Assessment of pulmonary perfusion with breath-hold and free-breathing dynamic contrast-enhanced magnetic resonance imaging: quantification and reproducibility

Abstract Objectives: The purpose of this study was to investigate whether quantification of pulmonary perfusion from dynamic contrast-enhanced (DCE) MRI yields more reproducible results with data acquired during free breathing than with data from conventional breath-hold measurements. Material and Methods: 10 healthy male volunteers underwent two imaging sessions at a clinical 1.5T-MRI system, separated by a week ± one day. Each of these sessions comprised two DCE MRI acquisitions, one performed during breath-hold, and one during free, shallow breathing; both acquisitions were separated by at least 20 minutes. For all DCE MRI measurements, a standard dose of Gadobutrol was used. Breath hold measurements lasted 53 seconds; free-breathing acquisitions were performed in a total acquisition time of 146 seconds. Lung tissue was segmented automatically to minimize user influence and pulmonary plasma flow (PPF) and volume (PPV) were quantified on a perpixel basis with a one-compartment model. Freebreathing measurements were analyzed twice, (a) including data from the entire acquisition duration and (b) after truncation to the duration of the breath-hold measurements. For further statistical analysis, median values of the resulting parameter maps were determined. To assess intra-individual reproducibility, intra-class correlation coefficients and coefficients of variation between first and second measurements were calculated for breathhold, truncated and full free-breathing measurements, respectively. Differences in the coefficients of variation were assessed with a non-parametric two-sided paired Wilcoxon signed-rank test. Results: All 40 measurements were completed successfully. Maps of PPF and PPV could be calculated from both measurement techniques; PPF and PPV in the breath-hold measurements were significantly lower (p<0.001) than in truncated and full free-breathing measurements. Both evaluations of the free-breathing measurements yielded higher intra-class correlation coefficients and lower coefficients of variation between first and second measurements than in the breath-hold measurements. Conclusions: Besides offering substantially higher patient comfort, free-breathing DCE MRI acquisitions allow for pixel-wise quantification of pulmonary perfusion and hence generation of parameter maps. Moreover, quantitative perfusion estimates derived from free-breathing DCE MRI measurements have better reproducibility than estimates from the conventionally used breath-hold measurements

Denitrifying pathways dominate nitrous oxide emissions from managed grassland during drought and rewetting

Nitrous oxide is a powerful greenhouse gas whose atmospheric growth rate has accelerated over the past decade. Most anthropogenic N2O emissions result from soil N fertilization, which is converted to N2O via oxic nitrification and anoxic denitrification pathways. Drought-affected soils are expected to be well oxygenated; however, using high-resolution isotopic measurements, we found that denitrifying pathways dominated N2O emissions during a severe drought applied to managed grassland. This was due to a reversible, drought-induced enrichment in nitrogen-bearing organic matter on soil microaggregates and suggested a strong role for chemo- or codenitrification. Throughout rewetting, denitrification dominated emissions, despite high variability in fluxes. Total N2O flux and denitrification contribution were significantly higher during rewetting than for control plots at the same soil moisture range. The observed feedbacks between precipitation changes induced by climate change and N2O emission pathways are sufficient to account for the accelerating N2O growth rate observed over the past decade

Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations

Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Correlation of Perfusion MRI and F-18-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

Objectives To investigate a multimodal, multiparametric perfusion MRI/F-18-fluoro-deoxyglucose (F-18-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation. Materials and Methods Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group;n = 7 control group) female athymic nude rats (Hsd: RH-Foxn1(mu)). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/F-18-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV,%) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In F-18-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67). Results Regorafenib significantly (p<0.01) suppressed PF (81.1 +/- 7.5 to 50.6 +/- 16.0 mL/100mL/min), PV (12.1 +/- 3.6 to 7.5 +/- 1.6%) and PS (13.6 +/- 3.2 to 7.9 +/- 2.3 mL/100mL/min) as well as TTB (3.4 +/- 0.6 to 1.9 +/- 1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0 +/- 2.4 vs. 16.1 +/- 5.9) and tumor cell proliferation (Ki-67, 434.0 +/- 62.9 vs. 663.0 +/- 98.3) in the therapy group. Perfusion MRI parameters Delta PF, Delta PV and Delta PS showed strong and significant (r = 0.67-0.78;p<0.01) correlations to the PET parameter Delta TTB and significant correlations (r = 0.57-0.67;p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55;p<0.05). Conclusions A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and F-18-FDG-PET validated by immunohistochemistry

Imaging NeuroVascular, Endothelial and STructural Integrity in prepAration to TrEat Small Vessel Diseases. The INVESTIGATE-SVDs study Protocol

Background: Sporadic cerebral small vessel disease (SVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) share clinical and neuroimaging features and possibly vascular dysfunction(s). However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre. The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres. Methods: We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) and CADASIL in Edinburgh, Maastricht and Munich. We will perform detailed clinical and neuropsychological phenotyping of the participants, and neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous and CSF flow and pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) and multishell diffusion imaging. Participants will measure their blood pressure (BP) and its variability over seven days using a telemetric device. Discussion: INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility and CSF flow in sporadic SVD and CADASIL using a multisite, multimodal MRI protocol. We aim to establish associations between these measures of vascular function, risk factors particularly BP and its variability, and brain parenchymal lesions in these two SVD phenotypes. Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures and sample size estimates for future trials

Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations

Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance. It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology. Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature. Although dynamic contrast-enhanced magnetic resonance imaging is well established, challenges emerge in cSVD because of the subtle nature of BBB impairment. The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified. We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Neuro Imaging Researc