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Background: Somatostatin receptor (SSR) targeting radiotracer 68 Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68 Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model's detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted., Results: The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68 Ga- DOTATATE PET scans., Conclusions: The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68 Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www., Clinicaltrials: gov/study/NCT03206060 , https://www., Clinicaltrials: gov/study/NCT04086485 , https://www., Clinicaltrials: gov/study/NCT05012098 ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose To evaluate the performance of an artificial intelligence (AI) model in detecting overall and clinically significant prostate cancer (csPCa)-positive lesions on paired external and in-house biparametric MRI (bpMRI) scans and assess performance differences between each dataset. Materials and Methods This single-center retrospective study included patients who underwent prostate MRI at an external institution and were rescanned at the authors' institution between May 2015 and May 2022. A genitourinary radiologist performed prospective readouts on in-house MRI scans following the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 or 2.1 and retrospective image quality assessments for all scans. A subgroup of patients underwent an MRI/US fusion-guided biopsy. A bpMRI-based lesion detection AI model previously developed using a completely separate dataset was tested on both MRI datasets. Detection rates were compared between external and in-house datasets with use of the paired comparison permutation tests. Factors associated with AI detection performance were assessed using multivariable generalized mixed-effects models, incorporating features selected through forward stepwise regression based on the Akaike information criterion. Results The study included 201 male patients (median age, 66 years [IQR, 62-70 years]; prostate-specific antigen density, 0.14 ng/mL 2 [IQR, 0.10-0.22 ng/mL 2 ]) with a median interval between external and in-house MRI scans of 182 days (IQR, 97-383 days). For intraprostatic lesions, AI detected 39.7% (149 of 375) on external and 56.0% (210 of 375) on in-house MRI scans ( P < .001). For csPCa-positive lesions, AI detected 61% (54 of 89) on external and 79% (70 of 89) on in-house MRI scans ( P < .001). On external MRI scans, better overall lesion detection was associated with a higher PI-RADS score (odds ratio [OR] = 1.57; P = .005), larger lesion diameter (OR = 3.96; P < .001), better diffusion-weighted MRI quality (OR = 1.53; P = .02), and fewer lesions at MRI (OR = 0.78; P = .045). Better csPCa detection was associated with a shorter MRI interval between external and in-house scans (OR = 0.58; P = .03) and larger lesion size (OR = 10.19; P < .001). Conclusion The AI model exhibited modest performance in identifying both overall and csPCa-positive lesions on external bpMRI scans. Keywords: MR Imaging, Urinary, Prostate Supplemental material is available for this article. © RSNA, 2024.

Rationale and Objectives: The increasing use of focal therapy (FT) in localized prostate cancer (PCa) management requires a standardized MRI interpretation system to detect recurrent clinically significant PCa (csPCa). This pilot study evaluates the novel Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) and compares its performance to that of the Prostate Imaging after Focal Ablation (PI-FAB) system., Materials and Methods: This retrospective study included 38 patients who underwent primary FT for localized PCa, with follow-up multiparametric MRI (mpMRI) and biopsy. Two radiologists assessed the mpMRIs using both PI-FAB and TARGET independently. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated. Inter-reader and intrareader agreement were assessed using Cohen's κ and Kendall's τ., Results: 14 patients had recurrent csPCa. PI-FAB showed high sensitivity (92.9% for both readers) and NPV (reader 1: 93.8%, reader 2: 92.9%) but moderate specificity (reader 1: 62.5%, reader 2: 54.2%). TARGET demonstrated lower sensitivity for one reader (reader 1: 78.6%, reader 2: 92.9%) but higher specificity (reader 1: 79.2%, reader 2: 62.5%) for both readers. Both systems displayed moderate inter-reader agreement (κ = 0.56 for PI-FAB, 0.57 for TARGET)., Conclusion: PI-FAB and TARGET exhibit similar performances in post-FT MRI. While PI-FAB had consistently high sensitivity, TARGET offered higher specificity for one reader. Moderate agreement levels demonstrate the viability of these systems in clinical settings and a promise for improvement., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B. J. Wood receives support as part of a cooperative research and development agreement (CRADA) between NIH and Philips Healthcare, receives royalties from NIH related to a licensing agreement with Philips Healthcare, and is party to patents or potential patents related to this work. P. L. Choyke receives royalties for MRI/ultrasound fusion biopsy patents licensed to Philips Medical. P. A. Pinto receives royalties from NIH related to a Philips licensing agreement and support as part of a CRADA between NIH and Philips Healthcare. B. Turkbey receives support as part of a CRADA between NIH and NVDIA and between NIH and Philips Healthcare, receives royalties from NIH, and is party to patents or potential patents related to this work. The remaining authors declare that there are no other disclosures relevant to the subject matter of this article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government., (Published by Elsevier Inc.)

