Publications

PURPOSE: To determine if the presence of a dark cortical rim around the ovary on magnetic resonance imaging (MRI) is associated with polycystic ovarian syndrome (PCOS).

MATERIALS AND METHODS: This retrospective study included 52 PCOS patients with 98 total ovaries and 52 age-matched controls with 104 total ovaries. The ovaries were evaluated on MRI with at least two orthogonal views on T2-weighted sequences. Ovarian volume and follicular count per ovary were measured. Each ovary was also assessed for a dark cortical rim around the ovary on T2-weighted imaging which involved equal to or more than 50% of the ovarian circumference. The degree of rim continuity was classified as continuous if the rim involved greater than 75% of the ovarian circumference, discontinuous if 50-75% of the ovarian circumference was covered, or absent if less than 50% of the ovarian circumference was involved. The rim thickness was measured if present. T test and χ2 tests were performed to compare continuous and categorical variables, correspondingly, between cases and controls. ROC curves and area under the curve (AUC) were used to assess predictive performance and DeLong's paired test was used to compare AUCs.

RESULTS: A higher percentage of PCOS patients exhibited a continuous cortical rim about the ovary (71%) and a lower percentage of an absent cortical rim (8%) compared to controls (25% and 37%, respectively) (p < 0.001). A continuous cortical ovarian rim has a sensitivity and specificity of 71% and 75%, respectively, for diagnosing PCOS. Mean cortical rim thickness is significantly higher in the PCOS group (1.4 mm) compared with controls (0.8 mm) (p < 0.001). Cortical rim thickness and presence of a continuous cortical rim are strongly correlated. Cortical rim thickness of 1.2 mm provides a sensitivity and specificity of 75% and 60%, correspondingly, for a diagnosis of PCOS. Cortical rim thickness combined with cortical rim continuity has an AUC of 0.77 for diagnosing PCOS, which is similar to conventional imaging features of ovarian volume and follicular count combined.

CONCLUSION: A dark cortical rim around the ovary is an MRI feature that can be used to support a diagnosis of PCOS.

BACKGROUND: Myelin specific imaging techniques to characterize white matter in demyelinating diseases such as multiple sclerosis (MS) have become an area of increasing focus. Gray matter myelination is an important marker of cortical microstructure, and its impairment is relevant in progressive MS. However, its assessment is challenging due to its thin layers. While myelin water imaging and ultra-short TE imaging have not yet been implemented to assess cortical myeloarchitecture, magnetization transfer (MT) shows promise. A recent development of the MT technique, ihMT, has demonstrated greater myelin sensitivity/specificity. Here we implemented a 3D ihMT acquisition and analysis to characterize cortical gray matter myeloarchitecture.

METHODS: 20 young healthy volunteers were imaged with a 3D ihMTRAGE sequence and quantitative metrics of ihMT (ihMTsat), and dual frequency-offset MT (dual MTsat) were calculated. Cortical surface-based analysis of ihMTsat and dual MTsat were performed and compared. We also compared the cortical ihMTsat map to a cortical surface-based map of T1-weighted images (T1w), defined as a proxy of myelin content.

RESULTS: Cortical ihMTsat and dual MTsat maps were in qualitative agreement with previous work and the cortical T1w map, showing higher values in primary cortices and lower values in the insula. IhMTsat and dual MTsat were significantly correlated but with important regional differences. The ratio ihMTsat/dual MTsat highlighted higher ihMTsat values in the primary cortices and sulci.

CONCLUSION: ihMTsat, a quantitative metric of ihMT, can be reliably measured in cortical gray matter and shows unique contrast between cortical regions.

OBJECTIVE: To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE).

METHODS: We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model.

RESULTS: Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC-mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (n = 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio [OR] 3.1 [95%CI 2.1-14.5]; p = 0.002). Mortality with severe (19.0%; OR 5.1 [95%CI 1.4-17.9]; p = 0.011), moderate (11.2%; OR 2.7 [95%CI 1.1-6.8]; p = 0.031), and mild CAC (12.6%; OR 3.1 [95%CI 1.4-6.9]; p = 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0-7.1; p = 0.050) and 2.6 (95%CI 0.9-7.1; p = 0.069) for the overall model. PE-related mortality was 4.0% (n = 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 [95%CI 1.1-10.7]; p = 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 [95%CI 1.0-34.0]; p = 0.049), with moderate CAC 6.7% (OR 4.0 [95%CI 1.1-14.6]; p = 0.033), and with mild 4.9% (OR 2.9 [95%CI 0.8-9.9]; p = 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9-20.7; p = 0.074) and 3.4 (95%CI 0.7-17.4; p = 0.141) for the overall model. Patients with sub-massive PE showed similar results.

CONCLUSION: CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients.

KEY POINTS: • Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.

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.

OBJECTIVE: To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model.

METHODS: All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30 days, and 6 months post-treatment.

