Deep learning MRI-only synthetic-CT generation for pelvis, brain and head and neck cancers.

BACKGROUND AND PURPOSE: MRI-only planning relies on dosimetrically accurate synthetic-CT (sCT) generation to allow dose calculation. Here we validated the dosimetric accuracy of sCTs generated using a deep learning algorithm for pelvic, brain and head and neck (H&N) cancer sites using variable MRI data from multiple scanners. METHODS: sCT generation models were trained using a cycle-GAN algorithm, using paired MRI-CT patient data. Input MRI sequences were: T2 for pelvis, T1 with gadolinium (T1Gd) and T2 FLAIR for brain and T1 for H&N. Patient validation sCTs were generated for each site (49 - pelvis, 25 - brain and 30 - H&N). VMAT plans, following local clinical protocols, were calculated on planning CTs and recalculated on sCTs. HU and dosimetric differences were assessed, including DVH differences and gamma index (2 %/2mm). RESULTS: Mean absolute error (MAE) HU differences were; 48.8 HU (pelvis), 118 HU (T2 FLAIR brain), 126 HU (T1Gd brain) and 124 HU (H&N). Mean primary PTV D95% dose differences for all sites were < 0.2 % (range: -0.9 to 1.0 %). Mean 2 %/2mm and 1 %/1mm gamma pass rates for all sites were > 99.6 % (min: 95.3 %) and > 97.3 % (min: 80.1 %) respectively. For all OARs for all sites, mean dose differences were < 0.4 %. CONCLUSION: Generated sCTs had excellent dosimetric accuracy for all sites and sequences. The cycle-GAN model, available on the research version of a commercial treatment planning system, is a feasible method for sCT generation with high clinical utility due to its ability to use variable input data from multiple scanners and sequences.

Minute-scale oscillatory sequences in medial entorhinal cortex.

The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.

CBCT-Based Dose Monitoring and Adaptive Planning Triggers in Head and Neck PBS Proton Therapy.

PURPOSE: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. METHODS: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. RESULTS: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. CONCLUSION: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

Clinical evaluation of synthetic computed tomography methods in adaptive proton therapy of lung cancer patients.

Background and purpose: Efficient workflows for adaptive proton therapy are of high importance. This study evaluated the possibility to replace repeat-CTs (reCTs) with synthetic CTs (sCTs), created based on cone-beam CTs (CBCTs), for flagging the need of plan adaptations in intensity-modulated proton therapy (IMPT) treatment of lung cancer patients. Materials and methods: Forty-two IMPT patients were retrospectively included. For each patient, one CBCT and a same-day reCT were included. Two commercial sCT methods were applied; one based on CBCT number correction (Cor-sCT), and one based on deformable image registration (DIR-sCT). The clinical reCT workflow (deformable contour propagation and robust dose re-computation) was performed on the reCT as well as the two sCTs. The deformed target contours on the reCT/sCTs were checked by radiation oncologists and edited if needed. A dose-volume-histogram triggered plan adaptation method was compared between the reCT and the sCTs; patients needing a plan adaptation on the reCT but not on the sCT were denoted false negatives. As secondary evaluation, dose-volume-histogram comparison and gamma analysis (2%/2mm) were performed between the reCT and sCTs. Results: There were five false negatives, two for Cor-sCT and three for DIR-sCT. However, three of these were only minor, and one was caused by tumour position differences between the reCT and CBCT and not by sCT quality issues. An average gamma pass rate of 93% was obtained for both sCT methods. Conclusion: Both sCT methods were judged to be of clinical quality and valuable for reducing the amount of reCT acquisitions.

An optimized framework for cone-beam computed tomography-based online evaluation for proton therapy.

