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4. PET Parametric Imaging: Past, Present, and Future

Author

Wang, Guobao, Rahmim, Arman, and Gunn, Roger N

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Bioengineering, Biomedical Imaging, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Dynamic imaging, image reconstruction, kinetic modeling, parametric imaging, positron emission tomography, PET, dynamic imaging
Abstract

Positron emission tomography (PET) is actively used in a diverse range of applications in oncology, cardiology, and neurology. The use of PET in the clinical setting focuses on static (single time frame) imaging at a specific time-point post radiotracer injection and is typically considered as semi-quantitative; e.g. standardized uptake value (SUV) measures. In contrast, dynamic PET imaging requires increased acquisition times but has the advantage that it measures the full spatiotemporal distribution of a radiotracer and, in combination with tracer kinetic modeling, enables the generation of multiparametric images that more directly quantify underlying biological parameters of interest, such as blood flow, glucose metabolism, and receptor binding. Parametric images have the potential for improved detection and for more accurate and earlier therapeutic response assessment. Parametric imaging with dynamic PET has witnessed extensive research in the past four decades. In this paper, we provide an overview of past and present activities and discuss emerging opportunities in the field of parametric imaging for the future.

Published
2020

6. Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge

Author

Erritzoe, David, Godlewska, Beata R., Rizzo, Gaia, Searle, Graham E., Agnorelli, Claudio, Lewis, Yvonne, Ashok, Abhishekh H., Colasanti, Alessandro, Boura, Iro, Farrell, Chloe, Parfitt, Hollie, Howes, Oliver, Passchier, Jan, Gunn, Roger N., Politis, Marios, Nutt, David J., Cowen, Philip J., Knudsen, Gitte M., and Rabiner, Eugenii A.

Published
2023
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8. GANsfer Learning: Combining labelled and unlabelled data for GAN based data augmentation

Author

Bowles, Christopher, Gunn, Roger, Hammers, Alexander, and Rueckert, Daniel

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Medical imaging is a domain which suffers from a paucity of manually annotated data for the training of learning algorithms. Manually delineating pathological regions at a pixel level is a time consuming process, especially in 3D images, and often requires the time of a trained expert. As a result, supervised machine learning solutions must make do with small amounts of labelled data, despite there often being additional unlabelled data available. Whilst of less value than labelled images, these unlabelled images can contain potentially useful information. In this paper we propose combining both labelled and unlabelled data within a GAN framework, before using the resulting network to produce images for use when training a segmentation network. We explore the task of deep grey matter multi-class segmentation in an AD dataset and show that the proposed method leads to a significant improvement in segmentation results, particularly in cases where the amount of labelled data is restricted. We show that this improvement is largely driven by a greater ability to segment the structures known to be the most affected by AD, thereby demonstrating the benefits of exposing the system to more examples of pathological anatomical variation. We also show how a shift in domain of the training data from young and healthy towards older and more pathological examples leads to better segmentations of the latter cases, and that this leads to a significant improvement in the ability for the computed segmentations to stratify cases of AD.

Published
2018

11. GAN Augmentation: Augmenting Training Data using Generative Adversarial Networks

Author

Bowles, Christopher, Chen, Liang, Guerrero, Ricardo, Bentley, Paul, Gunn, Roger, Hammers, Alexander, Dickie, David Alexander, Hernández, Maria Valdés, Wardlaw, Joanna, and Rueckert, Daniel

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

One of the biggest issues facing the use of machine learning in medical imaging is the lack of availability of large, labelled datasets. The annotation of medical images is not only expensive and time consuming but also highly dependent on the availability of expert observers. The limited amount of training data can inhibit the performance of supervised machine learning algorithms which often need very large quantities of data on which to train to avoid overfitting. So far, much effort has been directed at extracting as much information as possible from what data is available. Generative Adversarial Networks (GANs) offer a novel way to unlock additional information from a dataset by generating synthetic samples with the appearance of real images. This paper demonstrates the feasibility of introducing GAN derived synthetic data to the training datasets in two brain segmentation tasks, leading to improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage points under different conditions, with the strongest effects seen fewer than ten training image stacks are available.

