With the advancement of radiotherapy equipment, stereotactic radiotherapy (SRT) has been increasingly used. Among the many radiotherapy devices, Halcyon shows promising applications. This article reviews the dosimetric performance such as plan quality, plan complexity, and gamma passing rates of SRT plans with Halcyon to determine the effectiveness and safety of Halcyon SRT plans. This article retrieved the last 5 years of PubMed studies on the effectiveness and safety of the Halcyon SRT plans. Two authors independently reviewed the titles and abstracts to decide whether to include the studies. A search was conducted to identify publications relevant to evaluating the dosimetric performance of SRT plans on Halcyon using the key strings Halcyon, stereotactic radiosurgery, SRT, stereotactic body radiotherapy, and stereotactic ablative radiotherapy. A total of 18 eligible publications were retrieved. Compared to SRT plans on the TrueBeam, the Halcyon has advantages in terms of plan quality, plan complexity, and gamma passing rates. The high treatment speed of SRT plans on the Halcyon is impressive, while the results of its plan evaluation are also encouraging. As a result, Halcyon offers a new option for busy radiotherapy units while significantly improving patient comfort in treatment. For more accurate results, additional relevant publications will need to be followed up in subsequent studies. SRT includes stereotactic radiosurgery (SRS), fractionated SRT, and stereotactic body radiotherapy (SBRT). In recent years, with the development of radiotherapy equipment, SRT has been moving toward large-scale applications.Stereotactic radiotherapy (SRT) is a technique that delivers high doses of radiation to tumors while preserving normal tissue function. It has a gantry speed of up to 4 rotations a minute. Since there is no field light, optical distance indicator or source-skin distance (SSD) measuring device, only the laser on the machine shell is used for patient positioning. Therefore, the accuracy of patient positioning depends on MV or kV imaging. Simple and clear designs named “one-step patient setup and verification” significantly reduces the daily setup time, which improves patient comfort and compliance. The Halcyon has no beam-shaping jaws, only stacked and staggered multileaf collimators (MLC) that form a maximum field of 28 cm × 28 cm at the isocenter. Each leaf is 1 cm wide, with 29 pairs of leaves in the proximal single-layer and 28 pairs in the distal single-layer, for a total of 114 leaves. The proximal single-layer is displaced laterally by 0.5 cm relative to the distal single-layer to reduce inter-leaf leakage. As a result, the Halcyon MLC leakage and transmission is less than 0.4% compared to 1.5% for the 6MV beam on TrueBeam (TB). At the same time, the less rounded leaves provide smaller penumbra with a smaller dosimetric leaf gap of 0.1 mm compared to 6 MV TB’s 1 mm. The maximum velocity of the leaves is 5.0 cm/s, which is twice as fast as the Varian C-arm accelerator MLCs. The average dose differences for the dual-layer, proximal single-layer and distal single-layer leaf sequences were −1.35%, −1.20%, and −1.34%, respectively. Therefore, the dosimetric parameters are comparable to the TB platform.,6The Halcyon, which entered clinical application in 2017, is characterized by its “fast” nature, with many features that distinguish it from the C-arm accelerators. First, it has an enclosed, ring-mounted gantry and a 6 MV flattening-free filter (FFF) beam that is used for treatment and imaging with Halcyon version 1.0. Halcyon 2.0 imaging no longer requires MV-X rays but adds a dedicated kV imaging system with greatly improved soft tissue resolution.,8 Halcyon 2.0 has 2 types of beams, the dynamic flattening beam and the FFF beam. Some authors conducted intensity-modulated radiotherapy and volumetric-modulated arc therapy (VMAT) delivery accuracy and mechanical quality assurance (QA) of Halcyon 2.0 following International Atomic Energy Agency TRS-398 and American Association of Physicists in Medicine TG-119 and found that it met all criteria. Lloyd et al concluded that the results of profile measurements at Dmax for the Halcyon’s 6 MV-FFF beam varied by less than 0.5% with different active volumes of the Farmer ionization chambers. The results indicate that the Halcyon can perform reference dosimetry without a specialized chamber or lead filtering chamber and is well suited for resource-limited units. Bollinger et al studied the dosimetric features and limitations of the dynamic flattening beam on the Halcyon 2.0 and found that the transversal and radial profiles of ≥10 cm square fields were observed with <3% flatness under the conditions of 100 cm SSD and 10 cm water depth. The positioning accuracy of MLC, gantry angle, and couch shift were within 0.05 mm, 0.02°, and 0.03 mm, respectively. Therefore, the Halcyon demonstrates a potential of high delivery accuracy. Features of the Halcyon compared with C-arm accelerators are demonstrated in Table The Halcyon is equipped with a treatment planning system (TPS) of Eclipse 15.1 or 15.6, the beam model in Eclipse is pre-defined, including percentage depth dose, profiles, and output factors.,14–20 Because of the distinctive features of Halcyon gantry rotation speed, dual-layer MLC, no jaw, no light field or SSD indicator, and the high requirements of SRT treatment, the dosimetric performance such as plan quality, plan complexity, and gamma passing rates of Halcyon SRT plans need to be explicitly studied. Plan evaluation is generally achieved by analyzing the TPS-calculated dose distribution. However, it is challenging to quantify 3-dimensional dose distributions and comprehensively analyze the spatial characteristics of dose distributions. We still need to gain the knowledge to personalize the prediction of clinical outcomes based on patient-specific characteristics. The plan quality requires the evaluation of various dosimetric indices derived from dose volume histogram (DVH)-based data, such as conformity index (CI), gradient index (GI), and homogeneity index (HI). In addition, the theoretical dose distribution is different from the actual dose distribution delivered to the patient due to uncertainties in dose calculations, errors in patient positioning, and changes in anatomical structures during the treatment course. Therefore, the dosimetric performance evaluation of SRT plans includes plan quality indices derived from DVH, such as CI, GI, and HI, as well as plan complexity and gamma passing rates.Most Halcyon users are impressed with its treatment speed.This review analyzes the strengths and weaknesses of the Halcyon SRT plans to help radiotherapy practitioners better understand and implement the SRT plans on the Halcyon and to fully understand the effectiveness and safety of the Halcyon SRT plans.A PubMed search was performed to identify publications evaluating the dosimetric performance of SRT plans on Halcyon using the query strings Halcyon, SRS, SRT, SBRT, and stereotactic ablative radiotherapy. The SRT plans have the characteristics of a high fractionated dose (6–30 Gy/fraction), low fractions of treatments (1–5 fraction), high biological effect dose ≥ 100, high target conformality, and large off-target dose gradient compared with the conventional radiotherapy plans. Therefore, they have higher requirements for treatment equipment.We searched PubMed for each of the following keywords/strings: AND SRT; AND SBRT; AND SRS; AND SABR.The screening period was from November 19, 2017, to July 12, 2023. Studies were limited to the past 6 years and included only keywords in the title and/or abstract. The search was first conducted on November 19, 2022, and the supplemental search time is July 12, 2023. If titles and abstracts were considered relevant, the full text was retrieved. Only English publications were considered.In order to reduce the bias related to the selective reporting of outcomes and increase the availability and accessibility of our article, 2 authors independently reviewed titles and abstracts to decide on the study inclusion.Publications were selected if they contained information about SRT plan quality evaluation  and provided a discussion and summary of one or more following medical physics components.The Halcyon SRT plan complexity;The Halcyon SRT plan gamma passing rates. It starts to increase significantly in the last 3 years. The number of publications related to 2023 was incomplete because the inclusion criteria were limited to July 12, 2023.Based on the PubMed search results, 24 publications were identified. The results are shown in Figure Out of 24 records, one was excluded due to duplication. Five publications were excluded from the 23 records screened for the following reasons: not relevant to the question addressed (#4) and not addressing Halcyon (#1). Of the 18 full-text publications assessed as eligible, 18 were selected based on the medical physics-related issues 1 and 2 described in the study selection paragraph in Section 2. Brief information about Halcyon plan quality, complexity, and gamma passing rates is presented