Publications

2022

Haider, Maera, Brian G Jiang, John A Parker, Andrea J Bullock, Alexander Goehler, and Leo L Tsai. (2022) 2022. “Use of MRI and Ga-68 DOTATATE for the Detection of Neuroendocrine Liver Metastases.”. Abdominal Radiology (New York) 47 (2): 586-95. https://doi.org/10.1007/s00261-021-03341-z.

PURPOSE: To compare detection rates of NET liver metastases of MRI and Ga-68-DOTATATE PET/CT to provide more clarity when selecting diagnostic imaging tests for NET staging.

METHODS: In this IRB-approved single-institution retrospective study, all patients with pathology-proven NET who underwent Ga-68-DOTATATE and MRI scans within 8 weeks of each other (3/2017-2/2020) were reviewed. Number of metastases for each patient on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and Ga-68 DOTATATE were recorded by two blinded radiologists, followed by consensus review with two separate blinded readers for MRI and nuclear medicine. Per-lesion and -modality scoring at each lesion location were then performed in consensus. Per-patient linear regression was performed comparing MRI and Ga-68 DOTATATE detection rates for each reader and in consensus, and per-lesion-matched pair difference means were used to compare detection frequency between modalities.

RESULTS: 32 patients (mean age 59 years, 59.4% male) and 90 liver metastases were analyzed. Intraclass coefficients (ICC) [95% CI] between the two readers were 0.97 [0.95, 0.99], 0.89 [0.82, 0.94], and 0.98 [0.97, 0.99] for Ga-68 DOTATATE, DWI, and DCE, respectively. Matched per-lesion mean differences were + 0.17 ± 0.07 (p = 0.01) and + 0.22 ± 0.06 (p =  < 0.001) for DWI versus Ga-68 DOTATATE and DCE vs Ga-68 DOTATATE, respectively, favoring MRI. Case-based linear regressions estimate that DWI and DCE detect 1.28 [1.07, 1.49] and 1.33 [1.12, 1.54] lesions, respectively, for each one detected on Ga-68 DOTATATE.

CONCLUSION: MRI detects more hepatic NET metastasis in comparison to Ga-68 DOTATATE. Liver MRI should be performed in concert with Ga-68 DOTATATE in NET staging.

Cahill, Lucas C, Seymour Rosen, Tadayuki Yoshitake, Yubo Wu, Linda York, Leo L Tsai, Boris Gershman, James G Fujimoto, and Yue Sun. (2022) 2022. “Real-Time Diagnosis and Gleason Grading of Prostate Core Needle Biopsies Using Nonlinear Microscopy.”. Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc 35 (4): 539-48. https://doi.org/10.1038/s41379-021-00960-1.

Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses and research that could benefit from fresh tissue analysis. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can produce high-resolution images of freshly excised tissue resembling formalin-fixed paraffin-embedded (FFPE) H&E. NLM enables evaluation of tissue up to  100 µm below the surface, analogous to serial sectioning, but without requiring microtome sectioning. One hundred and seventy biopsies were collected from 63 patients who underwent in-bore MRI or MRI/ultrasound fusion biopsy procedures. Biopsies were stained in acridine orange and sulforhodamine 101, a nuclear and cytoplasmic/stromal fluorescent dye, for 45 s. Genitourinary pathologists evaluated the biopsies using NLM by translating the biopsies in real time to areas of interest and NLM images were recorded. After NLM evaluation, the biopsies were processed for standard FFPE H&E and similarities and differences between NLM and FFPE H&E were investigated. Accuracies of NLM diagnoses and Gleason scores were calculated using FFPE histology as the gold standard. Pathologists achieved a 92.4% sensitivity (85.0-96.9%, 95% confidence intervals) and 100.0% specificity (94.3-100.0%) for detecting carcinoma compared to FFPE histology. The agreement between the Grade Group determined by NLM versus FFPE histology had an unweighted Cohen's Kappa of 0.588. The average NLM evaluation time was 2.10 min per biopsy (3.08 min for the first 20 patients, decreasing to 1.54 min in subsequent patients). Further studies with larger patient populations, larger number of pathologists, and multiple institutions are warranted. NLM is a promising method for future rapid evaluation of prostate needle core biopsies.

