Uncertainty analysis of single-time-point organ dosimetry compared with the multi-time-point method in radioimmunotherapy
Nautiyal A, Lewis G, Gear JI, Orchard K, Guy MJ and Michopoulou S
A position paper released by the European Association of Nuclear Medicine emphasised the need for multidisciplinary engagement to establish dosimetry-based personalised treatment in Radionuclide therapy (RNT). The uncertainty analysis results often ignored in routine clinical practice should be incorporated into the dose calculations to improve the efficacy and accuracy of treatment. In this study, patients with haematological malignancies undergoing radioimmunotherapy were evaluated. Our study aimed to calculate the uncertainties associated with each parameter of the single time point (STP) dosimetry chain and compare the with multiple time points (MTP) in the bone marrow and liver results.
Correction: Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation
Orchard K, Langford J, Guy M, Lewis G, Michopoulou S, Cooper M, Zvavamwe C, Richardson D and Lewington V
Alzheimer's disease diagnosis support for brain perfusion SPECT scans in a real-world clinical cohort
Michopoulou S, Prosser A, O'Brien N, Dickson J, Guy M, Teeling JL and Kipps CM
BackgroundDementia diagnosis is challenging and often delayed. Brain imaging techniques such as single-photon emission computed tomography (SPECT) imaging can help identify subtle changes in brain perfusion. Artificial intelligence methods may support results interpretation for early diagnosis.ObjectiveTo develop and validate multivariate models for the early diagnosis of Alzheimer's disease (AD), using brain perfusion SPECT imaging and interpretable artificial intelligence methods in a real-world clinical setting.MethodsTwo logistic regression models were developed using a training dataset of 420 SPECT scans and tested on an independent clinical dataset of 443 scans. Model 1 was designed to identify abnormal perfusion patterns, while Model 2 identified perfusion changes associated with AD. Input features were extracted from anatomical volumes of interest, with feature selection performed using the Minimum Redundancy Maximum Relevance (MRMR) algorithm.ResultsThe models demonstrated good classification performance using real-world clinical data. Model 1 achieved an area under receiver operator characteristic (AUROC) Curve of 0.89 (Sensitivity 76%, Specificity 87%) in identifying abnormal brain perfusion. Model 2 achieved an AUROC of 0.86 (Sensitivity 87%, Specificity 72%) in identifying AD.ConclusionsMultivariate logistic regression models trained on real-world clinical data show promise as clinical decision support tools for the diagnosis of AD from brain perfusion SPECT imaging. The models use features from clinically relevant brain regions, which enhances interpretability. Future research should focus on expanding model applicability to other dementia types and on prospective evaluation of their utility in improving diagnostic accuracy, consistency, and care pathways in diverse clinical environments.
A novel SPECT-CT imaging platform for quantifying lung cytokine signals in COPD
Welham B, Bennett M, Ostridge K, Guy M, Zvavamwe C, Chilcott A, Johns S, Sundram F, Spalluto CM, Shaw E, Harden S, Alzetani A, Lee P, Lawson M, Lackie P, Michopoulou S, Henley D, Kong A, Fazleen A, Cellura D, McCrae C, Platt A, Belvisi MG, Staples KJ and Wilkinson T
Disease-modifying treatments such as monoclonal antibodies can be highly effective in chronic inflammatory diseases such as COPD, but often fail in clinical trials due to heterogeneity of inflammation and imperfect tools to stratify patients to select optimal therapeutic approaches. Molecular imaging provides the potential to transform precision medicine in this field.
Classification of Alzheimer's disease in a mixed clinical cohort using biofluid Raman spectroscopy
Devitt G, Michopoulou SK, Kadalayil L, Hanrahan N, Prosser A, Ghosh B, Mudher A, Kipps CM and Mahajan S
There is a critical unmet need for scalable, accessible and objective diagnostic tests for stratification in dementia. Biofluid Raman spectroscopy (RS) due to its simplicity, holistic and label-free nature, is a powerful approach that has the potential to offer differential diagnosis across dementia types including Alzheimer's disease (AD). RS is a laser-based optical method that can rapidly provide chemically rich information ('spectral biomarkers') from biofluids but its utility for AD diagnosis has not been established in a 'real-world' context, specifically from a clinically heterogenous cohort of patients. We carried out RS measurements on cerebrospinal fluid (CSF) samples of patients from a mixed clinical cohort (N = 143). All patients reported cognitive complaints and were clinically diagnosed over 2 years with conditions including AD and other neurodegenerative diseases, as well as developmental and long-term chronic conditions. Machine-learning algorithms were trained, optimised and evaluated on Raman spectra to classify AD from non-AD. AD was classified with 93% accuracy for patients in the testing set. Time from sample to classification was < 1 h. Spectral biomarkers explaining AD classification were identified and primarily assigned to protein-derived aromatic amino acids, representing a difference in proteome signature between AD and non-AD groups. Signals from a subset of spectral biomarkers directly correlated with pathological CSF biomarker concentrations including amyloid-β 42, phosphorylated-tau 181, and total tau. This pre-clinical study is a first step towards realising the real-world application of RS for dementia diagnosis. Compared to current and emerging methods, RS does not require sophisticated instrumentation or specialised labs. It is reagentless and simple, offering unprecedented rapidity, scalability, accessibility for dementia diagnosis.