Citations

Abstract INTRODUCTION M0 images were missing in Siemens ASL data in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, prohibiting cerebral blood flow (CBF) quantification. METHODS A conditional latent diffusion model was trained and evaluated on in‐house datasets, then applied to the Siemens data in ADNI‐3. Regional CBF differences by Alzheimer's disease (AD) stages, their accuracy for AD classification, and CBF trajectory slopes were compared between generated data (Siemens) and acquired data (General Electric). RESULTS The diffusion model generated M0 images with high fidelity (SSIM = 0.918 ± 0.023, PSNR = 31.361 ± 2.537) and minimal CBF bias (mean difference is 0.21 ± 1.58 mL/100 g/min). Both generated and acquired CBF showed similar spatial patterns and decreasing trends with AD progression in specific AD‐related regions. Generated CBF also improved accuracy in classifying AD stages compared to qualitative perfusion images. CONCLUSION This study shows the potential of diffusion models for imputing missing modalities in large‐scale studies exploring the use of ASL as a biomarker of AD. Highlights Using latent diffusion model, we can generate M0 image from control image in arterial spin labeling (ASL) with high fidelity. The generated M0 can be used for cerebral blood flow (CBF) quantification in Alzheimer's Disease Neuroimaging Initiative dataset. The performance of classification between Alzheimer's disease (AD) patients and cognitive normal people is better when using generated CBF maps than using non‐quantitative perfusion images. ASL CBF decreases with AD progression in key AD‐related brain regions.

Abstract Background Carbon ion radiotherapy (CIRT), characterized by its Bragg peak and a reduced lateral scattering compared to proton radiotherapy (PT), offers excellent dose conformity in radiation treatment. Meanwhile, compared to PT, CIRT causes more complex and severe DNA damage in tumor cells, which results in a higher relative biological effectiveness (RBE), making it particularly advantageous in treating radioresistant and hypoxia tissues than conventional radiotherapy. However, CIRT's high RBE and the nuclear fragmentation dose tail outside the target presents challenges in sparing organ at risk (OARs). Combining PT and CIRT offers a potential hybrid modality that leverages the biological effectiveness of carbon ions while minimizing normal tissue toxicity with high biological damage. Purpose Despite the potential of combining PT and CIRT, balancing their respective advantages while mitigating disadvantages remains a significant challenge. This study aims to develop an optimized treatment approach that automatically adjusts the relative contributions of protons and carbon ions, improving target dose conformity while minimizing biological impact on OARs. Methods We propose a biological optimization framework for multi‐modality combining PT and CIRT (CCIPRT). The biological dose is modeled as the product of the physical dose and RBE. Through iterative Jacobian‐based linearization, the biological dose of carbon ion is expressed in a linear model, enabling the formulation of a linear least‐square objective. The biological dose of proton is formulated as a linear model using the physical dose and dose‐averaged linear energy transfer (LET). The joint optimization problem is then solved using iterative convex relaxation and the alternating direction method of multipliers. For comparison, single‐modality PT and CIRT were also implemented. Results When the target dose of CCIPRT is prescribed in terms of the physical dose, compared to PT, CCIPRT increased the mean biological dose in the target by 37.7%, 29.6%, and 31.1% for brain, lung, and abdomen, respectively; compared to CIRT, CCIPRT reduced the biological dose in CTV1cm (ring surrounding CTV with 1 cm width) by 47.2%, 32.3%, and 40.4% for brain, lung, and abdomen, respectively. When the target dose of CCIPRT is prescribed in terms of the biological dose, compared to PT, CCIPRT achieved higher conformity index (CCIPRT: 0.96 and 0.97; PT: 0.93 and 0.96 for brain and liver cases, respectively) and reduced the dose in CTV1cm by 9.5% and 7.0% for brain and liver cases, respectively; compared to CIRT, CCIPRT enhanced healthy tissue sparing, reducing the dose to the body by 7.5% and 9.2% for brain and liver cases, respectively. Conclusions A novel multi‐modality CCIPRT treatment planning is developed with demonstrated superior performance over single‐modality PT or CIRT, with enhanced biological effectiveness and dose conformity compared to PT and reduced OAR dose compared to CIRT.