in Table The dosimetric performance evaluation of SRT plans on Halcyon requires plan quality evaluation to overcome the planning uncertainties due to planners’ subjective tendencies and lack of ability. The plan evaluation includes slice-by-slice checking the relationship between isodose lines and the target volume/OARs, evaluating the gradient measure (GM), the maximal dose at 2 cm away from the planning target volume in any direction (D2cm) that comes with the TPS, and DVH-based dose coverage, CI, GI, and HI dosimetric indices.The slice-by-slice checking of the relationship between isodose lines and the target volume/OARs can provide the observer with 3-dimensional dose information about the target volume and OARs. The checking can identify where there are cold spots and hot spots and whether modifications are needed, thus further improving the quality of SRT plans. and the International Commission on Radiation Units and Measurements method. A qualified CI guarantees plan quality among the dosimetric indices such as CI, GI, GM, D2cm, and HI. GI, GM, and D2cm take into account the dose fall-off outside the target and are helpful for OARs sparing, while HI is gradually marginalized in the quality evaluation of SRT plans. The CI of RTOG did not consider the location and shape of the prescriptive isodose line relative to the targets. To overcome the limitation, Paddick et al proposed the Paddick CI, which combines conformity and dose coverage and better solves the problem of the false perfect score. The steep dose fall-off is essential to reduce the dose of OARs adjacent to the targets, and GI, GM, and D2cm can quantify this tendency.–28 HI describes the degree of dose uniformity within the target. The pursuit of dose uniformity within the target will increase the dose of OARs and reduce the protection intensity of OARs by TPS. Therefore, when the targets of SRT plans do not contain functional tissue to be spared, the maximum target dose should be set carefully. The specific definitions of dose coverage, CI, GI, GM, D2cm, and HI are shown in Table The TPS comes with GM, D2cm, and other indices that can be read directly in the software. Among the DVH-based dosimetric indices, the target dose coverage can be visualized on the DVH and is, therefore, the most commonly used. There are 2 standard definitions of dose coverage, the radiation therapy oncology group (RTOG) method,31 Halcyon has a strong dose carving capability for SRT plans. The stacked and staggered MLC can produce highly conformal dose distribution to targets, comparable intermediate dose spillage, and similar doses to adjacent OARs compared to TB. See Table ,14–16,19 conducted VMAT-SBRT technique using Halcyon 2.0 and designed plans for abdominal/pelvic oligometastatic lymph nodes, double-vertebral segments, single-isocenter/2-lesion lung, prostate and accelerated partial breast irradiation patients respectively. They compared the CI, HI, GI, D2cm, and OARs of these plans with those of TB Millenium 120 MLC in the same group of patients. The differences between these indices were mainly not statistically significant. Petroccia et al studied the Halcyon VMAT-SBRT for vertebral metastases, using plan quality indices such as target coverage, HI, CI, and GI. They found that the Halcyon can generate comparable and clinically equivalent spine SBRT plans to TB plans with less rapid dose fall-off out of the targets. Li et al designed 20 cases of plans with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal, and the Halcyon VMAT-SBRT plans achieved similar target coverage  and CI  compared to the TB VMAT-SBRT plans. Despite the data were not statistically significant (P > .05), the GI  of Halcyon plans were higher. Roover et al compared the Halcyon 3-arc VMAT-SBRT plans with the TB 2-arc VMAT-SBRT plans in 20 prostate cancer cases and found that the Halcyon 3-arc plans showed higher planning target volume coverage (D99%) of the seminal vesicle, along with reduced high-dose spillage of the bladder (V37Gy) and urethral (D0.035cc). Altundal et al compared 20 prostate patients’ SBRT plans of Halcyon 2.0 and CyberKnife and found that all Halcyon SBRT plans met the goals and constraints of the RTOG 0938 protocol, with improved CI and target dose coverage, reduced maximum dose in the skin and urethra compared to the CyberKnife plans. Comparison of Halcyon SRT plans with their counterparts in high-end devices such as TB led to the optimistic conclusion that the Halcyon VMAT-SRT plans were dosimetrically equivalent to TB plans, and can achieve better dosimetric performance for some treatment sites.Most authors analyzed the plan quality of Halcyon by comparing it with TB, a state-of-the-art C-arm accelerator of Varian , which represents the latest achievement in radiotherapy equipment. used a simplified knowledge-based planning model to design the Halcyon VMAT-SBRT plans for lung cancer, and the plan quality was clinically acceptable. In order to validate the feasibility of Halcyon-based rapid SBRT plans for central lung cancer, Visak et al designed lung cancer SBRT plans using the KBP model, and new plans similar or better in dosimetry to the TB plans were obtained within 30 min, where the CI difference was not significant (P > .05). Halcyon SBRT plans had a mean lower GI of 0.43 (P = .006), an increase in maximum target dose of 2.9 Gy (P < .001), and a mean reduction in lung mean lung dose of 0.10 Gy (P = .004).The ability of Halcyon to treat patients rapidly is an undisputed fact. Meanwhile, the rapid generation of high-quality Halcyon plans is breaking through. Automated planning is an essential complement to the “rapid treatment matrix” of Halcyon and is the most feasible direction for rapid Halcyon planning. Wada et al Hence, the Halcyon linear accelerator cannot provide non-coplanar fields, which may lead to limitations in SRT implementations.,38 However, lateral head flexion can overcome the inability to design non-coplanar SRS plans and considerably increase beam entrance angles. It thus improves plan conformity and normal tissue sparing. Reynoso et al did the research and found that when comparing the head flexion technique with a fully coplanar geometry, the Halcyon SRS plans showed an average improvement in CI of 7.3% (1.46 ± 0.25 vs 1.36 ± 0.28), a decrease of 13% in intermediate dose fall-off (5.46 ± 1.14 vs 4.78 ± 1.12), a decrease of 32% in low dose spillage (85.7 ± 20.3 vs 58.2 ± 15.1), and a decrease of 7.8% in gradient measure (0.53 ± 0.05 vs 0.49 ± 0.04). Li et al conducted a retrospective study of ten patients with multiple intracranial metastases, each with 6 to 10 targets with a volume of 0.11 to 8.57 cc and a prescribed dose of 15 to 24 Gy. They compared CI, GI, and OARs from Halcyon and TB plans in single-isocenter VMAT-SRS treatment. They found that for targets > 1 cm in diameter, Halcyon could produce a CI value similar to TB with reduced low-dose leakage to normal brain tissue. The GI and intermediate dose fall-off for the Halcyon plans were inferior to the TB plans, probably because of the inability of Halcyon to achieve non-coplanar geometry and 1 cm wide MLC leaves.However, there is room for continued improvement of the Halcyon over conventional high-end C-arm accelerators. Because of the ring gantry, Halcyon can provide translational but not rotational couch corrections, allowing only 3 degrees of freedom (DoF) corrections. However, C-arm linear accelerators can provide translational and rotational couch corrections, allowing 6 DoF corrections.In conclusion, the quality of the Halcyon SRT plans is comparable with the TB SRT plans, which, combined with its fast treatment speed, thus significantly improves patient comfort and clinic workflow. It is an option for busy radiotherapy centers.