Series Of Images Research Articles

A modular platform for bioluminescent RNA tracking

AbstractA complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs. The RNA tags are engineered to recruit light-emitting luciferase fragments (termed RNA lanterns) upon transcription. Robust photon production is observed for RNA targets both in cells and in live animals. Importantly, only a single copy of the tag is necessary for sensitive detection, in sharp contrast to fluorescent platforms requiring multiple repeats. Overall, this work provides a foundational platform for visualizing RNA dynamics from the micro to the macro scale.

TOLGAN: An End-To-End Framework for Producing Traditional Orient Landscape

We present TOLGAN that generates traditional oriental landscape (TOL) image from a map that specifies the locations and shapes of the elements composing TOL. Users can create a TOL map by using a user interface or a segmentation scheme from a photograph. We design the generator of TOLGAN as a series of decoding layers where the map is applied between the layers. The generated TOL image is further enhanced through an AdaIN architecture. The discriminator of TOLGAN processes a generated image and its groundtruth TOL artwork image. TOLGAN is trained through a dataset composed of paired TOL artwork images and their TOL maps. We present a tool through which users can produce a TOL map by specifying and organizing the elements of TOL artworks. TOLGAN successfully generates a series of TOL images from the TOL map. We evaluate our approach using a quantitative way by estimating FID and ArtFID scores and a qualitative way by executing two user studies. Through these studies, we prove the excellence of our approach by comparing our results with those from several important existing works.

RARE TUMORS OF POSTERIOR CRANIAL FOSSA IN ADULTS

Objectives Tumors arising in the posterior cranial fossa pertain to a special category of neoplasm in the manner that they can cause cerebellar syndrome, obstructive hydrocephalus, brainstem compression – cranial nerve dysfunction – and herniation. In the cerebellopontine angle, the most common tumors are acoustic neuromas followed by meningiomas. Among the petroclival tumors, the most common benign tumors are meningiomas and the most common malign tumors are chordomas and metastases. Among jugular foramen tumors, the common tumors are schwannomas, paragangliomas and meningiomas. We report our unit’s experience with the neurosurgical management of rare posterior cranial fossa tumors as compared to the main literature results, taking into consideration the clinical, radiological aspects and the outcome. Materials and Methods Retrospective analysis of a single unit cohort of patients diagnosed with rare posterior cranial fossa tumors, who underwent surgical treatment in the Neurosurgery I Department of the University Emergency Hospital Bucharest between 2017 and 2024. Relevant literature review was analyzed, as well as serial clinical examinations, imaging studies, and operative records were taken into consideration. Conclusions Depending on the location, size, and pathology of the posterior cranial fossa tumors, there are different treatment options, which include microsurgical resection, observation, stereotactic radiotherapy. These type of lesions still represent a challenge and require electing the most suitable approach whilst preserving the neurologic function of the patient.

Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association.

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.

Immuno-PET Imaging of CD93 Expression with 64Cu-Radiolabeled NOTA-mCD93 ([64Cu]Cu-NOTA-mCD93) and Insulin-Like Growth Factor Binding Protein 7 ([64Cu]Cu-NOTA-IGFBP7).

