Person:

Li, Quanzheng

Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/64Cu dual-labeled cyclic RGD peptide. Methods: The integrin αvβ3 binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. Results: The dual-labeled probe 64Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026). Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.

This theme issue provides an overview on the basic quantitative methods, an in-depth discussion on the cutting-edge quantitative analysis approaches as well as their applications for both static and dynamic molecular diagnostic and therapeutic imaging.

Quantitative measures of image quality and reliability are critical for both qualitative interpretation and quantitative analysis of medical images. While, in theory, it is possible to analyze reconstructed images by means of Monte Carlo simulations using a large number of noise realizations, the associated computational burden makes this approach impractical. Additionally, this approach is less meaningful in clinical scenarios, where multiple noise realizations are generally unavailable. The practical alternative is to compute closed-form analytical expressions for image quality measures. The objective of this paper is to review statistical analysis techniques that enable us to compute two key metrics: resolution (determined from the local impulse response) and covariance. The underlying methods include fixed-point approaches, which compute these metrics at a fixed point (the unique and stable solution) independent of the iterative algorithm employed, and iteration-based approaches, which yield results that are dependent on the algorithm, initialization, and number of iterations. We also explore extensions of some of these methods to a range of special contexts, including dynamic and motion-compensated image reconstruction. While most of the discussed techniques were developed for emission tomography, the general methods are extensible to other imaging modalities as well. In addition to enabling image characterization, these analysis techniques allow us to control and enhance imaging system performance. We review practical applications where performance improvement is achieved by applying these ideas to the contexts of both hardware (optimizing scanner design) and image reconstruction (designing regularization functions that produce uniform resolution or maximize task-specific figures of merit).

Understanding network features of brain pathology is essential to reveal underpinnings of neurodegenerative diseases. In this paper, we introduce a novel graph regression model (GRM) for learning structural brain connectivity of Alzheimer's disease (AD) measured by amyloid-β deposits. The proposed GRM regards 11C-labeled Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging data as smooth signals defined on an unknown graph. This graph is then estimated through an optimization framework, which fits the graph to the data with an adjustable level of uniformity of the connection weights. Under the assumed data model, results based on simulated data illustrate that our approach can accurately reconstruct the underlying network, often with better reconstruction than those obtained by both sample correlation and ℓ1-regularized partial correlation estimation. Evaluations performed upon PiB-PET imaging data of 30 AD and 40 elderly normal control (NC) subjects demonstrate that the connectivity patterns revealed by the GRM are easy to interpret and consistent with known pathology. Moreover, the hubs of the reconstructed networks match the cortical hubs given by functional MRI. The discriminative network features including both global connectivity measurements and degree statistics of specific nodes discovered from the AD and NC amyloid-beta networks provide new potential biomarkers for preclinical and clinical AD.

Amyloid positron emission tomography (PET) imaging is a valuable tool for research and diagnosis in Alzheimer’s disease (AD). Partial volume effects caused by the limited spatial resolution of PET scanners degrades the quantitative accuracy of PET image. In this study, we have applied a method to evaluate the impact of a joint-entropy based partial volume correction (PVC) technique on brain networks learned from a clinical dataset of AV-45 PET image and compare network properties of both uncorrected and corrected image-based brain networks. We also analyzed the region-wise SUVRs of both uncorrected and corrected images. We further performed classification tests on different groups using the same set of algorithms with same parameter settings. PVC has sometimes been avoided due to increased noise sensitivity in image registration and segmentation, however, our results indicate that appropriate PVC may enhance the brain network structure analysis for AD progression and improve classification performance.

Federated learning (FL) is a method for training artificial intelligence (AI) models with data from multiple sources while maintaining the anonymity of the data, thus removing many barriers to data sharing. Here we use data from 20 institutes across the globe to train a FL model, called “EXAM” (EMR CXR AI Model), that predicts future oxygen requirements of symptomatic COVID-19 patients using inputs of vital signs, laboratory data, and chest X-rays. EXAM achieved an average area under the curve (AUC) greater than 0.92 for both 24/72h predictions, and it provided an average improvement in the avg. AUC of 16%, and an average increase in generalizability of 38% when compared to models trained at a single site using the same site’s data (‘local models’). For predicting mechanical ventilation (MV) treatment (or death) at 24h at the independent test site, EXAM achieved a sensitivity of 0.950 and a specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for predicting clinical outcomes in COVID-19 patients, setting the stage for broader use of FL in healthcare.