Positron emision [i.e. emission] tomography (PET) in non-malignant chest diseases

Aliyu, Shamsuddeen Ahmad

Medicine
October 2019

Thesis or dissertation


Rights
© 2019 Shamsuddeen Ahmad Aliyu. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Molecular imaging is a functional imaging that identify disease in its earliest stages and determine the exact location of metabolically active tissue such as tumours. Often before symptoms occur or abnormalities can be detected with other diagnostic tests. Two simultaneous studies to explore the potentials of Positron Emission tomography (PET) have been conducted. In the first study, the role of PET in pulmonary drug deposition has been evaluated whereas in the second study, it’s potential in monitoring disease progression and treatment response monitoring in IPF has been discovered.

Gamma imaging such as planer and Single Photon Emission computed tomography (SPECT) have been used for decades in the imaging of pulmonary drug deposition, despite numerous advantage of PET very few studies were found in the literature. Two studies were conducted using in-house developed lung surrogate phantom and Andersen cascade impactor to demonstrate PET role in pulmonary drug deposition. The lung surrogate phantom study is a ‘’proof of concept’’ in which series of experiments was conducted leading to the development of a usable model. Each experimental procedure was conducted repeatedly over time to reduce the level of experimental errors. To my knowledge, this is the first phantom experiment quantifying the deposition pattern of aerosolized [18F]-FDG while mimicking human tidal breathing. In a separate experiment the Andersen cascade impactor (ACI) have been used to measure distribution of beclometasone dipropionate (BDP), formoterol fumarate dihydrate (FFA) as well as [18F]-2-fluorp-2-deoxy-D-glucose ([18F]-FDG) along the stages of ACI.

The overall activity deposition within the phantom; cylinder and the extra-pulmonary section of the tube were 8.07 ± 3.51MBq. The deposition within the cylinder (lung surrogate) was 6.27 ± 2.55MBq. The average total internal dose (phantom cylinders and the extra-pulmonary section of the tube was calculated to be 0.2mSv/PET scan. These results are expected in human clinical trial under similar experimental conditions.

The Aerodynamic particle size distribution (APSD) along the fractionating part of the AIM comprises of large particle mass (LPM) and small particle mass (SPM). The LPM is APSD >5μg deposited on stage 1 (representing to upper respiratory tract), whereas, the SPM comprised of the particle size 1-5 μg and < 1 μg deposited on stage 2 (representing the small airways and lung parenchyma) and an exhalation filter. In general, the deposition of the drugs and [18F]-FDG within the fractionating part of the impactor was predominantly within 1-5μg, which is a desirable fine particle fraction (FPF) of the active pharmaceutical ingredients (API) leading to pulmonary deposition.

The potentials of PET imaging in pulmonary drug deposition has been demonstrated in these experiments using lung surrogate phantom and cascade impactor. [18F]-FDG PET imaging has the potentials in providing better understanding of regional distribution of pulmonary drug deposition. Standardization of these methods will enable PET imaging to be used in pulmonary drug development.

In the second study, A retrospective studies using PET data was carried out to measure uptake of [18F]-FDG in the region of apparently normal lung in IPF. This was compared to normal control lung images to ascertain differences in their uptake value.

HRCT is the current gold standard imaging the diagnosis of IPF. Recently there is growing interest in exploring the potentials of PET imaging in the disease progression and treatment response monitoring in IPF.

Patients with IPF that had undergone PET-CT imaging for investigation of concomitant cancer diagnosis were identified retrospectively in a single interstitial lung disease (ILD) tertiary referral centre. Non IPF patients that had a PET-CT scan in the same centre for cancer diagnosis without non-malignant lung disease were identified to form two control groups: a lung cancer control group and a control group with no evidence of intra-thoracic disease (extra-thoracic malignancy controls). These two control groups were identified to allow assessment of whether the presence of thoracic malignancy effected [18F]-FDG uptake. In the event of no effect being identified, a pooled analysis comparing IPF patients and all controls was planned.

No difference in standard uptake value (SUV) Maximum (Max) and SUV mean uptake was observed in the mean of 4 (Region of Interest) ROIs between lung cancer controls and extra-thoracic malignancy controls in all 3 normalizations (SUV Max body weight (BW), SUV body surface area (BSA) and SUV activity concentration (AC)) and therefore data from these groups were pooled for comparison with IPF patients. The SUV Max and SUV mean of radiologically normal lung in IPF patients was significantly higher than the normal lung in controls. However, the CT number/Hounsfield unit of the IPF patients and the control group are comparable. In addition, 20 textural features were identified in each ROI both in CT and PET data sets. Five out of the twenty CT textural features shows significant differences between the 2 controls as such, they were excluded. Fifteen were pooled together for comparison with IPF patients. Five out of the fifteen CT textural features shows significant differences when compared with IPF and all are consistent with five features that shows significant difference in PET dataset.

Increase [18F]-FDG PET signal within areas of areas of apparently normal lung parenchyma has been demonstrated using SUV with 3 different normalization methods as well as using textural feature analysis. These findings have shown the heterogeneous nature of the disease process indicating the possibility of the disease activity within the apparently normal lung CT lung images. These finding may provide insight into the pathogenesis of the disease and may be helpful in monitoring the disease progression and treatment response.

Publisher
Hull York Medical School, The University of Hull and The University of York
Supervisor
Morice, Alyn H.
Sponsor (Organisation)
Usmanu Danfodiyo University
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
3 MB
Identifier
hull:17721
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