BACKGROUND: Clinical evidence has demonstrated that proton therapy can achieve comparable tumor control probabilities compared to conventional photon therapy but with the added benefit of sparing healthy tissues. However, proton therapy is sensitive to inter-fractional anatomy changes. Online pre-fraction evaluation can effectively verify proton dose before delivery to patients, but there is a lack of guidelines for implementing this workflow. PURPOSE: The purpose of this study is to develop a cone-beam CT-based (CBCT) online evaluation framework for proton therapy that enables knowledge transparency and evaluates the efficiency and accuracy of each essential component. METHODS: Twenty-three patients with various lesion sites were included to conduct a retrospective study of implementing the proposed CBCT evaluation framework for the clinic. The framework was implemented on the RayStation 11B Research platform. Two synthetic CT (sCT) methods, corrected CBCT (cCBCT), and virtual CT (vCT), were used, and the ground truth images were acquired from the same-day deformed quality assurance CT (dQACT) for the comparisons. The evaluation metrics for the framework include time efficiency, dose-difference distributions (gamma passing rates), and water equivalent thickness (WET) distributions. RESULTS: The mean online CBCT evaluation times were 1.6 ± 0.3 min and 1.9 ± 0.4 min using cCBCT and vCT, respectively. The dose calculation and deformable image registration dominated the evaluation efficiency, and accounted for 33% and 30% of the total evaluation time, respectively. The sCT generation took another 19% of the total time. Gamma passing rates were greater than 91% and 97% using 1%/1 mm and 2%/2 mm criteria, respectively. When the appropriate sCT was chosen, the target mean WET difference from the reference were less than 0.5 mm. The appropriate sCT method choice determined the uncertainty for the framework, with the cCBCT being superior for head-and-neck patient evaluation and vCT being better for lung patient evaluation. CONCLUSIONS: An online CBCT evaluation framework was proposed to identify the use of the optimal sCT algorithm regarding efficiency and dosimetry accuracy. The framework is extendable to adopt advanced imaging methods and has the potential to support online adaptive radiotherapy to enhance patient benefits. It could be implemented into clinical use in the future.

Object-centered population coding in CA1 of the hippocampus.

Objects and landmarks are crucial for guiding navigation and must be integrated into the cognitive map of space. Studies of object coding in the hippocampus have primarily focused on activity of single cells. Here, we record simultaneously from large numbers of hippocampal CA1 neurons to determine how the presence of a salient object in the environment alters single-neuron and neural-population activity of the area. The majority of the cells showed some change in their spatial firing patterns when the object was introduced. At the neural-population level, these changes were systematically organized according to the animal's distance from the object. This organization was widely distributed across the cell sample, suggesting that some features of cognitive maps-including object representation-are best understood as emergent properties of neural populations.

Daily dose evaluation based on corrected CBCTs for breast cancer patients: accuracy of dose and complication risk assessment.

OBJECTIVES: The goal of this study is to validate different CBCT correction methods to select the superior method that can be used for dose evaluation in breast cancer patients with large anatomical changes treated with photon irradiation. MATERIALS AND METHOD: Seventy-six breast cancer patients treated with a partial VMAT photon technique (70% conformal, 30% VMAT) were included in this study. All patients showed at least a 5 mm variation (swelling or shrinkage) of the breast on the CBCT compared to the planning-CT (pCT) and had a repeat-CT (rCT) for dose evaluation acquired within 3 days of this CBCT. The original CBCT was corrected using four methods: (1) HU-override correction (CBCTHU), (2) analytical correction and conversion (CBCTCC), (3) deep learning (DL) correction (CTDL) and (4) virtual correction (CTV). Image quality evaluation consisted of calculating the mean absolute error (MAE) and mean error (ME) within the whole breast clinical target volume (CTV) and the field of view of the CBCT minus 2 cm (CBCT-ROI) with respect to the rCT. The dose was calculated on all image sets using the clinical treatment plan for dose and gamma passing rate analysis. RESULTS: The MAE of the CBCT-ROI was below 66 HU for all corrected CBCTs, except for the CBCTHU with a MAE of 142 HU. No significant dose differences were observed in the CTV regions in the CBCTCC, CTDL and CTv. Only the CBCTHU deviated significantly (p < 0.01) resulting in 1.7% (± 1.1%) average dose deviation. Gamma passing rates were > 95% for 2%/2 mm for all corrected CBCTs. CONCLUSION: The analytical correction and conversion, deep learning correction and virtual correction methods can be applied for an accurate CBCT correction that can be used for dose evaluation during the course of photon radiotherapy of breast cancer patients.

Visual stimulus features that elicit activity in object-vector cells.