Purpose: Osteosarcoma is an aggressive bone cancer lacking robust biomarkers for personalized treatment. Despite its scarcity in humans, it is relatively common in adult pet dogs. This study aimed to analyze clinically annotated bulk tumor transcriptomic datasets of canine and human osteosarcoma patients to identify potentially conserved patterns of disease progression., Experimental Design: Bulk transcriptomic data from 245 pet dogs with treatment-naïve appendicular osteosarcoma were analyzed using deconvolution to characterize the tumor microenvironment (TME). The TME of both primary and metastatic tumors derived from the same dog was compared, and its impact on canine survival was assessed. A machine learning model was developed to classify the TME based on its inferred composition using canine tumor data. This model was applied to 8 independent human osteosarcoma datasets to assess its generalizability and prognostic value., Results: This study found three distinct TME subtypes of canine osteosarcoma based on cell type composition of bulk tumor samples: Immune Enriched (IE), Immune Enriched Dense Extra-Cellular Matrix-like (IE-ECM), and Immune Desert (ID). These three TME-based subtypes of canine osteosarcomas were conserved in humans and could predict progression-free survival outcomes of human patients, independent of conventional prognostic factors such as percent tumor necrosis post standard of care chemotherapy treatment and disease stage at diagnosis., Conclusions: These findings demonstrate the potential of leveraging data from naturally occurring cancers in canines to model the complexity of the human osteosarcoma TME, offering a promising avenue for the discovery of novel biomarkers and developing more effective precision oncology treatments.

Background/objectives: Apparent Diffusion Coefficient (ADC) maps in prostate MRI can reveal tumor characteristics, but their accuracy can be compromised by artifacts related with patient motion or rectal gas associated distortions. To address these challenges, we propose a novel approach that utilizes a Generative Adversarial Network to synthesize ADC maps from T2-weighted magnetic resonance images (T2W MRI)., Methods: By leveraging contrastive learning, our model accurately maps axial T2W MRI to ADC maps within the cropped region of the prostate organ boundary, capturing subtle variations and intricate structural details by learning similar and dissimilar pairs from two imaging modalities. We trained our model on a comprehensive dataset of unpaired T2-weighted images and ADC maps from 506 patients. In evaluating our model, named AI-ADC, we compared it against three state-of-the-art methods: CycleGAN, CUT, and StyTr2., Results: Our model demonstrated a higher mean Structural Similarity Index (SSIM) of 0.863 on a test dataset of 3240 2D MRI slices from 195 patients, compared to values of 0.855, 0.797, and 0.824 for CycleGAN, CUT, and StyTr2, respectively. Similarly, our model achieved a significantly lower Fréchet Inception Distance (FID) value of 31.992, compared to values of 43.458, 179.983, and 58.784 for the other three models, indicating its superior performance in generating ADC maps. Furthermore, we evaluated our model on 147 patients from the publicly available ProstateX dataset, where it demonstrated a higher SSIM of 0.647 and a lower FID of 113.876 compared to the other three models., Conclusions: These results highlight the efficacy of our proposed model in generating ADC maps from T2W MRI, showcasing its potential for enhancing clinical diagnostics and radiological workflows.

With the ongoing revolution of artificial intelligence (AI) in medicine, the impact of AI in radiology is more pronounced than ever. An increasing number of technical and clinical AI-focused studies are published each day. As these tools inevitably affect patient care and physician practices, it is crucial that radiologists become more familiar with the leading strategies and underlying principles of AI. Multimodal AI models can combine both imaging and clinical metadata and are quickly becoming a popular approach that is being integrated into the medical ecosystem. This narrative review covers major concepts of multimodal AI through the lens of recent literature. We discuss emerging frameworks, including graph neural networks, which allow for explicit learning from non-Euclidean relationships, and transformers, which allow for parallel computation that scales, highlighting existing literature and advocating for a focus on emerging architectures. We also identify key pitfalls in current studies, including issues with taxonomy, data scarcity, and bias. By informing radiologists and biomedical AI experts about existing practices and challenges, we hope to guide the next wave of imaging-based multimodal AI research.

