Zarrintan, Armin

Background Failure of conventional imaging to detect pancreatic ductal adenocarcinoma (PDA) at its visually occult pre-diagnostic stage is a primary barrier to improving its otherwise poor rate of survival. Objective To develop and validate the Radiomics-based Early Detection MODel (REDMOD), an AI framework to identify subvisual radiomic signatures of pre-diagnostic PDA on standard-of-care CT. Designs REDMOD was trained on a multi-institutional cohort (n=969; 156 pre-diagnostic, 813 control) and tested on an independent set (n=493; 63 pre-diagnostic, 430 control), simulating a low prevalence (~1:6) early detection paradigm. The fully automated framework couples AI-driven segmentation with a heterogeneous ensemble architecture trained on a 40-feature radiomic signature derived from Synthetic Minority Over-sampling Technique (SMOTE)-balanced data. A tunable Youden Index-optimised classification threshold enables performance calibration without retraining. Validation included direct comparison with radiologists, longitudinal test–retest analysis and external specificity validation across two independent cohorts (n=539 and n=80). Results On an independent test set (n=493), REDMOD identified occult PDA (AUC 0.82; 73.0% sensitivity) at a median 475-day lead time. This represented nearly twofold higher sensitivity than radiologists (38.9%; p<0.001), which grew to nearly threefold (68.0% vs 23.0%) at >24 months lead time. REDMOD showed strong longitudinal stability (90–92% concordance) and generalisable specificity across multi-institutional (81.3%; n=539) and public (87.5%; n=80) datasets. Mechanistic analyses confirmed predictive power derived principally from multi-scale wavelet-filtered textural features (90% of selected signature), which outperformed unfiltered features (AUC 0.82 vs 0.74; p=0.007) in capturing subvisual architectural disruptions. Conclusions REDMOD is an automated, mechanistically grounded, longitudinally stable, externally validated AI that surpasses radiologists for PDA detection at its visually occult pre-diagnostic stage. These attributes position it for prospective validation in high-risk cohorts, a necessary step towards shifting the paradigm from late-stage symptomatic diagnosis to proactive pre-clinical interception.

Abstract Background: Early detection is the most potent strategy to improve survival in PDA, but its success hinges on an unresolved question: does radiologically invisible disease represent biologically early or indolent disease, or established malignancy beneath the threshold of detection? We leveraged prediagnostic CTs—incidental scans obtained 3-36 months prior to diagnosis without a focal mass—to define the relationship between imaging phenotype and tumor biology. Methods: From a multi-institutional pool of 5,046 biopsy-confirmed PDAs, we assembled a cohort of 346 prediagnostic CTs, which were independently evaluated by three radiologists using a standardized protocol. Based on majority vote, CTs were dichotomized into imaging-occult (IO) (normal pancreas) and imaging-apparent (IA) (abnormal pancreas with indirect signs such as focal atrophy, duct dilatation, etc.) groups. Tumor size and metastases (M) at diagnosis, and overall survival (OS) were compared using multivariable linear (size), logistic (M1), and Cox proportional hazards (OS) models, adjusting for lead time to diagnosis, age, sex, diabetes, CA 19-9, and surgical resection status, to isolate the independent biological relevance of the imaging phenotype. Results: IO phenotype was seen in 150 patients (mean age 66.7±11.2; 37.3% females) while 196 had IA phenotype (mean age 69.9±10.6; 49.5% females). Median lead time was 396 days (range: 90-1088) with the IA group being enriched in 3-12-month lead time (57.7% vs 33.3%; p&lt;0.001). Both groups had comparable diabetes rates (IA 33.2% vs IO 32.7%; p=1.0), median CA 19-9 (IA 193 vs IO 322 U/mL; p=0.41), and surgical resection (IA 38.3% vs IO 38.0%; p = 1.0). While unadjusted mean tumor size at diagnosis was larger in IA group (3.8 cm vs 3.2 cm), there was no difference after adjusting for clinical factors (-7.1% difference; 95% CI: -17.2, 4.2; p=0.21). Metastases were also comparable (M rate: IA 22.4% vs IO 27.3%; adjusted OR 0.97; 95% CI: 0.50, 1.88; p=0.93). Adjusted Cox models demonstrated equivalent OS (median: 18.7 vs 17.6 months; HR 1.06; p=0.66), which persisted even when stratified by surgical status (HR 1.07; 95% CI: 0.83, 1.38; p=0.61). Even in the critical 3-12 months lead time (n=163), OS remained equivalent (HR 0.89; p=0.62), and groups did not differ in either tumor size (-6.4%; 95% CI: -22.4, 12.9; p=0.49) or metastases (OR 0.48; 95% CI 0.14, 1.59; p=0.23). Conclusions: A normal-appearing pancreas on prediagnostic imaging is common yet signifies neither early nor indolent disease—it harbors PDA biologically equivalent to the imaging-apparent pancreatic phenotype. Because the disease at this stage lies beyond human perceptual capacity, AI augmentation represents the only potential path to realizing the survival benefit of early detection. Citation Format: Khurram Khaliq Bhinder, Sovanlal Mukherjee, Armin Zarrintan, Angela Ammirabile, Ahmed Khan Jadoon, Ziding Feng, Suresh T. Chari, Ajit H. Goenka. Dissociation between prediagnostic imaging phenotype and tumor biology defines the early detection challenge in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB205.