Published
2018

12. Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals

Author

Livingston, Nicholas R., Calsolaro, Valeria, Hinz, Rainer, Nowell, Joseph, Raza, Sanara, Gentleman, Steve, Tyacke, Robin J., Myers, Jim, Venkataraman, Ashwin V., Perneczky, Robert, Gunn, Roger N., Rabiner, Eugenii A., Parker, Christine A., Murphy, Philip S., Wren, Paul B., Nutt, David J., Matthews, Paul M., and Edison, Paul

Published
2022
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13. Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load

Author

Calsolaro, Valeria, Matthews, Paul M., Donat, Cornelius K., Livingston, Nicholas R., Femminella, Grazia D., Guedes, Sandra Silva, Myers, Jim, Fan, Zhen, Tyacke, Robin J., Venkataraman, Ashwin V., Perneczky, Robert, Gunn, Roger, Rabiner, Eugenii A., Gentleman, Steve, Parker, Christine A., Murphy, Philip S., Wren, Paul B., Hinz, Rainer, Sastre, Magdalena, Nutt, David J., and Edison, Paul

Published
2021
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15. A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [18F]flutemetamol amyloid PET images

Author

Bucci, Marco, Savitcheva, Irina, Farrar, Gill, Salvadó, Gemma, Collij, Lyduine, Doré, Vincent, Gispert, Juan Domingo, Gunn, Roger, Hanseeuw, Bernard, Hansson, Oskar, Shekari, Mahnaz, Lhommel, Renaud, Molinuevo, José Luis, Rowe, Christopher, Sur, Cyrille, Whittington, Alex, Buckley, Christopher, and Nordberg, Agneta

Published
2021
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18. The relationship between SV2A levels, neural activity, and cognitive function in healthy humans: A [11C]UCB-J PET and fMRI study

Author

Shatalina, Ekaterina, primary, Onwordi, Ellis Chika, additional, Whitehurst, Thomas, additional, Whittington, Alexander, additional, Mansur, Ayla, additional, Arumuham, Atheeshaan, additional, Statton, Ben, additional, Berry, Alaine, additional, Marques, Tiago Reis, additional, Gunn, Roger N., additional, Natesan, Sridhar, additional, Nour, Matthew M., additional, Rabiner, Eugenii A., additional, Wall, Matthew B., additional, and Howes, Oliver D., additional

Published
2024
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19. Estimating Braak stage from [18F]MK6240 PET scans

Author

Whittington, Alex, primary, Porat, Lily, additional, Christian, Bradley T., additional, Devanand, Devanand P., additional, Hostetler, Eric D., additional, Johnson, Keith A., additional, Johnson, Sterling C, additional, Klunk, William E, additional, Lao, Patrick J., additional, Rowe, Christopher C, additional, Devanarayan, Viswanath, additional, Reilhac, Anthonin, additional, Reyderman, Larisa, additional, Irizarry, Michael C., additional, Charil, Arnaud, additional, and Gunn, Roger N, additional

Published
2023
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21. The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study

Author

Onwordi, Ellis Chika, Whitehurst, Thomas, Mansur, Ayla, Statton, Ben, Berry, Alaine, Quinlan, Marina, O’Regan, Declan P., Rogdaki, Maria, Marques, Tiago Reis, Rabiner, Eugenii A., Gunn, Roger N., Vernon, Anthony C., Natesan, Sridhar, and Howes, Oliver D.

Published
2021
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24. Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study)

Author

Lukey, Pauline T., Coello, Christopher, Gunn, Roger, Parker, Christine, Wilson, Frederick J., Saleem, Azeem, Garman, Nadia, Costa, Maria, Kendrick, Stuart, Onega, Mayca, Kang’ombe, Arthur R., Listanco, Allan, Davies, James, Ramada-Magalhaes, Joaquim, Moz, Sara, Fahy, William A., Maher, Toby M., Jenkins, Gisli, Passchier, Jan, and Marshall, Richard P.