–43 In the planning process, the plan complexity increases as the minimum segment area decreases and the number of optimization iterations and the maximum number of segments increases. Therefore, excessive complex plans can lead to dose calculation and delivery uncertainties–47 and a decrease in treatment efficiency. In addition, patient respiratory movements and gastrointestinal motility can also affect the accuracy of dose delivery by producing effects such as the Interplay effect. In conclusion, plan complexity needs to be measured and controlled in advance for dose delivery accuracy and treatment efficiency.Plan evaluation includes plan complexity. Plan complexity is a corollary to the stringent requirements of SRT plans for dose coverage, CI, and GI. Meanwhile, SRT plans always have smaller targets. All the above factors yield results such as smaller and less regular beam apertures, more significant tongue-and-groove effects, more extensive modulation of machine parameters, and more monitor units (Mus). The leading indices are MUs, the ratio of total number of MUs per fraction to the prescription dose in cGy defined as the modulation factor (MF), aperture shape controller, modulation complexity score (MCS), etc. The smaller the value of all the above indices, the lower the complexity of the plans. Eclipse TPS includes aperture shape controller tools that can limit the complexity during plan optimization, partly by reducing the number of total MUs, stabilizing the gantry rotation speed, reducing the number of small-area segments, reducing the number of irregular fields, etc. Quintero et al considered that the complexity of plans is positively related to the number of MUs. McNiven et al and Masi et al found that smaller segments and irregular fields increase the beam-on time and dose calculation error, and designed the MCS index to analyze plan complexity. Different indices of plan complexity focus on different aspects of plan composition, ranging from studies of MF,,47 to analyses of field size and irregularity,,54 to studies of dose rates, the maximum range of MLC leaf motion, and gantry rotation speed.,56Many plan complexity indices are interrelated, and most can be used to describe different aspects and sources of plan complexity. using MD Anderson’s single-isocenter/multi-target (lung/spine targets) thorax phantom, compared the MUs, MF, and other indices of Halcyon and TB plans when performing double-vertebral segments VMAT-SBRT treatment. They found that the MUs and MF of Halcyon plans were reduced by 130 MU and 0.2, respectively. In the VMAT-SBRT treatment of lung cancer, Pokhrel et al found that the MUs per fraction  and MF  of Halcyon plans were significantly lower than those of TB plans. Li et al analyzed 20 cases of VMAT-SBRT plans with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal and found that the MUs of the Halcyon plans  were comparable to those of the TB plans. Li et al showed the same findings in VMAT-SRS treatment of multiple brain metastases with a single isocenter.Most authors analyzing Halcyon’s plan complexity compared it with TB, and many obtained favorable results. Pokhrel et al found that the TB Millennium 120 MLC SRT plans had a lower average MCS value of 0.18 ± 0.04 compared to the Halcyon 2.0 plans of 0.28 ± 0.03. Pokhrel et al found in the Halcyon 2.0 treatment of single-isocenter/2-lesion lung in the VMAT-SBRT plans that the Halcyon plans had an average increase in MUs and MF of 480 and 0.48, respectively, compared to the TB plans.However, many authors have also argued that the Halcyon SRT plans are more complex than the TB’s. Petroccia et al which is essential for implementing online adaptive radiotherapy and can significantly reduce the time spent on adaptive processes.Overall, literature supporting the Halcyon SRT plans as less complex than the TB SRT plans dominates. In clinical planning, planners should minimize plan complexity while meeting clinical dose requirements and dose delivery accuracy to reduce uncertainty in overall plan execution. Information on plan complexity helps planners make trade-offs between dosimetric indices and plan complexity. The plan complexity can also be used as a validation tool to reduce the QA workload. For example, low complexity plans may require little validation, The gamma passing rate is a parameter used to describe the dose discrepancy between theory and practice. Gamma passing rates are collected at criteria of x%/y mm  with a low threshold of 5% to 20%. Standard collection tools of gamma passing rates are 2D or 3D matrix devices and tools that come with the accelerator manufacturer, such as Varian portal dosimetry (PD). The patient anatomical site variations and structural differences, TPS algorithms, plan complexity, and device accuracy will likely affect gamma passing rates. Halcyon’s gantry rotation speed and MLC motion speed are faster than C-arm accelerators, so the dose delivery accuracy of SRT plans is a problem worth studying.Plans are designed to be used in radiotherapy practice, and there are often discrepancies between the theoretical dose distribution and the actual dose distribution.–16,19,20 conducted intensive multi-disease SRT plan delivery accuracy studies with the Halcyon platform from 2021 to 2022. The experimental results demonstrate that the delivery accuracy of SRT plans on the Halcyon platform can reach the level of TB. In Pokhrel et al 2021, they performed VMAT-SBRT treatment on 8 patients with 2 to 3 abdominal/pelvic oligometastatic lymph nodes, and the plan PD results showed a high gamma pass rate of 98.1 ± 1.6% at the 2%/2 mm criterion. In the same year, they performed VMAT-SBRT treatment on ten prostate cancer patients. The dose delivery accuracy of the Halcyon SRT plans and the corresponding TB SRT plans were 98.6 ± 1.5% (range 95.8–100.0%) and 98.3 ± 2.0% (range 95.3–100%), respectively, and there was no statistical difference (P > .05). Also, in Pokhrel et al 2021, they performed the same treatment on 15 lung cancer cases. They found that the gamma passing rates with a 2%/2 mm global gamma criterion with a low dose threshold of 10% of the TB plans and the corresponding Halcyon plans were 93.0 ± 2.5%  and 94.4 ± 2.1%  on average, respectively. Halcyon plans showed significantly better gamma passing rates (P = .041) compared to those of TB plans. In Pokhrel et al 2022, they replanned 6 patients with double-vertebral segments on the thoracic and/or lumber spine. The average results of patient-specific portal dosimetry QA performed on the Halcyon showed a mean gamma passing rate of 99.6% compared to a mean 96.8% of the SBRT-specific TB for 2%/2 mm criterion, indicating a more accurate treatment outcome with the Halcyon. Also, in Pokhrel et al 2022, they designed 16 pairs of single-isocenter/2-lesion lung VMAT-SBRT plans. Each plan’s delivery accuracy was assessed by PD with a criterion of 2%/2 mm and a low-dose threshold setting of 5%. The mean gamma passing rate was 98.9 ± 0.85% (range: 98.1–100%), and 98.45 ± 0.99% (range: 97.9–100%) for the clinical TB plans and the corresponding Halcyon plans, respectively, and P > .05 demonstrated similar treatment delivery accuracy. In Pokhrel et al 2023, they selected 10 accelerated partial breast irradiation VMAT-SBRT plans. Each plan’s delivery accuracy was assessed by PD with a criterion of 3%/2 mm and a low-dose threshold setting of 10%. The mean gamma passing rate (%) was 99.6 ± 0.39 (98.8–100) for Halcyon 2.0, 97.85 ± 2.63 (91.5–100) for TB-Millenium, P = .001 demonstrated better treatment delivery accuracy for Halcyon 2.0.Pokhrel et al found that the gamma passing rates for Halcyon 1.0 and 2.0 with 2%/2 mm criterion were 98.8 ± 0.2% and 96.9 ± 2.0%, respectively, and no statistical difference in gamma passing rates was observed between Halcyon and TB plans. Altundal et al analyzed 15 prostate cancer patients and found that Halcyon plans’ average gamma passing rate was 99.75 ± 0.08 with a 2%/2 mm criterion and a 10% threshold. With the same criterion, Roover et al used portal dosimetry to collect the gamma passing rates of 20 prostate cancer patients of the TB HD-MLC VMAT-SBRT plans and the Halcyon VMAT-SBRT plans. The results were 99.2%  and 99.7% , respectively. Wang et al analyzed 61 cases of Halcyon plans and found that the average gamma passing rate with a 2%/2 mm criterion for intensity-modulated radiotherapy/VMAT/SRT plans was 96.4% for ArcCHECK and 96.7% for portal dosimetry, respectively. With the 3%/3 mm criterion, the gamma passing rate of all plans was 99.1 ± 1.1% for ArcCHECK. All plans were within 3% of point dose measurements. Based on the results of Byrne et al, the median  gamma passing rates were 99.9% (99.4–100.0%) for Halcyon 2.0 in lung plans, 99.4% (98.1–99.9%) for Halcyon 2.0 in brain plans with 3%/2 mm criterion.Based on 15 spine SBRT plans, Petroccia et alBy comparing the gamma passing rates with those of TB, it was found that the Halcyon SRT plans frequently have higher values, which means that the Halcyon SRT plans have a higher plan deliverability.The application of Halcyon is exciting, but 3 critical issues must be highlighted. First, Halcyon’s SRT plan is good enough. The most considerable direction of improvement for Halcyon in the future lies in developing an automatically rotational 6-DOFs couch and a higher dose rate. Second, this review does not refer to planning issues. Indeed, planning issues are an essential aspect of SRT practice. Third, more relevant publications need to be tracked and studied later to get more results.This review indicated Halcyon could generate SRT plans with higher plan quality, less plan complexity, and higher gamma passing rates compared with those of the TB. The treatment time for Halcyon is significantly faster than TB, despite the former being currently limited by 800 MU/min dose rate. However, in some cases, TB is still preferred over Halcyon for the 6-DoFs couch and automatic rotational correction capabilities for image-guided radiotherapy. After overcoming the above limitations, the novel Halcyon platform is likely a more attractive option for SRT practice.Conceptualization: Yangyang Huang.Formal analysis: Yangyang Huang.Funding acquisition: Zongwen Liu.Investigation: Yangyang Huang.Methodology: Yangyang Huang.Project administration: Zongwen Liu.Resources: Zongwen Liu.Supervision: Zongwen Liu.Visualization: Yangyang Huang.Writing – original draft: Yangyang Huang.Writing – review & editing: Yangyang Huang, Zongwen Liu.


