Purpose

Single ventricle heart disease (SVHD) patients show injury in brain sites that regulate autonomic, mood, and cognitive functions. However, the nature (acute or chronic changes) and extent of brain injury in SVHD are unclear. Our aim was to examine regional brain tissue damage in SVHD over controls using DTI-based mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) procedures.

Methods

We collected two DTI series (3.0-T MRI), mood and cognitive data, from 27 SVHD and 35 control adolescents. Whole-brain MD, AD, RD, and FA maps were calculated from each series, realigned and averaged, normalized to a common space, smoothed, and compared between groups using ANCOVA (covariates, age and sex; false discovery rate, p < 0.05). Region-of-interest analyses were performed to calculate MD, AD, RD, and FA values for magnitude assessment between groups.

Results

SVHD patients showed impaired mood and cognitive functions over healthy adolescents. Multiple brain sites in SVHD showed increased MD values, including the insula, caudate, cingulate, hypothalamus, thalamus, medial prefrontal and frontal cortices, parahippocampal gyrus, hippocampus, precentral gyrus, amygdala, cerebellum, corpus callosum, basal forebrain, mammillary bodies, internal capsule, midbrain, fornix, and occipital, parietal, and temporal cortices, indicating chronic tissue changes. Similar areas showed either increased AD or RD values, with RD changes more enhanced over AD in SVHD compared to controls. Few brain regions emerged with increased or decreased FA values in SVHD patients over controls.

Conclusion

SVHD adolescents, more than a decade from their last surgical procedure, show widespread brain abnormalities in autonomic, mood, and cognitive regulatory areas. These findings indicate that brain injury is in a chronic stage in SVHD with predominantly myelin changes that may result from previous hypoxia/ischemia- or developmental-induced processes.

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P = 0.004) and changes (2.4 vs. 7.1; P = 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio = 1.49; P = 0.03). CONCLUSIONS: Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.

Lung cancer metastases comprise most of all brain metastases in adults and most brain metastases are diagnosed by magnetic resonance (MR) scans. The purpose of this study was to conduct an MR imaging-based radiomic analysis of brain metastatic lesions from patients with primary lung cancer to classify mutational status of the metastatic disease. We retrospectively identified lung cancer patients with brain metastases treated at our institution between 2009 and 2017 who underwent genotype testing of their primary lung cancer. Brain MR Images were used for segmentation of enhancing tumors and peritumoral edema, and for radiomic feature extraction. The most relevant radiomic features were identified and used with clinical data to train random forest classifiers to classify the mutation status. Of 110 patients in the study cohort (mean age 57.51 ± 12.32 years; M: F = 37:73), 75 had an EGFR mutation, 21 had an ALK translocation, and 15 had a KRAS mutation. One patient had both ALK translocation and EGFR mutation. Majority of radiomic features most relevant for mutation classification were textural. Model building using both radiomic features and clinical data yielded more accurate classifications than using either alone. For classification of EGFR, ALK, and KRAS mutation status, the model built with both radiomic features and clinical data resulted in area-under-the-curve (AUC) values based on cross-validation of 0.912, 0.915, and 0.985, respectively. Our study demonstrated that MR imaging-based radiomic analysis of brain metastases in patients with primary lung cancer may be used to classify mutation status. This approach may be useful for devising treatment strategies and informing prognosis.

Non-small cell lung cancer (NSCLC) has a high rate of brain metastasis. The purpose of this study was to assess the differential distribution of brain metastases from primary NSCLC based on mutation status. Brain MRI scans of patients with brain metastases from primary NSCLC were retrospectively analyzed. Brain metastatic tumors were grouped according to mutation status of their primary NSCLC and the neuroimaging features of these brain metastases were analyzed. A total of 110 patients with 1386 brain metastases from primary NSCLC were included in this study. Gray matter density at the tumor center peaked at ~0.6 for all mutations. The median depths of tumors were 7.9 mm, 8.7 mm and 9.1 mm for EGFR, ALK and KRAS mutation groups, respectively (p = 0.044). Brain metastases for the EGFR mutation-positive group were more frequently located in the left cerebellum, left cuneus, left precuneus and right precentral gyrus. In the ALK mutation-positive group, brain metastases were more frequently located in the right middle occipital gyrus, right posterior cingulate, right precuneus, right precentral gyrus and right parietal lobe. In the KRAS mutation-positive patient group, brain metastases were more frequently located in the posterior left cerebellum. Our study showed differential spatial distribution of brain metastases in patients with NSCLC according to their mutation status. Information regarding distribution of brain metastases is clinically relevant as it could be helpful to guide treatment planning for targeted therapy, and for predicting prognosis.

Background

Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment.

Study design

Cross-sectional study.

Setting & participants

588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Predictor

Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels.

Outcomes

Neuropsychological battery of 6 cognitive tests.

Measurements

Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions.

Results

The mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment.

Limitations

Unknown temporal relationship between retinopathy and impairment.

Conclusions

In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.

Lung cancer can be classified into two main categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which are different in treatment strategy and survival probability. The lung CT images of SCLC and NSCLC are similar such that their subtle differences are hardly visually discernible by the human eye through conventional imaging evaluation. We hypothesize that SCLC/NSCLC differentiation could be achieved via computerized image feature analysis and classification in feature space, as termed a radiomic model. The purpose of this study was to use CT radiomics to differentiate SCLC from NSCLC adenocarcinoma. Patients with primary lung cancer, either SCLC or NSCLC adenocarcinoma, were retrospectively identified. The post-diagnosis pre-treatment lung CT images were used to segment the lung cancers. Radiomic features were extracted from histogram-based statistics, textural analysis of tumor images and their wavelet transforms. A minimal-redundancy-maximal-relevance method was used for feature selection. The predictive model was constructed with a multilayer artificial neural network. The performance of the SCLC/NSCLC adenocarcinoma classifier was evaluated by the area under the receiver operating characteristic curve (AUC). Our study cohort consisted of 69 primary lung cancer patients with SCLC (n = 35; age mean ± SD = 66.91± 9.75 years), and NSCLC adenocarcinoma (n = 34; age mean ± SD = 58.55 ± 11.94 years). The SCLC group had more male patients and smokers than the NSCLC group (P < 0.05). Our SCLC/NSCLC classifier achieved an overall performance of AUC of 0.93 (95% confidence interval = [0.85, 0.97]), sensitivity = 0.85, and specificity = 0.85). Adding clinical data such as smoking history could improve the performance slightly. The top ranking radiomic features were mostly textural features. Our results showed that CT radiomics could quantitatively represent tumor heterogeneity and therefore could be used to differentiate primary lung cancer subtypes with satisfying results. CT image processing with the wavelet transformation technique enhanced the radiomic features for SCLC/NSCLC classification. Our pilot study should motivate further investigation of radiomics as a non-invasive approach for early diagnosis and treatment of lung cancer.

BACKGROUND: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTOR: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. OUTCOMES: Neuropsychological battery of 6 cognitive tests. MEASUREMENTS: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. RESULTS: The mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. LIMITATIONS: Unknown temporal relationship between retinopathy and impairment. CONCLUSIONS: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.

Purpose

To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Design

Prospective cohort study within a randomized clinical trial.

Participants

The 1185 CATT participants.

Methods

Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.

Main outcome measures

Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.

Results

Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).

Conclusions

In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.