Direct inference of Patlak parametric images in whole-body PET/CT imaging using convolutional neural networks

Purpose: This study proposed and investigated the feasibility of estimating Patlak-derived influx rate constant (Ki) from standardized uptake value (SUV) and/or dynamic PET image series. Methods: Whole-body 18F-FDG dynamic PET images of 19 subjects consisting of 13 frames or passes were employed for training a residual deep learning model with SUV and/or dynamic series as input and Ki-Patlak (slope) images as output. The training and evaluation were performed using a nine-fold cross-validation scheme. Owing to the availability of SUV images acquired 60 min post-injection (20 min total acquisition time), the data sets used for the training of the models were split into two groups: “With SUV” and “Without SUV.” For “With SUV” group, the model was first trained using only SUV images and then the passes (starting from pass 13, the last pass, to pass 9) were added to the training of the model (one pass each time). For this group, 6 models were developed with input data consisting of SUV, SUV plus pass 13, SUV plus passes 13 and 12, SUV plus passes 13 to 11, SUV plus passes 13 to 10, and SUV plus passes 13 to 9. For the “Without SUV” group, the same trend was followed, but without using the SUV images (5 models were developed with input data of passes 13 to 9). For model performance evaluation, the mean absolute error (MAE), mean error (ME), mean relative absolute error (MRAE%), relative error (RE%), mean squared error (MSE), root mean squared error (RMSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) were calculated between the predicted Ki-Patlak images by the two groups and the reference Ki-Patlak images generated through Patlak analysis using the whole acquired data sets. For specific evaluation of the method, regions of interest (ROIs) were drawn on representative organs, including the lung, liver, brain, and heart and around the identified malignant lesions. Results: The MRAE%, RE%, PSNR, and SSIM indices across all patients were estimated as 7.45 ± 0.94%, 4.54 ± 2.93%, 46.89 ± 2.93, and 1.00 ± 6.7 × 10−7, respectively, for models predicted using SUV plus passes 13 to 9 as input. The predicted parameters using passes 13 to 11 as input exhibited almost similar results compared to the predicted models using SUV plus passes 13 to 9 as input. Yet, the bias was continuously reduced by adding passes until pass 11, after which the magnitude of error reduction was negligible. Hence, the predicted model with SUV plus passes 13 to 9 had the lowest quantification bias. Lesions invisible in one or both of SUV and Ki-Patlak images appeared similarly through visual inspection in the predicted images with tolerable bias. Conclusion: This study concluded the feasibility of direct deep learning-based approach to estimate Ki-Patlak parametric maps without requiring the input function and with a fewer number of passes. This would lead to shorter acquisition times for WB dynamic imaging with acceptable bias and comparable lesion detectability performance.</p

Joint Analysis of PET/MR Data for Improved PET Quantification

Quantitative pharmacokinetic analysis of Positron Emission Tomography (PET) data typically requires a dynamic scan of at least one hour, which poses a challenge for both clinical and research studies. Instead, in standard practice, a static 10 minute scan is used to calculate the standardised uptake value ratio (SUVR). SUVR approximates tracer binding but is biased by blood flow changes, rendering it unsuitable for longitudinal studies. In this thesis, the availability of magnetic resonance imaging (MRI) data, simultaneously acquired from a PET-MR scanner is exploited to reduce the time required for accurate PET quantification. The main body of this work comprises the development of a framework to incorporate blood flow information from arterial spin labelled (ASL) MRI data into the existing simplified reference tissue model (SRTM) to replace the early phase of the PET data, reducing the acquisition time. This reduced acquisition time (RT-) SRTM was evaluated on [18F]-florbetapir data for the estimation of both regional average and voxelwise amyloid burden (BPND), and was validated against the gold standard BPND using a 60 minute scan. The first step of the RT-SRTM requires the PET tracer delivery parameter, R1, to be estimated from the ASL cerebral blood flow (CBF) maps. Several methods were evaluated: linear regression using region as a covariate, multi-atlas propagation with image fusion, and deep learning based regression using a convolutional neural network. The RT-SRTM was shown to facilitate accurate regional voxelwise quantification in half the acquisition time (30 minutes). Additionally, deep learning based regression was used to learn the model which maps ASL-CBF and dynamic PET data to BPND in a single step (SSDL). The SS-DL model exploits all available information, and avoids noise sensitive voxelwise fitting. This allows the acquisition time to be cut to 15 minutes, and facilitates accurate voxelwise BPND quantification on a timescale manageable for almost all patients and studies

