Publications

2021

Appel, Elisabeth, Johannes Boos, Jieming Fang, Da Zhang, Carol Wilcox, Andrés Camacho, Sujithraj Dommaraju, Alexander Brook, and Olga R Brook. (2021) 2021. “Minimizing Radiation Dose Outliers Through Systematic Analysis, Computed Tomography Technologist Education, and Standardized System Solutions.”. Journal of Computer Assisted Tomography 45 (1): 78-83. https://doi.org/10.1097/RCT.0000000000000985.

OBJECTIVES: The aims of the study were to systematically analyze causes for radiation dose outliers in emergency department noncontrast head computed tomographies (CTs), to develop and implement standardized system solutions, and audit program success for an extended period of time.

METHODS: This study was performed in a large, tertiary academic center between January 2015 and September 2017. Four phases of radiation dose data collection with and without prior interventions were performed. Outliers from 5 categories were evaluated for appropriateness in consensus by 2 radiologists and a senior CT technologist.

RESULTS: A total of 275 ± 15 CTs per period were included. Fifty-seven inappropriate scanning parameters were found in 24 (9%) of 254 CTs during the first analysis, 27 in 21 (7%) of 290 CTs during the second, 11 in 10 (4%) of 276 during the third assessment (P = 0.006). After a year without additional intervention, the number remained stable (14 in 11/281 CTs, 4%).

CONCLUSIONS: Combining a dose reporting system, individual case analysis, staff education, and implementation of systemic solutions lead to sustained radiation exposure improvement.

Bezuidenhout, Abraham F, Ekkehard M Kasper, Olivier Baledent, Rafael Rojas, and Rafeeque A Bhadelia. (2021) 2021. “Relationship Between Pineal Cyst Size and Aqueductal CSF Flow Measured by Phase Contrast MRI.”. Journal of Neurosurgical Sciences 65 (1): 63-68. https://doi.org/10.23736/S0390-5616.18.04258-3.

BACKGROUND: Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI.

METHODS: Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test.

RESULTS: Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13,752±3738 mm3; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 μL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 μL/cardiac cycle (P=0.008).

CONCLUSIONS: Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

Karimi, Zahra, Jordana Phillips, Priscilla Slanetz, Parisa Lotfi, Vandana Dialani, Jane Karimova, and Tejas Mehta. (2021) 2021. “Factors Associated With Background Parenchymal Enhancement on Contrast-Enhanced Mammography.”. AJR. American Journal of Roentgenology 216 (2): 340-48. https://doi.org/10.2214/AJR.19.22353.

OBJECTIVE. The purpose of this study was to determine the relationship between background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM) and breast tissue density, menstrual status, endocrine therapy, and risk factors for breast cancer and also to evaluate interreader agreement on classification of BPE on CEM. MATERIALS AND METHODS. Five subspecialty-trained breast radiologists independently and blindly graded tissue density (with fatty tissue and scattered fibroglandular tissue classified as nondense tissue and with heterogeneously dense and extremely dense classified as dense tissue) and BPE (with minimal or mild BPE categorized as low BPE and moderate or marked BPE categorized as high BPE) on CEM examinations performed from 2014 to 2018. Electronic medical charts were reviewed for information on menstrual status, endocrine therapy, history of breast surgery, and other risk factors for breast cancer. Comparisons were performed using the Kruskal-Wallis test, Mann-Whitney test, and Spearman rank correlation. Interreader agreement was estimated using the Fleiss kappa test. RESULTS. A total of 202 patients (mean [± SD] age, 54 ± 10 years; range, 25-84 years) underwent CEM. Tissue density was categorized as fatty in two patients (1%), scattered fibroglandular in 67 patients (33%), heterogeneously dense in 117 patients (58%), and extremely dense in 16 patients (8%). Among the 202 patients, BPE was minimal in 77 (38%), mild in 80 (40%), moderate in 31 (15%), and marked in 14 (7%). Dense breasts, younger age, premenopausal status, no history of endocrine therapy, and no history of breast cancer were significantly associated with high BPE. Among premenopausal patients, no association was found between BPE and time from last menstrual period to CEM. Overall interreader agreement on BPE was moderate (κ = 0.41; 95% CI, 0.40-0.42). Interreader agreement on tissue density was substantial (κ = 0.67; 95% CI, 0.66-0.69). CONCLUSION. Women with dense breasts, premenopausal status, and younger age are more likely to have greater BPE. Targeting CEM to the last menstrual period is not indicated.

