Mesenchymal stromal cells to treat patients with non-ischaemic heart failure: Results from SCIENCE II pilot study.

Aims: Allogeneic stem cell therapy is more logistically suitable compared with autologous cell therapy for large-scale patient treatment. We aim to investigate the clinical safety and efficacy profile of the allogeneic adipose tissue derived mesenchymal stromal cell product (CSCC_ASC) as an add-on therapy in patients with chronic non-ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) < 40%.

Methods And Results: This is a single-centre investigator-initiated randomized phase I/II study with direct intra-myocardial injections of 100 million allogeneic CSCC_ASC.

Performing [F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.

Meta-[I]iodobenzylguanidine ([I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [I]MIBG with the new PET tracer meta-[F]fluorobenzylguanidine ([F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [F]MFBG LAFOV PET/CT and compare it with [I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children.

Improved Positron Emission Tomography Quantification: Evaluation of a Maximum-Likelihood Scatter Scaling Algorithm.

Incorrect scatter scaling of positron emission tomography (PET) images can lead to halo artifacts, quantitative bias, or reconstruction failure. Tail-fitted scatter scaling (TFSS) possesses performance limitations in multiple cases. This study aims to investigate a novel method for scatter scaling: maximum-likelihood scatter scaling (MLSS) in scenarios where TFSS tends to induce artifacts or are observed to cause reconstruction abortion.

Potential Clinical Impact of LAFOV PET/CT: A Systematic Evaluation of Image Quality and Lesion Detection.

We performed a systematic evaluation of the diagnostic performance of LAFOV PET/CT with increasing acquisition time. The first 100 oncologic adult patients referred for 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose PET/CT on the Siemens Biograph Vision Quadra were included. A standard imaging protocol of 10 min was used and scans were reconstructed at 30 s, 60 s, 90 s, 180 s, 300 s, and 600 s.

Estimation of brain amyloid accumulation using deep learning in clinical [C]PiB PET imaging.

Introduction: Estimation of brain amyloid accumulation is valuable for evaluation of patients with cognitive impairment in both research and clinical routine. The development of high throughput and accurate strategies for the determination of amyloid status could be an important tool in patient selection for clinical trials and amyloid directed treatment. Here, we propose the use of deep learning to quantify amyloid accumulation using standardized uptake value ratio (SUVR) and classify amyloid status based on their PET images.

Scanner agnostic large-scale evaluation of MS lesion delineation tool for clinical MRI.

Introduction: Patients with MS are MRI scanned continuously throughout their disease course resulting in a large manual workload for radiologists which includes lesion detection and size estimation. Though many models for automatic lesion segmentation have been published, few are used broadly in clinic today, as there is a lack of testing on clinical datasets. By collecting a large, heterogeneous training dataset directly from our MS clinic we aim to present a model which is robust to different scanner protocols and artefacts and which only uses MRI modalities present in routine clinical examinations.

DeepDixon synthetic CT for [ PET/MRI attenuation correction of post-surgery glioma patients with metal implants.

Purpose: Conventional magnetic resonance imaging (MRI) can for glioma assessment be supplemented by positron emission tomography (PET) imaging with radiolabeled amino acids such as O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET), which provides additional information on metabolic properties. In neuro-oncology, patients often undergo brain and skull altering treatment, which is known to challenge MRI-based attenuation correction (MR-AC) methods and thereby impact the simplified semi-quantitative measures such as tumor-to-brain ratio (TBR) used in clinical routine. The aim of the present study was to examine the applicability of our deep learning method, DeepDixon, for MR-AC in [F]FET PET/MRI scans of a post-surgery glioma cohort with metal implants.

Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial.

Aims: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF).

Methods And Results: The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II-III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml.

Danish phase II trial using adipose tissue derived mesenchymal stromal cells for patients with ischaemic heart failure.

Aims: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add-on therapy in patients with chronic HFrEF.

Optimizing an immunomodulatory potency assay for Mesenchymal Stromal Cell.

The expeditious progress of Mesenchymal Stromal Cells (MSC) for therapeutic intervention calls for means to compare differences in potency of cell products. The differences may be attributed to innumerable sources including tissue origin, production methods, or even between batches. While the immunomodulatory potential of MSC is recognized and well-documented by an expansive body of evidence, the methodologies and findings vary markedly.

A zero-dose synthetic baseline for the personalized analysis of [F]FDG-PET: Application in Alzheimer's disease.

Purpose: Brain 2-Deoxy-2-[F]fluoroglucose ([F]FDG-PET) is widely used in the diagnostic workup of Alzheimer's disease (AD). Current tools for uptake analysis rely on non-personalized templates, which poses a challenge as decreased glucose uptake could reflect neuronal dysfunction, or heterogeneous brain morphology associated with normal aging. Overcoming this, we propose a deep learning method for synthesizing a personalized [F]FDG-PET baseline from the patient's own MRI, and showcase its applicability in detecting AD pathology.

Automatic detection and delineation of pediatric gliomas on combined [F]FET PET and MRI.

Introduction: Brain and central nervous system (CNS) tumors are the second most common cancer type in children and adolescents. Positron emission tomography (PET) imaging with radiolabeled amino acids visualizes the amino acid uptake in brain tumor cells compared with the healthy brain tissue, which provides additional information over magnetic resonance imaging (MRI) for differential diagnosis, treatment planning, and the differentiation of tumor relapse from treatment-related changes. However, tumor delineation is a time-consuming task subject to inter-rater variability.