RESULTS: Sixty radioembolizations were performed in 54 patients (age 68 ± 9 years, 48-87 years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200 Gy for primary and 80-200 Gy for metastatic liver cancers) was 1.7 GBq (0.3-6.4) compared with 0.6 GBq (0.12-2.1) if BSA had been used (p < 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30 days (10%) and 6 months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred.

CONCLUSION: MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200 Gy can be successfully administered without prophylactic embolization in selected patients.

KEY POINTS: •MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

PURPOSE: To compare clinical and technical outcomes of transradial (TRA) uterine artery embolization (UAE) with those of the transfemoral (TFA) approach.

MATERIALS AND METHODS: Consecutive patients who underwent UAE with TRA and TFA in an academic hospital between May 2014 and June 2018 were included in this study. The ability to perform the procedure as planned, complication rates, and reduction in uterine volume, fibroid enhancement, and symptomatic improvement were compared using descriptive statistics, Student t-test, and chi-square test.

RESULTS: There were 91 patients in the TFA group and 91 patients in the TRA group, with 1 crossover to TFA due to vasospasm (1 of 91; 1%). The tallest patient in the TRA UAE group was 178 cm and 4 patients taller than 178 cm in the TFA UAE group. Larger particles (900-1,200 μm) were more often used in the TFA group than in the TRA group (P < .001). There were similar low rates of minor access site complications. In the TFA group (6 of 91, 7%), 5 patients had groin hematomas, and 2 patients had groin pain compared to the TRA group (5 of 91, 5%): in which 4 patients had transient focal occlusion of the radial artery and 1 patient had focal pain, all of which resolved with conservative management. There were similar rates of uterine volume reduction in 40% ± 17% in the TFA versus 36% ± 16% in the TRA group (P = .22) and no residual enhancement in 49 of 58 [84%] in the TFA group versus 66 of 77 [86%] in the TRA group (P = .84). There were similar reductions in modifying symptoms (60 of 64 [94%] in the TRA group; and 37 of 40 [93%] in the TFA group; P = NS) was noted at follow-up.

CONCLUSIONS: Transradial UAE in women up to 178 cm tall and transfemoral UAE have similar technical and clinical outcomes, with low rates of access site complications.

INTRODUCTION: Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where pathologic diagnosis has been essentially limited to three histologic subtypes.

METHODS: A multidisciplinary group (pathologists, molecular biologists, surgeons, radiologists, and oncologists), sponsored by European Network for Rare Adult Solid Cancers/International Association for the Study of Lung Cancer, met in 2018 to critically review the current classification.

RESULTS: Recommendations include: (1) classification should be updated to include architectural patterns and stromal and cytologic features that refine prognostication; (2) subject to data accrual, malignant mesothelioma in situ could be an additional category; (3) grading of epithelioid malignant pleural mesotheliomas should be routinely undertaken; (4) favorable/unfavorable histologic characteristics should be routinely reported; (5) clinically relevant molecular data (programmed death ligand 1, BRCA 1 associated protein 1 [BAP1], and cyclin dependent kinase inhibitor 2A) should be incorporated into reports, if undertaken; (6) other molecular data should be accrued as part of future trials; (7) resection specimens (i.e., extended pleurectomy/decortication and extrapleural pneumonectomy) should be pathologically staged with smaller specimens being clinically staged; (8) ideally, at least three separate areas should be sampled from the pleural cavity, including areas of interest identified on pre-surgical imaging; (9) image-acquisition protocols/imaging terminology should be standardized to aid research/refine clinical staging; (10) multidisciplinary tumor boards should include pathologists to ensure appropriate treatment options are considered; (11) all histologic subtypes should be considered potential candidates for chemotherapy; (12) patients with sarcomatoid or biphasic mesothelioma should not be excluded from first-line clinical trials unless there is a compelling reason; (13) tumor subtyping should be further assessed in relation to duration of response to immunotherapy; and (14) systematic screening of all patients for germline mutations is not recommended, in the absence of a family history suspicious for BAP1 syndrome.

CONCLUSIONS: These multidisciplinary recommendations for pathology classification and application will allow more informative pathologic reporting and potential risk stratification, to support clinical practice, research investigation and clinical trials.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon.

EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases.

RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months.

CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy.

IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Medical documentation is one of the primary methods by which physicians share clinical information and impressions over time with one another. As the adage says, "a picture is worth a thousand words," and physicians have started leveraging consumer mobile technology to share images with one another. However, image sharing often uses short message service texting and similar methods, which can be noncompliant with privacy regulations and can also limit the ability to communicate information longitudinally and across specialties. Sharing of such information is increasingly important, however, as smaller practices are joining to create large geographically spread out health care networks. To this end, we developed an application to acquire and store images via smartphone and seamlessly transfer into the patient's electronic medical record (EMR) to enable digital consults and longitudinal evaluation in a private and compliant method.