Tsai, Leo L, Rupal S Bhatt, Meaghan F Strob, Opeyemi A Jegede, Maryellen R M Sun, David C Alsop, Paul Catalano, et al. (2021) 2021. “Arterial Spin Labeled Perfusion MRI for the Evaluation of Response to Tyrosine Kinase Inhibition Therapy in Metastatic Renal Cell Carcinoma.”. Radiology 298 (2): 332-40. https://doi.org/10.1148/radiol.2020201763.

Background Tumor perfusion may inform therapeutic response and resistance in metastatic renal cell carcinoma (RCC) treated with antiangiogenic therapy. Purpose To determine if arterial spin labeled (ASL) MRI perfusion changes are associated with tumor response and disease progression in metastatic RCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Materials and Methods In this prospective study (ClinicalTrials.gov identifier: NCT00749320), metastatic RCC perfusion was measured with ASL MRI before and during sunitinib or pazopanib therapy between October 2008 and March 2014. Objective response rate (ORR) and progression-free survival (PFS) were calculated. Perfusion was compared between responders and nonresponders at baseline, at week 2, after cycle 2 (12 weeks), after cycle 4 (24 weeks), and at disease progression and compared with the ORR by using the Wilcoxon rank sum test and with PFS by using the log-rank test. Results Seventeen participants received sunitinib (mean age, 59 years ± 7.0 [standard deviation]; 11 men); 11 participants received pazopanib (mean age, 63 years ± 6.6; eight men). Responders had higher baseline tumor perfusion than nonresponders (mean, 404 mL/100 g/min ± 213 vs 199 mL/100 g/min ± 136; P = .02). Perfusion decreased from baseline to week 2 (-53 mL/100 g/min ± 31; P < .001), after cycle 2 (-65 mL/100 g/min ± 25; P < .001), and after cycle 4 (-79 mL/100 g/min ± 15; P = .008). Interval reduction in perfusion at those three time points was not associated with ORR (P = .63, .29, and .27, respectively) or PFS (P = .28, .27, and .32). Perfusion increased from cycle 4 to disease progression (51% ± 11; P < .001). Conclusion Arterial spin labeled perfusion MRI may assist in identifying responders to vascular endothelial growth factor receptor tyrosine kinase inhibitors and may help detect early evidence of disease progression in patients with metastatic renal cell carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Goh and De Vita in this issue.

Weinstein, Jeffrey L, Fady El-Gabalawy, Ammar Sarwar, Sarah Schroeppel DeBacker, Salomao Faintuch, Seth J Berkowitz, Julie C Bulman, et al. (2021) 2021. “Analysis of Kinematic Differences in Hand Motion Between Novice and Experienced Operators in IR: A Pilot Study.”. Journal of Vascular and Interventional Radiology : JVIR 32 (2): 226-34. https://doi.org/10.1016/j.jvir.2020.10.010.

PURPOSE: To prospectively validate electromagnetic hand motion tracking in interventional radiology to detect differences in operator experience using simulation.

METHODS: Sheath task: Six attending interventional radiologists (experts) and 6 radiology trainees (trainees) placed a wire through a sheath and performed a "pin-pull" maneuver, while an electromagnetic motion detection system recorded the hand motion. Radial task: Eight experts and 12 trainees performed palpatory radial artery access task on a radial access simulator. The trainees repeated the task with the nondominant hand. The experts were classified by their most frequent radial artery access technique as having either palpatory, ultrasound, or overall limited experience. The time, path length, and number of movements were calculated. Mann-Whitney U tests were used to compare the groups, and P < .05 was considered significant.