Object-vector (OV) cells are cells in the medial entorhinal cortex (MEC) that track an animal's distance and direction to objects in the environment. Their firing fields are defined by vectorial relationships to free-standing 3-dimensional (3D) objects of a variety of identities and shapes. However, the natural world contains a panorama of objects, ranging from discrete 3D items to flat two-dimensional (2D) surfaces, and it remains unclear what are the most fundamental features of objects that drive vectorial responses. Here we address this question by systematically changing features of experimental objects. Using an algorithm that robustly identifies OV firing fields, we show that the cells respond to a variety of 2D surfaces, with visual contrast as the most basic visual feature to elicit neural responses. The findings suggest that OV cells use plain visual features as vectorial anchoring points, allowing vector-guided navigation to proceed in environments with few free-standing landmarks.

Technical Note: Efficient and accurate MRI-only based treatment planning of the prostate using bulk density assignment through atlas-based segmentation.

PURPOSE: This study investigates the dosimetric accuracy as well as the robustness of a bulk density assignment approach to magnetic resonance imaging (MRI)-only based treatment planning of the prostate, with bulk density regions automatically identified using atlas-based segmentation (ABS). METHODS: Twenty prostate radiotherapy patients received planning computed tomography (CT) and MRI scans and were treated with volumetric modulated arc therapy (VMAT). Two bulk densities were set, one for bone and one for soft tissue. The bone contours were created by using ABS followed by manual modification if considered necessary. A range of soft tissue and bone density pairs, between 0.95 and 1.03 g/cm3 with increments of 0.01 for soft tissue, and between 1.15 and 1.65 g/cm3 with increments of 0.05 for bone, were evaluated. Using the density pair giving the lowest dose difference compared to the CT-based dose, dose differences were calculated using both the manually modified bone contours and the bone contours from ABS. Contour overlap measurements between the ABS contours and the manually modified contours were calculated. RESULTS: The dose comparison shows a very good agreement with the CT when using 0.98 g/cm3 for soft tissue and 1.20 g/cm3 for bone, with a dose difference less than 1 % in average dose in all regions of interest. The mean Dice similarity coefficient for bone was 0.94 and the Mean Distance to Agreement was <1 mm in most cases. CONCLUSIONS: Using bulk density assignment on MR images with suitable densities for bone and soft tissue results in clinically acceptable dose differences compared to dose calculated on the CT, for both atlas-based and manual bone contours. This demonstrates that an integrated MRI-only pathway utilizing a bulk density assignment for two tissue types is a feasible and robust approach for patients with prostate cancer treated with VMAT.

EndoVAC hybrid therapy for salvage of patients with infected femoral artery reconstructions.

BACKGROUND: EndoVAC hybrid therapy for infected femoral artery reconstructions consists of endovascular relining with a stent graft, surgical debridement and vacuum-assisted wound closure (VAC), and may be considered as a bailout procedure. The aim of this study was to analyze differences in risk factors of patients receiving EndoVAC compared to standard VAC therapy for perivascular infected femoral artery reconstructions, and to describe the technique, complications and outcome of EndoVAC therapy. MATERIAL AND METHODS: Retrospective analysis of 183 patients receiving VAC or EndoVAC therapy for perivascular infections in the groin from January 2004 to December 2017 was performed. Failure of wound treatment was defined as a wound not healed within four months, visible graft material or native artery after one month, bleeding from the wound leading to discontinuation of treatment, death or amputation due to groin infection. RESULTS: The EndoVAC patients (n = 13) more often had ischemic heart disease (P = 0.008), more late wound infections after index operation (P < 0.001), had more often undergone previous ipsilateral groin incisions (P = 0.006) and presented more often with hemorrhage/femoral pseudoaneurysm (P < 0.001), compared to the standard VAC patients (n = 170). Major complications after EndoVAC therapy were stent graft occlusion (n = 3), major hemorrhage from the repaired reconstruction (n = 2), major amputation within six months (n = 4) and death due to infected reconstruction (n = 2). Ten (77%) groins healed, eight without major complications. CONCLUSION: EndoVAC therapy appears to be a life-saving minimally invasive treatment option in surgical high-risk patients with infected femoral artery reconstruction and disrupted vascular anastomosis.

Object-vector coding in the medial entorhinal cortex.