ABSTRACT Purpose Abnormal restrictions at myofascial interfaces are a key factor in chronic low back pain (CLBP) with myofascial pain syndrome (MPS), but no established imaging method exists for quantitative assessment. This pilot study evaluated the clinical feasibility of MR elastography (MRE)‐based slip interface imaging (SII) for visualizing myofascial mobility in CLBP‐MPS patients versus age−/sex‐/BMI‐matched healthy participants. A new SII biomarker, maximal normalized displacement discontinuity (), was introduced, and the previously developed normalized octahedral shear strain (NOSS) map was used for comparison. Preliminary assessments of vibration‐frequency effects, repeatability, and group differences in inter‐muscular mobility were conducted. Methods MRE was conducted at 30, 60, and 90 Hz to compare with NOSS for visualizing inter‐muscular slip interfaces at the quadratus lumborum‐erector spinae (QL‐ES) and erector spinae‐multifidus (ES‐M) muscle boundaries at L3‐L4. Repeatability of and NOSS was assessed at 30 Hz (identified as the best‐performing frequency) using within‐subject coefficients of variation and a linear mixed‐effects model from within‐ and between‐day scans. Clinical feasibility was then assessed via Wilcoxon rank‐sum tests in six CLBP‐MPS patients and matched controls. Results at 30 Hz exhibited superior delineation of slip interfaces compared to higher frequencies and NOSS. demonstrated significantly lower variation and better repeatability than NOSS. Healthy participants showed continuous, well‐defined slip interfaces, whereas CLBP‐MPS patients displayed disrupted interfaces with significant mobility reduction at L4 ES‐M. Conclusion SII with lower vibration frequency and map enhances visualization of lower back myofascial mobility and shows potential for assessing differences between healthy individuals and CLBP‐MPS patients.

Normothermic machine perfusion (NMP) enables preservation and functional assessment of liver allografts, improving outcomes, particularly in marginal organs. However, the TransMedics Organ Care System (OCS) permits only single hepatic artery (HA) cannulation, limiting its use in grafts with variant arterial anatomy. Arterial reconstruction before NMP may overcome this limitation and expand the pool of grafts eligible for perfusion. We conducted a retrospective single-center cohort study of adult liver transplants utilizing OCS from January 2022 to September 2024. Allografts with variant hepatic artery anatomy requiring arterial reconstruction before NMP initiation were identified. Postoperative outcomes, including vascular and biliary complications, were compared between reconstructed and non-reconstructed grafts. Among 541 OCS-preserved grafts, 74 (13.7%) underwent arterial reconstruction. Compared with non-reconstructed grafts, reconstructed grafts had longer cross-clamp to cannulation time (2.8 vs. 2.4 h, p <0.001), but similar rates of early allograft dysfunction (23.0% vs. 20.8%, p =0.65), ischemic cholangiopathy (4.1% vs. 4.1%, p =1.00), and primary nonfunction (0.0% vs. 0.4%, p =1.00). Early (2.7% vs. 0.2%, p =0.05) and late hepatic artery thrombosis (HAT) (4.1% vs. 2.1%, p =0.40) were infrequent and not significantly different between non-reconstructed and reconstructed groups, respectively. Hepatic artery stenosis occurred more often in reconstructed grafts (12.2% vs. 4.1%, p =0.008), though most cases were managed with interventional radiology or surgical revision. Only one reconstructed graft required retransplantation due to vascular complications. Arterial reconstruction before NMP is safe and feasible, enabling successful perfusion and transplantation of liver allografts with variant HA anatomy. These findings support the broader application of NMP in anatomically complex donor livers.

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.

Comparative analysis of fibrin sealant and recombinant thrombin hydrogels reveals distinct microarchitectures and cellular responses, emphasizing recombinant thrombin’s potential to enhance cellular activity and enable vesicle delivery.

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.

