[18F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [18F]FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann-Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan-Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69-132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [18F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). Conclusion: Previous work has used [18F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [18F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis.

Fully automated grey and white matter spinal cord segmentation.

Axonal loss in the spinal cord is one of the main contributing factors to irreversible clinical disability in multiple sclerosis (MS). In vivo axonal loss can be assessed indirectly by estimating a reduction in the cervical cross-sectional area (CSA) of the spinal cord over time, which is indicative of spinal cord atrophy, and such a measure may be obtained by means of image segmentation using magnetic resonance imaging (MRI). In this work, we propose a new fully automated spinal cord segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: The Optimized PatchMatch Label fusion (OPAL) algorithm for localising and approximately segmenting the spinal cord, and the Similarity and Truth Estimation for Propagated Segmentations (STEPS) algorithm for segmenting white and grey matter simultaneously. In a retrospective analysis of MRI data, the proposed method facilitated CSA measurements with accuracy equivalent to the inter-rater variability, with a Dice score (DSC) of 0.967 at C2/C3 level. The segmentation performance for grey matter at C2/C3 level was close to inter-rater variability, reaching an accuracy (DSC) of 0.826 for healthy subjects and 0.835 people with clinically isolated syndrome MS.

The use of the lumbosacral enlargement as an intrinsic imaging biomarker: feasibility of grey matter and white matter cross-sectional area measurements using MRI at 3T.

Histopathological studies have demonstrated the involvement of spinal cord grey matter (GM) and white matter (WM) in several diseases and recent research has suggested the use of magnetic resonance imaging (MRI) as a promising tool for in vivo assessment of the upper spinal cord. However, many neurological conditions would benefit from quantitative assessment of tissue integrity at different levels and relatively little work has been done, mainly due to technical challenges associated with imaging the lower spinal cord. In this study, the value of the lumbosacral enlargement (LSE) as an intrinsic imaging biomarker was determined by exploring the feasibility of obtaining within it reliable GM and WM cross-sectional area (CSA) measurements by means of a commercially available MRI system at 3 tesla (T). 10 healthy volunteers (mean age 27.5 years, 6 female) gave written informed consent and high resolution images of the LSE were acquired and analysed using an optimised MRI acquisition and analysis protocol. GM and WM mean CSA measurements were obtained from a 15 mm section at the level of the LSE and the reproducibility of the measurements was determined by means of scan-rescan, intra- and inter-observer assessments. Mean (±SD) LSE cross-sectional area (LSE-CSA) was 62.3 (±4.1) mm2 and mean (±SD) LSE grey matter cross-sectional area (LSE-GM-CSA) was 19.8 (±3.3) mm2. The mean scan-rescan, intra- and inter-observer % coefficient of variation (COV) for measuring the LSE-CSA were 2%, 2% and 2.5%, respectively and for measuring the LSE-GM-CSA were 7.8%, 8% and 8.6%, respectively. This study has shown that the LSE can be used reliably as an intrinsic imaging biomarker. The method presented here can be potentially extended to study the LSE in the diseased state and could provide a solid foundation for subsequent multi-parametric MRI investigations.