To explore the results of hypertension improvement and renal function preservation after renal artery aneurysm (RAA) repair.This study retrospectively analyzed the change in blood pressure (BP) and renal outcomes of 59 RAA patients throughout either open or endovascular operations and follow-up at a large center. Patients were grouped according to the difference in their BP at the last follow-up vs. their baseline value. Logistic regression was conducted to explore risk factors for perioperative BP relief and long-term hypertension reonset. Previous studies of RAA with records of BP, blood creatinine level, or GFR/eGFR results are reviewed.2. The median follow-up was 854  days. Both open and endovascular techniques significantly relieved hypertension and did not impair renal function much. Lower preoperative systolic BP (SBP) was significantly associated with hypertension relief . Among patients with normal BP after the operation, higher postoperative SBP was significantly associated with new-onset hypertension . Literature review indicated that renal function usually remained normal at follow-up, whereas relief of hypertension varied.Hypertension was observed in 62.7% (37/59) of the patients included. Postoperative BP declined from 132.20 ± 16.46/79.92 ± 9.64 mmHg to 122.41 ± 11.17/71.10 ± 9.82 mmHg, while eGFR changed from 108.17 ± 24.73 to 98.92 ± 23.87 ml/min/1.73 mPatients with lower preoperative SBP were likely to benefit more from the operation, while higher postoperative SBP indicated a higher chance of hypertension reonset. Creatinine level and eGFR generally remained stable regardless of operation type. Renal artery aneurysm (RAA) is a relatively rare condition that entails high risk if ruptured . Around In this study, we retrospectively analyzed the changes in BP and renal outcomes in 59 RAA patients during either open or endovascular operation and throughout follow-up at our institution. Previous studies that had recorded the detailed values of BP, blood creatinine, or glomerular filtration rate (GFR) in patients undergoing RAA open or endovascular operation are reviewed. Multivariable logistic regression was conducted to identify the predictive factors of perioperative BP relief and long-term hypertension reonset.From 2009 to 2021, patients diagnosed with RAA who underwent therapy at the Department of Vascular Surgery, Peking Union Medical College Hospital (PUMCH) were consecutively included in the study. Patients without a detailed record of BP levels were excluded. Computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA) was utilized for RAA diagnosis and evaluation. All participating subjects provided written informed consent, and the study was approved by the institutional review board.Baseline characteristics, perioperative results, and follow-up information were retrospectively collected and analyzed. Indications for intervention included aneurysm diameter >2 cm and symptomatic RAA . Both endovascular and open techniques were applied for treatment.Regarding treatment strategies, coil embolization, as a minimally invasive endovascular procedure with good efficacy and safety, was the first-line treatment if suitable. Stent-assisted coiling (SAC) or simple stent implantation was applied for complicated lesions. For those who were unsuitable for endovascular therapy or too young, open surgery including aneurysmoplasty, resection and primary anastomosis, tailoring, ex vivo repair, and resection and graft reconstruction with either the saphenous vein or a prosthetic graft, was selectively conducted. Detailed procedures can be found in previous literature and in supplemental (1)Always normal patients had normal BP throughout the study.(2)Complete relief of hypertension was defined as SBP and DBP at three or more clinical measurements below 140/90 mmHg without anti-hypertensive drugs.(3)Partial relief was defined as SBP and/or DBP below 140/90 mmHg while taking the same number or reduced number of medications, or a reduction in DBP by at least 15-mm Hg while on the same or reduced number of medications.(4)No relief was defined as no change or inability to meet the above criteria.(5)New onset referred to patients with newly-diagnosed hypertension at follow-up.(6)Relief and new onset was defined as BP relief at discharge but had new-onset hypertension at follow-up.Chronic kidney disease was graded according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative classification  or diastolic BP (DBP) levels of three or more clinical measurements above 140/90 mmHg or taking antihypertensive drugs on admission . BP leveThirty-day and long-term follow-up data were recorded and explored. Technical primary success was defined as the successful introduction and deployment of the device in the absence of surgical conversion or any complication. Color Doppler, CTA, or angiography was applied to evaluate arterial patency, which was defined as evidence of blood flow within the target renal artery or bypass and perfusion in the respective renal parenchyma. Laboratory tests, including creatinine (µmol/L), white blood cell count , hemoglobin , platelet count (PLT 109/L), and D-dimer (mg/L), as well as ultrasounds of the kidney or renal artery, were done at least once preoperatively, postoperatively before discharge, and at three months, six months, and one year or yearly after discharge.Logistic regression of hypertension relief was done between group 2, group 3, group 4, and group 5 patients, who had hypertension before the operation. Patients were divided into complete relief (group 2 and group 5) and incomplete relief (group 3 and group 4). Ordinal regression was first performed between the complete relief group and the incomplete relief group to identify factors with significant associations, which were then incorporated into the multivariate logistic regression model.Logistic regression of new-onset hypertension was run between group 1, group 2, group 5, and group 6 patients who had normal BP after the operation. Patients were divided into new-onset (groups 5 and 6) and no onset (groups 1 and 2) groups. Similar factors as from the ordinal regression model were incorporated.Literature searches in English and Chinese were performed in PubMed, EMBASE and Scopus using the keyword “renal artery aneurysm”. Studies that reported the detailed preoperative, postoperative, follow-up, or changed values of BP, blood creatinine level, or GFR/eGFR level in patients who underwent open or endovascular operation for RAA were included. Single-case reports were excluded. Two authors (SL and FL) reviewed the original articles and identified 10 papers on BP and 16 papers on renal function published from 2001 to 2022.χ2 test or Fisher's exact test, as appropriate. The Wilcoxon test or the Kruskal‒Wallis and Friedman tests were employed for cross- or within-group comparisons, respectively. p < 0.05 was considered significant.Statistical analysis was performed using SPSS 26.0 software . Continuous variables were checked for normality and are reported as median and interquartile range (IQR) or mean ± standard deviation. Categorical variables are presented as frequencies and were compared by the 2.The median follow-up was 64.5 [IQR: 65.2] and 25.1 [IQR: 33.1] months for patients receiving endovascular repair and open surgery, respectively . No signAn average number of types of 0.53 ± 0.63 antiplatelet drugs (aspirin or clopidogrel) were prescribed for patients at the last follow-up . Laboratp < 0.001), prevalence of hypertension history (p < 0.001), preoperative SBP and DBP values (p < 0.001 and =0.005), and postoperative SBP (p = 0.007).All patients were divided into 6 groups according to their BP pattern . Eighteep = 0.047), but no significant difference was observed in the long-term results.BP and renal function alterations were also explored and compared between patients who underwent open or endovascular repair . There wTo further investigate the risk factors for perioperative BP relief and long-term hypertension reonset, logistic regression was conducted in two different sets of groups . Higher The present study demonstrated good results from our twelve-year experience with RAA repair. No significant difference was found in the perioperative laboratory parameters between the open and endovascular groups. Patients receiving open surgery had a transient increase in D-dimer and PLT levels, but their long-term laboratory tests returned to normal. A significantly higher rate of reintervention was observed among patients with new-onset hypertension than for those with other BP statuses. Since RAA patients were generally younger and healthier than other patients in the vascular surgery ward, hypertension improvement and renal function preservation were crucial to reduce morbidity and minimize any potential risk for cardiovascular events in the long run.The mechanism of hypertension in RAA remains unclear. Concurrent RAS or compression might play a part, while microembolization in the distal renal parenchyma and hemodynamic changes from turbulent blood flow within the aneurysm could also contribute . The resConcerning renal function, most RAA patients in this study had normal baseline levels of creatinine and eGFR. During operation, the introduction of nephrotoxic iodinated contrast medium, embolization of a part of the renal parenchyma, failure of artery reconstruction, and clamping of blood supply may all increase the risk of renal impairment . NeverthTo further explore the problem of RAA and BP or renal function, we reviewed the results of BP and indicators of renal function reported in previous studies. Although expertise in RAA repair has accumulated rapidly over the last decade, few studies have reported on the exact values of these parameters. Ten papers that reported the value of BP for RAA were included  3, 7, 8, 19–23. Since controversial results exist, we sought to explore the underlying factors that may contribute to BP alteration using logistic regression models. As for hypertension relief after the operation, we found that patients with lower SBP and higher blood LDL levels preoperatively achieve better outcomes, which could provide predictive value for BP alteration after the operation. Several previous studies concerning BP response after operation for RAS have identified the level of SBP or DBP as a positive predictor of hypertension relief , 31. HowPatients with higher postoperative SBP, though within the normal range, might still be at higher risk of new-onset hypertension. For these patients, renal aneurysm may not be the primary factor causing the hypertension. Thus, the operation could not fully stop the progression of hypertension. A previous study also suggested that a longer duration of hypertension may bring an unfavorable outcome . Since hThis study has some limitations. Besides blood creatinine and eGFR, a more thorough evaluation of renal function, such as urine tests and CTA, was not normally conducted at follow-up, and ambulatory BP monitoring was not done. Subgroup analysis was hampered by the small subject numbers, making it difficult to reach robust conclusions. The activity of the renin-angiotensin system (RAAS) was not routinely tested, so the underlying pathophysiology and etiology of BP change might not be fully explained. More evidence is required to set the optimal RAA diameter threshold for surgical intervention. Nevertheless, through a literature review, we discussed the nature of BP and renal function alteration after RAA operation, which could assist in prognostic prediction for these patients. Larger multicenter studies are necessary to validate our findings.Both open and endovascular techniques for RAA repair demonstrated significant relief of hypertension and little impairment of renal function, yet baseline BP conditions and the extent of hypertension relief or long-term occurrence varied. Patients with lower preoperative SBP were likely to benefit more from the operation, while higher postoperative SBP indicated a higher chance of long-term hypertension reonset. Creatinine level and eGFR generally remained stable regardless of operation type.


