Publications

2021

Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA). Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model.
Gupta K, Kalra R, Pate M, Nagalli S, Ather S, Rajapreyar I, Arora P, Gupta A, Zhou W, Estepar RSJ, et al. Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification. Mayo Clin Proc. 2021;96(7):1812–21. doi:10.1016/j.mayocp.2020.11.027
OBJECTIVE: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. METHODS: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/μL [to convert to cells ×10/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality. RESULTS: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (>=0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score. CONCLUSION: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.
en GR-L, anchez-Ferrero GV-S, Liao C, Westin C-F, Setsompop K, Rathi Y. SNR-enhanced diffusion MRI with structure-preserving low-rank denoising in reproducing kernel Hilbert spaces. Magn Reson Med. 2021;86(3):1614–32. doi:10.1002/mrm.28752
PURPOSE: To introduce, develop, and evaluate a novel denoising technique for diffusion MRI that leverages nonlinear redundancy in the data to boost the SNR while preserving signal information. METHODS: We exploit nonlinear redundancy of the dMRI data by means of kernel principal component analysis (KPCA), a nonlinear generalization of PCA to reproducing kernel Hilbert spaces. By mapping the signal to a high-dimensional space, a higher level of redundant information is exploited, thereby enabling better denoising than linear PCA. We implement KPCA with a Gaussian kernel, with parameters automatically selected from knowledge of the noise statistics, and validate it on realistic Monte Carlo simulations as well as with in vivo human brain submillimeter and low-resolution dMRI data. We also demonstrate KPCA denoising on multi-coil dMRI data. RESULTS: SNR improvements up to 2.7 were obtained in real in vivo datasets denoised with KPCA, in comparison to SNR gains of up to 1.8 using a linear PCA denoising technique called Marchenko-Pastur PCA (MPPCA). Compared to gold-standard dataset references created from averaged data, we showed that lower normalized root mean squared error was achieved with KPCA compared to MPPCA. Statistical analysis of residuals shows that anatomical information is preserved and only noise is removed. Improvements in the estimation of diffusion model parameters such as fractional anisotropy, mean diffusivity, and fiber orientation distribution functions were also demonstrated. CONCLUSION: Nonlinear redundancy of the dMRI signal can be exploited with KPCA, which allows superior noise reduction/SNR improvements than the MPPCA method, without loss of signal information.
Lampinen B, Lätt J, Wasselius J, van Westen D, Nilsson M. Time dependence in diffusion MRI predicts tissue outcome in ischemic stroke patients. Magn Reson Med. 2021;86(2):754–64. doi:10.1002/mrm.28743
PURPOSE: Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4-6 hours. However, tissue progression from ischemia to infarction is variable, and some patients benefit from treatment up until 24 hours. Improved imaging techniques are needed to identify these patients. Here, it was hypothesized that time dependence in diffusion MRI may predict tissue outcome in ischemic stroke. METHODS: Diffusion MRI data were acquired with multiple diffusion times in five non-reperfused patients at 2, 9, and 100 days after stroke onset. Maps of "rate of kurtosis change" (k), mean kurtosis, ADC, and fractional anisotropy were derived. The ADC maps defined lesions, normal-appearing tissue, and the lesion tissue that would either be infarcted or remain viable by day 100. Diffusion parameters were compared (1) between lesions and normal-appearing tissue, and (2) between lesion tissue that would be infarcted or remain viable. RESULTS: Positive values of k were observed within stroke lesions on day 2 (P = .001) and on day 9 (P = .023), indicating diffusional exchange. On day 100, high ADC values indicated infarction of 50 ± 20% of the lesion volumes. Tissue infarction was predicted by high k values both on day 2 (P = .026) and on day 9 (P = .046), by low mean kurtosis values on day 2 (P = .043), and by low fractional anisotropy values on day 9 (P = .029), but not by low ADC values. CONCLUSIONS: Diffusion time dependence predicted tissue outcome in ischemic stroke more accurately than the ADC, and may be useful for predicting reperfusion benefit.
Diaz AA, Colangelo LA, Okajima Y, Yen A, Sala MA, Dransfield MT, Tino G, Ross JC, epar R ul SJ e E, Washko GR, et al. Association between Cardiorespiratory Fitness and Bronchiectasis at CT: A Long-term Population-based Study of Healthy Young Adults Aged 18-30 Years in the CARDIA Study. Radiology. 2021;300(1):190–6. doi:10.1148/radiol.2021203874
Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespiratory fitness and bronchiectasis. Materials and Methods This was a secondary analysis of a prospective observational study: the Coronary Artery Risk Development in Young Adults cohort (from 1985-1986 [year 0] to 2015-2016 [year 30]). During a 30-year period, healthy participants (age at enrollment 18-30 years) underwent treadmill exercise testing at year 0 and year 20 visits. Cardiorespiratory fitness was determined according to the treadmill exercise duration. The 20-year difference in cardiorespiratory fitness was used as the fitness measurement. At year 25, chest CT was performed to assess bronchiectasis and was used as the primary outcome. Multivariable logistic models were performed to determine the association between cardiorespiratory fitness changes and bronchiectasis. Results Of 2177 selected participants (at year 0: mean age, 25 years ± 4 [standard deviation]; 1224 women), 209 (9.6%) had bronchiectasis at year 25. After adjusting for age, race-sex group, study site, body mass index, pack-years smoked, history of tuberculosis, pneumonia, asthma and myocardial infarction, peak lung function, and cardiorespiratory fitness at baseline, preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT at year 25 (per 1-minute-longer treadmill duration from year 0 to year 20: odds ratio [OR], 0.88; 95% CI: 0.80, 0.98; = .02). A consistent strong association was found when cough and phlegm were included in bronchiectasis (OR, 0.72; 95% CI: 0.59, 0.87; < .001). Conclusion In a long-term follow-up, the preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT. © RSNA, 2021 See also the editorial by Stojanovska in this issue.
