Radiogenomic Models Using Machine Learning Techniques to Predict EGFR Mutations in Non-Small Cell Lung Cancer.

BACKGROUND: The purpose of this study was to build radiogenomics models from texture signatures derived from computed tomography (CT) and 18F-FDG PET-CT (FDG PET-CT) images of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor (EGFR) mutations. METHODS: Fifty patients diagnosed with NSCLC between 2011 and 2015 and with known EGFR mutation status were retrospectively identified. Texture features extracted from pretreatment CT and FDG PET-CT images by manual contouring of the primary tumor were used to develop multivariate logistic regression (LR) models to predict EGFR mutations in exon 19 and exon 20. RESULTS: An LR model evaluating FDG PET-texture features was able to differentiate EGFR mutant from wild type with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.87, 0.76, 0.66, and 0.71, respectively. The model derived from CT texture features had an AUC, sensitivity, specificity, and accuracy of 0.83, 0.84, 0.73, and 0.78, respectively. FDG PET-texture features that could discriminate between mutations in EGFR exon 19 and 21 demonstrated AUC, sensitivity, specificity, and accuracy of 0.86, 0.84, 0.73, and 0.78, respectively. Based on CT texture features, the AUC, sensitivity, specificity, and accuracy were 0.75, 0.81, 0.69, and 0.75, respectively. CONCLUSION: Non-small cell lung cancer texture analysis using FGD-PET and CT images can identify tumors with mutations in EGFR. Imaging signatures could be valuable for pretreatment assessment and prognosis in precision therapy.

Imaging-Based Surrogate Markers of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma: A Local Perspective.

PURPOSE: To identify computed tomography (CT) features of epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma in Canadian population and whether imaging-based surrogate markers of EGFR mutation in our population were similar to those found in the Asian population. MATERIALS AND METHODS: Pretreatment CT scans of 223 patients with adenocarcinoma of the lung (112 with EGFR mutation and 111 without mutation) were retrospectively assessed for 20 specific CT features by 2 radiologists, who were blinded to the status of EGFR mutation. Univariate and multivariate logistic regression analyses as well as areas under the receiver operating characteristic curve were performed to discriminate characteristics of EGFR-activating mutation features. RESULTS: Epidermal growth factor receptor mutation-positive adenocarcinomas were more frequently found in female (P < .03), less than 20 pack-year smoking history (P < .001), smaller tumor (P < .01), spiculated margins (P < .05), without centrilobular emphysema (P < .001), and without lymphadenopathy (P < .05), similarly to the Asian population. Multivariate logistic regression analyses of combined clinical and radiological features identified less than 20 pack-year smoking history, smaller tumor diameter, fine or coarse spiculations, noncentral location of the tumor, and lack of centrilobular emphysema and pleural attachment as the strongest independent prognostic factors for the presence of an EGFR mutation. These combined features improved prognostic ability area under the curve to 0.879, compared to 0.788 for clinical features only. CONCLUSION: Several CT findings may help predict the presence of an activating mutation in EGFR in lung adenocarcinomas in our Canadian population. Combining clinical and radiological features improves prognostic ability to determine the EGFR mutation status compared to clinical features alone.

The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience.

One of the major challenges in biomarker development is the collection of tumor tissue of adequate quality for analysis. A prospective clinical trial was initiated to collect tissues from triple negative breast cancers prior to and after neoadjuvant chemotherapy in order to study the mechanisms of chemoresistance. Sixty patients had pre-chemotherapy biopsies performed by either a surgeon or a radiologist, while those with residual tumor after chemotherapy had research-only biopsies and/or surgical samples collected in liquid nitrogen, RNA-later and formalin. We examined each core for tumor cellularity, stromal content, and necrosis after which, RNA and DNA extraction was performed. We found that biopsies collected with ultrasound guidance were more likely to contain tumor than those collected by the surgeon. Patient reluctance to undergo research-only biopsies after chemotherapy was not a problem. Pre-chemotherapy tumor biopsies frequently did not contain any tumor cells (15%) or did not have ≥50% tumor content (63%). Indeed, 50% of patients had at least 2 pre-chemotherapy core biopsies with <50% tumor content. After chemotherapy, 30% of biopsy or surgical samples in patients with incomplete response did not contain any tumor. Finally, RNA-later not only made histopathological assessment of tumor content difficult, but yielded less DNA than fresh snap frozen samples. We recommend that high-quality tissue procurement can be best accomplished if at least three image-guided core biopsies be obtained per sample, each of these cores be examined for tumor cellularity and that at least some of them be freshly snap frozen in liquid nitrogen.

