Faculty Bibliography

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Purpose: Develop an integrated intra-site and inter-site radiomics-clinical-genomic marker of high grade serous ovarian cancer (HGSOC) outcomes and explore the biological basis of radiomics with respect to molecular signaling pathways and the tumor microenvironment (TME). Method: Seventy-five stage III-IV HGSOC patients from internal (N = 40) and external factors via the Cancer Imaging Archive (TCGA) (N = 35) with pre-operative contrast enhanced CT, attempted primary cytoreduction, at least two disease sites, and molecular analysis performed within TCGA were retrospectively analyzed. An intra-site and inter-site radiomics (cluDiss) measure was combined with clinical-genomic variables (iRCG) and compared against conventional (volume and number of sites) and average radiomics (N = 75) for prognosticating progression-free survival (PFS) and platinum resistance. Correlation with molecular signaling and TME derived using a single sample gene set enrichment that was measured. Results: The iRCG model had the best platinum resistance classification accuracy (AUROC of 0.78 [95% CI 0.77 to 0.80]). CluDiss was associated with PFS (HR 1.03 [95% CI: 1.01 to 1.05], p = 0.002), negatively correlated with Wnt signaling, and positively to immune TME. Conclusions: CluDiss and the iRCG prognosticated HGSOC outcomes better than conventional and average radiomic measures and could better stratify patient outcomes if validated on larger multi-center trials.

For clinically significant, locally confined prostate cancer, whole-gland radical prostatectomy and radiotherapy are established effective treatment strategies that, however, come at a cost of significant morbidity related to urinary and sexual side effects. The concept of risk stratification paired with a better understanding of prognostic factors has led to the development of alternative management options including active surveillance and focal therapy for appropriately selected patients with localized disease. High-intensity focused ultrasound (HIFU) is one such minimally invasive, image-guided treatment option for prostate cancer. Due to the relative novelty of HIFU and the increased use of magnetic resonance imaging in prostate cancer, many radiologists are not yet familiar with imaging findings related to HIFU, their temporal evolution as well as imaging appearance of recurrent disease after this type of focal therapy. HIFU induces sharply demarcated, localized coagulative necrosis of a tumor through thermal energy delivered via an endorectal or transurethral ultrasound transducer. In this pictorial review, we aim at providing relevant background information that will guide the reader through the general principles of HIFU in the prostate, as well as demonstrate the imaging appearance of expected post-HIFU changes versus recurrent tumor.

To date, there is little consensus on the role of pelvic imaging in assessing local disease extent during initial staging in patients with endometrial carcinoma, with practices differing widely across centers. However, when pretreatment assessment of local tumor extent is indicated, MRI is the preferred imaging modality. Preoperative imaging of endometrial carcinoma can define the extent of disease and indicate the need for subspecialist referral in the presence of deep myometrial invasion, cervical extension, or suspected lymphadenopathy. If distant metastatic disease is clinically suspected, preoperative assessment with cross-sectional imaging or PET/CT may be performed. However, most patients with low-grade disease are at low risk of lymph node and distant metastases. Thus, this group may not require a routine pretreatment evaluation for distant metastases. Recurrence rates in patients with endometrial carcinoma are infrequent. Therefore, radiologic evaluation is typically used only to investigate suspicion of recurrent disease due to symptoms or physical examination and not for routine surveillance after treatment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen's Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78-0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader's experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; p= 0.003 and 0.036, SE: 0.009; p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.

OBJECTIVES/OBJECTIVE:To review the diagnostic performance of contemporary imaging modalities for determining local disease extent and nodal metastasis in patients with newly diagnosed cervical cancer. METHODS:Pubmed and Embase databases were searched for studies published from 2000 to 2019 that used ultrasound (US), CT, MRI, and/or PET for evaluating various aspects of local extent and nodal metastasis in patients with newly diagnosed cervical cancer. Sensitivities and specificities from the studies were meta-analytically pooled using bivariate and hierarchical modeling. RESULTS:Of 1311 studies identified in the search, 115 studies with 13,999 patients were included. MRI was the most extensively studied modality (MRI, CT, US, and PET were evaluated in 78, 12, 9, and 43 studies, respectively). Pooled sensitivities and specificities of MRI for assessing all aspects of local extent ranged between 0.71-0.88 and 0.86-0.95, respectively. In assessing parametrial invasion (PMI), US demonstrated pooled sensitivity and specificity of 0.67 and 0.94, respectively-performance levels comparable with those found for MRI. MRI, CT, and PET performed comparably for assessing nodal metastasis, with low sensitivity (0.29-0.69) but high specificity (0.88-0.98), even when stratified to anatomical location (pelvic or paraaortic) and level of analysis (per patient vs. per site). CONCLUSIONS:MRI is the method of choice for assessing any aspect of local extent, but where not available, US could be of value, particularly for assessing PMI. CT, MRI, and PET all have high specificity but poor sensitivity for the detection of lymph node metastases. KEY POINTS/CONCLUSIONS:• Magnetic resonance imaging is the method of choice for assessing local extent. • Ultrasound may be helpful in determining parametrial invasion, especially in lower-resourced countries. • Computed tomography, magnetic resonance imaging, and positron emission tomography perform similarly for assessing lymph node metastasis, with high specificity but low sensitivity.

