Low-count whole-body PET/MRI restoration: an evaluation of dose reduction spectrum and five state-of-the-art artificial intelligence models.

PURPOSE: To provide a holistic and complete comparison of the five most advanced AI models in the augmentation of low-dose 18F-FDG PET data over the entire dose reduction spectrum. METHODS: In this multicenter study, five AI models were investigated for restoring low-count whole-body PET/MRI, covering convolutional benchmarks - U-Net, enhanced deep super-resolution network (EDSR), generative adversarial network (GAN) - and the most cutting-edge image reconstruction transformer models in computer vision to date - Swin transformer image restoration network (SwinIR) and EDSR-ViT (vision transformer). The models were evaluated against six groups of count levels representing the simulated 75%, 50%, 25%, 12.5%, 6.25%, and 1% (extremely ultra-low-count) of the clinical standard 3 MBq/kg 18F-FDG dose. The comparisons were performed upon two independent cohorts - (1) a primary cohort from Stanford University and (2) a cross-continental external validation cohort from Tübingen University - in order to ensure the findings are generalizable. A total of 476 original count and simulated low-count whole-body PET/MRI scans were incorporated into this analysis. RESULTS: For low-count PET restoration on the primary cohort, the mean structural similarity index (SSIM) scores for dose 6.25% were 0.898 (95% CI, 0.887-0.910) for EDSR, 0.893 (0.881-0.905) for EDSR-ViT, 0.873 (0.859-0.887) for GAN, 0.885 (0.873-0.898) for U-Net, and 0.910 (0.900-0.920) for SwinIR. In continuation, SwinIR and U-Net's performances were also discreetly evaluated at each simulated radiotracer dose levels. Using the primary Stanford cohort, the mean diagnostic image quality (DIQ; 5-point Likert scale) scores of SwinIR restoration were 5 (SD, 0) for dose 75%, 4.50 (0.535) for dose 50%, 3.75 (0.463) for dose 25%, 3.25 (0.463) for dose 12.5%, 4 (0.926) for dose 6.25%, and 2.5 (0.534) for dose 1%. CONCLUSION: Compared to low-count PET images, with near-to or nondiagnostic images at higher dose reduction levels (up to 6.25%), both SwinIR and U-Net significantly improve the diagnostic quality of PET images. A radiotracer dose reduction to 1% of the current clinical standard radiotracer dose is out of scope for current AI techniques.

Diabetes complications and extracellular vesicle therapy.

Diabetes is a chronic disorder characterized by dysregulated glycemic conditions. Diabetic complications include microvascular and macrovascular abnormalities and account for high morbidity and mortality rates in patients. Current clinical approaches for diabetic complications are limited to symptomatic treatments and tight control of blood sugar levels. Extracellular vesicles (EVs) released by somatic and stem cells have recently emerged as a new class of potent cell-free therapeutic delivery packets with a great potential to treat diabetic complications. EVs contain a mixture of bioactive molecules and can affect underlying pathological processes in favor of tissue healing. In addition, EVs have low immunogenicity and high storage capacity while maintaining nearly the same regenerative and immunomodulatory effects compared to current cell-based therapies. Therefore, EVs have received increasing attention for diabetes-related complications in recent years. In this review, we provide an outlook on diabetic complications and summarizes new knowledge and advances in EV applications. Moreover, we highlight recommendations for future EV-related research.

Update on Pediatric Interventional Radiology.

The field of pediatric interventional radiology encompasses the treatment of a broad range of patients. Whether treating a premature infant who weighs less than 1 kg or treating an adult-sized teenager who weighs more than 100 kg, the innovative skills of the interventional radiologist are required to adapt equipment designed for adult patients, to meet the needs of children. Moreover, children cannot be treated simply as small adults owing to a number of factors, including differences in physiology, disease processes, and treatment techniques between pediatric and adult patients. In this article, the unique medical needs of children are highlighted, noting specific areas the interventional radiologist should be aware of when treating patients of all ages. Specific focus is placed on the unique considerations related to children in terms of their periprocedural needs and the procedural modifications required for routine pediatric procedures, with specific diseases of the liver, chest, and musculoskeletal system highlighted. The broader topic of vascular anomalies, although an important part of pediatric interventional radiology, was intentionally excluded to highlight some of the lesser-known procedures performed. ©RSNA, 2022.

Human placenta-derived mesenchymal stromal cells transfusion in a critically Ill infant diagnosed with Coronavirus Disease 2019 (COVID-19): A case report.