Rationale and Objectives: Extraprostatic extension (EPE) is well established as a significant predictor of prostate cancer aggression and recurrence. Accurate EPE assessment prior to radical prostatectomy can impact surgical approach. We aimed to utilize a deep learning-based AI workflow for automated EPE grading from prostate T2W MRI, ADC map, and High B DWI., Material and Methods: An expert genitourinary radiologist conducted prospective clinical assessments of MRI scans for 634 patients and assigned risk for EPE using a grading technique. The training set and held-out independent test set consisted of 507 patients and 127 patients, respectively. Existing deep-learning AI models for prostate organ and lesion segmentation were leveraged to extract area and distance features for random forest classification models. Model performance was evaluated using balanced accuracy, ROC AUCs for each EPE grade, as well as sensitivity, specificity, and accuracy compared to EPE on histopathology., Results: A balanced accuracy score of .390 ± 0.078 was achieved using a lesion detection probability threshold of 0.45 and distance features. Using the test set, ROC AUCs for AI-assigned EPE grades 0-3 were 0.70, 0.65, 0.68, and 0.55 respectively. When using EPE≥ 1 as the threshold for positive EPE, the model achieved a sensitivity of 0.67, specificity of 0.73, and accuracy of 0.72 compared to radiologist sensitivity of 0.81, specificity of 0.62, and accuracy of 0.66 using histopathology as the ground truth., Conclusion: Our AI workflow for assigning imaging-based EPE grades achieves an accuracy for predicting histologic EPE approaching that of physicians. This automated workflow has the potential to enhance physician decision-making for assessing the risk of EPE in patients undergoing treatment for prostate cancer due to its consistency and automation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B. J. Wood receives support as part of a cooperative research and development agreement (CRADA) between NIH and Philips Healthcare, receives royalties from NIH related to a licensing agreement with Philips Healthcare, and is party to patents or potential patents related to this work. P. L. Choyke receives royalties for MRI/ultrasound fusion biopsy patents licensed to Philips Medical. P. A. Pinto receives royalties from NIH related to a Philips licensing agreement and support as part of a CRADA between NIH and Philips Healthcare. B. Turkbey receives support as part of a CRADA between NIH and NVDIA and between NIH and Philips Healthcare, receives royalties from NIH, and is party to patents or potential patents related to this work. Jesse Tetreault: employee of NVIDIA Corporation. The remaining authors declare that there are no other disclosures relevant to the subject matter of this article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government., (Published by Elsevier Inc.)

Objective: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm., Materials and Methods: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE., Results: A total of 773 consecutive patients (median age 61 [IQR 56-67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67-76%] vs. 63% [95% CI 56-69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62-80%] vs. 75% [95% CI 63-85%]), positive predictive value (44% [95% CI 39-49%] vs. 38% [95% CI 32-43%]), or negative predictive value (89% [95% CI 86-92%] vs. 89% [95% CI 85-93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54-5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63-4.24; P = 0.24)., Conclusion: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate. However, at 9 months, quantified radiographic abnormalities resolve in the majority of patients, and yet compared to healthy persons, all showed ongoing activation of cellular repair processes and depression of the renin-kallikrein-kinin, coagulation, and complement systems. This dissociation of prolonged reparative processes from symptom and radiographic resolution suggests that occult ongoing disruption of the lung proteome is underrecognized and may be relevant to recovery from other serious viral pneumonias., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Purpose: Prostate-specific membrane antigen (PSMA)-targeting PET radiotracers reveal physiologic uptake in the urinary system, potentially misrepresenting activity in the prostatic urethra as an intraprostatic lesion. This study examined the correlation between midline 18 F-DCFPyL activity in the prostate and hyperintensity on T2-weighted (T2W) MRI as an indication of retained urine in the prostatic urethra., Patients and Methods: Eighty-five patients who underwent both 18 F-DCFPyL PSMA PET/CT and prostate MRI between July 2017 and September 2023 were retrospectively analyzed for midline radiotracer activity