CD93 is overexpressed in multiple solid tumor types, serving as a novel target for antiangiogenic therapy. The goal of this study was to develop a 64Cu-based positron emission tomography (PET) tracer for noninvasive imaging of CD93 expression. Antimouse-CD93 mAb (mCD93) and the CD93 ligand IGFBP7 were conjugated to a bifunctional chelator, p-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-NOTA) and labeled with 64Cu. To evaluate the pharmacokinetic properties and tumor-targeting efficacy of [64Cu]Cu-NOTA-mCD93 and [64Cu]Cu-NOTA-IGFBP7, PET imaging and biodistribution were performed on both 4T1 murine breast tumor-bearing mice and MDA-MB-231 human breast tumor-bearing mice. The tumor model HT1080-FAP, which does not overexpress CD93, was used as a negative control. Fluorescent immunostaining was conducted on different tissues to correlate radiotracer uptake with CD93 expression. 64Cu-labeling was achieved with high yield and specific activity. Serial PET imaging revealed that the in vivo performance of [64Cu]Cu-NOTA-IGFBP7 was superior to that of [64Cu]Cu-NOTA-mCD93, and that the tracer [64Cu]Cu-NOTA-IGFBP7 exhibited elevated tumor uptake values and excellent tumor retention in MDA-MB-231 mice, rather than in 4T1 murine mice. The MDA-MB-231 tumor uptake of [64Cu]Cu-NOTA-IGFBP7 was 2.85 ± 0.15, 3.69 ± 0.60, 6.91 ± 0.88, and 6.35 ± 0.55%ID/g at 1, 4, 24, and 48 h p.i., respectively, which were significantly higher than that in the CD93-negative HT1080-FAP tumor (0.73 ± 0.15, 0.97 ± 0.31, 1.00 ± 0.07, and 1.02 ± 0.11%ID/g, respectively). The significant difference between positive and negative tumors indicated [64Cu]Cu-NOTA-IGFBP7 was specifically binding to CD93. Biodistribution data as measured by gamma counting were consistent with the PET analysis. Ex vivo histology further confirmed the high CD93 expression on MDA-MB-231 tumor tissues. Herein, we prepared two novel radiotracers, [64Cu]Cu-NOTA-mCD93 and [64Cu]Cu-NOTA-IGFBP7, for the first immune-PET imaging of CD93 expression. Our results suggest that [64Cu]Cu-NOTA-IGFBP7 is a more potential radiotracer for visualizing angiogenesis due to its sensitive, persistent, and CD93-specific characteristics.

Abstract 4144548: High Morbidity and Mortality in Adults With Turner Syndrome and Aortic Dilation: A Retrospective Cohort Study from the Healthy Heart Project

Introduction: Turner syndrome (TS) is caused by the partial or complete absence of one sex chromosome and affects 1 in 2500 liveborn infants. Hypertension, bicuspid aortic valve (BAV), and thoracic aortic aneurysms (TAAs) are more prevalent in TS compared to the general population and predispose to aortic dissections, which may occur in young adults with TS. We hypothesize that adults with TS who have TAAs experience a high rate of adverse cardiovascular outcomes. Methods: Adults with TS who had Healthy Heart Project (HHP) echocardiograms at national conferences between 2003 and 2023 were contacted for enrollment in descending order of the aortic size index (ASI, cm/m 2 ), defined as the ratio of the maximum ascending aortic diameter to body surface area. After informed consent, clinical characteristics and outcomes (as numbers of participants or median and interquartile range) were abstracted from questionnaires and medical records. Results: Sixty-four of 704 total HHP participants were contacted and 19 (with 10 of the 20 highest ASI values) were enrolled with complete data. The baseline ASI was 2.19 (0.48), compared to 1.51 (0.36) for all other HHP participants. The median age was 59 (13) years. The most prevalent characteristics were 45,X (10) or 45,X/46,XX (6) karyotypes; BAV (9), coarctation (4), or no congenital lesions (6); and hypertension (12). A mean of 10 serial aortic images were available for each participant over a follow up period of 14 (9.8) years. The median increase in aortic diameter was 0.09 (0.29) mm/yr at the sinuses of Valsalva and 0.26 (0.44) mm/yr at the ascending aorta. Seven participants underwent aortic operations due to enlarging TAAs when the median ascending diameter was 3.83 (0.67) cm (ASI 2.58 (0.11) cm/m 2 ). In 3 cases, operations were urgent due to cardiovascular symptoms or rapid aortic dilation, but there were no acute aortic dissections. The median time between the index image and subsequent repair was 3.5 (7.0) years. Three HHP participants with the 8th, 15th, and 42nd largest ASI values died prior to follow up. One death was caused by complications after surgical aortic valve replacement at age 20. Conclusions: In a cohort of adults with TS and TAAs, 40% (7/19) developed progressive aortic enlargement requiring aortic repairs and there were 3 deaths. These observations underscore the importance of lifelong surveillance and timely intervention to prevent deaths due to cardiovascular disease in TS.

FET PET to differentiate between post-treatment changes and recurrence in high-grade gliomas: a single center multidisciplinary clinic controlled study.