Hartigan, Philip M, Sergey Karamnov, Ritu R Gill, Ju-Mei Ng, Stephanie Yacoubian, Hisashi Tsukada, Jeffrey Swanson, Julianne Barlow, Timothy L McMurry, and Randal S Blank. (2022) 2022. “Mediastinal Masses, Anesthetic Interventions, and Airway Compression in Adults: A Prospective Observational Study.”. Anesthesiology 136 (1): 104-14. https://doi.org/10.1097/ALN.0000000000004011.

BACKGROUND: Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency.

METHODS: Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases.

RESULTS: No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase.

CONCLUSIONS: These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients.

Soustelle, Lucas, Thomas Troalen, Andreea Hertanu, Samira Mchinda, Jean-Philippe Ranjeva, Maxime Guye, Gopal Varma, David C Alsop, Guillaume Duhamel, and Olivier M Girard. (2022) 2022. “A Strategy to Reduce the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) Imaging to Radiofrequency Transmit Field Variations at 3 T.”. Magnetic Resonance in Medicine 87 (3): 1346-59. https://doi.org/10.1002/mrm.29055.

PURPOSE: To minimize the sensitivity of inhomogeneous magnetization transfer gradient-echo (ihMT-GRE) imaging to radiofrequency (RF) transmit field ( B1+ ) inhomogeneities at 3 T.

METHODS: The ihMT-GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to B1+ variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global B1+ drop. The resulting relative variations (δihMTR ) were evaluated voxelwise as a function of the local B1+ distribution. The reproducibility of the protocol providing minimal B1+ bias was assessed in a test-retest experiment.

RESULTS: In line with simulations, ihMT-GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the B1+ inhomogeneity effects in the human WM. Under the optimal conditions of 350-ms TR and 3-µT root mean square (RMS) saturation power, 73% of all WM voxels presented δihMTR below 10%. Reproducibility analysis yielded a close-to-zero systematic bias (ΔihMTR = -0.081%) and a high correlation (ρ² = 0.977) between test and retest experiments.

CONCLUSION: Concentrating RF saturation energy in ihMT-GRE sequences mitigates the sensitivity of the ihMTR to B1+ variations and allows for clinical-ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra-high field applications.

Asrani, Sumeet K, Marwan S Ghabril, Alexander Kuo, Raphael B Merriman, Timothy Morgan, Neehar D Parikh, Nadia Ovchinsky, et al. (2022) 2022. “Quality Measures in HCC Care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.”. Hepatology (Baltimore, Md.) 75 (5): 1289-99. https://doi.org/10.1002/hep.32240.

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Grossman, Joseph E, Lakshmi Muthuswamy, Ling Huang, Dipikaa Akshinthala, Sofia Perea, Raul S Gonzalez, Leo L Tsai, et al. (2022) 2022. “Organoid Sensitivity Correlates With Therapeutic Response in Patients With Pancreatic Cancer.”. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 28 (4): 708-18. https://doi.org/10.1158/1078-0432.CCR-20-4116.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.

EXPERIMENTAL DESIGN: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes.

RESULTS: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients.

CONCLUSIONS: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

van der Pol, Christian B, Matthew D F McInnes, Jean-Paul Salameh, Brooke Levis, Victoria Chernyak, Claude B Sirlin, Mustafa R Bashir, et al. (2022) 2022. “CT/MRI and CEUS LI-RADS Major Features Association With Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.”. Radiology 302 (2): 326-35. https://doi.org/10.1148/radiol.2021211244.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Eisenberg, Ronald Lee. (2022) 2022. “Burnout.”. Academic Radiology 29 (2): 284-86. https://doi.org/10.1016/j.acra.2021.10.003.
Camacho, Andrés, Andrew D Chung, Francesca Rigiroli, Mehmet Ali Sari, Alexander Brook, Bettina Siewert, Muneeb Ahmed, and Olga Rachel Brook. (2022) 2022. “Concordance Assessment of Pathology Results With Imaging Findings After Image-Guided Biopsy.”. Journal of Vascular and Interventional Radiology : JVIR 33 (2): 159-168.e1. https://doi.org/10.1016/j.jvir.2021.11.001.