and retained urine on postvoid T2W MRIs. Fisher's exact tests and unpaired t tests were used to compare residual urine presence and prostatic urethra measurements between patients with and without midline radiotracer activity. The influence of anatomical factors including prostate volume and urethral curvature on urinary stagnation was also explored., Results: Midline activity on PSMA PET imaging was seen in 14 patients included in the case group, whereas the remaining 71 with no midline activity constituted the control group. A total of 71.4% (10/14) and 29.6% (21/71) of patients in the case and control groups had urethral hyperintensity on T2W MRI, respectively ( P < 0.01). Patients in the case group had significantly larger mean urethral dimensions, larger prostate volumes, and higher incidence of severe urethral curvature compared with the controls., Conclusions: Stagnated urine within the prostatic urethra is a potential confounding factor on PSMA PET scans. Integrating PET imaging with T2W MRI can mitigate false-positive calls, especially as PSMA PET/CT continues to gain traction in diagnosing localized prostate cancer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor, defined by nearly uniform rapid progression despite the current standard of care involving maximal surgical resection followed by radiation therapy (RT) and temozolomide (TMZ) or concurrent chemoirradiation (CRT), with an overall survival (OS) of less than 30% at 2 years. The diagnosis of tumor progression in the clinic is based on clinical assessment and the interpretation of MRI of the brain using Response Assessment in Neuro-Oncology (RANO) criteria, which suffers from several limitations including a paucity of precise measures of progression. Given that imaging is the primary modality that generates the most quantitative data capable of capturing change over time in the standard of care for GBM, this renders it pivotal in optimizing and advancing response criteria, particularly given the lack of biomarkers in this space. In this study, we employed artificial intelligence (AI)-derived MRI volumetric parameters using the segmentation mask output of the nnU-Net to arrive at four classes (background, edema, non-contrast enhancing tumor (NET), and contrast-enhancing tumor (CET)) to determine if dynamic changes in AI volumes detected throughout therapy can be linked to PFS and clinical features. We identified associations between MR imaging AI-generated volumes and PFS independently of tumor location, MGMT methylation status, and the extent of resection while validating that CET and edema are the most linked to PFS with patient subpopulations separated by district rates of change throughout the disease. The current study provides valuable insights for risk stratification, future RT treatment planning, and treatment monitoring in neuro-oncology.

Rationale and Objectives: Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs. metastatic lesion classification on staging CTs and to compare its performance with radiologists., Materials and Methods: This retrospective study developed two AI models using 297 staging CT scans (81 metastatic) with 4601 benign and 1911 metastatic lesions in PCa patients. Metastases were validated by follow-up scans, bone biopsy, or PET/CT. Segmentation AI (3DAISeg) was developed using the lesion contours delineated by a radiologist. 3DAISeg performance was evaluated with the Dice similarity coefficient, and classification AI (3DAIClass) performance on AI and radiologist contours was assessed with F1-score and accuracy. Training/validation/testing data partitions of 70:15:15 were used. A multi-reader study was performed with two junior and two senior radiologists within a subset of the testing dataset (n = 36)., Results: In 45 unseen staging CT scans (12 metastatic PCa) with 669 benign and 364 metastatic lesions, 3DAISeg detected 73.1% of metastatic (266/364) and 72.4% of benign lesions (484/669). Each scan averaged 12 extra segmentations (range: 1-31). All metastatic scans had at least one detected metastatic lesion, achieving a 100% patient-level detection. The mean Dice score for 3DAISeg was 0.53 (median: 0.59, range: 0-0.87). The F1 for 3DAIClass was 94.8% (radiologist contours) and 92.4% (3DAISeg contours), with a median false positive of 0 (range: 0-3). Using radiologist contours, 3DAIClass had PPV and NPV rates comparable to junior and senior radiologists: PPV (semi-automated approach AI 40.0% vs. Juniors 32.0% vs. Seniors 50.0%) and NPV (AI 96.2% vs. Juniors 95.7% vs. Seniors 91.9%). When using 3DAISeg, 3DAIClass mimicked junior radiologists in PPV (pure-AI 20.0% vs. Juniors 32.0% vs. Seniors 50.0%) but surpassed seniors in NPV (pure-AI 93.8% vs. Juniors 95.7% vs. Seniors 91.9%)., Conclusion: Our lesion detection and classification