To determine the association between sleep disorders and Triglyceride glucose index.A cross-sectional analysis of the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) was performed. The 2005 to 2008 NHANES national household survey for adults ≥ 20 years was examined for the sleep disorders.TyG index: ln [triglyceride (mg/ dL) × fasting blood glucose (mg/dL)/2].Multivariable logistic and linear regression models were used to explore the association between the TyG index and sleep disorders.A total of 4,029 patients were included. Higher TyG index is significantly associated with elevated sleep disorders in U.S. adults. TyG was moderately correlated with HOMA-IR (Spearman r = 0.51). TyG was associated with higher odds of sleep disorders, Sleep apnea , Insomnia, and Restless legs .In this study, our result shown that population with higher TyG index are significantly more likely to have sleep disorders in U.S. adults.The online version contains supplementary material available at 10.1186/s12888-022-04434-9. Humans spend about one-third of their time sleeping, either to recover or to rest . Sleep dSeveral observational studies in large populations suggest that insulin resistance (IR) may be a major cause of sleep disturbance . The triThis is a cross-sectional study with data from the National Health and Nutrition Examination Survey (2005–2008). The survey component included diet, questionnaires, and physiological measurements, as well as laboratory tests supervised by trained medical staff. In addition, NHANES employs various modern equipment to make data collection more reliable and efficient. In addition, each participant receives compensation and medical outcome reporting, which increases participant compliance. A total sample size of 20,497 adults was assessed from 2005–2008, Fig. TyG index was calculated as ln [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2] . HOMA-IRAge, gender, race  were obtained by interviews and physical examinations. Existing smokers were defined as those who smoked 100 or more cigarettes and smoked at the time of the survey. Heavy alcohol consumption was defined as those who had consumed 12 or more glasses of alcohol/for life and who had consumed alcohol at the time of the survey.Leisure levels were calculated as the number of minutes per week during which participants reported participating in moderate to vigorous physical activity (MVPA).Participants with a BMI of 25 kg/m2 were considered overweight in accordance with the limit values.Pre-existing co-morbidities initially included a history of CVD, including coronary artery disease, angina pectoris, myocardial infarction and stroke (yes/no);diabetes (categorised as physician-diagnosed and undiagnosed diabetes); hypertension (categorised as diagnosed hypertension and no hypertension);cancer (categorised as diagnosed cancer and no cancer).P < 0.05 considered statistically significant.Sample weights were used for analysis in order to account for complex survey design and non-response to NHANES.Continuous variables were summarized as mean 95%CI or median (interquartile range) depending on variable distribution, and categorical variables as count (proportion). TyG was compared with HOMA-IR by using Spearman correlation and with sleep disorders. Calculated the area under a receiver-operating characteristic curve generated without covariate adjustment.Multivariate logistic regression and linear analysis was then performed to assess the contribution of TyG index to sleep disorders,Model 1 was unadjusted. Model 2 was adjusted for age, gender, and race.Model 3 was adjusted for age,gender,race,BMI,smoke,drink,MVPA,Hypertension,Diabetes,CVD and cancer.The dose–response association was assessed on a continuous scale with restricted cubic spline curves. The subgroup variable stratified analysis was presented with a fully adjusted Model 3. The log-likelihood test was used to evaluate the interaction effects of the TyG index with subgroup variables.Sensitivity analysis was performed to evaluate which was not affected by taking hypotensive drugs, lipid-lowering drugs or hypoglycemic drugs.All statistical analyses were performed by using SAS version 9.4  and R version 4.1.3 (R Core Team 2020) with a 2-sided Figure There were 959 (24.98%) persons with self-reported sleep disorders,4.43% of participants with sleep apnea,1.42% persons suffered from Insomnia.The prevalence of self-reported Restless Legs was 14(0.28%). Average time(mean 95%CI) tofall asleep costed was 21.24(20.28–22.19)minutes.In the analyzed samples, TyG is Moderately correlated with HOMA-IR, corresponding to The population-weighted Spearman r was 0.51. Figure Figure In Table As shown in Fig. Sensitivity analysis e_table. was perfIn this nationally representative study, the relationship between TyG and sleep disorders was evaluated.The main finding of this paper is that TyG was associated with sleep disorders in the American adult population.This finding was also validated in adjusting the influence of HOMA-IR and was not affected by the use of lipid-lowering, hypotensive or hypoglycemic medications.We also found that increased exposure to TyG could increase the risk for Restless Legs, and the effect of HOMA-IR on Restless Legs was not significant,associations with Restless Legs seemed largely independent of IR (insulin resistance).A previous study showed that participants with a higher TyG index had a higher risk of obstructive sleep apnea than the low-level group in Korean adult . It may Another significant finding was drawn from our linear trend analysis. This study shown that higher TyG means longer time to fall asleep,Edward etl found that longer periods to fall asleep (> 30 min) were associated with higher fasting insulin only for women , it confResults from our study shown that a linear dose–response relationship between TyG and various sleep disorders, suggesting that regardless of their causal relationship, the earlier interventions on these two modifiable indicators, the greater the benefit.The American Heart Association proposed to take sleep health as one of Life’s Essential 8 , blood lOur study was the first to investigate the relationship between TyG and sleep disorders, and the positive relationship has been observed. In this study, the sleep disorders includes several kinds of sleep problems, which could largely reflect people's state of sleep. the findings would serve as a reminder to the public to pay more attention to sleep health.This study provides a foundation for future multi-centre cohort studies on sleep disorders and TyG index.Previous studies showed insulin resistance were associated with sleep disorders , which mAfter adjusting for case complexity, a high TyG index was associated with higher odds of individuals with sleep disorders in the general population. Insulin resistance did not fully explain the findings.Our finding suggests that the TyG index may be an independent predictor of the development of sleep disorders.Additional file 1:e_table.1. Association of triglyceride-glucose index (TyG) with study outcomes, stratified by age.Additional file 2:e_table.2. Association of triglyceride-glucose index (TyG) with study outcomes, stratified by gender.Additional file 3:e_table.3. Association of triglyceride-glucose index (TyG) with study outcomes, stratified by raceAdditional file 4:e_table.4. Association of triglyceride-glucose index (TyG) with study outcomes


To investigate texture analysis (TA) based on apparent diffusion coefficient (ADC) map in predicting acute ischemic stroke (AIS) prognosis and discriminating TA features in stroke subtypes.This retrospective study included patients with AIS between January 2018 and April 2021. The patients were assigned to the favorable [modified Rankin Scale (mRS) score ≤ 2] and unfavorable (mRS score > 2) outcome groups. All patients underwent stroke subtyping according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. The TA features were extracted from infarction lesions on the ADC map. The demographic characteristics, clinical characteristics, and texture features were used to construct prediction models with recurrent neural network (RNN). The receiver operating characteristic (ROC) curves were implemented to evaluate the performance of the predictive models.p < 0.05). The AUC of combined prediction models for LAA and SAO subtypes was 0.80 and 0.81.A total of 1,003 patients  with AIS having documented the 90-day mRS score were identified, including 840 with favorable outcomes. In the validation set, the area under the curve (AUC) of the predictive model using only clinical characteristics achieved an AUC of 0.56, texture model 0.77, the model combining both clinical and texture features showed better with an AUC of 0.78. The texture feature profiles differed between large artery atherosclerosis (LAA) and small artery occlusion (SAO) subtypes (all Texture analysis based on ADC map could be useful as an adjunctive tool for predicting ischemic stroke prognosis. Stroke remains the second-leading cause of death and the third-leading cause of death and disability combined globally . The burTexture analysis (TA) is an effective quantitative image analysis tool to explore the microstructural changes that cannot be explored by humans visually. TA defines the measure of voxel intensities, voxel inter-relationships, and the gray-level patterns in the image. TA has been successfully used for characterizing multiple sclerosis , small vDiffusion-weighted imaging (DWI) is the most important and commonly used part of routine clinical stroke neuroimaging protocols as it facilitates the identification of stroke lesions. The apparent diffusion coefficient (ADC) yielded by DWI is sensitive to the initial cell swelling of a cytotoxic edema. ADC maps have been found to reveal the early indications and progression of cerebral ischemic infarction . Each voWe hypothesized that the ADC-based texture features might differ between patients with AIS having favorable and unfavorable clinical outcomes. Thus, this study aimed to explore the role of texture features in predicting AIS prognosis. We further investigated the characteristics difference of texture features in different stroke subtypes.n = 21), traumatic brain injury (n = 7), previous neurological or psychiatric disorder (n = 163), severe MRI artifacts (n = 17), contradiction to MR examination (n = 9), feature extraction failure (n = 80), or loss to follow-up (n = 280). The flowchart is shown in Between January 2018 and April 2021, all participants, aged >18 years, presenting to our stroke center with signs and symptoms of