The clinico-radiological dilemma in post-treatment high-grade gliomas, between disease recurrence (TR) and treatment-related changes (TRC), still persists. FET (Fluoro-ethyl-tyrosine) PET has been extensively used as problem-solving modality for cases where MR imaging is inconclusive. We incorporated a systematic imaging and clinical follow-up algorithm in a multi-disciplinary clinic (MDC) setting to analyse our cohort of FET PET in post-treatment gliomas. We retrospectively analyzed 171 patients of post-treatment grade III and IV glioma with equivocal findings on MRI. 185-222 MBq of 18F-FET was injected and dedicated static imaging of brain was performed at 20min. TBR (Tumor to background ratio) was used as semi-quantitative parameter. Cutoff of 2.5 was used for image interpretation. Imaging findings were confirmed with histopathological diagnosis, wherever available or in a multidisciplinary joint clinic based on serial imaging. 121 of 171 patients showed recurrent disease on FET PET, on follow up, 109 were confirmed with recurrence; 7 patients showed TRC, whereas 5 were treated with bevacizumab, with no further clinico-radiological deterioration, thus confirming TRC. 50 patients showed TRC on FET PET, on follow up on follow up, 40 were confirmed as true-negative. 10 patients who showed TBR less than 2.5 had confirmed TR on subsequent MR imaging. The overall sensitivity and specificity was 91.6 and 76.9% respectively, with a diagnostic accuracy of 87.13%. There is potential for FET PET to be used along with MRI in the post treatment algorithm of high-grade glial tumors.

SURG-41. OPTIMIZING PATIENT OUTCOMES IN PETROCLIVAL MENINGIOMA TREATMENT: EVALUATING SURGICAL, RADIOSURGICAL, RADIOTHERAPY AND COMBINED TREATMENT APPROACHES

Abstract Petroclival meningiomas pose a formidable challenge due to their proximity to critical neurovascular structures, necessitating complex surgical interventions with a high risk of complications. Stereotactic radiosurgery (SRS) offers an alternative or complementary treatment option, yet the optimal treatment strategy remains undefined. We aimed to evaluate the local control rates following surgical resection, radiotherapy, and SRS for petroclival meningiomas and to assess the incidence of cranial nerve palsies associated with each treatment modality. This retrospective study reviewed medical records of patients treated for petroclival meningiomas at Stanford University between 1980-April 2024. Pre- and post-treatment radiological data were analyzed to assess local control. Cranial nerve function was evaluated pre- and post-treatment, and at last follow-up. A total of 171 patients (129 females; median age 54.65 years) diagnosed with petroclival meningioma were identified. Treatment modalities included: 31 patients underwent surgical resection alone, 27 received SRS alone, 11 received radiotherapy alone, 36 underwent combined surgical resection and SRS, 28 received combined surgical resection and radiotherapy, 9 were treated with a triad of surgical resection, SRS, and radiotherapy, and 29 were managed with serial imaging alone. The percentage change of tumor volume from diagnosis to follow-up for these groups was -55.6%, 28.9%, 73.0%, -64.9%, -12.0%, 35.3%, and -8.8%, respectively. The incidence of new cranial nerve palsies was highest (68%) in patients who underwent surgical resection. The percentage of worsening pre-existing palsies was greater in patients receiving single-modality non-surgical treatment. Surgery, radiotherapy, and SRS demonstrated promising local control rates for specific patient cohorts with petroclival meningiomas. Patients receiving combination therapies generally fared better than those receiving single-modality treatments, with surgery followed by SRS yielding the best outcome. The incidence of cranial nerve palsies was lower following SRS and radiotherapy compared to surgery. Future research should focus on refining multi-modal treatment strategies to minimize complications and improve patient quality of life.

NCOG-11. FACTORS PREDICTING SPEECH AND GAIT RECOVERY IN CHILDREN WITH POST-OPERATIVE POSTERIOR FOSSA SYNDROME (PFS)

