Drug-Induced Interstitial Lung Disease: A Systematic Review

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Drug-Induced Interstitial Lung Disease: A Systematic Review

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DIILD Review

Drug-Induced Interstitial Lung Disease: A Systematic Review

Sarah Skeoch, Nicholas Weatherley , Andrew J. Swift, Alexander Oldroyd, Christopher Johns, Conal Hayton, Alessandro Giollo, James M. Wild, John C. Waterton, Maya Buch, Kim Linton, Ian N. Bruce, Colm Leonard, Stephen Bianchi and Nazia Chaudhuri


J. Clin. Med. 2018, 7(10), 356 doi: 10.3390/jcm7100356.

 

Background

Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents. Methods: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD. Results: Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3–5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at presentation was the most reliable predictor of mortality. Glucocorticoids (GCs) were commonly used to treat DIILD, but no prospective studies examined their effect on outcome. Conclusions: Overall high-quality evidence in DIILD is lacking, and the current review will inform larger prospective studies to investigate the diagnosis and management of DIILD.

DIILD REVIEW
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Feasibility of PET/CT system performance harmonisation

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Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

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PET/CT Harmonization for Multicenter Studies

Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

Andres Kaalep, Marc Huisman, Terez Sera, Danielle Vugts, Ronald Boellaard, on behalf of EARL, EATRIS and the TRISTAN Consortium


EJNMMI Physics 2018 (5):26 doi: 10.1186/s40658-018-0226-7.

 

Purpose

The aim of this study was to investigate the variability in quantitative performance and feasibility of quantitative harmonisation in 89Zr PET/CT imaging.

Methods

Eight EANM EARL-accredited (Kaalep A et al., Eur J Nucl Med Mol Imaging 45:412-22, 2018) PET/CT systems were investigated using phantom acquisitions of uniform and NEMA NU2-2007 body phantoms. The phantoms were filled according to EANM EARL guidelines for 18F-FDG, but 18F-FDG solution was replaced by a 89Zr calibration mixture. For each system, standard uptake value (SUV) accuracy and recovery coefficients (RC) using SUVmean, SUVmax and SUVpeak metrics were determined.

Results

All eight investigated systems demonstrated similarly shaped RC curves, and five of them exhibited closely aligning recoveries when SUV bias correction was applied. From the evaluated metrics, SUVpeak was found to be least sensitive to noise and reconstruction differences among different systems.

Conclusions

Harmonisation of PET/CT scanners for quantitative 89Zr studies is feasible when proper scanner-dose calibrator cross-calibration and harmonised image reconstruction procedures are followed. An accreditation programme for PET/CT scanners would facilitate multicentre 89Zr quantitative studies.

PET/CT HARMONIZATION FOR MULTICENTER STUDIES
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Integrating molecular nuclear imaging in clinical research

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Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

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Review: PET to improve anti-cancer therapy

Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

Elisabeth G. E. de Vries, Laura Kist de Ruijter, Marjolijn N. Lub-de Hooge, Rudi A. Dierckx, Sjoerd G. Elias & Sjoukje F. Oosting


Nature Reviews Clinical Oncology (2018); doi: 10.1038/s41571-018-0123-y.

Abstract

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug–target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

REVIEW: PET TO IMPROVE ANTI-CANCER THERAPY
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Accuracy, repeatability, and reproducibility of R1 in 12

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Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

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Conference Abstract: Accuracy of R1 determination

Accuracy, repeatability, and reproducibility of R1 in 12 small-animal MRI systems (Conference Abstract)

Waterton JC, Hines CDG, Hockings PD, Laitinen I, Ziemian S, Campbell S, Gottschalk M, Green C, Haase M, Hoffmann K, Juretschke H-P, Koehler S, Lloyd W, Y Luo Y, Mahmutovic Persson I, O’Connor JPB, Olsson LE, Parker GJM, Pindoria K, Schneider JE, Steinmann D, Strobel K, Teh I, Veltien A, Zhang X, Schütz G