PURPOSE/OBJECTIVE:Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown promise for detecting nodal and distant prostate cancer (PCa) metastases. However, its performance for local tumor staging is not as well established. The purpose of this study was to review the diagnostic performance of PSMA-PET for determining seminal vesical invasion (SVI) and extraprostatic extension (EPE). METHODS:Pubmed and Embase databases were searched until January 12, 2020. Studies assessing accuracy of PSMA-PET in determining SVI and EPE were included. Study quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity were calculated using hierarchical summary receiver operating characteristics modeling. Heterogeneity was explored using meta-regression analyses for anatomical imaging component (MRI vs CT) and by testing for a threshold effect. RESULTS:Twelve studies (615 patients) were included. Pooled sensitivity and specificity were 0.68 (95% CI 0.53-0.81) and 0.94 (95% CI 0.90-0.96) for SVI and 0.72 (95% CI 0.56-0.84) and 0.87 (95% CI 0.72-0.94) for EPE. Meta-regression analyses showed that for SVI, PET/MRI demonstrated greater sensitivity than PET/CT (0.87 [95% CI 0.75-0.98] vs 0.60 [95% CI 0.47-0.74]; p = 0.02 for joint model) while specificity was comparable (0.91 [95% CI 0.84-0.97] vs. 0.96 [95% CI 0.93-0.99]) but not for EPE (p = 0.08). A threshold effect was present for studies assessing EPE (correlation coefficient = 0.563 [95% CI, -0.234-0.908] between sensitivity and false-positive rate). CONCLUSION/CONCLUSIONS:PSMA-PET has moderate sensitivity and excellent specificity for assessing local tumor extent in patients with PCa. PET/MRI showed potential for greater sensitivity than PET/CT in assessing SVI.

Accurate staging of bladder cancer (BC) is critical, with local tumor staging directly influencing management decisions and affecting prognosis. However, clinical staging based on clinical examination, including cystoscopy and transurethral resection of bladder tumor (TURBT), often understages patients compared to final pathology at radical cystectomy and lymph node (LN) dissection, mainly due to underestimation of the depth of local invasion and the presence of LN metastasis. MRI has now become established as the modality of choice for the local staging of BC and can be additionally utilized for the assessment of regional LN involvement and tumor spread to the pelvic bones and upper urinary tract (UUT). The recent development of the Vesical Imaging-Reporting and Data System (VI-RADS) recommendations has led to further improvements in bladder MRI, enabling standardization of image acquisition and reporting. Multiparametric magnetic resonance imaging (mpMRI) incorporating morphological and functional imaging has been proven to further improve the accuracy of primary and recurrent tumor detection and local staging, and has shown promise in predicting tumor aggressiveness and monitoring response to therapy. These sequences can also be utilized to perform radiomics, which has shown encouraging initial results in predicting BC grade and local stage. In this article, the current state of evidence supporting MRI in local, regional, and distant staging in patients with BC is reviewed. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:649-667.

Purpose/UNASSIGNED:To investigate the feasibility of accelerating prostate diffusion-weighted imaging (DWI) by reducing the number of acquired averages and denoising the resulting image using a proposed guided denoising convolutional neural network (DnCNN). Materials and Methods/UNASSIGNED:-value DW image as a guidance input. Quantitative and qualitative reader evaluations were performed on the denoised hb DW images. A cumulative link mixed regression model was used to compare the readers' scores. The agreement between the apparent diffusion coefficient (ADC) maps (denoised vs reference) was analyzed using Bland-Altman analysis. Results/UNASSIGNED:/sec). Conclusion/UNASSIGNED:© RSNA, 2020.

OBJECTIVES/OBJECTIVE:To investigate the association between CT imaging traits and texture metrics with proteomic data in patients with high-grade serous ovarian cancer (HGSOC). METHODS:This retrospective, hypothesis-generating study included 20 patients with HGSOC prior to primary cytoreductive surgery. Two readers independently assessed the contrast-enhanced computed tomography (CT) images and extracted 33 imaging traits, with a third reader adjudicating in the event of a disagreement. In addition, all sites of suspected HGSOC were manually segmented texture features which were computed from each tumor site. Three texture features that represented intra- and inter-site tumor heterogeneity were used for analysis. An integrated analysis of transcriptomic and proteomic data identified proteins with conserved expression between primary tumor sites and metastasis. Correlations between protein abundance and various CT imaging traits and texture features were assessed using the Kendall tau rank correlation coefficient and the Mann-Whitney U test, whereas the area under the receiver operating characteristic curve (AUC) was reported as a metric of the strength and the direction of the association. P values < 0.05 were considered significant. RESULTS:Four proteins were associated with CT-based imaging traits, with the strongest correlation observed between the CRIP2 protein and disease in the mesentery (p < 0.001, AUC = 0.05). The abundance of three proteins was associated with texture features that represented intra-and inter-site tumor heterogeneity, with the strongest negative correlation between the CKB protein and cluster dissimilarity (p = 0.047, τ = 0.326). CONCLUSION/CONCLUSIONS:This study provides the first insights into the potential associations between standard-of-care CT imaging traits and texture measures of intra- and inter-site heterogeneity, and the abundance of several proteins. KEY POINTS/CONCLUSIONS:• CT-based texture features of intra- and inter-site tumor heterogeneity correlate with the abundance of several proteins in patients with HGSOC. • CT imaging traits correlate with protein abundance in patients with HGSOC.