Abstract Objective To examine the effectiveness of treatment strategies for medication‐overuse headache (MOH) in children and adolescents. Background There are no guidelines for the treatment of adult or pediatric patients with MOH. However, research pertaining to MOH in adults is far outpacing research in children and adolescents. Methods A systematic review of evidence on treatment for MOH in children and adolescents was performed via PubMed, Embase, Web of Science, PsycINFO, and Cochrane from database inception to October 2024 for articles with the subject headings and keywords for MOH and pediatric, children, and/or adolescent. Inclusion criteria were: (i) randomized controlled trials and retrospective and prospective observational studies, (ii) children and adolescents aged <18 years with chronic headaches and with medication overuse (MO) or MOH, and (iii) interventions addressing MO or MOH, including pharmacologic and behavioral interventions. At least two independent reviewers screened citations and full‐text articles independently. Results A total of 16 studies (one randomized control trial, six prospective observational studies and nine retrospective observational studies) were identified as meeting final inclusion criteria, resulting in 7978 total participants with a subset of those having MO, MOH or probable MOH. Participants ranged in mean age from 10 to 14.7 years, with 7.1%–46.2% male participants. All the studies recruited patients from an outpatient setting. Interventions used in the studies included withdrawal of the overused acute medication, initiation of preventive medication, patient education, physiotherapy and psychological treatment, and motivational interviewing. Multimodal therapy was studied more than single therapeutic intervention. There was vast heterogeneity across the studies, including study design, diagnostic criteria, intervention type, and outcomes. Conclusion From the data available, there does not seem to be a singular superior treatment approach. Accordingly, the most appropriate treatment modality will need to be tailored to the patient and their caregivers. Further research is required regarding management of MOH in children and adolescents.

604 Background: The addition of OFS to standard endocrine therapy (ET) improves iDFS for preM women with early-stage hormone receptor positive (HR+) breast cancer (BC). Incomplete OFS occurs in a subset of women, the long-term clinical significance of which is unclear. This study evaluates local sE2 levels in preM women receiving OFS with an oral SERD in the neoadjuvant (NA) setting. Methods: The EOP is a I-SPY2 sub-study investigating NA endocrine-based strategies in pts with HR+ HER2- Stage 2/3 BC predicted to have lower benefit from chemotherapy. Pts were randomized to oral amcenestrant 200 mg/d, alone or in combination with either letrozole 2.5 mg/d or abemaciclib 150 mg bid. Additional pts were randomized to a standard of care (SOC) arm consisting of an aromatase inhibitor. All PreM pts received OFS with monthly GnRHa up to 2 wks prior to C1D1 of study therapy. Pts were treated for 6 months prior to surgery. sE2 levels were collected locally prior to each GnRHa injection. Tumor Ki67 was assessed at 3 weeks and surgery, and associated with sE2 level. Statistical significance was determined using a two-sided Student’s t-test and a significance level 0.05. Results: Between 5/2021-8/2022, 74 pts were enrolled to an amcenestrant containing arm, 40 of whom were preM. 38/40 pts had at least one local sE2 level measured in follow up. Of these 38 pts (median age 45 years), 37 suppressed sE2 into the postmenopausal (postM) range at one or more follow-up timepoints. Of the 37 pts that completely suppressed into the postM range, 6 pts had sE2 levels rebound into the preM range (mean 319 pg/mL, range 20-848 pg/mL) with peak sE2 levels occurring at a median of 12 weeks from C1D1. One pt never suppressed to the postM range (peak sE2 1227 pg/mL) and was found to have an ovarian cyst after 3 months on amcenestrant, requiring surgery. One additional pt had multiple ovarian cysts (sE2 84 pg/mL). Median age of the 7 pts who had sE2 rebound was 43 years. There was no significant difference in Ki67 at 3 weeks and surgery between pts whose sE2 levels remained suppressed (median Ki67 2.0%) compared to those whose estradiol rebounded into the preM range or never suppressed (median Ki67 1.5%). In the 5 pts whose sE2 rebounded to > 200 pg/mL, all pts had tumor Ki67 < 10% at 3 weeks and surgery. Between 12/2022 and 8/2023, 20 pts were enrolled to AI +/- OFS and 11 pts were preM. Of the 11 preM pts, all pts suppressed sE2 to the postM range. No SOC patients had sE2 levels rebound into the preM range. Conclusions: In this study of neoadjuvant oral SERD with monthly OFS, 7/38 (18.4%) preM pts had sE2 levels remain or rebound into the preM range. sE2 levels did not appear to impact Ki67 suppression on NA ET. Work up for ovarian cysts should be considered in pts with symptoms, or significantly elevated or persistent sE2 levels. Clinical trial information: NCT01042379 .