Osteosarcopenia and Mortality in Older Adults Undergoing Transcatheter Aortic Valve Replacement.

Importance: Osteosarcopenia is an emerging geriatric syndrome characterized by age-related deterioration in muscle and bone. Despite the established relevance of frailty and sarcopenia among older adults undergoing transcatheter aortic valve replacement (TAVR), osteosarcopenia has yet to be investigated in this setting. Objective: To determine the association between osteosarcopenia and adverse outcomes following TAVR. Design, Setting, and Participants: This is a post hoc analysis of the Frailty in Aortic Valve Replacement (FRAILTY-AVR) prospective multicenter cohort study and McGill extension that enrolled patients aged 70 years or older undergoing TAVR from 2012 through 2022. FRAILTY-AVR was conducted at 14 centers in Canada, the United States, and France between 2012 and 2016, and patients at the McGill University-affiliated center in Montreal, Québec, Canada, were enrolled on an ongoing basis up to 2022. Exposure: Osteosarcopenia as measured on computed tomography (CT) scans prior to TAVR. Main Outcomes and Measures: Clinically indicated CT scans acquired prior to TAVR were analyzed to quantify psoas muscle area (PMA) and vertebral bone density (VBD). Osteosarcopenia was defined as a combination of low PMA and low VBD according to published cutoffs. The primary outcome was 1-year all-cause mortality. Secondary outcomes were 30-day mortality, hospital length of stay, disposition, and worsening disability. Multivariable logistic regression was used to adjust for potential confounders. Results: Of the 605 patients (271 [45%] female) in this study, 437 (72%) were octogenarian; the mean (SD) age was 82.6 (6.2) years. Mean (SD) PMA was 22.1 (4.5) cm2 in men and 15.4 (3.5) cm2 in women. Mean (SD) VBD was 104.8 (35.5) Hounsfield units (HU) in men and 98.8 (34.1) HU in women. Ninety-one patients (15%) met the criteria for osteosarcopenia and had higher rates of frailty, fractures, and malnutrition at baseline. One-year mortality was highest in patients with osteosarcopenia (29 patients [32%]) followed by those with low PMA alone (18 patients [14%]), low VBD alone (16 patients [11%]), and normal bone and muscle status (21 patients [9%]) (P < .001). Osteosarcopenia, but not low VBD or PMA alone, was independently associated with 1-year mortality (odds ratio [OR], 3.18; 95% CI, 1.54-6.57) and 1-year worsening disability (OR, 2.11; 95% CI, 1.19-3.74). The association persisted in sensitivity analyses adjusting for the Essential Frailty Toolset, Clinical Frailty Scale, and geriatric conditions such as malnutrition and disability. Conclusions and Relevance: The findings suggest that osteosarcopenia detected using clinical CT scans could be used to identify frail patients with a 3-fold increase in 1-year mortality following TAVR. This opportunistic method for osteosarcopenia assessment could be used to improve risk prediction, support decision-making, and trigger rehabilitation interventions in older adults.

Sex difference in normal thymic appearance in adults 20-30 years of age.