AIS were enrolled in this retrospective study. The study had approval from the institutional ethics committee of our hospital . Patients with confirmed acute DWI lesions on brain MRI scans performed within 72 h of symptom onset were included in this analysis. Of 1,580 participants, we excluded participants with cerebral hemorrhage  score, antecedent hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, tobacco or alcohol use, low-density lipoprotein cholesterol (LDL-C), and discharge medications were abstracted from the medical record. The AIS subtypes were assigned according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification .Patients or their caregivers were interviewed in person or by telephone at 90 days after stroke to assess the functional outcomes using the modified Rankin Scale (mRS) score. The patients were assigned to the favorable (mRS score ≤ 2) and unfavorable (mRS score > 2) outcome groups .2, b values = 0 and 1,000 s/mm2, and matrix = 96 × 96. The scan parameters for the 3.0-T scanner were axial DWI based on the SSEPI sequence, with TR/TE = 2,800 ms/75.4 ms, slice thickness/gap = 5 mm/1.5 mm, FOV = 230 × 220 mm2, b values = 0 and 1,000 s/mm2, and matrix = 128 × 128.All MRI examinations were performed on a 1.5-T MRI scanner  or a 3.0-T MRI scanner . The scan parameters for the 1.5-T scanner were axial DWI based on a single-shot echo planar imaging (SSEPI) sequence, with repetition time (TR)/echo time (TE) = 3,203 ms/83.9 ms, slice thickness/gap = 5 mm/1.5 mm, FOV = 240 × 240 mmA total of 100 patients were randomly selected for manual segmentation by ITK-SNAP 3.8.Texture features extraction were performed on the MATLAB 2019a . Based on the extraction results of texture features and clinical characteristics, we use sparse representation for feature selection to reduce the redundant information in features and improve classification model accuracy. Specifically, we use sample features for sparse representation in sample labeling, so the highest label correlated feature subsets are selected. Meanwhile, the sparsity constraints on the model effectively removed the correlation and redundancy in the features of the feature subsets. Following is the model: The following features were extracted: eight gray-level co-occurrence matrix (GLCM) features, thirteen gray-level run-length matrix (GLRLM) features, thirteen gray-level size zone matrix (GLSZM) features, and five neighborhood gray-tone difference matrix (NGTDM) features. Additional information on TA features is provided in Based on the selected feature subsets, we established our classification prediction models based on recurrent neural network (RNN) . WeighteThe patients were randomly divided into the training and validation sets by stratified sampling. Due to the imbalance of sample number in our study, we used under-sampling method to build the dataset. The unfavorable-outcome group was randomly divided into training and validation sets at the ratio of 2:1. Then, the patients in the favorable-outcome group were randomly assorted into the training set 1.5 times the number in the training set with an unfavorable outcome. The remaining patients were included in the validation set to validate the reliability and robustness of the models.t-test or Mann–Whitney U test for continuous variables and the chi-square for categorical dependent variables between favorable-outcome and unfavorable-outcome groups, as appropriate. The receiver operating characteristic (ROC) curve was generated to evaluate the performances of the predictive models. All statistical analyses were carried out using SPSS . All the reported p values were based on the two-tailed tests, and p values less than 0.05 indicated a statistically significant difference.The continuous variables with normal distribution were reported as mean ± standard deviation, non-normally distributed variables as median (interquartile range), and classification variables as frequency (%). We used the independent-samples We included 1,003 patients with AIS having a 90-day mRS score available for this analysis. Of these, 682 (68.0%) were men, and the mean age was 65.90 years (SD 12.44 years). p < 0.001). The stroke subtype showed a significant difference between the two groups (p = 0.012). The patients with unfavorable outcomes were less likely to receive antiplatelet therapy after discharge (p = 0.030)  showed functional independence (mRS ≤ 2) at 90 days. Further, 163 participants (16.3%) had unfavorable outcomes . Strokes with favorable outcomes had a lower admission NIHSS score and smaller stroke volume (both = 0.030) .Eleven texture features, including five GLRLM features, five GLSZM features, and one NGTDM feature demonstrated statistically significant differences. The information of the 11 features is provided in Based on RNN, all the clinical models and texture models were constructed, the clinical characteristics and texture feature selection was shown in the p < 0.001). The proportion of statin after discharge in the unfavorable-outcome group was higher than that in the favorable group (p = 0.045).A summary of the demographic and clinical features of the patients with large artery atherosclerosis (LAA) having different clinical outcomes is shown in Thirteen texture features, including five GLRLM features, seven GLSZM features, and one NGTDM feature demonstrated statistically significant differences. The information of the 13 features is provided in The clinical model, including stroke volume, NIHSS score, discharge statin, discharge anticoagulant and LDL-C, exhibited an AUC of 0.58 with accuracy, sensitivity and specificity of 0.61, 0.55 and 0.61, respectively, in the validation cohort. The effectiveness of clinical model was lower than the texture model (AUC: 0.80) and the combined model (AUC: 0.80) .A total of 298 patients, including 262 with favorable outcomes and 36 with unfavorable outcomes, were classified into the small artery occlusion (SAO) type. No significant differences were found in demographic and clinical data .p = 0.022) and contrast (p = 0.022) were higher in the unfavorable-outcome group, whereas homogeneity was higher in the favorable-outcome group (p = 0.048) (Three GLCM texture features were significantly different in these two outcome groups. GLCM dissimilarity (= 0.048) .In the validation set, the AUC of clinical-texture model was 0.81, and the accuracy, sensitivity and specificity were 0.84, 0.75, and 0.84, respectively. The texture model showed an AUC of 0.74 with accuracy, sensitivity and specificity of 0.84, 0.67, and 0.85, while the AUC of clinical model was 0.64, and the accuracy, sensitivity and specificity were 0.79, 0.50, and 0.81 .In this study, we developed new models that could predict 90-day functional outcomes in patients with AIS. Our findings indicated that the second-order texture characteristics reflected the heterogeneity of stroke lesions. The predictive models of LAA and SAO stroke outcomes had moderate sensitivity and specificity. We demonstrated that the texture feature profiles differed between LAA and SAO subtypes.TA features proved to be efficient in describing the voxel inter-relationships and the gray-level distributions within images, allowing the quantification of the intrinsic heterogeneity invisible to the naked eye. We extracted the second-order features of texture features, which consisted of GLCM, GLRLM, GLSZM, and NGTDM. The GLCM features quantified the relationship between gray levels by counting the pairs with predefined distance and direction that had the same distribution of gray-level values . The GLRThe pathophysiological mechanisms underlying ischemic stroke termed the ischemic cascade, which consisted of the formation of reactive oxygen species, release of glutamate, accumulation of intracellular calcium, and induction of inflammatory processes. A previous study showed that the texture features based on DWI were closely related to edema after cerebral infarction . ElectriA recent study found that the radiomics signatures based on ADC maps were associated with unfavorable outcomes and served as a risk factor . The radIn a previous study, several texture features, principally the GLRLM features, differed between patients with AIS undergoing mechanical thrombectomy with good versus bad outcomes . AlthougAs expected, a larger volume of infarct lesions and increasing stroke severity in terms of the admission NIHSS score were associated with unfavorable outcomes in both the entire cohort and the LAA subtype. This finding was in accordance with the previous literature . The reaThis study had several limitations. First, the retrospective data might lead to selection bias. Second, the clinical symptoms of patients in this cohort were relatively mild, and a large proportion of patients had a good prognosis. We used deep learning algorithms to tackle the imbalance of data distribution and hence improve the performance of our predictive models. Third, considering our small study population, we did not analyze the textures of the other three subtypes of TOAST. Fourth, we included patients with AIS, however, we did not analyze whether different therapies vary different texture features. Further research is still needed in the future. Fifth, other relevant factors were not accounted for, such as hemorrhagic transformation or white matter hyperintensities, which were previously linked to texture features , 41. FutIn conclusion, the TA base on ADC maps showed potential value in predicting the prognosis of patients with AIS. TA features differed in LAA and SAO stroke subtypes. Combined with clinical characteristics, TA could be used to improve the efficacy for predicting the functional outcomes in AIS.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the institutional ethics committee of Minhang Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.HW: conceptualization. YS: methodology and writing – original draft preparation. BS: formal analysis. JZ: investigation. YZ: project administration. HW: writing – review and editing. YS and HW: funding acquisition. All authors contributed to the article and approved the submitted version.This research was funded by the Natural Science Foundation of Minhang Hospital, Fudan University (2022MHBJ04 and 2022MHPY04), Science and Technology Commission of Minhang District, Shanghai (021MHZ051), and Health Commission of Minhang District, Shanghai (mwyjyx17).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.https://www.frontiersin.org/articles/10.3389/fneur.2023.1132318/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.Click here for additional data file.