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

 

CONFERENCE ABSTRACT: ACCURACY OF R1 DETERMINATION
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Inter-site repeatability and quantitative assessment

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Inter-site repeatability and quantitative assessment of hepatic transporter function with DCE-MRI in rats (Conference Abstract)

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Conference Abstract: Repeatability of liver transporter function assessment

Inter-site repeatability and quantitative assessment of hepatic transporter function with DCE-MRI in rats (Conference Abstract)

Claudia Green, Sirisha Tadimalla, Denise Steinmann, Steven Sourbron, Sascha Koehler, Hans-Paul Juretschke, Iina Laitinen, John C. Waterton, Paul D. Hockings, Catherine D. G. Hines, Gunnar Schütz


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

CONFERENCE ABSTRACT: REPEATABILITY OF LIVER TRANSPORTER FUNCTION ASSESSMENT
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Hyperpolarised 129xenon MR spectroscopy and diffusion-weighted

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Hyperpolarised 129xenon MR spectroscopy and diffusion-weighted MRI at baseline in patients with interstitial lung disease (Conference Abstract)

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Conference Abstract: Hyperpolarised 129xenon MRS in ILD

Hyperpolarised 129xenon MR spectroscopy and diffusion-weighted MRI at baseline in patients with interstitial lung disease (Conference Abstract)

James Eaden, Paul Hughes, Ho-Fung Chan, Guilhem Collier, Oliver Rodgers, Graham Norquay, Matthew Austin, Laurie Smith, Steve Renshaw, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff Parker, Stephen Bianchi, and Jim Wild


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

CONFERENCE ABSTRACT: HYPERPOLARISED 129XENON MRS IN ILD
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Evaluation of automatic methods for arterial input function extraction

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Evaluation of automatic methods for arterial input function extraction for perfusion quantification in the lung (Conference Abstract)

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Conference Abstract: Automated AIF extraction

Evaluation of automatic methods for arterial input function extraction for perfusion quantification in the lung (Conference Abstract)

Marta Tibiletti, Josephine H Naish, Paul J.C. Hughes, Helen Marshall, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Ian Bruce, James Eaden, Stephen Bianchi, Jim M Wild, Geoff JM Parker


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

 

CONFERENCE ABSTRACT: AUTOMATED AIF EXTRACTION
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Comparison of algorithm to determine Ventilated Volume Fraction

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Comparison of algorithm to determine Ventilated Volume Fraction from Oxygen-Enhanced MRI in Cystic Fibrosis (Conference Abstract)

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Conference Abstract: Determine ventilated volume fraction

Comparison of algorithm to determine Ventilated Volume Fraction from Oxygen-Enhanced MRI in Cystic Fibrosis (Conference Abstract)

Marta Tibiletti, Josephine H Naish, Katharina Martini, Thomas Frauenfelder, Geoff JM Parker


Proceedings of the International Society of Magnetic Resonance in Medicine 27th Scientific Meeting and Exhibition, Montréal, Canada 11th-16th May 2019

 

CONFERENCE ABSTRACT: DETERMINE VENTILATED VOLUME FRACTION
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Repeatability and reproducibility of longitudinal relaxation rate

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Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems

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R1 repeatability and reproducibility for animal MRI

Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems

Waterton JC, Hines CDG, Hockings PD, Laitinen I, Ziemian S, Campbell S, Gottschalk M, Green C, Haase M, Hoffmann K, Juretschke H-P, Koehler S, Lloyd W, Y Luo Y, Mahmutovic Persson I, O’Connor JPB, Olsson LE, Parker GJM, Pindoria K, Schneider JE, Steinmann D, Strobel K, Teh I, Veltien A, Zhang X, Schütz G


Magnetic Resonance Imaging, Volume 59, June 2019, Pages 121-129 doi:10.1016/j.mri.2019.03.008

 

Abstract

Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R1, but evidence for between-site reproducibility of R1 in small-animal MRI is lacking.