RESULTS: Sheath task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (11.7 seconds ± 3.3 vs 19.7 seconds ± 6.5, P < .01; 1.1 m ± 0.3 vs 1.4 m ± 0.4, P < .01; and 19.5 movements ± 8.5 vs 31.0 movements ± 8.0, P < .01, respectively). Radial task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (24.2 seconds ± 10.6 vs 33.1 seconds ± 16.9, P < .01; 2.0 m ± 0.5 vs 3.0 m ± 1.9, P < .001; and 36.5 movements ± 15.0 vs 54.5 movements ± 28.0, P < .001, respectively). The trainees had a shorter path length for their dominant hand than their nondominant hand (3.0 m ± 1.9 vs 3.5 m ± 1.9, P < .05). The expert palpatory group had a shorter path length than the ultrasound and limited experience groups (1.8 m ± 0.4 vs 2.0 m ± 0.4 and 2.3 m ± 1.2, respectively, P < .05).

CONCLUSIONS: Electromagnetic hand motion tracking can differentiate between the expert and trainee operators for simulated interventional tasks.

Sehgal, Kartik, Ritu R Gill, Page Widick, Poorva Bindal, Danielle C McDonald, Meghan Shea, Deepa Rangachari, and Daniel B Costa. (2021) 2021. “Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy.”. JAMA Network Open 4 (2): e2037120. https://doi.org/10.1001/jamanetworkopen.2020.37120.

IMPORTANCE: Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group.

OBJECTIVE: To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020.

EXPOSURES: ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability.

MAIN OUTCOMES AND MEASURES: PFS and OS, measured from initiation of pembrolizumab monotherapy.

RESULTS: Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004).

CONCLUSIONS AND RELEVANCE: In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.

Maragkos, Georgios A, Aristotelis S Filippidis, Sasank Chilamkurthy, Mohamed M Salem, Swetha Tanamala, Santiago Gomez-Paz, Pooja Rao, et al. (2021) 2021. “Automated Lateral Ventricular and Cranial Vault Volume Measurements in 13,851 Patients Using Deep Learning Algorithms.”. World Neurosurgery 148: e363-e373. https://doi.org/10.1016/j.wneu.2020.12.148.

BACKGROUND: No large dataset-derived standard has been established for normal or pathologic human cerebral ventricular and cranial vault volumes. Automated volumetric measurements could be used to assist in diagnosis and follow-up of hydrocephalus or craniofacial syndromes. In this work, we use deep learning algorithms to measure ventricular and cranial vault volumes in a large dataset of head computed tomography (CT) scans.

METHODS: A cross-sectional dataset comprising 13,851 CT scans was used to deploy U-Net deep learning networks to segment and quantify lateral cerebral ventricular and cranial vault volumes in relation to age and sex. The models were validated against manual segmentations. Corresponding radiologic reports were annotated using a rule-based natural language processing framework to identify normal scans, cerebral atrophy, or hydrocephalus.

RESULTS: U-Net models had high fidelity to manual segmentations for lateral ventricular and cranial vault volume measurements (Dice index, 0.878 and 0.983, respectively). The natural language processing identified 6239 (44.7%) normal radiologic reports, 1827 (13.1%) with cerebral atrophy, and 1185 (8.5%) with hydrocephalus. Age-based and sex-based reference tables with medians, 25th and 75th percentiles for scans classified as normal, atrophy, and hydrocephalus were constructed. The median lateral ventricular volume in normal scans was significantly smaller compared with hydrocephalus (15.7 vs. 82.0 mL; P < 0.001).

CONCLUSIONS: This is the first study to measure lateral ventricular and cranial vault volumes in a large dataset, made possible with artificial intelligence. We provide a robust method to establish normal values for these volumes and a tool to report these on CT scans when evaluating for hydrocephalus.

Baker, Gabrielle M, Yaileen D Guzman-Arocho, Vanessa C Bret-Mounet, Vanda F Torous, Stuart J Schnitt, Adam M Tobias, Richard A Bartlett, et al. (2021) 2021. “Testosterone Therapy and Breast Histopathological Features in Transgender Individuals.”. Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc 34 (1): 85-94. https://doi.org/10.1038/s41379-020-00675-9.