Background: Identifying optimal candidates for endovascular treatment (EVT) remains an ongoing priority to maximize treatment efficacy. The recent large core trials have called into question the use of infarct volume alone for selecting patients. This study aimed at exploring the feasibility of using routinely acquired Computed Tomography Perfusion (CTP) to capture how lesion location impacts brain connectivity and how this in turn affects the ability to benefit from EVT. Methods: Consecutive patients from a multi-centric stroke imaging registry were included in this study if they had a proven anterior circulation large vessel occlusion (LVO) and available baseline CTP data. Hypoperfusion (Tmax >6 seconds) and ischemic core (relative cerebral blood flow <30%) maps were automatically generated using e-CTP (Brainomix, UK) and used to derive disconnection maps via a DTI template. A voxel-based, multivariate method (Sparse Canonical-Correlation-Analysis – LESYMAPS) was used to explore associations between disconnection maps and NIHSS subitems in recanalized patients. The mismatch between Tmax and core disconnection volumes (disconnection mismatch volume) (Figure 1) was used to predict modified Rankin Scale (mRS) at 3-months using an ordinal shift regression adjusted for age, recanalization status and infarct volume. Results: One-hundred and seventy-one patients were included. The median NIHSS was 16 (11.5 to 22). The total NIHSS was associated with disconnection predominantly within the left basal ganglia, brainstem and corpus callosum. Upper and lower limb deficits (NIHSS 5a, 5b, 6a, 6b) were associated with corticospinal tract disconnection, with negative correlations within the contralateral tracts (Figure 2). Language deficits were associated with left hemisphere tract disconnection, also showing negative correlations within the contralateral tracts. The disconnection mismatch volume was an independent predictor of functional outcome at 3-months (Table 1). Conclusion: The results from this study showed that it is possible to use routinely acquired CTP to capture the effects of stroke lesion on brain connectivity and its impact on functional outcome following recanalization treatment. Such an approach could enable more nuanced treatment selection for patients based on specific neurological deficits.

Background Identifying eloquent regions associated with poor outcomes based on CT perfusion (CTP) may help inform personalized decisions on selection for endovascular therapy (EVT) in patients with large vessel occlusion (LVO) ischemic stroke. This study aimed to characterize the relationship between CTP-defined hypoperfusion and National Institutes of Health Stroke Scale (NIHSS) subitem deficits. Methods Patients with anterior circulation LVO, baseline CTP, itemized NIHSS at presentation and 24 hours were included. CTP was analyzed using e-CTP (Brainomix, UK). Time to maximal contrast (Tmax) prolongation was defined as >6 s, and penumbra as the difference between Tmax and ischemic core (relative cerebral blood flow<30%). Voxel-lesion-symptom mapping was performed using sparse canonical correlation analysis. For each NIHSS subitem, and total NIHSS, the associations were plotted between Tmax voxels with baseline NIHSS, and penumbra voxels with delta NIHSS (24 hours minus baseline). Results This study included 171 patients. Total NIHSS was predicted by hypoperfusion in left frontal cortex and subcortical white matter tracts. Voxels associated with neurological recovery were symmetrical and subcortical. Limb deficits were associated with respective motor cortex regions and descending motor tracts, with negative correlation within the contralateral hemispheres. A similar but smaller cluster of voxels within the penumbra was associated with NIHSS improvement. Language impairment correlated with left frontal cortex and superior temporal gyrus voxels. With the exception of dysarthria, significant associations were observed and more diffusely distributed in all other NIHSS subitems. Conclusions These results demonstrate the feasibility of hypoperfusion-to-symptom mapping in LVO. Symptom-based mapping from presenting imaging could refine treatment decisions targeting specific neurological deficits.

Background: Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives: We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design: This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods: A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results: The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion: Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.