AI model performs on par with junior and senior radiologists in discerning benign and metastatic lesions on staging CTs obtained for PCa., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bradford J. Wood: Principal investigator on cooperative research and development agreement (CRADA) between National Institutes of Health (NIH) and Philips and CRADAs with industry partners unrelated to this work; travel support related to CRADAs; royalties from NIH related to Philips licensing agreement; patents planned, issued, or pending. Peter L. Choyke: Receives payment from royalties paid to the U.S. government for patents on MRI US fusion biopsy licensed to Philips Medical. Peter A. Pinto: Institutional CRADA with Philips; royalties from NIH related to Philips licensing agreement; NIH-related patents planned, issued, or pending (U.S. patent nos. 8 447 384 and 10 215 830). Baris Turkbey: CRADAs with NVIDIA and Philips; royalties from NIH; patents planned, issued, or pending in the field of artificial intelligence. Dong Yang, Ziyue Xu, Jesse Tetreault, Daguang Xu: employee of NVIDIA Corporation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Image quality evaluation of prostate MRI is important for successful implementation of MRI into localized prostate cancer diagnosis., Purpose: To examine the impact of image quality on prostate cancer detection using an in-house previously developed artificial intelligence (AI) algorithm., Study Type: Retrospective., Subjects: 615 consecutive patients (median age 67 [interquartile range [IQR]: 61-71] years) with elevated serum PSA (median PSA 6.6 [IQR: 4.6-9.8] ng/mL) prior to prostate biopsy., Field Strength/sequence: 3.0T/T2-weighted turbo-spin-echo MRI, high b-value echo-planar diffusion-weighted imaging, and gradient recalled echo dynamic contrast-enhanced., Assessments: Scans were prospectively evaluated during clinical readout using PI-RADSv2.1 by one genitourinary radiologist with 17 years of experience. For each patient, T2-weighted images (T2WIs) were classified as high-quality or low-quality based on evaluation of both general distortions (eg, motion, distortion, noise, and aliasing) and perceptual distortions (eg, obscured delineation of prostatic capsule, prostatic zones, and excess rectal gas) by a previously developed in-house AI algorithm. Patients with PI-RADS category 1 underwent 12-core ultrasound-guided systematic biopsy while those with PI-RADS category 2-5 underwent combined systematic and targeted biopsies. Patient-level cancer detection rates (CDRs) were calculated for clinically significant prostate cancer (csPCa, International Society of Urological Pathology Grade Group ≥2) by each biopsy method and compared between high- and low-quality images in each PI-RADS category., Statistical Tests: Fisher's exact test. Bootstrap 95% confidence intervals (CI). A P value <0.05 was considered statistically significant., Results: 385 (63%) T2WIs were classified as high-quality and 230 (37%) as low-quality by AI. Targeted biopsy with high-quality T2WIs resulted in significantly higher clinically significant CDR than low-quality images for PI-RADS category 4 lesions (52% [95% CI: 43-61] vs. 32% [95% CI: 22-42]). For combined biopsy, there was no significant difference in patient-level CDRs for PI-RADS 4 between high- and low-quality T2WIs (56% [95% CI: 47-64] vs. 44% [95% CI: 34-55]; P = 0.09)., Data Conclusion: Higher quality T2WIs were associated with better targeted biopsy clinically significant cancer detection performance for PI-RADS 4 lesions. Combined biopsy might be needed when T2WI is lower quality., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Therapeutic approaches targeting proteins on the surface of cancer cells have emerged as an important strategy for precision oncology. To capitalize on the potential impact of drugs targeting surface proteins, detailed knowledge about the expression patterns of the target proteins in tumor tissues is required. In castration-resistant prostate cancer (CRPC), agents targeting prostate-specific membrane antigen (PSMA) have demonstrated clinical activity. However, PSMA expression is lost in a significant number of CRPC tumors. The identification of additional cell surface targets is necessary to develop new therapeutic approaches. Here, we performed a comprehensive analysis of the expression heterogeneity and co-expression patterns of trophoblast cell-surface antigen 2 (TROP2), delta-like ligand 3 (DLL3), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in CRPC samples from a rapid autopsy cohort. We show that DLL3 and CEACAM5 exhibit the highest expression in neuroendocrine prostate cancer (NEPC), while TROP2 is expressed across different CRPC molecular subtypes, except for NEPC. We further demonstrated that AR alterations were associated