The hippocampus and the medial entorhinal cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. In this system, correlations between neural firing and an animal's position or orientation are so evident that cell types have been given simple descriptive names, such as place cells3, grid cells4, border cells5,6 and head-direction cells7. While the number of identified functional cell types is growing at a steady rate, insights remain limited by an almost-exclusive reliance on recordings from rodents foraging in empty enclosures that are different from the richly populated, geometrically irregular environments of the natural world. In environments that contain discrete objects, animals are known to store information about distance and direction to those objects and to use this vector information to guide navigation8-10. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects11,12 or boundaries13,14 to determine the animal's location, but-although some cells with vector-coding properties may be present in the hippocampus15 and subiculum16,17-it remains to be determined whether and how vectorial operations are implemented in the wider neural representation of space. Here we show that a large fraction of medial entorhinal cortex neurons fire specifically when mice are at given distances and directions from spatially confined objects. These 'object-vector cells' are tuned equally to a spectrum of discrete objects, irrespective of their location in the test arena, as well as to a broad range of dimensions and shapes, from point-like objects to extended surfaces. Our findings point to vector coding as a predominant form of position coding in the medial entorhinal cortex.

MR and CT data with multiobserver delineations of organs in the pelvic area-Part of the Gold Atlas project.

PURPOSE: We describe a public dataset with MR and CT images of patients performed in the same position with both multiobserver and expert consensus delineations of relevant organs in the male pelvic region. The purpose was to provide means for training and validation of segmentation algorithms and methods to convert MR to CT like data, i.e., so called synthetic CT (sCT). ACQUISITION AND VALIDATION METHODS: T1- and T2-weighted MR images as well as CT data were collected for 19 patients at three different departments. Five experts delineated nine organs for each patient based on the T2-weighted MR images. An automatic method was used to fuse the delineations. Starting from each fused delineation, a consensus delineation was agreed upon by the five experts for each organ and patient. Segmentation overlap between user delineations with respect to the consensus delineations was measured to describe the spread of the collected data. Finally, an open-source software was used to create deformation vector fields describing the relation between MR and CT images to further increase the usability of the dataset. DATA FORMAT AND USAGE NOTES: The dataset has been made publically available to be used for academic purposes, and can be accessed from https://zenodo.org/record/583096. POTENTIAL APPLICATIONS: The dataset provides a useful source for training and validation of segmentation algorithms as well as methods to convert MR to CT-like data (sCT). To give some examples: The T2-weighted MR images with their consensus delineations can directly be used as a template in an existing atlas-based segmentation engine; the expert delineations are useful to validate the performance of a segmentation algorithm as they provide a way to measure variability among users which can be compared with the result of an automatic segmentation; and the pairwise deformably registered MR and CT images can be a source for an atlas-based sCT algorithm or for validation of sCT algorithm.

Outcome and Complications Using Negative Pressure Wound Therapy in the Groin for Perivascular Surgical Site Infections after Vascular Surgery.

BACKGROUND: The aim of this study was to investigate graft preservation, major bleeding, and reinfection rate using negative pressure wound therapy (NPWT) for perivascular surgical site infections (SSIs) in the groin after vascular surgery and factors associated with failure of treatment. METHODS: Retrospective data were collected during 2004-2015. Failure of wound treatment was defined as a wound not healed within 4 months, visible graft material or native artery after 1 month, bleeding from the wound leading to discontinuation of treatment, or death or amputation due to the groin infection. RESULTS: The median age of the 161 patients was 71 years; 63% were men. The rate of graft preservation rate was 81%; 64% for synthetic grafts. Major bleeding during NPWT occurred in 7.1% and local reinfection in 6.4%. Synthetic graft infection (odds ratio [OR] = 6.1, 95% confidence interval [CI] = 2.6-14.4) and bleeding/pseudoaneurysm as presenting symptom (OR = 2.9, 95% CI = 1.0-8.2) were independently associated with increased failure rate of treatment. CONCLUSIONS: NPWT is a good option for perivascular SSI in the groin after vascular surgery. Patients with a synthetic graft infection and/or presenting with pseudoaneurysm or bleeding may be considered for an adjunctive or alternative treatment option.