Maziero MP, Seitz-Holland J, Cho KIK, Goldenberg JE, Tanamatis T \is W, Diniz JB, Cappi C, de Mathis MA, Otaduy MCG, Martin M da G ca M, et al. Cellular and Extracellular White Matter Abnormalities in Obsessive-Compulsive Disorder: A Diffusion MRI Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6(10):983–91. doi:10.1016/j.bpsc.2021.04.001
BACKGROUND: While previous studies have implicated white matter (WM) as a core pathology of Obsessive-Compulsive Disorder (OCD), the underlying neurobiological processes remain elusive. This study utilizes free-water imaging derived from diffusion MRI to identify cellular and extracellular WM abnormalities in patients with OCD compared to controls (Cs). Next, we investigate the association between diffusion measures, and clinical variables in patients. METHODS: We collected diffusion-weighted MRI and clinical data from eighty-three patients with OCD (56 females/27 males, age=37.7 ± 10.6) and 52 Cs (27 females/25 males, age=32.8 ± 11.5). Fractional anisotropy (FA), fractional anisotropy of cellular tissue (FAT), and extracellular free-water (FW) maps were extracted and compared between patients and Cs using tract-based spatial statistics, and voxel-wise comparison in FSL’s Randomise. Next, we correlated these WM measures with clinical variables (age-of-onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. RESULTS: Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), FAт (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared to Cs. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. CONCLUSIONS: Our findings of widespread FA, FAт, and FW abnormalities suggest that OCD is associated with both microstructural cellular and extracellular abnormalities beyond the cortico-striato-thalamo-cortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.
ani MJ, Kikinis Z, ak JL s\, Pasternak O, Szczepankiewicz F, Heller C, Swago S, Silva A, Bouix S, Kubicki M, et al. Emotional Awareness in Schizophrenia Is Associated With Gray Matter Volume of Right Precuneus. Front Psychiatry. 2021;12:601742. doi:10.3389/fpsyt.2021.601742
We assessed the relationship between emotional awareness (e.g., the ability to identify and differentiate our own feelings and feelings of others) and regional brain volumes in healthy and in schizophrenia groups. Magnetic resonance images of 29 subjects with schizophrenia and 33 matched healthy controls were acquired. Brain gray matter was parcellated using FreeSurfer and 28 regions of interest associated with emotional awareness were analyzed. All participants were assessed using the Levels of Emotional Awareness Scale (LEAS) of Self and of Other. LEAS scores were correlated with gray matter volume for each hemisphere on the 14 brain regions of the emotional awareness network. Individuals with schizophrenia showed decreased emotional awareness on both LEAS Self and LEAS Other compared to healthy controls. There were no statistically significant between-group differences in gray matter volumes of the emotional awareness network. The performance on LEAS Other correlated negatively with right precuneus gray matter volume only in the schizophrenia group. Our findings suggest a relationship between gray matter volume of the right precuneus and deficits in understanding of emotional states of others in schizophrenia.
Guder S, Pasternak O, Gerloff C, Schulz R. Strengthened Structure-Function Relationships of the Corticospinal Tract by Free Water Correction After Stroke. Brain Commun. 2021;3(2):fcab034. doi:10.1093/braincomms/fcab034
The corticospinal tract is the most intensively investigated tract of the human motor system in stroke rehabilitative research. Diffusion-tensor-imaging gives insights into its microstructure, and transcranial magnetic stimulation assesses its excitability. Previous data on the interrelationship between both measures are contradictory. Correlative or predictive models which associate them with motor outcome are incomplete. Free water correction has been developed to enhance diffusion-tensor-imaging by eliminating partial volume with extracellular water, which could improve capturing stroke-related microstructural alterations, thereby also improving structure-function relationships in clinical cohorts. In the present cross-sectional study, data of 18 chronic stroke patients and 17 healthy controls, taken from a previous study on cortico-cerebellar motor tracts, were re-analysed: The data included diffusion-tensor-imaging data quantifying corticospinal tract microstructure with and without free water correction, transcranial magnetic stimulation data assessing recruitment curve properties of motor evoked potentials and detailed clinical data. Linear regression modelling was used to interrelate corticospinal tract microstructure, recruitment curves properties and clinical scores. The main finding of the present study was that free water correction substantially strengthens structure-function associations in stroke patients: Specifically, our data evidenced a significant association between fractional anisotropy of the ipsilesional corticospinal tract and its excitability ( = 0.001, adj. = 0.54), with free water correction explaining additional 20% in recruitment curve variability. For clinical scores, only free water correction leads to the reliable detection of significant correlations between ipsilesional corticospinal tract fractional anisotropy and residual grip ( = 0.001, adj. = 0.70) and pinch force ( < 0.001, adj. = 0.72). Finally, multimodal models can be improved by free water correction as well. This study evidences that corticospinal tract microstructure directly relates to its excitability in stroke patients. It also shows that unexplained variance in motor outcome is considerably reduced by free water correction arguing that it might serve as a powerful tool to improve existing models of structure-function associations and potentially also outcome prediction after stroke.
Synn AJ, Byanova KL, Li W, Gold DR, Di Q, Kloog I, Schwartz J, epar R ul SJ e E, Washko GR, O\textquoterightConnor GT, et al. Ambient air pollution exposure and radiographic pulmonary vascular volumes. Environ Epidemiol. 2021;5(2):e143. doi:10.1097/EE9.0000000000000143
Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown. Methods: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area