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

Torous, Vanda F, Nancy A Resteghini, Jordana Phillips, Vandana Dialani, Priscilla J Slanetz, Stuart J Schnitt, and Gabrielle M Baker. (2021) 2021. “Histopathologic Correlates of Nonmass Enhancement Detected by Breast Magnetic Resonance Imaging.”. Archives of Pathology & Laboratory Medicine 145 (10): 1264-69. https://doi.org/10.5858/arpa.2020-0266-OA.

CONTEXT.—: Dynamic, contrast-enhanced magnetic resonance imaging (MRI) is a highly sensitive imaging modality used for screening and diagnostic purposes. Nonmass enhancement (NME) is commonly seen on MRI of the breast. However, the pathologic correlates of NME have not been extensively explored. Consequently, concordance between MRI and pathologic findings in such cases may be uncertain and this uncertainty may cause the need for additional procedures.

OBJECTIVE.—: To examine the histologic alterations that correspond to NME on MRI.

DESIGN.—: We performed a retrospective search for women who underwent breast MRI between March 2014 and December 2016 and identified 130 NME lesions resulting in biopsy. The MRI findings and pathology slides for all cases were reviewed. The follow-up findings on any subsequent excisions were also noted.

RESULTS.—: Among the 130 cases, the core needle biopsy showed 1 or more benign lesions without atypia in 80 cases (62%), atypical lesions in 21 (16%), ductal carcinoma in situ in 22 (17%), and invasive carcinoma in 7 (5%). Review of the imaging features demonstrated some statistically significant differences in lesions that corresponded to malignant lesions as compared with benign alterations, including homogeneous or clumped internal enhancement, type 3 kinetics, and T2 dark signal; however, there was considerable overlap of features between benign and malignant lesions overall. Of 130 cases, 54 (41.5%) underwent subsequent excision with only 6 cases showing a worse lesion on excision.

CONCLUSIONS.—: This study illustrates that NME can be associated with benign, atypical, and/or malignant pathology and biopsy remains indicated given the overlap of radiologic features.

Ali, Aamir, Komal Manzoor, Yu-Ming Chang, Pritesh J Mehta, Alexander Brook, David B Hackney, Jonathan A Edlow, and Rafeeque A Bhadelia. (2021) 2021. “Role of C-Reactive Protein in Effective Utilization of Emergent MRI for Spinal Infections.”. Emergency Radiology 28 (3): 573-80. https://doi.org/10.1007/s10140-020-01892-0.

PURPOSE: Emergent spinal MRI is recommended for patients with back pain and red flags for infection. However, many of these studies are negative due to low prevalence of spinal infections. Our purpose was to assess if C-reactive protein (CRP) can be used to guide effective utilization of emergent MRI for spinal infections.

METHODS: 316/960 (33%) MRIs performed for infection by the emergency department over 75-month period had CRP levels obtained at presentation, after excluding patients receiving antibiotic or had spinal surgery in < 1 month. An MRI was considered positive when there was imaging evidence of spinal infection confirmed on follow-up by surgery/biopsy/drainage or definitive therapy. A CRP of ≤ 10 mg/L was considered normal and > 100 mg/L as highly elevated.

RESULTS: CRP was normal in 95/316 (30%) and abnormal in 221/316 (70%) patients. MRI was positive in 43/316 (13.6%) patients, all of whom had abnormal CRP. CRP (p < 0.001) and intravenous drug use (IVDU; p = 0.002) were independently associated with a positive MRI. Receiver operator characteristic (ROC) analysis showed AUC of 0.76 for CRP, slightly improving with IVDU. Sensitivity, specificity, and negative predictive values for CRP level cut-off: 10 mg/L, 100%, 35%, and 100%, and 100 mg/L, 58%, 70% and 91%, respectively.

CONCLUSION: Abnormal CRP, although extremely sensitive, lacks specificity in predicting a positive MRI for spinal infection unless highly elevated. However, a normal CRP (absent recent antibiotic or surgery) makes spinal infection unlikely, and its routine use as a screening test can help reducing utilization of emergent MRI for this purpose.