GMP Compliant Production of a Cryopreserved Adipose-Derived Stromal Cell Product for Feasible and Allogeneic Clinical Use.

The emerging field of advanced therapy medicinal products (ATMP) holds promise of treating a variety of diseases. Adipose-derived stromal cells (ASCs) are currently being marketed or tested as cell-based therapies in numerous clinical trials. To ensure safety and efficacy of treatments, high-quality products must be manufactured.

Deep learning based low-activity PET reconstruction of [C]PiB and [F]FE-PE2I in neurodegenerative disorders.

Purpose: Positron Emission Tomography (PET) can support a diagnosis of neurodegenerative disorder by identifying disease-specific pathologies. Our aim was to investigate the feasibility of using activity reduction in clinical [F]FE-PE2I and [C]PiB PET/CT scans, simulating low injected activity or scanning time reduction, in combination with AI-assisted denoising.

Methods: A total of 162 patients with clinically uncertain Alzheimer's disease underwent amyloid [C]PiB PET/CT and 509 patients referred for clinically uncertain Parkinson's disease underwent dopamine transporter (DAT) [F]FE-PE2I PET/CT.

Adipose-derived stromal cells increase the formation of collagens through paracrine and juxtacrine mechanisms in a fibroblast co-culture model utilizing macromolecular crowding.

Background: Adipose-derived stromal cells (ASCs) possess a multitude of regenerative capabilities, which include immunomodulation, angiogenesis, and stimulation of extracellular matrix (ECM) remodeling. However, the underlying mechanisms leading to ECM remodeling remain largely elusive and highlight the need for functional in vitro models for mode of action studies. Therefore, the purpose of this study was to develop an in vitro co-culture model to investigate the capabilities of ASCs to modulate fibroblasts and ECM.

The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy.

Mesenchymal stromal cells have proven capable of improving cardiac pump function in patients with chronic heart failure, yet little is known about their mode of action. The aim of the study was to investigate the short-term effect of cryopreserved allogeneic rat adipose tissue-derived stromal cells (ASC) on cardiac composition, cellular subpopulations, and gene transcription in a rat model of chronic ischemic cardiomyopathy (ICM). Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery.

Assessment of Artificial Intelligence Automatic Multiple Sclerosis Lesion Delineation Tool for Clinical Use.

Purpose: To implement and validate an existing algorithm for automatic delineation of white matter lesions on magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) on a local single-center dataset.

Methods: We implemented a white matter hyperintensity segmentation model, based on a 2D convolutional neural network, using the conventional T2-weighted fluid attenuated inversion recovery (FLAIR) MRI sequence as input. The model was adapted for delineation of MS lesions by further training on a local dataset of 93 MS patients with a total of 3040 lesions.

Comparison of prospective and retrospective motion correction in 3D-encoded neuroanatomical MRI.

Purpose: To compare prospective motion correction (PMC) and retrospective motion correction (RMC) in Cartesian 3D-encoded MPRAGE scans and to investigate the effects of correction frequency and parallel imaging on the performance of RMC.

Methods: Head motion was estimated using a markerless tracking system and sent to a modified MPRAGE sequence, which can continuously update the imaging FOV to perform PMC. The prospective correction was applied either before each echo train (before-ET) or at every sixth readout within the ET (within-ET).

Deep-learning-based attenuation correction in dynamic [O]HO studies using PET/MRI in healthy volunteers.

Quantitative [O]HO positron emission tomography (PET) is the accepted reference method for regional cerebral blood flow (rCBF) quantification. To perform reliable quantitative [O]HO-PET studies in PET/MRI scanners, MRI-based attenuation-correction (MRAC) is required. Our aim was to compare two MRAC methods (RESOLUTE and DeepUTE) based on ultrashort echo-time with computed tomography-based reference standard AC (CTAC) in dynamic and static [O]HO-PET.

The effect of reduced scan time on response assessment FDG-PET/CT imaging using Deauville score in patients with lymphoma.

Purpose: [F]Fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for response assessment during therapy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Clinicians report the scans visually using Deauville criteria. Improved performance in modern PET/CT scanners could allow for a reduction in scan time without compromising diagnostic image quality.

Diagnostic accuracy and clinical impact of [18F]FET PET in childhood CNS tumors.

Background: Central nervous system (CNS) tumors cause the highest death rates among childhood cancers, and survivors frequently have severe late effects. Magnetic resonance imaging (MRI) is the imaging modality of choice, but its specificity can be challenged by treatment-induced signal changes. In adults, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET can assist in interpreting MRI findings.

Low-dose PET image noise reduction using deep learning: application to cardiac viability FDG imaging in patients with ischemic heart disease.

Introduction: Cardiac [F]FDG-PET is widely used for viability testing in patients with chronic ischemic heart disease. Guidelines recommend injection of 200-350 MBq [F]FDG, however, a reduction of radiation exposure has become increasingly important, but might come at the cost of reduced diagnostic accuracy due to the increased noise in the images. We aimed to explore the use of a common deep learning (DL) network for noise reduction in low-dose PET images, and to validate its accuracy using the clinical quantitative metrics used to determine cardiac viability in patients with ischemic heart disease.