PURPOSE: To determine whether there is a sex difference in the appearance of the normal thymus in 20-30-year-old men and women. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and was compliant with HIPAA. The requirement for informed consent was waived. Images and medical records of 238 consecutive subjects without known thymic disease (175 men, 63 women) who underwent chest computed tomography with intravenous contrast material in 2008 were reviewed. Average thymic region of interest (ROI), subjective assessment of thymic attenuation by using a scale of grades 0-3, thymic anteroposterior measurement, and mean maximal thymic lobe thickness were recorded by two independent thoracic radiologists, blinded to subject age and sex. Thymic morphologic characteristics were assessed in consensus. The two-sided Wilcoxon rank-sum test, Student t test, test for linear regression, analysis of covariance, two-way factorial analysis of variance, and continuity-adjusted χ(2) test were used for statistical analysis. RESULTS: There was a significant sex difference in thymic attenuation as measured objectively by using mean thymic ROI measurement (P < .0001) and subjectively by using a scale of grades 0-3 (P < .0001), which held true when corrected for age (P < .0001). A sex difference was also found in regard to the rate of decrease in mean thymic attenuation with age, with men's thymuses exhibiting a significant decrease in attenuation during the decade, unlike women (P = .0479). There was no significant sex difference in mean maximal thymic lobe thickness (P = .8697). A quadrilateral, as opposed to triangular, configuration of the thymus was more common in women than men (P = .0034). CONCLUSION: There is a significant sex difference in normal thymic appearance in 20-30-year-old men and women. The thymus of 20-30-year-old women typically exhibits higher attenuation and more commonly exhibits a quadrilateral configuration.

Percutaneous Closure of a Giant Aortic Pseudoaneurysm Using Multimodality Imaging Guidance.

Ascending aortic pseudoaneurysm is a rare, life-threatening complication of cardiac surgery. Surgical management is recommended, however, transcatheter techniques offer a less invasive alternative. We describe successful percutaneous closure, guided by using multimodality imaging, in a patient with high surgical risk.

Pericarditis Secondary to an Acupuncture Needle Extracted Via a Transjugular Approach.

Acupuncture is generally considered safe; however, cardiac complications can occur. We describe a case of refractory pericarditis requiring transvenous extraction of an acupuncture needle from within the right ventricular cavity. (Level of Difficulty: Intermediate.).

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Diagnostic and prognostic value of cardiac magnetic resonance in acute myocarditis: a systematic review and meta-analysis.

While diagnostic criteria were elaborated for acute myocarditis using cardiac magnetic resonance (CMR) in 2009, studies have since examined the yield of traditional and novel CMR parameters to achieve greater accuracy and to predict clinical outcomes. The purpose of this systematic review and meta-analysis was to determine the diagnostic and prognostic value of CMR parameters for acute myocarditis. MEDLINE and EMBASE were systematically searched for original studies that reported CMR parameters in adult patients suspected of acute myocarditis. Each CMR parameter's binary prevalence, mean value and standard deviation were extracted. Parameters were meta-analyzed using a random-effects model to generate standardized mean differences. After screening 1492 abstracts, 53 studies were included encompassing 2823 myocarditis patients and 803 controls. Pooled standardized mean differences between myocarditis patients and controls were: T2 mapping time 2.26 (95% CI 1.50-3.02), extracellular volume 1.64 (95% CI 0.87-2.42), LGE percentage 1.30 (95% CI 0.95-1.64), T1 mapping time 1.18 (95% CI 0.35-2.01), T2 ratio 1.17 (95% CI 0.80-1.54), and EGE ratio 0.93 (95% CI 0.66-1.19). Prolonged T1 mapping time had the highest sensitivity (82%), pericardial effusion had the highest specificity (99%). Baseline LV dysfunction and the presence of LGE were predictive of major adverse cardiac events. The results support integration of parametric mapping criteria in the diagnostic criteria for myocarditis. The presence of baseline LV dysfunction and LGE predict patients at higher risk of adverse events.

The role of abdominal radiography in the evaluation of the nontrauma emergency patient.