Published
2020
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26. Preclinical evaluation of [18F]FB-A20FMDV2 as a selective marker for measuring αVβ6 integrin occupancy using positron emission tomography in rodent lung

Author

Onega, Mayca, Parker, Christine A., Coello, Christopher, Rizzo, Gaia, Keat, Nicholas, Ramada-Magalhaes, Joaquim, Moz, Sara, Tang, Sac-Pham, Plisson, Christophe, Wells, Lisa, Ashworth, Sharon, Slack, Robert J., Vitulli, Giovanni, Wilson, Frederick J., Gunn, Roger, Lukey, Pauline T., and Passchier, Jan

Published
2020
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27. Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study

Author

Wilson, Heather, Dervenoulas, George, Pagano, Gennaro, Koros, Christos, Yousaf, Tayyabah, Picillo, Marina, Polychronis, Sotirios, Simitsi, Athina, Giordano, Beniamino, Chappell, Zachary, Corcoran, Benjamin, Stamelou, Maria, Gunn, Roger N, Pellecchia, Maria Teresa, Rabiner, Eugenii A, Barone, Paolo, Stefanis, Leonidas, and Politis, Marios

Published
2019
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29. Evaluation of Intraperitoneal [ 18 F]-FDOPA Administration for Micro-PET Imaging in Mice and Assessment of the Effect of Subchronic Ketamine Dosing on Dopamine Synthesis Capacity.

Author

Halff, Els F., Natesan, Sridhar, Bonsall, David R., Veronese, Mattia, Garcia-Hidalgo, Anna, Kokkinou, Michelle, Tang, Sac-Pham, Riggall, Laura J., Gunn, Roger N., Irvine, Elaine E., Withers, Dominic J., Wells, Lisa A., Howes, Oliver D., and Vasdev, Neil

Subjects
KETAMINE, DOPAMINE, DOPAMINERGIC neurons, POSITRON emission tomography, INTRACLASS correlation, METHYL aspartate receptors, JUGULAR vein, RADIOACTIVE tracers
Abstract

Positron emission tomography (PET) using the radiotracer [18F]-FDOPA provides a tool for studying brain dopamine synthesis capacity in animals and humans. We have previously standardised a micro-PET methodology in mice by intravenously administering [18F]-FDOPA via jugular vein cannulation and assessment of striatal dopamine synthesis capacity, indexed as the influx rate constant K i Mod of [18F]-FDOPA, using an extended graphical Patlak analysis with the cerebellum as a reference region. This enables a direct comparison between preclinical and clinical output values. However, chronic intravenous catheters are technically difficult to maintain for longitudinal studies. Hence, in this study, intraperitoneal administration of [18F]-FDOPA was evaluated as a less-invasive alternative that facilitates longitudinal imaging. Our experiments comprised the following assessments: (i) comparison of [18F]-FDOPA uptake between intravenous and intraperitoneal radiotracer administration and optimisation of the time window used for extended Patlak analysis, (ii) comparison of K i Mod in a within-subject design of both administration routes, (iii) test-retest evaluation of K i Mod in a within-subject design of intraperitoneal radiotracer administration, and (iv) validation of K i Mod estimates by comparing the two administration routes in a mouse model of hyperdopaminergia induced by subchronic ketamine. Our results demonstrate that intraperitoneal [18F]-FDOPA administration resulted in good brain uptake, with no significant effect of administration route on K i Mod estimates (intraperitoneal: 0.024 ± 0.0047 min − 1 , intravenous: 0.022 ± 0.0041 min − 1 , p = 0.42) and similar coefficient of variation (intraperitoneal: 19.6%; intravenous: 18.4%). The technique had a moderate test-retest validity (intraclass correlation coefficient ICC = 0.52 , N = 6) and thus supports longitudinal studies. Following subchronic ketamine administration, elevated K i Mod as compared to control condition was measured with a large effect size for both methods (intraperitoneal: Cohen's d = 1.3 ; intravenous: Cohen's d = 0.9), providing further evidence that ketamine has lasting effects on the dopamine system, which could contribute to its therapeutic actions and/or abuse liability. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Disease-related patterns of in vivo pathology in Corticobasal syndrome