Objective: To assess R1 repeatability and multi-site reproducibility in phantoms for preclinical MRI.

Methods: R1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1-13 days. R1 was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured.

Results: CoV for day-to-day repeatability (N=180 regions of interest) was 2.34% and for between-centre reproducibility (N=9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R1-based MR biomarkers were found to be quite sensitive even to such small errors in R1, notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni2+ in 2% agarose varied between 0.66 s-1mM-1 at 3T and 0.94 s-1mM-1 at 11.7T.

Interpretation: While several factors affect the reproducibility of R1-based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases special care in R1-accuracy is warranted.

R1 REPEATABILITY AND REPRODUCIBILITY FOR ANIMAL MRI
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Experimental and quantitative imaging techniques

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Experimental and quantitative imaging techniques in interstitial lung disease

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Imaging Techniques in ILD

Experimental and quantitative imaging techniques in interstitial lung disease

Nicholas D Weatherley, James A Eaden, Neil J Stewart, Brian J Bartholmai, Andrew J Swift, Stephen Mark Bianchi, Jim M Wild


Thorax 2019;74:611-619. doi:10.1136/thoraxjnl-2018-211779.

 

Abstract

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions, with a wide and complex variety of imaging features. Difficulty in monitoring, treating and exploring novel therapies for these conditions is in part due to the lack of robust, readily available biomarkers. Radiological studies are vital in the assessment and follow-up of ILD, but currently CT analysis in clinical practice is qualitative and therefore somewhat subjective. In this article, we report on the role of novel and quantitative imaging techniques across a range of imaging modalities in ILD and consider how they may be applied in the assessment and understanding of ILD. We critically appraised evidence found from searches of Ovid online, PubMed and the TRIP database for novel and quantitative imaging studies in ILD. Recent studies have explored the capability of texture-based lung parenchymal analysis in accurately quantifying several ILD features. Newer techniques are helping to overcome the challenges inherent to such approaches, in particular distinguishing peripheral reticulation of lung parenchyma from pleura and accurately identifying the complex density patterns that accompany honeycombing. Robust and validated texture-based analysis may remove the subjectivity that is inherent to qualitative reporting and allow greater objective measurements of change over time. In addition to lung parenchymal feature quantification, pulmonary vessel volume analysis on CT has demonstrated prognostic value in two retrospective analyses and may be a sign of vascular changes in ILD which, to date, have been difficult to quantify in the absence of overt pulmonary hypertension. Novel applications of existing imaging techniques, such as hyperpolarised gas MRI and positron emission tomography (PET), show promise in combining structural and functional information. Although structural imaging of lung tissue is inherently challenging in terms of conventional proton MRI techniques, inroads are being made with ultrashort echo time, and dynamic contrast-enhanced MRI may be used for lung perfusion assessment. In addition, inhaled hyperpolarised 129Xenon gas MRI may provide multifunctional imaging metrics, including assessment of ventilation, intra-acinar gas diffusion and alveolar-capillary diffusion. PET has demonstrated high standard uptake values (SUVs) of 18F-fluorodeoxyglucose in fibrosed lung tissue, challenging the assumption that these are ‘burned out’ and metabolically inactive regions. Regions that appear structurally normal also appear to have higher SUV, warranting further exploration with future longitudinal studies to assess if this precedes future regions of macroscopic structural change. Given the subtleties involved in diagnosing, assessing and predicting future deterioration in many forms of ILD, multimodal quantitative lung structure-function imaging may provide the means of identifying novel, sensitive and clinically applicable imaging markers of disease. Such imaging metrics may provide mechanistic and phenotypic information that can help direct appropriate personalised therapy, can be used to predict outcomes and could potentially be more sensitive and specific than global pulmonary function testing. Quantitative assessment may objectively assess subtle change in character or extent of disease that can assist in efficacy of antifibrotic therapy or detecting early changes of potentially pneumotoxic drugs involved in early intervention studies.

IMAGING TECHNIQUES IN ILD
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