Multiple cerebral infarcts are usually secondary to cardiogenic embolism, particularly through atrial fibrillation (AF). The three-territory sign (TTS) is an imaging marker that reflects multiple cerebral lesions involving three vascular territories measured by diffusion-weighted imaging (DWI), and the most common etiology is an underlying malignancy. Recent studies have shown that TTS is six times more frequently observed in acute ischemic stroke (AIS) patients with malignancy than in those with AF-related AIS. However, the relevance of TTS to the prognosis of IS patients with malignancy remains unclear.Over a 5-year period (May 2016 to 31 June 2021), AIS admissions with DWI were identified from the First Affiliated Hospital of Xi’an Jiaotong University. Patients were divided into two groups according to whether they had malignancy or AF, resulting in a total of 80 patients with known malignancy  and 92 patients with AF (AF group). All DWI images were reviewed to determine the territory lesion count. Demographic, clinical, and laboratory data, together with radiographic examination data and modified Rankin Scale (mRS) score within a year, were collected. The main outcome was the association between TTS and the prognosis of AIS patients with malignancy, analyzed by a multivariate logistic regression model.A total of 172 patients met the selection criteria, including 17 (21.3%) patients in the malignancy group and 8 (8.7%) patients in the AF group with TTS. Age and sex distributions were similar for AIS patients of malignancy and AF. The TTS was 2.4 times more likely to be observed in AIS patients with malignancy compared to AF-related IS patients. The univariate analysis showed that hypertension , D-dimer , fibrin degradation product , and lactate dehydrogenase  were the risk factors for the high mortality rate. Multivariate analysis showed that TTS was the independent risk factor for mortality in AIS patients with malignancy .TTS was more frequently observed in AIS patients with malignancy than AF-related AIS and substantially related to high poor outcome (mRS > 2) in AIS patients with malignancy, indicating diagnostic and prognostic value in malignancy-associated hypercoagulation stroke. MAIS alMagnetic resonance imaging (MRI) using diffusion-weighted imaging facilitates the identification of ischemic infarction in malignancy as small infarctions that involve multiple vascular territories. Moreover, the number of territories involved is associated with the risk of disease , 8. ReceTherefore, this study aimed to assess the clinical and imaging features of AIS patients with malignancy, investigate the incidence of TTS in AIS patients with malignancy compared to those with AF-related AIS, and explore the association between TTS and the prognoses of AIS patients with malignancy.2.2.1.This retrospective study collected anonymized clinical data of consecutively admitted patients with a primary diagnosis of all AIS from the Biobank of The First Affiliated Hospital of Xi’an Jiaotong University from 1 May 2016 through 31 June 2021. AIS patients (aged ≥18 years) meeting the following criteria were included: (1) diagnosis meeting the AIS criteria of the 2018 AHA/ACA guidelines ; (2) hav2.2.The baseline demographic information of the patients was abstracted from the electronic medical records, including sex, age, risk factors for atherosclerosis, type of malignancy, and laboratory data. The included patients had adequate clinical evaluations, which were as follows: vital sign monitoring, brain/chest CT and brain MRI, ultra-sound of cervical vessels, 24-h ECG, echocardiography, intravenous ultrasound, and laboratory tests (routine hematology and biochemistry). The modified Rankin scale (mRS) within a year of follow-up was determined by the patients’ medical records from outpatient clinics or by telephone. The primary outcome was the association between TTS and prognosis of AIS patients with malignancy, and the second outcome was the incidence of TTS in AIS patients with malignancy.2.3.All participants were scanned using the same 3.0-T Siemens Skyra scanner  with a completed neuroradiology report. We analyzed the DWI imaging features of all participants and recorded the vascular territories involved. For imaging, three ischemic stroke MRI-DWI patterns were identified in both groups as follows , 10: One2.4.2, or Fisher tests to establish differences between the clinical groups. One-way analysis of variance was used to make the mean comparisons between the groups. To examine the correlation between TTS and prognosis, a binary logistic regression model was used to calculate the adjusted odds ratio (OR) and 95% confidence intervals (CIs). Multivariate logistic regression analysis was also applied to identify independent risk factors for prognosis. A p < 0.05 was considered statistically significant. All statistical analysis was performed by the SPSS version 26.0 .The data are expressed as mean ± standard deviation (SD) for continuous variables and as percentages for categorical variables. We performed statistical assessments between the groups using t-test, χ3.3.1.In the study, 9,160 patients were diagnosed with IS, and 550 patients were enrolled according to the inclusion and exclusion criteria. According to the TOAST classification criteria , 92 patiThe three most common malignancies were colorectal, mammary, and lung in origin . The malp < 0.05). Low-density lipoprotein (LDL) and eosinophils values were higher in the malignancy group than in the AF group, while red blood cell (RBC) and hemoglobin (Hb) counts were lower (p < 0.05). In the malignancy group, MRI assessment showed multiple scattered lesions. Patients with two- and three-territory signs accounted for 49 (28.5%) and 25 (14.5%), respectively. Age and sex distributions were similar for the malignancy group and the AF group . Patient3.2.p < 0.001).The distribution of mRS scores of the two groups is shown in n = 92), 58 (63.0%) patients had a 1-territory stroke pattern, 26 (28.3%) had a 2-territory pattern, and only 8 (8.7%) had the TTS. The overall association between the number of territories and the diagnostic group was significant, and there was also a significant difference in the number of patients with the TTS (p = 0.029). Furthermore, the TTS was 2.4 times more likely to be present in the malignancy group than in the AF group.Of the patients within the malignancy group, 40 (50.0%) patients had a 1-territory infarct pattern, and 23 (28.7%) patients had a 2-territory pattern. The TTS was observed in 17 patients (21.3%), representing one-fifth of patients with malignancy. In the AF group , while Model 2 had an OR of 6.866 . The results of the multivariate analysis are shown in In the binary logistic regression model analysis, TTS was statistically significantly associated with mortality in AIS patients with malignancy  in AIS patients with malignancy. Furthermore, studies have shown that acute infarction in ≥2 territories was observed in 84% of patients with malignancy who also had D-dimer levels >3 μg/ml (p < 0.001). Further studies involving larger patient numbers are needed to clarify this finding. An investigation for underlying malignancy is valuable in the presence of the TTS, especially if echocardiography and ambulatory ECG do not demonstrate valvular disease, intracardiac thrombus, or AF. Furthermore, the TTS may offer important diagnostic information to facilitate the identification of other under-recognized causes of stroke.It has been reported that the risk of mortality associated with AIS was higher in patients with malignant tumors than those without such tumors . This is>3 μg/ml . In the >3 μg/ml , CRP 16p < 0.001>3 μg/ml , or unde>3 μg/ml . In the The limitations of our study include its small sample size and being a single-center retrospective study. Because the sample size was small, other characteristics of AIS patients with malignancy could not be adequately evaluated, which may lead to a failure to obtain accurate results. Furthermore, the clinical data available from the national biobank studies are incomplete, leading to an absence of many useful markers (constituting an information bias), such as cancer stage and treatment given.5.In AIS patients with malignancy, imaging is characterized by the TTS, which is observed more frequently than in AF-related AIS. The TTS is the independent prognostic risk factor of poor outcome (mRS > 2) in AIS patients with malignancy. In patients with TTS of undetermined etiology, it is valuable to investigate the presence of an underlying malignancy.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving humans were approved by the First Affiliated Hospital of Xi'an Jiaotong University (No. XJTU1AF2021LSK-117). The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from primarily isolates as part of our previous study for which ethical approval was obtained. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements.YC: Formal analysis, Writing – original draft, Writing – review & editing. YN: Formal analysis, Writing – original draft, Writing – review & editing. YZ: Data curation, Formal analysis, Methodology, Writing – original draft. XC: Data curation, Formal analysis, Investigation, Methodology, Writing – original draft. HL: Data curation, Methodology, Writing – review & editing. TS: Conceptualization, Investigation, Writing – original draft, Writing – review & editing.