Author

Niccolini, Flavia, Wilson, Heather, Hirschbichler, Stephanie, Yousaf, Tayyabah, Pagano, Gennaro, Whittington, Alexander, Caminiti, Silvia P., Erro, Roberto, Holton, Janice L., Jaunmuktane, Zane, Esposito, Marcello, Martino, Davide, Abdul, Ali, Passchier, Jan, Rabiner, Eugenii A., Gunn, Roger N., Bhatia, Kailash P., Politis, Marios, and for the Alzheimer’s Disease Neuroimaging Initiative

Published
2018
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33. Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of Synaptic Vesicle Glycoprotein 2A

Author

Onwordi, Ellis Chika, primary, Whitehurst, Thomas, additional, Shatalina, Ekaterina, additional, Mansur, Ayla, additional, Arumuham, Atheeshaan, additional, Osugo, Martin, additional, Marques, Tiago Reis, additional, Jauhar, Sameer, additional, Gupta, Susham, additional, Mehrotra, Ravi, additional, Rabiner, Eugenii A., additional, Gunn, Roger N., additional, Natesan, Sridhar, additional, and Howes, Oliver D., additional

Published
2023
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34. Pseudo-healthy Image Synthesis for White Matter Lesion Segmentation

Author

Bowles, Christopher, Qin, Chen, Ledig, Christian, Guerrero, Ricardo, Gunn, Roger, Hammers, Alexander, Sakka, Eleni, Dickie, David Alexander, Hernández, Maria Valdés, Royle, Natalie, Wardlaw, Joanna, Rhodius-Meester, Hanneke, Tijms, Betty, Lemstra, Afina W., van der Flier, Wiesje, Barkhof, Frederik, Scheltens, Philip, Rueckert, Daniel, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Tsaftaris, Sotirios A., editor, Gooya, Ali, editor, Frangi, Alejandro F., editor, and Prince, Jerry L., editor

Published
2016
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37. Guidelines for the content and format of PET brain data in publications and archives: A consensus paper

Author

Knudsen, Gitte M, Ganz, Melanie, Appelhoff, Stefan, Boellaard, Ronald, Bormans, Guy, Carson, Richard E, Catana, Ciprian, Doudet, Doris, Gee, Antony D, Greve, Douglas N, Gunn, Roger N, Halldin, Christer, Herscovitch, Peter, Huang, Henry, Keller, Sune H, Lammertsma, Adriaan A, Lanzenberger, Rupert, Liow, Jeih-San, Lohith, Talakad G, Lubberink, Mark, Lyoo, Chul H, Mann, J John, Matheson, Granville J, Nichols, Thomas E, Nørgaard, Martin, Ogden, Todd, Parsey, Ramin, Pike, Victor W, Price, Julie, Rizzo, Gaia, Rosa-Neto, Pedro, Schain, Martin, Scott, Peter JH, Searle, Graham, Slifstein, Mark, Suhara, Tetsuya, Talbot, Peter S, Thomas, Adam, Veronese, Mattia, Wong, Dean F, Yaqub, Maqsood, Zanderigo, Francesca, Zoghbi, Sami, and Innis, Robert B

Published
2020
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38. Synaptic terminal density early in the course of schizophrenia: an in vivo UCB-J positron emission tomographic imaging study of synaptic vesicle glycoprotein 2A (SV2a)

Author

Onwordi, Ellis Chika, Whitehurst, Thomas, Shatalina, Ekaterina, Mansur, Ayla, Arumuham, Atheeshaan, Osugo, Martin, Reis Marques, Tiago, Jauhar, Sameer, Gupta, Susham, Mehrotra, Ravi, Rabiner, Eugenii A., Gunn, Roger N., Natesan, Sridhar, and Howes, Oliver

