Publications by Year: 2019

Background The differential diagnosis of progressive supranuclear palsy (PSP) and Lewy body disorders, which include Parkinson disease and dementia with Lewy bodies, is often challenging due to the overlapping symptoms. Purpose To develop a diagnostic tool based on diffusion tensor imaging (DTI) to distinguish between PSP and Lewy body disorders at the individual-subject level. Materials and Methods In this retrospective study, skeletonized DTI metrics were extracted from two independent data sets: the discovery cohort from the Swedish BioFINDER study and the validation cohort from the Penn Frontotemporal Degeneration Center (data collected between 2010 and 2018). Based on previous neuroimaging studies and neuropathologic evidence, a combination of regions hypothesized to be sensitive to pathologic features of PSP were identified (ie, the superior cerebellar peduncle and frontal white matter) and fractional anisotropy (FA) was used to compute an FA score for each individual. Classification performances were assessed by using logistic regression and receiver operating characteristic analysis. Results In the discovery cohort, 16 patients with PSP (mean age ± standard deviation, 73 years ± 5; eight women, eight men), 34 patients with Lewy body disorders (mean age, 71 years ± 6; 14 women, 20 men), and 44 healthy control participants (mean age, 66 years ± 8; 26 women, 18 men) were evaluated. The FA score distinguished between clinical PSP and Lewy body disorders with an area under the curve of 0.97 ± 0.04, a specificity of 91% (31 of 34), and a sensitivity of 94% (15 of 16). In the validation cohort 34 patients with PSP (69 years ± 7; 22 women, 12 men), 25 patients with Lewy body disorders (70 years ± 7; nine women, 16 men), and 32 healthy control participants (64 years ± 7; 22 women, 10 men) were evaluated. The accuracy of the FA score was confirmed (area under the curve, 0.96 ± 0.04; specificity, 96% [24 of 25]; and sensitivity, 85% [29 of 34]). Conclusion These cross-validated findings lay the foundation for a clinical test to distinguish progressive supranuclear palsy from Lewy body disorders. © RSNA, 2019 See also the editorial by Shah in this issue.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PURPOSE: To evaluate the performance of the new SOFA-based sepsis definition in trauma patients. MATERIALS AND METHODS: A single-centre, retrospective, observational study. Primary outcome was 30-day mortality including a censoring analysis for early deaths. The primary outcome was evaluated with logistic regression, receiver operating characteristics (ROC) curves and Kaplan-Meier survival analyses. RESULTS: 722 severely injured patients were included between 2007 and 2016. 315 patients fulfilled the sepsis-2 criteria and 148 fulfilled the sepsis-3 criteria during the first ten days in the ICU. The odds ratios for 30-day mortality were 0.7 (CI 0.4-1.2) for sepsis-2 and 1.5 (CI 0.8-2.6) for sepsis-3. When censoring patients dying at day 1, sepsis-3 became associated with 30-day mortality whereas sepsis-2 did not. This finding was persistent and enhanced through continuing day-by-day censoring of early deaths. The same pattern was seen for the ROC curves analyses, censoring of early deaths resulted in significant discriminatory properties for sepsis-3 but not for sepsis-2. CONCLUSIONS: The sepsis-3 definition identifies much fewer patients and is more strongly associated with adverse outcomes than the sepsis-2 definition. The sepsis-3 definition seems to be useful in the post trauma setting.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