Background and purpose Treatment of recurrent intracranial aneurysms after their initial therapy has been a significant challenge in the field of neurointervention. Recently flow diverters stents are widely used for treating intracranial aneurysms. In this systematic review and meta-analysis, we assessed the safety and efficacy of flow diverter in treating recurrent or recanalized intracranial aneurysms. Methods This meta-analysis is reported following the PRISMA 2020 guidelines. We conducted a systematic review of literature in the PubMed, Embase, Web of Sciences, and Scopus databases. Pooled prevalence and the corresponding 95% are calculated from extracted data using a random-effect model. Results The systematic literature search included 21 studies involving 411 patients, with 135 (32.8%) being male and 276 (67.2%) being females with a total number of 447 aneurysms. The overall rate of adequate occlusion was 90.67% (95% CI: 84.23%–94.65%), and the rates were comparable between the surgery (93.48%), coiling (91.78%), and stenting (85.77%) groups. The overall pooled rate of complete occlusion was 81.80 (95% CI: 71.14%–89.13%). On doing a subgroup analysis, the complete occlusion rates were 89.68%, 84.39%, and 73.47% for the surgery, coiling, and stenting groups, respectively. The overall mortality rate and achieving modified Rankin scale score of 0-2 was 1.28% (95% CI: 0.45%–3.64%) and (95% CI: 89.92%–97.84%), respectively. No significant heterogeneity is noted in the included studies. Conclusion Flow diverter stents are an effective and safe method for retreating recurrent or residual intracranial aneurysms with a high rate of complete and adequate occlusion. The rate of mortality, intracerebral hemorrhage, and overall and procedural complications following using flow diverters for intracranial aneurysms is low.

Background Sealing of the aneurysm neck with a Woven EndoBridge (WEB) device is recommended for disrupting the blood flow inside the aneurysm. This study investigates the relationship between WEB neck apposition and aneurysm occlusion rates. Methods Aneurysms treated with a WEB from March 2017 to May 2022 at a single center were included. WEB neck apposition (poor/good) and WEB protrusion (yes/no) were evaluated on post-detachment high resolution cone beam CT images. Angiographic occlusion was assessed with the Bicêtre Occlusion Scale score (BOSS). Univariate and multivariable analysis tested the association between neck apposition and occlusion rates. Results The study included 159 aneurysms in 141 patients (mean age 55.8±11.2 years; 64.2% women). Good neck apposition and protrusion were noted in 123 (77.4%) and 30 (18.9%) cases, respectively. Inter-rater agreements were good for neck apposition (κ=0.75) and protrusion (κ=0.78). Complete and adequate occlusion was achieved in 104 (65%) and 130 (82%) cases, respectively (median follow-up 18 months). Good neck apposition was a strong independent predictor for both adequate (adjusted OR (aOR)=5.9, 95% CI 2.4 to 14.9; P<0.001) and complete occlusion (aOR=7.1, 95% CI 3.0 to 18.1; P<0.001). Protrusion was more frequent in the adequate occlusion group versus the aneurysm recurrence group without reaching statistical significance (P=0.06), but was associated with more thromboembolic complications (9/30 (30%) vs 12/129 (9%); P<0.01). WEB shape modification was significantly greater in poor apposition cases (P=0.03). Conclusions Achieving good neck apposition of the WEB strongly predicts aneurysm occlusion during follow-up. WEB protrusion should be minimized due to the increase in thromboembolic risk with limited impact on aneurysm occlusion.

AbstractBackground and PurposeThe Alberta Stroke Program Early CT Score (ASPECTS) is a widely used scoring system for evaluating ischemic stroke to determine therapeutic strategy. However, there is variation in the interobserver agreement of ASPECTS. This systematic review and meta‐analysis aimed to investigate the interobserver agreement of total and regional ASPECTS.MethodsA comprehensive search was conducted in the Web of Sciences, PubMed, and Scopus databases to identify relevant studies. Inclusion criteria were studies of noncontrast CT performed within 24 hours of ischemic stroke in the middle cerebral artery territory.ResultsA total of 20 studies, with 3482 patients, reporting interobserver agreement of total and regional ASPECTS were included in the meta‐analysis. The interobserver agreement for total ASPECTS in studies using Kappa coefficient (κ) analysis was substantial (κ = .67, 95% confidence interval [CI]: .57‐.78). In studies using intraclass correlation coefficient (ICC) analysis, agreement was excellent (ICC = .84, 95% CI: .77‐.90). Interobserver agreement was higher in studies in which the observer was unblinded to clinical scenario in both groups (κ = .74, 95% CI: .59‐.89, and ICC = .82, 95% CI: .79‐.85). Per‐region analysis showed that the caudate nucleus had the highest agreement (κ = .68, 95% CI: .60‐.76, and ICC = .84, 95% CI: .74‐.93), while M2 and internal capsule in Kappa studies (κ = .45, 95% CI: .34‐.55 and κ = .47, 95% CI: .28‐.66), and M4 and internal capsule in ICC studies (ICC = .54, 95% CI: .43‐.64 and ICC = .55, 95% CI: .18‐.91) had the lowest agreement.ConclusionThis meta‐analysis demonstrates substantial to excellent interobserver agreement for total ASPECTS, which supports using this method for stroke treatment. However, findings emphasize the need to consider interobserver agreement in specific regions of ASPECTS for treatment decisions.