PURPOSE: To assess the impact of radiology review for discordance between pathology results from computed tomography (CT)-guided biopsies versus imaging findings performed before a biopsy.

MATERIALS AND METHODS: In this retrospective review, which is compliant with the Health Insurance Portability and Accountability Act and approved by the institutional review board, 926 consecutive CT-guided biopsies performed between January 2015 and December 2017 were included. In total, 453 patients were presented in radiology review meetings (prospective group), and the results were classified as concordant or discordant. Results from the remaining 473 patients not presented at the radiology review meetings were retrospectively classified. Times to reintervention and to definitive diagnosis were obtained for discordant cases; of these, 49 (11%) of the 453 patients were in the prospective group and 55 (12%) of the 473 patients in the retrospective group.

RESULTS: Pathology results from CT-guided biopsies were discordant with imaging in 11% (104/926) of the cases, with 57% (59/104) of these cases proving to be malignant. In discordant cases, reintervention with biopsy and surgery yielded a shorter time to definitive diagnosis (28 and 14 days, respectively) than an imaging follow-up (78 days) (P < .001). The median time to diagnosis was 41 days in the prospective group and 56 days in the retrospective group (P = .46). When radiologists evaluated the concordance between pathology and imaging findings and recommended a repeat biopsy for the discordant cases, more biopsies were performed (50% [11/22] vs 13% [4/31]; P = .005).

CONCLUSIONS: Eleven percent of CT-guided biopsies yielded pathology results that were discordant with imaging findings, with 57% of these proving to be malignant on further workup.

Ghadimi, Maryam, Jason Birnbaum, Ihab R Kamel, Claude B Sirlin, and Victoria Chernyak. (2022) 2022. “What Proportion of LI-RADS 5 Observations Reported in Clinical Practice Do Not Meet LI-RADS 5 Criteria?”. European Radiology 32 (5): 3327-33. https://doi.org/10.1007/s00330-021-08389-5.

OBJECTIVES: Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 (definite hepatocellular carcinoma [HCC]) is assigned based on combinations of major imaging features (MFs): size, arterial-phase hyperenhancement (APHE), washout (WO), enhancing capsule, and threshold growth. The criteria were simplified in v2018 compared to v2017. The goal of this study is to assess the proportion of LR-5 observations reported in clinical practice with LI-RADS v2017 or v2018 that did not meet LR-5 criteria based on reported MFs.

METHODS: All MR and CT reports using a standardized LI-RADS template between April 2017 and September 2020 were identified retrospectively. For each reported LR-5 observation, size, MFs, and LI-RADS version (v2017 or v2018) were extracted. Reported MFs were used to determine whether LR-5 criteria were met using the applied version of LI-RADS. The data was summarized descriptively.

RESULTS: Three hundred eight observations in 234 patients (67.6% male, mean age 66.2 years) were reported as LR-5, including 136 (44.2%) with v2017 and 172 (55.8%) with v2018. 8/136 (6%) v2017 LR-5 observations and 6/172 (3%) v2018 LR-5 observations did not meet LR-5 criteria. Of 8 incorrectly categorized v2017 observations, 3 (43%) lacked APHE, 1 (14%) was a 16-mm new observation with APHE only, and 4 (43%) were 10-19 mm with APHE and WO. Of the 6 incorrectly categorized v2018 observations, 5 (83%) lacked APHE and 1 (17%) was < 10 mm.

CONCLUSIONS: Depending on the LI-RADS version, 3-6% of LR-5 observations reported in clinical practice do not meet LR-5 criteria based on reported MFs. Key Points • Depending on the LI-RADS version, 3-6% of LR-5 observations in clinical practice do not meet LR-5 criteria based on reported major imaging features. • Assigning LR-5 category to observations without nonrim arterial-phase hyperenhancement was the most common error.