Abstract Posterior fossa syndrome/cerebellar mutism syndrome is a surgical complication of posterior fossa tumor resection, especially midline tumors. Initially thought to involve complete mutism, PFS is now recognized as a complex syndrome involving loss of language (complete [PFS1] and incomplete [PFS2]). Additional symptoms include apraxia, movement disorder, motor and coordination deficits, and emotional lability. The aim of this study was to identify factors that influence delayed speech and independent gait recovery in children with PFS. We prospectively studied 73 children ≥3 years of age with medulloblastoma who developed PFS (SJMB12, NCT01878617). Enrolled children received standardized neurologic examinations and serial imaging before, during and up to five years after completion of therapy. Neurological examinations included scale for assessment and rating of ataxia (SARA), CTCAE grading of neurologic deficits, and severity of injury to the superior cerebellar peduncles (SCP) on post-operative MRI. Median time to speech recovery was 1.4 months (range 0.3-14.3); 81% had return of speech at 3 months and 97% at 12 months. On multivariable Cox regression analysis, complete mutism (HR 0.17, p&amp;lt;0.0001) and inability to sit (HR 0.40, p=0.001) were associated with delayed speech return. Independent ambulation was regained by 80.8% at a median of 2.3 (range 0.3-71.3) months. 70% had a return of ambulation at 12 months and 77% at 24 months. On multivariable Cox regression analysis, complete mutism (HR 0.32, p=0.016), inability to sit (HR 0.30, p=0.002), SARA score (HR 0.94, p=0.002), and right SCP injury (HR 0.47, p=0.014) were significantly associated with delayed return of ambulation. Presence of mutism, inability to sit unassisted, higher SARA score, and right SCP injury at the time of PFS diagnosis are associated with time to recovery of speech/language and ambulation. Our findings have prognostic implications for families and to help identify children in need of more intensive interventions.

Ultra-High-Resolution Photon-Counting-Detector CT with a Dedicated Denoising Convolutional Neural Network for Enhanced Temporal Bone Imaging.

Ultra-high-resolution (UHR) photon-counting-detector (PCD) CT improves image resolution but increases noise, necessitating use of smoother reconstruction kernels that reduce resolution below the system's 0.110 mm maximum spatial resolution. To address this, a denoising convolutional neural network (CNN) was developed to reduce noise in images reconstructed with the available sharpest reconstruction kernel while preserving resolution for enhanced temporal bone visualization. With IRB approval, CNN was trained on 6 clinical temporal bone patient cases (1,885 images) and tested on 20 independent cases using a dual-source PCD-CT (NAEOTOM Alpha, Siemens). Images were reconstructed using iterative reconstruction at strength 3 (QIR3) with both clinical routine (Hr84) and the sharpest available head kernel (Hr96). The CNN was applied to images reconstructed with Hr96 and QIR1. Three image series (Hr84-QIR3, Hr96-QIR3, and Hr96-CNN) for each case were randomized for review by two neuroradiologists, assessing overall quality and delineation of the modiolus, stapes footplate, and incudomallear joint. CNN reduced noise by 80% compared to Hr96-QIR3 and 50% relative to Hr84-QIR3, while maintaining high resolution. When compared to the conventional method at the same kernel (Hr96-QIR3), Hr96-CNN significantly decreased image noise (from 204.63 HU to 47.35 HU) and improved SSIM (from 0.72 to 0.99). Hr96-CNN images ranked higher than Hr84-QIR3 and Hr96-QIR3 in overall quality (p<0.001). Readers preferred Hr96-CNN for all three structures. The proposed CNN significantly reduced image noise in UHR PCD-CT, enabling the use of sharpest kernel. This combination greatly enhanced diagnostic image quality and anatomical visualization.ABBREVIATIONS: PCD = Photon-counting-detector; UHR = Ultra-high-resolution; IR = Iterative reconstruction; CNN = Convolutional neural network; SSIM: Structural similarity index.

TMIC-80. HIGH-DIMENSIONAL HISTOPATHOLOGIC EVALUATION OF THE HYPOXIC TUMOR MICROENVIRONMENT IN GLIOBLASTOMA

Abstract Gliobastoma (GBM) is a highly aggressive solid tumor of the brain, characterized by a hypoxic tumor microevironment (TME) leading to histopathological features of necrosis, microvascular proliferation and deregulated hypervascularization. The heterogeneous nature of GBM results in a gradient of intra-tumoral hypoxia that causes molecular changes to specific cell populations within the bulk of the tumor. Our study is the first clinical study to utilize the exogenous oxygen-independent marker pimonidazole (PIMO) to identify the hypoxic TME using high-dimensional spatial and single-cell proteomics of specific cell populations within GBM. A cohort of 35 patients with primary GBM, recurrent GBM or IDH-mutant glioma were administered PIMO prior to surgical resection of tumor tissue for downstream bulk proteomic analysis of bulk tissue by serial immunohistochemistry and imaging mass cytometry (IMC) and single-cell analysis of dissociated tissue by Cytometry by time-of-flight (CyTOF). We utilized high-resolution imaging analyses to validate PIMO as a sensitive and stable marker for hypoxia against a panel of transiently expressed HIF-target genes and examine the inter- and intra-tumoral heterogeneity of hypoxia within each tumor subtype. A custom CyTOF marker panel was developed for further single-cell analyses of T-cell subsets and their functional states, myeloid cell subpopulations, natural killer cells, glial cells, and tumor cells in the hypoxic TME. We demonstrate the utility of PIMO to effectively study the hypoxic TME through spatial and single cell methods and further elucidate mechanisms of hypoxia-driven treatment resistance.