PURPOSE: To characterize the utility of abdominal radiography for nontrauma emergency patients in a single-institution setting. MATERIALS AND METHODS: Following approval from the Director of Professional Services, a retrospective review of radiography and of patient records was conducted for patients who presented to a nontrauma emergency department over a period of 6 months and who were imaged by using abdominal radiography. Only the first radiograph per patient was used for analysis. The interpretations were sorted as normal, nonspecific, or abnormal. The patients' medical records were reviewed to determine whether further imaging was performed (computed tomography, ultrasonography, or upper gastrointestinal imaging) and results were compared with abdominal radiography. Chart reviews were conducted to identify patients in whom abdominal radiography alone influenced treatment. RESULTS: In 874 patients, interpretation of abdominal radiography was normal in 34% (n = 300), nonspecific in 46% (n = 406), and abnormal in 19% (n = 168). Further imaging was performed for 50% (436) of all patients. Of 300 patients whose abdominal radiography results were normal, 42% (n = 125) had follow-up imaging; 72% (n = 90) of these showed abnormal, 78% (165 of 212) showed nonspecific, and 87% (86 of 99) showed abnormal findings. Of 438 patients who did not undergo follow-up imaging, 75% (n = 327) were discharged. For all indications other than catheter placement, abdominal radiography helped confirm the suspected diagnosis in 2%-8% of cases. In 37 (4%) of 874 patients, abdominal radiography was possibly helpful in changing patient treatment without a follow-up study. CONCLUSION: Abdominal radiography is often requested; however, its results contribute to patient treatment in a small percentage of cases. With the exception of catheter placement, if a patient requires investigation beyond clinical history, physical examination, and lab results, the emergency physician should be encouraged to request more definitive imaging.

Performing Cardiac Magnetic Resonance Imaging in Patients With Cardiac Implantable Electronic Devices: A Contemporary Review.

There are expanding indications for cardiac magnetic resonance imaging (CMR) in patients with cardiac implantable electronic devices (CIEDs). The presence of a CIED had been regarded as a contraindication to CMR due to concerns of arrhythmias, significant changes to lead parameters, and detrimental changes to device programming. The risk of these potential adverse events is theoretically higher in patients undergoing CMR as compared with other anatomic sites. Recent studies have observed low rates of adverse events in patients undergoing CMR (< 1% to 2%), prompting a shift in the recommendations on CMR in patients with CIEDs. The 2017 Heart Rhythm Society Expert Consensus Statement now states that CMR can be performed in patients with both conditional and nonconditional CIEDs at a magnetic strength of 1.5 T, provided there are no fractured, abandoned, or epicardial leads and modifications to MRI parameters are made. The purpose of this review is to (a) outline the potential concerns of performing CMR in patients with CIEDs, (b) define categories of CIEDs as they pertain to MRI safety, (c) summarize the emerging data on adverse events, and (d) provide a practical approach, integrating the key modifications required to perform CMR in patients with CIEDs.

Relationship between response to methylphenidate treatment in children with ADHD and psychopathology in their families.

OBJECTIVE: To compare the pattern of familial aggregation of psychopathology in children who are good responders (GR) to methylphenidate (MPH) versus those who are poor responders (PR). METHOD: A total of 118 clinically referred children ages 6 to 12 years, diagnosed with ADHD participated in a double-blind, placebo-controlled, randomized 2-week crossover trial of MPH from 1999 to 2004. A low dose of 0.5 mg/kg of body weight of MPH divided in two equal doses was used. Family history was obtained by interviewing at least one key historian relative of each subject using Family Interview for Genetic Studies. Information was collected on 342 first-degree and 1,151 second-degree relatives of children with attention-deficit/hyperactivity disorder. RESULTS: Forty-four subjects showed mild or no improvement (PR) and 74 showed moderate or very much improvement (GR) on MPH over placebo. First-degree relatives of GR subjects were at significantly higher risk of attention-deficit/hyperactivity disorder than the relatives of PR subjects (p<.05). Second-degree relatives of the GR were at significantly higher risk of antisocial personality disorder compared to the relatives of PR subjects (p<.05). CONCLUSIONS: The significantly higher presence of attention-deficit/hyperactivity disorder in the first-degree relatives and of antisocial personality disorder in the second-degree relatives of GR children suggests that this group may, at least partially, be distinct from the PR group on the basis of genetic determinants.

Percutaneous CT guided lung biopsy in patients with pulmonary hypertension: Assessment of complications.

