions: Preliminary studies demonstrated the feasibility of generating real-time VC-MRI for on-board localization of moving targets in radiation therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Human consciousness is inextricable from communication. The conditions of communication in the clinical context are defined by the caring intention and the unequal relationship, which imply special responsibilities on the part of the clinician. The conventional hermeneutic model of communication proposes a close examination of the context of the other, and an objective effort to get close to their consciousness by interpretation of their expressions. The clinician is supposed to lay aside subjective factors but make use of her/his clinical knowledge and skills. At University College Hospital Critical Care follow-up clinic, the communicative task involves history taking; partly by questionnaire and partly by attention to the patient's agenda - assessing needs, providing information and facilitating access to further help. In recent years the provision of Critical Care has become ever more complex, both in terms of the sophisticated medical and nursing techniques it can offer to patients and in the range of conditions it can undertake to treat. This range and complexity is reflected in the variety of problems and consequences that may be encountered at follow-up. Communicative techniques should take account of the emotional vulnerability of patients emerging from severe illness. Attentive listening should identify special anxieties, and care with phraseology aims to avoid further distress. Issues of memory, depression and trauma may be expected, and the interview technique must be flexible enough to offer emotional containment if need be. The consultation should be therapeutic in its conduct but should not embark upon actual psychotherapy or seek to dismantle the patient's defences. Contemporary hermeneutic perspectives emphasise the contextual situatedness of the clinician's consciousness, and propose a model of communication as 'blending of horizons' rather than as objective interpretation. Systems theory contributes to an understanding of the influence on communication of social contexts. With his theory of communicative action, from within the perspective of critical theory, Habermas restores the influence of rational critique in the practice of communication, but also as an ethical regulator, especially through the notions of dignity, vulnerability and needfulness., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Issue Addressed: 'Celebrate - do it Safely' is a project aimed at reducing youth alcohol-related harm on the Central Coast, New South Wales (NSW). The primary focus for 2003 was to use the world wide web and the website www.celebratesafely.com.au to raise awareness and reinforce the message of how to party safely to young people., Methods: A creative, interactive website was set up to be a local and reliable source of information regarding the risks associated with alcohol misuse. It was supported by a steering committee with diverse representation from key organisations. Content pages and links were developed to ensure access to information and contact details were simple and comprehensive. Topics such as a safe party checklist, safe driving, safe sex and protection from violence were included. Games and competitions emphasised the safe party message with clever actions and graphics created within a virtual party environment. The website was promoted by distribution of postcards throughout the school network. Radio campaigning, plus display of posters and banners throughout the area, raised the profile in the wider community. Key rings were given to young people along with free 'mocktails' to reinforce the message of safe partying., Results: There has been an increase in website hits from 758 in 2002 to more than 65,000 in 2003. Written feedback from young people suggests the content and format is well designed for the target group., Conclusions: Promoting the message of safe celebration on the world wide web is an effective way of raising awareness in a local community about safe partying.

Issue Addressed: To assess whether the strategies used to sell the 'ready-to-drink' (RTD) category of alcoholic beverages is contributing to alcohol-related harm among adolescents., Methods: An initial investigation of bottleshops, which included an observational study designed to analyse methods employed by the liquor industry to market RTDs in bottleshops, on the central coast of New South Wales. We measured the number of glass-door display refrigerators to determine refrigerated space allocated to display RTDs compared with other alcoholic products. This measure was used to establish a quantitative baseline as an indicator for the in-store marketing of these products. We then randomly selected a dozen bottleshops from those previously visited and conducted semi-structured interviews with the staff., Results: The display of colourful, youth-oriented products and packaging in glass-door display refrigerators appears to be the primary in-store method for marketing RTD products. More than 40% of all glass-door display refrigerators in bottleshops on the central coast are dedicated to the storage and display of RTDs. More than half of the staff interviewed at bottleshops reported they believed that RTD products were marketed to under 18s, particularly girls., Conclusion: There is already a high level of consumption of RTDs by under 18s. There is very strong marketing of these products by the liquor industry. This trend will further compound the already high-risk level of consumption of these products by young people.

A panel of 10 clinical isolates of herpes simplex virus (HSV) deficient in the expression of thymidine kinase (TK) and phenotypically resistant to aciclovir was characterized. Sequence analysis revealed a variety of mutations in TK (nucleotide substitutions, insertions and deletions), most of which resulted in truncated TK polypeptides. In line with previous reports, the most common mutation was a single G insertion in the 'G-string' motif. One HSV-1 isolate and two HSV-2 isolates appeared to encode full-length polypeptides and, in each case, an amino acid substitution likely to be responsible for the phenotype was identified. Pathogenicity was determined using a zosteriform model of HSV infection in BALB/c mice. The majority of isolates appeared to show impaired growth at the inoculation site compared with wild-type virus. They also showed poor replication in the peripheral nervous system and little evidence of zosteriform spread. One exception was isolate 4, which had a double G insertion in the G-string but, nevertheless, exhibited zosteriform spread. These studies confirmed that TK-deficient viruses display a range of neurovirulence with respect to latency and zosteriform spread. These results are discussed in the light of previous experience with TK-deficient viruses.

A clinical isolate of herpes simplex virus type 1 that is aciclovir resistant but neurovirulent in mice was described previously. The mutation in this virus is a double G insertion in a run of seven G residues that has been shown previously to be a mutational hotspot. Using a sensitive assay, it has been demonstrated that preparations of this virus are able to induce low but consistent levels of thymidine kinase (TK) activity. However, this activity results from a high frequency mutational event that inserts a further G into the 'G-string' motif and thus restores the TK open reading frame. Passage of this virus through the nervous system of mice results in the rapid selection of the TK-positive variant. Thus, this variant is the major component in virus reactivated from latently infected ganglia. Mutation frequency appears to be influenced by the genetic background of the virus.

Previous data have indicated that the development of resistance to amprenavir, an inhibitor of the human immunodeficiency virus type 1 protease, is associated with the substitution of valine for isoleucine at residue 50 (I50V) in the viral protease. We present further findings from retrospective genotypic and phenotypic analyses of plasma samples from protease inhibitor-naïve and nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients who experienced virological failure while participating in a clinical trial where they had been randomized to receive either amprenavir or indinavir in combination with NRTIs. Paired baseline and on-therapy isolates from 31 of 48 (65%) amprenavir-treated patients analyzed demonstrated the selection of protease mutations. These mutations fell into four distinct categories, characterized by the presence of either I50V, I54L/I54M, I84V, or V32I+I47V and often included accessory mutations, commonly M46I/L. The I50V and I84V genotypes displayed the greatest reductions in susceptibility to amprenavir, although each of the amprenavir-selected genotypes conferred little or no cross-resistance to other protease inhibitors. There was a significant association, for both amprenavir and indinavir, between preexisting baseline resistance to NRTIs subsequently received during the study and development of protease mutations (P = 0.014 and P = 0.031, respectively). Our data provide a comprehensive analysis of the mechanisms by which amprenavir resistance develops during clinical use and present evidence that resistance to concomitant agents in the treatment regimen predisposes to the development of mutations associated with protease inhibitor resistance and treatment failure.