EPID-09. THE NATURAL HISTORY AND MOLECULAR ARCHITECTURE OF INCIDENTAL MENINGIOMAS

Abstract The prevalence of asymptomatic, incidental meningiomas is increasing due to greater frequency of brain imaging. This retrospective cohort study of adult patients presenting at a single institution from 1996-2020 integrated clinical data, serial magnetic resonance imaging (MRI) volumetrics, DNA methylation profiling, and targeted gene expression profiling to define the natural history and molecular architecture of incidental meningiomas. Volumetrics were calculated from contrast-enhanced brain MRIs at time of diagnosis compared to serial surveillance MRIs (average 3 MRIs per patient pre-intervention, range: 1-12) DNA methylation groups and gene expression risk scores were defined for 123 samples that underwent resection. Time-to-event analyses were performed for progression-free survival (PFS), symptom-free survival (SFS), and treatment-free survival (TFS). The cohort included 238 meningiomas from 207 patients. Median age at diagnosis was 59 years and 81.5% of patients were female. Median clinical and imaging follow-up were 9.1 and 6.7 years, respectively, during which time 50.8% progressed. Median maximum diameter and volume at diagnosis were 2.20 cm and 4.25 cm3, respectively, and median pre-treatment volumetric growth rate was 19.2% per year. Median pre-treatment PFS and TFS were 3.10 and 1.27 years, respectively, and median SFS and post-treatment PFS were not reached. Cox proportional hazards regression identified maximum diameter at diagnosis as a significant predictor of worse pre-treatment PFS (multivariate HR 1.65 per 1 cm [95% CI 1.19–2.28], p=0.0027) and worse TFS (multivariate HR 1.44 per 1 cm [95% CI 1.17–1.76], p&amp;lt;0.001). Skull base tumors had with worse SFS (multivariate HR 2.48 [95% CI 1.02–6.00], p=0.045). Molecular and histological features among incidental meningiomas that ultimately underwent resection (n=176, 74.0%) were reassuring (89.2% WHO grade 1, 10.2% WHO grade 2). These findings suggest maximum diameter at diagnosis of incidental meningiomas is significantly associated with earlier progression and eventual treatment, and skull base tumors have earlier symptom development.

BIOM-72. INTEGRATION OF ULTRASENSITIVE ELECTROLUMINESCENT IMMUNOASSAY AND CELL-FREE DNAMETHYLATION ANALYSIS FOR NON-INVASIVE MONITORING OF ADULT DIFFUSE GLIOMAS

Abstract Gliomas are highly aggressive brain tumors with nearly universal recurrence rate. Despite this, the ability to accurately predict and identify tumor recurrence relies solely on serial MRI imaging, which is marred by treatment effects such as radiation necrosis, and necessarily identifies progression retrospectively. It is believe that tumor undergo molecular changes upon tumor progression, however the resampling of tumors upon recurrence imposes significant risks. This highlights the need for novel non-invasive biomarkers capable of identifying tumor recurrence. Due to the low accuracies of individual biomarkers, we have proposed the use of an integrated, multi-platform approach to biomarker discovery. A cohort of 107 glioma plasma samples, including 30 pairs, underwent plasma proteomic analysis, consisting of a panel of serum proteins (FABP4, GFAP, NFL, Tau and MMP3,4 &amp;7) quantified through ultrasensitive electrochemiluminescence multiplexed immunoassays, and plasma DNA methylation analysis, captured through cell-free methylated DNA immunoprecipitation and high-throughput sequencing. Unsupervised hierarchal clustering revealed robust separation of primary and recurrent tumors through plasma proteomics, associated with a distinct plasma methylation signature. NFL, Tau and MMP3 levels differed between primary and recurrent samples; pair-wise analysis revealed increased in NFL and Tau concentrations upon recurrence. Tau levels predicted outcome independent of WHO Grade and IDH status. A predictive generalized linear regression model created through the integration of the proteomic and methylation signatures allowed for the discrimination of primary and recurrent samples in 83% of cases. This work suggests that the combination of DNA methylation and plasma proteomics may improve the ability of these techniques for the serial monitoring of gliomas patients.

NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR

Abstract BACKGROUND Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma. METHODS Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET. RESULTS Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET. DISCUSSION [68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.

SYMPATHIQUE: image-based tracking of symptoms and monitoring of pathogenesis to decompose quantitative disease resistance in the field

BackgroundQuantitative disease resistance (QR) is a complex, dynamic trait that is most reliably quantified in field-grown crops. Traditional disease assessments offer limited potential to disentangle the contributions of different components to overall QR at critical crop developmental stages. Yet, a better functional understanding of QR could greatly support a more targeted, knowledge-based selection for QR and improve predictions of seasonal epidemics. Image-based approaches together with advanced image processing methodologies recently emerged as valuable tools to standardize relevant disease assessments, increase measurement throughput, and describe diseases along multiple dimensions.ResultsWe present a simple, affordable, and easy-to-operate imaging set-up and imaging procedure for in-field acquisition of wheat leaf image sequences. The development of Septoria tritici blotch and leaf rusts was monitored over time via robust methods for symptom detection and segmentation, spatial alignment of images, symptom tracking, and leaf- and symptom characterization. The average accuracy of the spatial alignment of images in a time series was approximately 5 pixels (~ 0.15 mm). Leaf-level symptom counts as well as individual symptom property measurements revealed stable patterns over time that were generally in excellent agreement with visual impressions. This provided strong evidence for the robustness of the methodology to variability typically inherent in field data. Contrasting patterns in the number of lesions resulting from separate infection events and lesion expansion dynamics were observed across wheat genotypes. The number of separate infection events and average lesion size contributed to different degrees to overall disease intensity, possibly indicating distinct and complementary mechanisms of QR.ConclusionsThe proposed methodology enables rapid, non-destructive, and reproducible measurement of several key epidemiological parameters under field conditions. Such data can support decomposition and functional understanding of QR as well as the parameterization, fine-tuning, and validation of epidemiological models. Details of pathogenesis can translate into specific symptom phenotypes resolvable using time series of high-resolution RGB images, which may improve biological understanding of plant-pathogen interactions as well as interactions in disease complexes.

Neural Correlates of Retrieval Success and Precision: A Functional Magnetic Resonance Imaging Study.

Prior studies examining the neural mechanisms underlying retrieval success and precision have yielded inconsistent results. Here, the neural correlates of success and precision were examined with a memory task that assessed precision for spatial location. A sample of healthy young adults underwent functional magnetic resonance imaging scanning during a single study-test cycle. At study, participants viewed a series of object images, each placed at a randomly selected location on an imaginary circle. At test, studied images were intermixed with new images and presented to the participants. The requirement was to move a cursor to the location of the studied image, guessing if necessary. Participants then signaled whether the presented image had been studied. Memory precision was quantified as the angular difference between the studied location and the location selected by the participant. A precision effect was evident in the left angular gyrus, where BOLD activity covaried with location accuracy. In addition, multivoxel pattern analysis revealed a significant item-level reinstatement effect in the angular gyrus for high-precision trials. There was no evidence of a retrieval success effect in this region. BOLD activity in the hippocampus was insensitive to both success and precision. These findings are partially consistent with prior evidence that success and precision are dissociable features of memory retrieval.

Enhancing the diagnostic capacity of [18F]PSMA-1007 PET/MRI in primary prostate cancer staging with artificial intelligence and semi-quantitative DCE: an exploratory study