with higher expression of PSMA and TROP2. Conversely, PSMA and TROP2 expression was lower in RB1-altered tumors. In addition to genomic alterations, we show a tight correlation between epigenetic states, particularly histone H3 lysine 27 methylation (H3K27me3) at the transcriptional start site and gene body of TACSTD2 (encoding TROP2), DLL3, and CEACAM5, and their respective protein expression in CRPC patient-derived xenografts. Collectively, these findings provide insights into patterns and determinants of expression of TROP2, DLL3, and CEACAM5 with implications for the clinical development of cell surface targeting agents in CRPC., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Purpose: Sequential PET/CT studies oncology patients can undergo during their treatment follow-up course is limited by radiation dosage. We propose an artificial intelligence (AI) tool to produce attenuation-corrected PET (AC-PET) images from non-attenuation-corrected PET (NAC-PET) images to reduce need for low-dose CT scans., Methods: A deep learning algorithm based on 2D Pix-2-Pix generative adversarial network (GAN) architecture was developed from paired AC-PET and NAC-PET images. 18 F-DCFPyL PSMA PET-CT studies from 302 prostate cancer patients, split into training, validation, and testing cohorts ( n = 183, 60, 59, respectively). Models were trained with two normalization strategies: Standard Uptake Value (SUV)-based and SUV-Nyul-based. Scan-level performance was evaluated by normalized mean square error (NMSE), mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Lesion-level analysis was performed in regions-of-interest prospectively from nuclear medicine physicians. SUV metrics were evaluated using intraclass correlation coefficient (ICC), repeatability coefficient (RC), and linear mixed-effects modeling., Results: Median NMSE, MAE, SSIM, and PSNR were 13.26%, 3.59%, 0.891, and 26.82, respectively, in the independent test cohort. ICC for SUV max and SUV mean were 0.88 and 0.89, which indicated a high correlation between original and AI-generated quantitative imaging markers. Lesion location, density (Hounsfield units), and lesion uptake were all shown to impact relative error in generated SUV metrics (all p < 0.05)., Conclusion: The Pix-2-Pix GAN model for generating AC-PET demonstrates SUV metrics that highly correlate with original images. AI-generated PET images show clinical potential for reducing the need for CT scans for attenuation correction while preserving quantitative markers and image quality.

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.

Objective: Automated methods for prostate segmentation on MRI are typically developed under ideal scanning and anatomical conditions. This study evaluates three different prostate segmentation AI algorithms in a challenging population of patients with prior treatments, variable anatomic characteristics, complex clinical history, or atypical MRI acquisition parameters., Materials and Methods: A single institution retrospective database was queried for the following conditions at prostate MRI: prior prostate-specific oncologic treatment, transurethral resection of the prostate (TURP), abdominal perineal resection (APR), hip prosthesis (HP), diversity of prostate volumes (large ≥ 150 cc, small ≤ 25 cc), whole gland tumor burden, magnet strength, noted poor quality, and various scanners (outside/vendors). Final inclusion criteria required availability of axial T2-weighted (T2W) sequence and corresponding prostate organ segmentation from an expert radiologist. Three previously developed algorithms were evaluated: (1) deep learning (DL)-based model, (2) commercially available shape-based model, and (3) federated DL-based model. Dice Similarity Coefficient (DSC) was calculated compared to expert. DSC by model and scan factors were evaluated with Wilcox signed-rank test and linear mixed effects (LMER) model., Results: 683 scans (651 patients) met inclusion criteria (mean prostate volume 60.1 cc [9.05-329 cc]). Overall DSC scores for models 1, 2, and 3 were 0.916 (0.707-0.971), 0.873 (0-0.997), and 0.894 (0.025-0.961), respectively, with DL-based models demonstrating significantly higher performance (p < 0.01). In sub-group analysis by factors, Model 1 outperformed Model 2 (all p < 0.05) and Model 3 (all p < 0.001). Performance of all models was negatively impacted by prostate volume and poor signal quality (p < 0.01). Shape-based factors influenced DL models (p < 0.001) while signal factors influenced all (p < 0.001)., Conclusion: Factors affecting anatomical and signal conditions of the prostate gland can adversely impact both DL and non-deep learning-based segmentation models., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Rationale and Objectives: Prostate MRI quality is essential in