BACKGROUND: Prior work demonstrated that free water in the posterior substantia nigra (SN) was elevated in Parkinson’s disease (PD) compared to healthy controls (HC) across single- and multi-site cohorts, and increased over 1 year in Parkinson’s disease but not in relation with the iron deposition in SN with the relaxometry T2*. OBJECTIVES: The main objective of the present study was to evaluate changes in the SN using relaxometry T2*, single- and bi-tensor models of diffusion magnetic resonance imaging between PD patients and HC. METHODS: 39 subjects participated in this study, including 21 HCs and 18 PD patients, in moderate stage (7 years), whose data were collected at two visits separated by approximately 2 years, underwent 3-T MRI comprising: T2*-weighted, T1-weighted and diffusion tensor imaging (DTI) scans. Relaxometry T2*, bi-tensor free water (FW), free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior, posterior and whole substantia nigra. RESULTS: In the anterior SN, relaxometry T2* values were greater for PD patients than HCs. In the posterior SN, free water, single- and bi-tensor mean diffusivity values were greater for PD patients than HCs. No significant change were found over time in FW/MD/R2* maps for PD patients with moderate stage. CONCLUSION: The specific increase of R2* in the anterior SN concomitant with the specific increase of FW in posterior SN suggests a complementary aspect of the two parameters and, perhaps, different underlying pathophysiological processes.

Estimation of uncertainty of MAP-MRI metrics is an important topic, for several reasons. Bootstrap derived uncertainty, such as the standard deviation, provides valuable information, and can be incorporated in MAP-MRI studies to provide more extensive insight. In this paper, the uncertainty of different MAP-MRI metrics was quantified by estimating the empirical distributions using the wild bootstrap. We applied the wild bootstrap to both phantom data and human brain data, and obtain empirical distributions for the MAP-MRI metrics return-to-origin probability (RTOP), non-Gaussianity (NG), and propagator anisotropy (PA). We demonstrated the impact of diffusion acquisition scheme (number of shells and number of measurements per shell) on the uncertainty of MAP-MRI metrics. We demonstrated how the uncertainty of these metrics can be used to improve group analyses, and to compare different preprocessing pipelines. We demonstrated that with uncertainty considered, the results for a group analysis can be different. Bootstrap derived uncertain measures provide additional information to the MAP-MRI derived metrics, and should be incorporated in ongoing and future MAP-MRI studies to provide more extensive insight.

BACKGROUND: Exposure to cigarette smoke has been shown to lead to vascular remodelling. Computed tomography (CT) imaging measures of vascular pruning have been associated with pulmonary vascular disease, an important morbidity associated with smoking. In this study we compare CT-based measures of distal vessel loss to histological vascular and parenchymal changes.

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The back-and-forth debate on radiation risk, in the recent years, has unscientifically drifted away from proportionality and become increasingly antagonistic. A handful of authors have used exaggerated claims which are corroborated by their own previous work and presented using heated and superlative language. With unwarranted certainty, many have also referenced studies which report inconclusive findings and given undue weight to the results of laboratory animal and cellular studies, regardless of their exact positions on radiation risk. The passion and subjective interpretation with which the debate is now presented detracts from rational, scientific evaluation. A reform of the debate is needed to reach grounded consensus in the community and, if appropriate, begin the process of amending the legislation to reflect it. In this article we have analysed key research on the topic and discussed the fundamental limitations of science in providing satisfactory answers to our questions.

Characterization of porous media is essential in a wide range of biomedical and industrial applications. Microstructural features can be probed non-invasively by diffusion magnetic resonance imaging (dMRI). However, diffusion encoding in conventional dMRI may yield similar signatures for very different microstructures, which represents a significant limitation for disentangling individual microstructural features in heterogeneous materials. To solve this problem, we propose an augmented multidimensional diffusion encoding (MDE) framework, which unlocks a novel encoding dimension to assess time-dependent diffusion specific to structures with different microscopic anisotropies. Our approach relies on spectral analysis of complex but experimentally efficient MDE waveforms. Two independent contrasts to differentiate features such as cell shape and size can be generated directly by signal subtraction from only three types of measurements. Analytical calculations and simulations support our experimental observations. Proof-of-concept experiments were applied on samples with known and distinctly different microstructures. We further demonstrate substantially different contrasts in different tissue types of a post mortem brain. Our simultaneous assessment of restriction size and shape may be instrumental in studies of a wide range of porous materials, enable new insights into the microstructure of biological tissues or be of great value in diagnostics.