Abstract

BACKGROUND: The synaptic hypothesis is an influential theory of the pathoaetiology of schizophrenia. Supporting this, there is lower uptake of the synaptic terminal density marker UCB-J in patients with chronic schizophrenia compared to controls. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with schizophrenia (SCZ) recruited from first-episode services compared to healthy volunteers (HV). METHODS: Forty-two volunteers (SCZ n = 21, HV n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio (DVR) in the anterior cingulate, frontal, and dorsolateral prefrontal cortices, temporal, parietal and occipital lobes, hippocampus, thalamus and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale (PANSS). RESULTS: We found no significant effects of group on [11C]UCB-J VT or DVR in most regions of interest (effect sizes from d=0.0 to 0.7, p>0.05), other than lower DVR in the temporal lobe (d=0.7, uncorrected p

Published
2023

39. A PET-CT study on neuroinflammation in Huntington’s disease patients participating in a randomized trial with laquinimod

Author

Roussakis, Andreas-Antonios, primary, Gennaro, Marta, additional, Gordon, Mark Forrest, additional, Reilmann, Ralf, additional, Borowsky, Beth, additional, Rynkowski, Gail, additional, Lao-Kaim, Nicholas P, additional, Papoutsou, Zoe, additional, Savola, Juha-Matti, additional, Hayden, Michael R, additional, Owen, David R, additional, Kalk, Nicola, additional, Lingford-Hughes, Anne, additional, Gunn, Roger N, additional, Searle, Graham, additional, Tabrizi, Sarah J, additional, and Piccini, Paola, additional

Published
2023
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42. Mathematical modelling and identifiability applied to positron emission tomography data

Author

Gunn, Roger

Subjects
571.4, QA Mathematics, RC Internal medicine
Abstract

Positron emission tomography (PET) is an in vivo tracer kinetic technique. This thesis is concerned with the analysis of data derived from PET studies in humans. There are two related themes in the thesis. Firstly, the derivation of mathematical models with particular reference to the modelling of radiolabelled metabolite formation in plasma and tissue. Secondly, the identifiability of model structures is examined, and a method for the reparameterisation of unidentifiable models is derived. Compartmental models describing the accumulation of radiolabelled metabolites in plasma following the intravenous administration of [11C]flumazenil and [11C]diprenorphine are presented. A theorem is presented which gives conditions for a unique solution to the spectral analysis approach (a kinetic modelling technique used in PET which is based on the a priori definition of a large set of basis functions). Mathematical techniques are presented for the analysis of expired 11CO2, a major labelled metabolite in many PET studies. This range of analytical and modelling techniques is then applied to the analysis of [11C]thymidine scans. [11C]Thymidine is a PET tracer being developed for the measure of tumour proliferation in cancer patients. The techniques developed in the thesis allow for the removal of the confounding labelled metabolite signals from both plasma and tissue data.

Published
1996

47. Application of Aligned-UMAP to longitudinal biomedical studies

Author

Dadu, Anant, primary, Satone, Vipul K., additional, Kaur, Rachneet, additional, Koretsky, Mathew J., additional, Iwaki, Hirotaka, additional, Qi, Yue A., additional, Ramos, Daniel M., additional, Avants, Brian, additional, Hesterman, Jacob, additional, Gunn, Roger, additional, Cookson, Mark R., additional, Ward, Michael E., additional, Singleton, Andrew B, additional, Campbell, Roy H, additional, Nalls, Mike A, additional, and Faghri, Faraz, additional

Published
2022
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49. In Vivo Head‐To‐Head Comparison of [ 18 F]GTP1 and [ 18 F]PI2620 in Alzheimer’s Disease

Author

Bohorquez, Sandra Sanabria, primary, Constantinescu, Cristian, additional, Manser, Paul T, additional, Gunn, Roger N, additional, Russell, David S, additional, Tonietto, Matteo, additional, Bullich, Santiago, additional, Stephens, Andrew W, additional, Mueller, Andre, additional, Klein, Gregory, additional, Teng, Edmond, additional, and Pickthorn, Karen, additional

Published
2022
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