Coronavirus disease 2019 (COVID-19) is still an emergency in many countries. Herein, we report treatment with human placental-derived mesenchymal stromal cells transfusion (hPD-MSCT) in a critically ill infant diagnosed with COVID-19. A 28-day-old male infant with a history of pneumonia was referred to our center with decreased SpO2 (92%) and fever (38.5 °C). Real-time reverse transcription polymerase chain reaction (RT-PCR) and chest computed tomography (CT) confirmed COVID-19 infection. Considering the deteriorating clinical status of the patient despite the routine treatments (SpO2 82%), human placental derived mesenchymal stromal cells (hPD-MSCs) was transfused to him on day 9 and 11 (7 × 106 cells/session). The patient's general condition started to change 3 days after hPD-MSCT and poor feeding and low SpO2 improved day by day. On day 20, the patient was discharged (SpO2 97%) and our one-year follow-up showed a successful response to the treatment with no reported complications. hPD-MSCT may be considered as a possible treatment option in infants/children diagnosed with COVID-19 who fail to respond to conventional therapies. However, required dose, safety, and mechanistic studies are still warranted to further investigate this treatment.

Autologous conditioned serum for degenerative diseases and prospects.

Autologous conditioned serum (ACS) is a blood-derived product that is prepared by the incubation of whole blood with medical-grade glass beads, resulting in serum enrichment in interleukin-1 receptor antagonist (IL-1Ra), anti-inflammatory cytokines (IL-4, IL-10, and IL-13), and high concentrations of growth factors. ACS has shown qualitatively and quantitatively better therapeutic effects than most established pharmacological treatments and surgery for joint diseases given its ability to both target the inflammatory cascade to decrease cartilage destruction as well as improve endogenous repair mechanisms. ACS application is simple and safe with limited adverse effects. This article reviews the role of ACS in degenerative joint disease, in addition to other inflammatory and autoimmune diseases, given its regenerative and immune-modulating properties.

Artificial intelligence enables whole-body positron emission tomography scans with minimal radiation exposure.

PURPOSE: To generate diagnostic 18F-FDG PET images of pediatric cancer patients from ultra-low-dose 18F-FDG PET input images, using a novel artificial intelligence (AI) algorithm. METHODS: We used whole-body 18F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3-30 years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose 18F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose 18F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics. RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p < 0.001). Compared to the ground-truth standard-dose PET, SUVmax values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUVmax values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers' diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa = 0.942) than 6.25% dose scans (kappa = 0.650). CONCLUSIONS: Our CNN model could generate simulated clinical standard 18F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.

In the present study, we created a nanoscale platform that can deliver nutrients to pancreatic islets in a controlled manner. Our platform consists of a mesoporous silica nanoparticle (MSNP), which can be loaded with glutamine (G: an essential amino acid required for islet survival and function). To control the release of G, MSNPs were coated with a polydopamine (PD) layer. With the optimal parameters (0.5 mg/mL and 0.5 h), MSNPs were coated with a layer of PD, which resulted in a delay of G release from MSNPs over 14 d (57.4 ± 4.7% release). Following syngeneic renal subcapsule islet transplantation in diabetic mice, PDG-MSNPs improved the engraftment of islets (i.e., enhanced revascularization and reduced inflammation) as well as their function, resulting in re-establishment of glycemic control. Collectively, our data show that PDG-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.

A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation.

The aim of this work was to develop, characterize and test a novel 3D bioscaffold matrix which can accommodate pancreatic islets and provide them with a continuous, controlled and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, we made a collagen based cryogel bioscaffold which incorporated calcium peroxide (CPO) into its matrix. The optimal concentration of CPO integrated into bioscaffolds was 0.25wt.% and this generated oxygen at 0.21±0.02mM/day (day 1), 0.19±0.01mM/day (day 6), 0.13±0.03mM/day (day 14), and 0.14±0.02mM/day (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds had a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds or islets cultured alone on traditional cell culture plates; these findings were supported by data from quantitative computational modelling. When syngeneic islets were transplanted into the epididymal fat pad (EFP) of diabetic mice, our cryogel-0.25wt.%CPO bioscaffold improved islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25wt.%CPO bioscaffolds showed faster responses to intraperitoneal glucose injections and had a higher level of insulin content in their EFP compared to those transplanted with islets alone (P<0.05). Biodegradability studies predicted that our cryogel-CPO bioscaffolds will have long-lasting biostability for approximately 5 years (biodegradation rate: 16.00±0.65%/year). Long term implantation studies (i.e. 6 months) showed that our cryogel-CPO bioscaffold is biocompatible and integrated into the surrounding fat tissue with minimal adverse tissue reaction; this was further supported by no change in blood parameters (i.e. electrolyte, metabolic, chemistry and liver panels). Our novel oxygen-generating bioscaffold (i.e. cryogel-0.25wt.%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.