PURPOSE: To assess the complications of CT-guided percutaneous transthoracic needle aspiration and/or core biopsy (PTNAB) of lung nodules in patients with pulmonary arterial hypertension (PHTN). METHOD AND MATERIALS: We analyzed PTNAB of 74 lung lesions (mean size: 3.6 ± 2.1 cm) in 74 patients (M: F 38:36; age 68 ± 15 years) with documented PHTN on cardiac ultrasound. 39 patients with lung lesions (M: F 24:15; age 65 ± 14) who underwent PTNAB in the same period with right ventricle systolic pressure (RVSP) <35 mm Hg were selected as controls. Pulmonary arterial pressures were estimated on cardiac ultrasounds by using the tricuspid regurgitation jet method. Two thoracic radiologists reviewed the medical records and PTNAB images on a PACS station and documented nodule size, location, distance traversed in lung, technical success and complications. RESULTS: Fine needle aspirates were obtained in all and core biopsy in 23% (17/74) of the nodules. 61% (45/74) of the nodules were in the middle and 39% (29/74) were in the outer third of lung. PHTN was mild, moderate and severe in 84% (62/74), 13% (10/74) and 3% (2/74) of the patients. Biopsy was complicated by hemorrhage in 26% (19/74), moderate hemoptysis in 1.3% (1/74), pneumothorax in 17% (12/74), chest tube in 1.3% (1/74) and hemothorax in 1.3% (1/74) of the patients. The complications rate in control group was similar, hemorrhage in 33% (19/39) (p=0.6), moderate hemoptysis in 5% (2/39) (p=0.3), pneumothorax in 28% (11/39) (p=0.2), chest tube in (0/39) (p=0.3), and hemothorax in 3% (1/39) of the patients (p=0.7). CONCLUSION: Percutaneous needle biopsy of lung lesions in patients with mild to moderate PHTN can be performed without significant increase in complications.

Lung cancer histologies associated with emphysema on computed tomography.

BACKGROUND: Multiple studies have demonstrated an increased risk of lung cancer in the presence of emphysema detected visually on computed tomography (CT) independent of smoking history and airflow obstruction. The relationship between emphysema and specific histologic subtypes of lung cancer remains uncertain. OBJECTIVE: To determine the extent to which emphysema on chest CT is associated with lung cancer histology. METHODS: Cross-sectional analysis of consecutive lung cancer patients referred to the Jewish General Hospital was performed (2001-2009). All those with demographic data, smoking history (pack-years), documented histology and chest CT were included. Emphysema was graded on CT by three readers, using a standardized rubric. Odds of each lung cancer subtype were compared between patients with and without emphysema, and adjusted for age, sex, physician diagnosed COPD and smoking history by multiple logistic regression. RESULTS: Complete data were available for 498 lung cancer patients (mean age 68 years; 44% female; 16% never smokers; 53% without emphysema on CT). The most common histologies were adenocarcinoma (242 [49%]), squamous (71 [14%]), undifferentiated (48 [10%]) and small cell carcinoma (42 [8%]). The presence of emphysema was associated with increased odds of squamous (OR 3.1; 95% CI 1.8-5.3) and small cell (OR 2.1; 95% CI 1.1-4.1) carcinoma. After adjustment for age, sex, COPD and smoking history, emphysema was associated with squamous (adjusted OR 2.6; 95% CI 1.4-4.8) but not small cell (adjusted OR 1.5; 95% CI 0.76-3.1) carcinoma. Sensitivity analysis was performed by sequential censoring of each histologic subtype yielding similar results. Adenocarcinoma was less common in the presence of emphysema relative to squamous and small cell carcinoma (adjusted OR 0.62; 95% CI 0.41-0.92). When these latter histologies were censored, no significant association between adenocarcinoma and emphysema was observed (adjusted OR 1.0; 95% CI 0.49-2.1). CONCLUSIONS: Relative to other histologic subtypes, the odds of squamous carcinoma were significantly increased among lung cancer patients with emphysema after adjustment for age, sex, COPD and smoking history. Other common subtypes were not independently associated with emphysema.