Deep MR to CT Synthesis for PET/MR Attenuation Correction

Positron Emission Tomography - Magnetic Resonance (PET/MR) imaging combines the functional information from PET with the flexibility of MR imaging. It is essential, however, to correct for photon attenuation when reconstructing PETs, which is challenging for PET/MR as neither modality directly image tissue attenuation properties. Classical MR-based computed tomography (CT) synthesis methods, such as multi-atlas propagation, have been the method of choice for PET attenuation correction (AC), however, these methods are slow and suffer from the poor ability to handle anatomical abnormalities. To overcome this limitation, this thesis explores the rising field of artificial intelligence in order to develop novel methods for PET/MR AC. Deep learning-based synthesis methods such as the standard U-Net architecture are not very stable, accurate, and robust to small variations in image appearance. Thus, the first proposed MR to CT synthesis method deploys a boosting strategy, where multiple weak predictors build a strong predictor providing a significant improvement in CT and PET reconstruction accuracy. Standard deep learning-based methods as well as more advanced methods like the first proposed method show issues in the presence of very complex imaging environments and large images such as whole-body images. The second proposed method learns the image context between whole-body MRs and CTs through multiple resolutions while simultaneously modelling uncertainty. Lastly, as the purpose of synthesizing a CT is to better reconstruct PET data, the use of CT-based loss functions is questioned within this thesis. Such losses fail to recognize the main objective of MR-based AC, which is to generate a synthetic CT that, when used for PET AC, makes the reconstructed PET as close as possible to the gold standard PET. The third proposed method introduces a novel PET-based loss that minimizes CT residuals with respect to the PET reconstruction

Is attention all you need in medical image analysis? A review

Medical imaging is a key component in clinical diagnosis, treatment planning and clinical trial design, accounting for almost 90% of all healthcare data. CNNs achieved performance gains in medical image analysis (MIA) over the last years. CNNs can efficiently model local pixel interactions and be trained on small-scale MI data. The main disadvantage of typical CNN models is that they ignore global pixel relationships within images, which limits their generalisation ability to understand out-of-distribution data with different 'global' information. The recent progress of Artificial Intelligence gave rise to Transformers, which can learn global relationships from data. However, full Transformer models need to be trained on large-scale data and involve tremendous computational complexity. Attention and Transformer compartments (Transf/Attention) which can well maintain properties for modelling global relationships, have been proposed as lighter alternatives of full Transformers. Recently, there is an increasing trend to co-pollinate complementary local-global properties from CNN and Transf/Attention architectures, which led to a new era of hybrid models. The past years have witnessed substantial growth in hybrid CNN-Transf/Attention models across diverse MIA problems. In this systematic review, we survey existing hybrid CNN-Transf/Attention models, review and unravel key architectural designs, analyse breakthroughs, and evaluate current and future opportunities as well as challenges. We also introduced a comprehensive analysis framework on generalisation opportunities of scientific and clinical impact, based on which new data-driven domain generalisation and adaptation methods can be stimulated

Application of artificial intelligence in nuclear medicine and molecular imaging: a review of current status and future perspectives for clinical translation.

Artificial intelligence (AI) will change the face of nuclear medicine and molecular imaging as it will in everyday life. In this review, we focus on the potential applications of AI in the field, both from a physical (radiomics, underlying statistics, image reconstruction and data analysis) and a clinical (neurology, cardiology, oncology) perspective. Challenges for transferability from research to clinical practice are being discussed as is the concept of explainable AI. Finally, we focus on the fields where challenges should be set out to introduce AI in the field of nuclear medicine and molecular imaging in a reliable manner