guiding prostate biopsies. However, assessment of MRI quality is subjective with variation. Quality degradation sources exert varying impacts based on the sequence under consideration, such as T2W versus DWI. As a result, employing sequence-specific techniques for quality assessment could yield more advantageous outcomes. This study aims to develop an AI tool that offers a more consistent evaluation of T2W prostate MRI quality, efficiently identifying suboptimal scans while minimizing user bias., Materials and Methods: This retrospective study included 1046 patients from three cohorts (ProstateX [n = 347], All-comer in-house [n = 602], enriched bad-quality MRI in-house [n = 97]) scanned between January 2011 and May 2022. An expert reader assigned T2W MRIs a quality score. A train-validation-test split of 70:15:15 was applied, ensuring equal distribution of MRI scanners and protocols across all partitions. T2W quality AI classification model was based on 3D DenseNet121 architecture using MONAI framework. In addition to multiclassification, binary classification was utilized (Classes 0/1 vs. 2). A score of 0 was given to scans considered non-diagnostic or unusable, a score of 1 was given to those with acceptable diagnostic quality with some usability but with some quality distortions present, and a score of 2 was given to those considered optimal diagnostic quality and usability. Partial occlusion sensitivity maps were generated for anatomical correlation. Three body radiologists assessed reproducibility within a subgroup of 60 test cases using weighted Cohen Kappa., Results: The best validation multiclass accuracy of 77.1% (121/157) was achieved during training. In the test dataset, multiclassification accuracy was 73.9% (116/157), whereas binary accuracy was 84.7% (133/157). Sub-class sensitivity for binary quality distortion classification for class 0 was 100% (18/18), and sub-class specificity for T2W classification of absence/minimal quality distortions for class 2 was 90.5% (95/105). All three readers showed moderate to substantial agreement with ground truth (R1-R3 κ = 0.588, κ = 0.649, κ = 0.487, respectively), moderate to substantial agreement with each other (R1-R2 κ = 0.599, R1-R3 κ = 0.612, R2-R3 κ = 0.685), fair to moderate agreement with AI (R1-R3 κ = 0.445, κ = 0.410, κ = 0.292, respectively). AI showed substantial agreement with ground truth (κ = 0.704). 3D quality heatmap evaluation revealed that the most critical non-diagnostic quality imaging features from an AI perspective related to obscuration of the rectoprostatic space (94.4%, 17/18)., Conclusion: The 3D AI model can assess T2W prostate MRI quality with moderate accuracy and translate whole sequence-level classification labels into 3D voxel-level quality heatmaps for interpretation. Image quality has a significant downstream impact on ruling out clinically significant cancers. AI may be able to help with reproducible identification of MRI sequences requiring re-acquisition with explainability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background and Objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI)., Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen's kappa ( κ ), and the system's efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated., Key Findings and Limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring ( κ  = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied., Conclusions and Clinical Implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance., Patient Summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3 + monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3 - classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients., Competing Interests: Declaration of interests C.J.W. receives research funding from Pharmacyclics and hold equity in BioNTech, Inc. F.M. is a cofounder of and has equity in Harbinger Health, has equity in Zephyr AI, and serves as a consultant for Harbinger Health, Zephyr AI, and Red Cell Partners and Exscientia. F.M. declares that none of these relationships are directly or indirectly related to the content of this manuscript. E.S. consults for and holds equity in Lyell Immunopharma and consults for Lepton Pharmaceuticals and Galaria. M.S.M. is currently employed at Normunity and holds stock in AstraZeneca; her contributions to this work were made prior to these industry positions which are not relevant to the content of this manuscript. C.L.M. is an inventor on numerous patents and patents pending related to CAR-T cell therapies. C.L.M. holds equity in and receives research funding from Lyell Immunopharma and holds equity in and consults for CARGO Therapeutics and Link Cell Therapies. C.L.M. consults for Immatics, Mammoth, Ensoma, and Red Tree Venture Capital., (Published by Elsevier Inc.)