To build prediction models with radiomics features, clinical/conventional radiographic signs and combined scores for the discrimination of micropapillary or solid subtypes (high-risk subtypes) of lung adenocarcinoma.This retrospective study enrolled 351 patients with and without high-risk subtypes. Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation was performed to determine the optimal features of radiomics model. Missing clinical data were imputed by Multiple Imputation with Chain Equations (MICE). Clinical model with radiographic signs was built and scores of both models were integrated to establish combined model. Receiver operating characteristics (ROC) curves, area under ROC curves and decision curve analysis (DCA) were plotted to evaluate the model performance and clinical application.Stratified splitting allocated 246 patients into training set. MICE for missing values obtained complete and unbiased data for the following analysis. Ninety radiomic features and four clinical/conventional radiographic signs were used to predict the high-risk subtypes. The radiomic model, clinical model and combined model achieved AUCs of 0.863 (95%CI: 0.817–0.909), 0.771 (95%CI: 0.713–0.713) and 0.872 (95%CI: 0.829–0.916) in the training set, and 0.849 (95%CI: 0.774–0.924), 0.778 (95%CI: 0.687–0.868) and 0.853 (95%CI: 0.782–0.925) in the test set. Decision curve showed that the radiomic and combined models were more clinically useful when the threshold reached 37.5%.Radiomics features could facilitate the prediction of subtypes of lung adenocarcinoma. A simple combination of radiomics and clinical scores generated a robust model with high performance for the discrimination of micropapillary or solid subtype of lung adenocarcinoma.The online version contains supplementary material available at 10.1186/s12931-023-02592-2. Lung adenocarcinoma is the most common type of lung cancer . AccordiSurgery for early-stage lung cancer is resecting “as less lung tissue as possible”. For small-sized, peripheral lung cancer, researchers recommend segmentectomy or wedge resection instead of lobectomy as standard surgical treatment , 9. HoweRadiomics is emerging as a novel quantitative analysis with abundant features extracted from CT images and served as “big data” in further machine learning . It has Thus, in our study, we aimed to establish a robust prediction model on the presence of micropapillary or solid pattern of lung adenocarcinoma based on the radiomics features. Moreover, we will also compare the prediction value of radiomics model with conventional clinical and radiographic variables.This study was approved by the institutional ethnic committee and informed consent was waived due to the retrospective nature. Study procedure is demonstrated by the flowchart Fig. .Patients diagnosed with lung adenocarcinoma from January 1 2018 to December 31 2018 were recruited firstly. Then the patients were selected according to the inclusion criteria as follows: (1) patients receiving surgical resection of the tumour; (2) pathological report including subtypes of adenocarcinoma; (3) patients with major clinical data; (4) patients CT images taken 2 weeks before surgery; (5) availability of CT images in DICOM. The exclusion criteria were as follows: (1) malignant tumour other than lung adenocarcinoma; (2) incomplete clinical and radiological data. In addition, to balance the sample size of high-risk group and low-risk group, patients of low-risk group were enrolled consequently until the sample size reach the high-risk group. We met unknow problems when extracting radiomics features from 3 patients in the low-risk group . Finally, 351 patients were enrolled in this study. Patients were randomly allocated to the training set or test set. This was perfomed by the “createDataPartition” function in R package “caret”. This function creates indices of the training and test set according to the set ratio. The recruiting process was shown in Fig. CT scanners used in the study were: SIEMENS SOMATOM Definition Flash, SIEMENS Sensation Open, GE MEDICAL SYSTEMS LightSpeed Pro 32, Philips iCT 256. During scanning, patients were instructed to hold their breath until the scanning finished. The scanning parameters were as follows: tube voltage 120 kV, tube current automatic, matrix 512*512, slice thickness 1, 1.25 or 1.5 mm. Contract enhanced chest CT was taken with a bolus dose of (70–90 mL) nonionic contrast agent iohexol or ioversol (300 mg·I/mL) injecting through the cubital vein by a high-pressure syringe with 20 s scan delay. The scanning range from the inlet of the thoracic cavity to the base of the lungs.CT images were analyzed by a thoracic radiologist and a thoracic surgeon (NZ and ZW) with 8 and 10 years of experience respectively. Both doctors were blinded to the pathological report of the patients. Report on the CT images were performed independently by both doctors. Any discrepancies on the description and measurement of the lesion on the CT images were resolved through discussion. The following conventional features were reported: (1) nodule type: pure-ground glass opacity, sub-solid opacity with CTR (consolidation tumor ratio) less than 50%, sub-solid opacity with CTR (consolidation tumor ratio) more than 50%, pure solid nodule; (2) lobulated sign presented; (3) spiculated sign presented; (4) pleural traction presented; (5) bronchograms presented; (6) vessel retraction presented; (7) vacuole sign presented; (8) tumour edge smooth or blur; (9) adjacent to pleura ; (10) maximum tumour diameter.The region of interest (ROI) was delineated by the two doctors independently without knowing the information of pathological results. Lung window was set to 1200 HU width and − 600 HU in level, while mediastinal window was 350 HU in width and 40 HU in level. Syngo.via platform  was used for the ROI segmentation and radiomics features extraction. A built-in PyRadiomics based module in Syngo.via was used to extract the radiomics features. Extraction parameters following the PyRadimics package were also set before extraction to normalize the image heterogeneity: ResampledVoxelSize = 1*1*1, ResampledPixelSpacing = [Electronic clinical records were reviewed, and characteristics relevant to the study were collected, including age, sex, smoking history, family cancer history, serum biomarker . These clinical variables were commonly selected for cancer risk factor analysis or prediction models based on researchers experience.Missing data in serum biomarkers were analyzed and imputed by MICE package in R. Multiple Imputation by Chained Equations (MICE) is a stable, informative method that handle the missing data. The method uses a series of iterable prediction model to impute the missing data. For continues data like serum biomarker, MICE use PMM (predictive mean matching to impute the missing data). PMM builds prediction models with existing data and then predicts a series of data in the “missing data column”. Then it chooses a “predicted data” in the “prediction column” which is nearest to the “missing ones”. Finally, the real data in the “missing column” whose position is the same with the “predicted data” is used to fill the missing place.Several steps of radiomics features dimension reduction was performed to get the most predictable features. First, all the patients were randomly split into training and test set by a ratio of 7:3. All data were standardized by the scaling parameters of training set. Observer 1 (ZW) delineated all the patients ROI and observer 2 (NZ) repeated 50 of randomly selected patients. The interobserver consistency of radiomics feature extraction was assessed and features with intraclass correlation coefficient (ICC) over 0.75 were kept. Student t test and Mann-Whitney U test was then performed for each feature, according to the normality Shapiro test results. Features of values significantly different in two groups were selected with P value set to 0.05. Next, Spearman correlation analysis and Pearson correlation analysis were performed for non-normally and normally distributed features. Features with correlation coefficients over 0.9 were removed. Afterwards, least absolute shrinkage and selection operator (LASSO) were applied to training cohorts, with 10 folds cross validation tuning the optimal lambda. The lambda was decided when the mean square error of the prediction model reached one standard error, also known as “lambda.1se”. LASSO regression is an effective method for features reduction in high dimension data like radiomics study, while “lambda.1se” balanced the prediction value and number of features. Radscore was calculated by the features and coefficients selected by LASSO regression.The radiomics and clinical model was established by logistic regression. As mentioned above, radiomics features selected by LASSO were used to build radiomics model. For clinical model, we performed univariate analysis first and clinical variables with P value less than 0.05 were included into multivariate logistics regression model to select the optimal clinical variables for logistics regression model. A cliscore was also calculated with this model for each patient. A combined dataset with radscore, cliscore and group labels was built for combined model construction using logistics regression. Logistic regression is one of a favorable algorithm in machine learning. Research compared logistic regression, random forest, and support vector machine classifiers in radiomics-based machine learning in different cancers. Logistic regression showed equivalent prediction values with others , 20. MorThe receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used as main methods to evaluate the performance of the three models. Other model evaluation indicators including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. DeLong test and Bland-Altman analysis were used to compare the ROC curves. Calibration curves were used to visualize the Hosmer-Lemeshow test for the logistic regression. Decision curves were used to evaluate the clinical significance of the models.All statistical analyses were performed using R . Major packages used in this study included ‘caret’ (version 6.0), ‘glmnet’ (version 4.1), ‘glm’ function in ‘stats’ (version 4.3.0), ‘pROC’ (version 1.18.4), ‘blandr’ (version 0.5.1), ‘tidyverse’ (version 2.0.0), ‘mice’ (version 3.16.0). Continuous variables were presented as mean ± standard deviation, while categorical variables were presented as count numbers. Shapiro test was used for the normality test. For varaibles normally distributed, Student t test was used to compare the statistical difference. Other variables were compared by Mann-Whitney U test. Significance level was set to 0.05, two sided.A total of 351 patients were included in this analysis. Among them, 246 were randomly split into training set and 105 in test set. Clinical and conventional radiographic characteristics of baseline between training and test set were shown in Table The missing value distribution in the lung cancer biomarker was shown in Fig. Out of the 246 patients in the training set, there were significantly more male in high-risk group than the low-risk group . Moreover, lesion size was larger in the high-risk group . Solid lesion is also the predominant type in high-risk group . Univariate analysis also showed that high-risk group had less signs of air bronchus , vessel in the lesion , and lobular . Furthermore, smoking history was much more often in high-risk group as well . In multivariate analysis, diameter max, type, air bronchus and lobular sign were shown to be significantly different between two groups. Full univariate and multivariate results were shown in Table After a series of preprocessing including interobserver analysis, Student t test, Mann-Whitney U test and correlation analysis, a total of 116 radiomics features were filtered from the overall 1226 features extracted from ROIs. Then LASSO regression with 10-fold cross validation was used for dimension reduction, with lambda set to one-standard-error of model mean square error (MSE). Ninety features were finally selected and radiomics prediction model was then established. Radscore was calculated by multiply the value of each feature with their coefficients. This process results were shown in Fig. Clinical prediction model was built with the four clinical-conventional radiographic characteristics by logistic regression , while clinical model also had acceptable prediction value with AUC of 0.778 95%CI: 0.687–0.868) in test set  and air bronchus, and they somehow mutually confirmed each other . TherefoMultiple imputation by chain equation is an advanced and widely accepted technique for missing data manipulating. The statistical theory is based on regression models, which is built from existing data and then predicts the missing values. Multiple imputation by chain equation is typically performed by MICE package in R . In thisLASSO regression is popular in dimension reduction and feature selection for “big data”. Almost every radiomics study adopted cross validation of LASSO regression as a main approach in the data processing. However, concerns have been raise that randomness exists in the cross validation, which lead to inconsistent optimal values of lambda . During This study, nevertheless, has certain limitations. First, this was a retrospective study from a single centre, with inevitable selection bias and other confounding factors. A multi-centre prospective study with larger population is required in further analysis. Second, as a single centre study, there was no external validation set recruited. The model would be more convincible if validated in independent external validation set. Third, study data was consisted of radiomic features extracted from various scanners. Though 1*1*1 mm voxel isotropic resampling was applied, a single scanner data analysis would be conducted in future investigation.In conclusion, our study revealed that radiomics features by themselves could facilitate the prediction of subtypes of lung adenocarcinoma. Additionally, clinical missing data could be imputed by MICE and then be used to calculate clinical scores, forming a simple but discriminative dataset with radiomic scores. Radiomics and combined models had reasonable prediction value for micropapillary or solid subtype of lung adenocarcinoma.Below is the link to the electronic supplementary material.Supplementary Material 1