Functional Magnetic Resonance Imaging of Breast Cancer

This thesis examines the use of magnetic resonance imaging (MRI) techniques in the detection of breast cancer and the prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT). This thesis compares the diagnostic performance of diffusion-weighted imaging (DWI) models in the breast using a systematic review and meta-analysis. Advanced diffusion models have been proposed that may improve the performance of standard DWI using the apparent diffusion coefficient (ADC) to discriminate between malignant and benign breast lesions. Pooling the results from 73 studies, comparable diagnostic accuracy is shown using the ADC and parameters from the intra-voxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) models. This work highlights a lack of standardisation in DWI protocols and methodology. Conventional acquisition techniques used in DWI often suffer from image artefacts and low spatial resolution. A multi-shot DWI technique, multiplexed sensitivity encoding (MUSE), can improve the image quality of DWI. A MUSE protocol has been optimised through a series of phantom experiments and validated in 20 patients. Comparing MUSE to conventional DWI, statistically significant improvements are shown in distortion and blurring metrics and qualitative image quality metrics such as lesion conspicuity and diagnostic confidence, increasing the clinical utility of DWI. This thesis investigates the use of dynamic contrast-enhanced MRI (DCE-MRI) in the detection of breast cancer and the prediction of pCR. Abbreviated MRI (ABB-MRI) protocols have gained increasing attention for the detection of breast cancer, acquiring a shortened version of a full diagnostic protocol (FDP-MRI) in a fraction of the time, reducing the cost of the examination. The diagnostic performance of abbreviated and full diagnostic protocols is systematically compared using a meta-analysis. Pooling 13 studies, equivalent diagnostic accuracy is shown for ABB-MRI in cohorts enriched with cancers, and lower but not significantly different diagnostic performance is shown in screening cohorts. Higher order imaging features derived from pre-treatment DCE-MRI could be used to predict pCR and inform decisions regarding targeted treatment, avoiding unnecessary toxicity. Using data from 152 patients undergoing NACT, radiomics features are extracted from baseline DCE-MRI and machine learning models trained to predict pCR with moderate accuracy. The stability of feature selection using logistic regression classification is demonstrated and a comparison of models trained using features from different time points in the dynamic series demonstrates that a full dynamic series enables the most accurate prediction of pCR.GE Healthcare funded PhD Studentshi

Dynamic PET-Tau Quantification for Progressive Supranuclear Palsy Diagnosis

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2023-2024. Tutor: Raúl Tudela ; Director: Aida Niñerola, Raúl TudelaTauopathies are neurodegenerative diseases caused by the abnormal accumulation of tau proteins in the brain. One uncommon tauopathy is progressive supranuclear palsy (PSP), whose symptoms often overlap with other brain disorders, and its detection is only possible postmortem since there is not an available ideal biomarker. PET-tau imaging has the potential to revolutionize the early detection of this disease. PET is a nuclear imaging test which allows seeing the functionality of organs and tissues in vivo using a radiotracer that emits radiation from inside the body. A new PET tracer called 18F-PI-2620 has shown promising results concerning the detection of PSP, with high affinity to tau aggregates and low off-target binding. This project consists of designing and testing a software for the quantification of PET images of the brain with a dynamic acquisition, which show the radiotracer distribution through time. The software performs a coregistration of the images to the standard space, where the different regions of the brain can be segmented using an atlas, and provides two physiologically meaningful parameters which are the Distribution Volume Ratio (DVR) and Standardized Uptake Value Ratio (SUVR). It gives out the DVR and SUVR values for any region of interest, as well as parametric images which help visualizing the radiotracer distribution in the brain. A set of brain PET images from 13 subjects acquired using 18F-PI-2620 has been used for the development and testing of the software, divided into healthy controls, subjects with Down syndrome, some of whom have developed Alzheimer’s disease (AD), which also implies a higher amount of abnormal deposited tau proteins. The results have shown higher DVR and SUVR values for several brain regions in those subjects who have developed AD, confirming that they have a higher radiotracer uptake and a greater amount of deposited tau proteins. This proves the correct functionality of the software and its potential as a future tool for detecting tauopathies such as PSP in combination with the radiotracer

Quantitative PET and SPECT

Since the introduction of personalized medicine, the primary focus of imaging has moved from detection and diagnosis to tissue characterization, the determination of prognosis, prediction of treatment efficacy, and measurement of treatment response. Precision (personalized) imaging heavily relies on the use of hybrid technologies and quantitative imaging biomarkers. The growing number of promising theragnostics require accurate quantification for pre- and post-treatment dosimetry. Furthermore, quantification is required in the pharmacokinetic analysis of new tracers and drugs and in the assessment of drug resistance. Positron Emission Tomography (PET) is, by nature, a quantitative imaging tool, relating the time–activity concentration in tissues and the basic functional parameters governing the biological processes being studied. Recent innovations in single photon emission computed tomography (SPECT) reconstruction techniques have allowed for SPECT to move from relative/semi-quantitative measures to absolute quantification. The strength of PET and SPECT is that they permit whole-body molecular imaging in a noninvasive way, evaluating multiple disease sites. Furthermore, serial scanning can be performed, allowing for the measurement of functional changes over time during therapeutic interventions. This Special Issue highlights the hot topics on quantitative PET and SPECT