BackgroundTo investigate the ability of artificial intelligence (AI)-based and semi-quantitative dynamic contrast enhanced (DCE) multiparametric MRI (mpMRI), performed within [18F]-PSMA-1007 PET/MRI, in differentiating benign from malignant prostate tissues in patients with primary prostate cancer (PC).ResultsA total of seven patients underwent whole-body [18F]-PSMA-1007 PET/MRI examinations including a pelvic mpMRI protocol with T2w, diffusion weighted imaging (DWI) and DCE image series. Conventional analysis included visual reading of PET/MRI images and Prostate Imaging Reporting & Data System (PI-RADS) scoring of the prostate. On the prostate level, we performed manual segmentations for time-intensity curve parameter formation and semi-quantitative analysis based on DCE segmentation data of PC-suspicious lesions. Moreover, we applied a recently introduced deep learning (DL) pipeline previously trained on 1010 independent MRI examinations with systematic biopsy-enhanced histopathological targeted biopsy lesion ground truth in order to perform AI-based lesion detection, prostate segmentation and derivation of a deep learning PI-RADS score. DICE coefficients between manual and automatic DL-acquired segmentations were compared. On patient-based analysis, PET/MRI revealed PC-suspicious lesions in the prostate gland in 6/7 patients (Gleason Score-GS ≥ 7b) that were histologically confirmed. Four of these patients also showed lymph node metastases, while two of them had bone metastases. One patient with GS 6 showed no PC-suspicious lesions. Based on DCE segmentations, a distinction between PC-suspicious and normal appearing tissue was feasible with the parameters fitted maximum contrast ratio (FMCR) and wash-in-slope. DICE coefficients (manual vs. deep learning) were comparable with literature values at a mean of 0.44. Further, the DL pipeline could identify the intraprostatic PC-suspicious lesions in all six patients with clinically significant PC.ConclusionFirstly, semi-quantitative DCE analysis based on manual segmentations of time-intensity curves was able to distinguish benign from malignant tissues. Moreover, DL analysis of the MRI data could detect clinically significant PC in all cases, demonstrating the feasibility of AI-supported approaches in increasing diagnostic certainty of PSMA-radioligand PET/MRI.

Analysis of Serial Foot Radiographs to Determine Foot Height Multipliers.

The multiplier method is an arithmetic calculation that estimates the amount of growth remaining until skeletal maturity. When predicting lower limb length discrepancy, differences in foot height are added to femur and tibia discrepancies. Foot height multipliers have not been calculated using radiographic measurements, so it is unclear whether foot height develops at the same pace as the femur and tibia. This study used serial images to calculate foot height multipliers and compared them to published lower limb and foot length multipliers. The Bolton Brush radiograph collection was used to measure foot height on the lateral foot view. Multipliers were calculated for ages with at least 10 serial study visits. 212 patients (2195 radiographs) were included in the study (102 female, 110 male patients). Foot height multipliers were calculated for ages 0 to 17 years (females) and 0 to 18 years (males). Multipliers decreased with age, but qualitatively plateau at age 13 (females) and age 15 (males). Lower extremity multipliers have a more dramatic growth curve, indicating comparatively greater lower extremity growth after birth. However, when comparing the limb length discrepancy calculation using the lower extremity multiplier versus the foot height multiplier for the foot portion, the difference was negligible. This paper provides a database of foot height multipliers. Foot height seems to grow on a different trajectory than other lower limb components, confirming that one should consider separate multiplier values. The difference created by the foot height multiplier versus the lower extremity multiplier appears to be modest. Separate use of the foot height multiplier may only be necessary for young children with large foot height discrepancies, but further study to confirm the lack of impact of the foot height multiplier on limb length discrepancy calculations is needed. Our data were derived from normal children, so it is unknown if the presence of a talo-calcaneal coalition would affect foot height on the involved side. Level III-retrospective comparative study.

Exploring the potential of historical images for the investigation of glacier changes: the case of Belvedere Glacier, Italian Alps

Historical images dispersed in various archives can be instrumental in documenting processes connected to glacier changes in mountains. A series of more than 29 engravings and photographs of the Monte Rosa east face have been found covering the period since 1789. Some images were produced by a combination of photography and engraving, a common approach before practical techniques for printing halftone images were introduced. Using a repeat photography approach, the present study documents the changes in the extent and debris cover of the Belvedere Glacier. Based on visual comparison of images, it appears that the debris cover of the lower part of the glacier developed mainly during the period of the 1860s–1880s. Furthermore, the image series documents the evolution of the terminus both in terms of elevation and shape, as well as a breach in lateral moraine which could be dated back to the end of the 19th century, well before the reported glacier lake outburst flood in 1904.

AlGrow: a graphical interface for easy, fast and accurate area and growth analysis of heterogeneously colored targets.

AlGrow software provides a graphical interface to define target color volumes as hulls in color space and applies them to image segmentation and growth rate analysis across a multiplexed image series.