BACKGROUND. Precise risk stratification through MRI/ultrasound (US) fusion-guided targeted biopsy (TBx) can guide optimal prostate cancer (PCa) management. OBJECTIVE. The purpose of this study was to compare PI-RADS version 2.0 (v2.0) and PI-RADS version 2.1 (v2.1) in terms of the rates of International Society of Urological Pathology (ISUP) grade group (GG) upgrade and downgrade from TBx to radical prostatectomy (RP). METHODS. This study entailed a retrospective post hoc analysis of patients who underwent 3-T prostate MRI at a single institution from May 2015 to March 2023 as part of three prospective clinical trials. Trial participants who underwent MRI followed by MRI/US fusion-guided TBx and RP within a 1-year interval were identified. A single genitourinary radiologist performed clinical interpretations of the MRI examinations using PI-RADS v2.0 from May 2015 to March 2019 and PI-RADS v2.1 from April 2019 to March 2023. Upgrade and downgrade rates from TBx to RP were compared using chi-square tests. Clinically significant cancer was defined as ISUP GG2 or greater. RESULTS. The final analysis included 308 patients (median age, 65 years; median PSA density, 0.16 ng/mL 2 ). The v2.0 group ( n = 177) and v2.1 group ( n = 131) showed no significant difference in terms of upgrade rate (29% vs 22%, respectively; p = .15), downgrade rate (19% vs 21%, p = .76), clinically significant upgrade rate (14% vs 10%, p = .27), or clinically significant downgrade rate (1% vs 1%, p > .99). The upgrade rate and downgrade rate were also not significantly different between the v2.0 and v2.1 groups when stratifying by index lesion PI-RADS category or index lesion zone, as well as when assessed only in patients without a prior PCa diagnosis (all p > .01). Among patients with GG2 or GG3 at RP ( n = 121 for v2.0; n = 103 for v2.1), the concordance rate between TBx and RP was not significantly different between the v2.0 and v2.1 groups (53% vs 57%, p = .51). CONCLUSION. Upgrade and downgrade rates from TBx to RP were not significantly different between patients whose MRI examinations were clinically interpreted using v2.0 or v2.1. CLINICAL IMPACT. Implementation of the most recent PI-RADS update did not improve the incongruence in PCa grade assessment between TBx and surgery.

Purpose: To evaluate CycleGAN's ability to enhance T2-weighted image (T2WI) quality., Method: A CycleGAN algorithm was used to enhance T2WI quality. 96 patients (192 scans) were identified from patients who underwent multiple axial T2WI due to poor quality on the first attempt (RAD1) and improved quality on re-acquisition (RAD2). CycleGAN algorithm gave DL classifier scores (0-1) for quality quantification and produced enhanced versions of QI1 and QI2 from RAD1 and RAD2, respectively. A subset (n = 20 patients) was selected for a blinded, multi-reader study, where four radiologists rated T2WI on a scale of 1-4 for quality. The multi-reader study presented readers with 60 image pairs (RAD1 vs RAD2, RAD1 vs QI1, and RAD2 vs QI2), allowing for selecting sequence preferences and quantifying the quality changes., Results: The DL classifier correctly discerned 71.9 % of quality classes, with 90.6 % (96/106) as poor quality and 48.8 % (42/86) as diagnostic in original sequences (RAD1, RAD2). CycleGAN images (QI1, QI2) demonstrated quantitative improvements, with consistently higher DL classifier scores than original scans (p < 0.001). In the multi-reader analysis, CycleGAN demonstrated no qualitative improvements, with diminished overall quality and motion in QI2 in most patients compared to RAD2, with noise levels remaining similar (8/20). No readers preferred QI2 to RAD2 for diagnosis., Conclusion: Despite quantitative enhancements with CycleGAN, there was no qualitative boost in T2WI diagnostic quality, noise, or motion. Expert radiologists didn't favor CycleGAN images over standard scans, highlighting the divide between quantitative and qualitative metrics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)