Nanooncology: the future of cancer diagnosis and therapy.

In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. Nanoparticles have unique biological properties given their small size and large surface area-to-volume ratio, which allows them to bind, absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and probes with high efficiency. Their tunable size, shape, and surface characteristics also enable them to have high stability, high carrier capacity, the ability to incorporate both hydrophilic and hydrophobic substances and compatibility with different administration routes, thereby making them highly attractive in many aspects of oncology. This review article will discuss how nanoparticles are able to function as carriers for chemotherapeutic drugs to increase their therapeutic index; how they can function as therapeutic agents in photodynamic, gene, and thermal therapy; and how nanoparticles can be used as molecular imaging agents to detect and monitor cancer progression.

HSP70-Mediated NLRP3 Inflammasome Suppression Underlies Reversal of Acute Kidney Injury Following Extracellular Vesicle and Focused Ultrasound Combination Therapy.

Acute kidney injury (AKI) is the abrupt loss of renal function, for which only supportive therapies exist. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have been shown to be therapeutically effective in treating AKI by spurring endogenous cell proliferation and survival while suppressing inflammation. Pre-treating kidneys with pulsed focused ultrasound (pFUS) has also been shown to enhance MSC therapy for AKI, but its role in MSC-derived EV therapy remains unexplored. Using a mouse model of cisplatin-induced AKI, we show that combination therapy with pFUS and EVs restores physiological and molecular markers of kidney function, more so than either alone. Both pFUS and EVs downregulate heat shock protein 70 (HSP70), the NLRP3 inflammasome, and its downstream pro-inflammatory cytokines IL-1ß and IL-18, all of which are highly upregulated in AKI. In vitro knockdown studies suggest that HSP70 is a positive regulator of the NLRP3 inflammasome. Our study therefore demonstrates the ability of pFUS to enhance EV therapy for AKI and provides further mechanistic understanding of their anti-inflammatory and regenerative effects.

Adipose tissue-derived mesenchymal stem cells rescue the function of islets transplanted in sub-therapeutic numbers via their angiogenic properties.

A significant proportion of islets are lost following transplantation due to hypoxia and inflammation. We hypothesize that adipose tissue-derived mesenchymal stem cells (AD-MSCs) can rescue a sub-therapeutic number of transplanted islets by helping them establish a new blood supply and reducing inflammation. Diabetic mice received syngeneic transplantation with 75 (minimal), 150 (sub-therapeutic), or 225 (therapeutic) islets, with or without 1 × 106 mouse AD-MSCs. Fasting blood glucose (FBG) values were measured over 6 weeks with tissue samples collected for islet structure and morphology (H&E, insulin/glucagon staining). Histological and immunohistochemical analyses of islets were also performed at 2 weeks in animals transplanted with a sub-therapeutic number of islets, with and without AD-MSCs, to determine new blood vessel formation, the presence of pro-angiogenic factors facilitating revascularization, and the degree of inflammation. AD-MSCs had no beneficial effect on FBG values when co-transplanted with a minimal or therapeutic number of islets. However, AD-MSCs significantly reduced FBG values and restored glycemic control in diabetic animals transplanted with a sub-therapeutic number of islets. Islets co-transplanted with AD-MSCs preserved their native morphology and organization and exhibited less aggregation when compared to islets transplanted alone. In the sub-therapeutic group, AD-MSCs significantly increased islet revascularization and the expression of angiogenic factors including hepatocyte growth factor (HGF) and angiopoietin-1 (Ang-1) while also reducing inflammation. AD-MSCs can rescue the function of islets when transplanted in a sub-therapeutic number, for at least 6 weeks, via their ability to maintain islet architecture while concurrently facilitating islet revascularization and reducing inflammation.

Role of interventional radiology in managing pediatric liver tumors : Part 2: percutaneous interventions.

Hepatoblastoma and hepatocellular carcinoma (HCC) are the most common pediatric liver malignancies, with hepatoblastoma occurring more commonly in younger children and HCC occurring more commonly in older children and adolescents. Although surgical resection (including transplant when necessary) and systemic chemotherapy have improved overall survival rate for hepatoblastoma to approximately 80% from 30%, a number of children with this tumor type are not eligible for operative treatment. In contradistinction, pediatric HCC continues to carry a dismal prognosis with an overall 5-year survival rate of 30%. The Paediatric Hepatic International Tumour Trial (PHITT) is an international trial aimed at evaluating both existing and emerging oncologic therapies for primary pediatric liver tumors. Interventional radiology offers a number of minimally invasive procedures that aid in diagnosis and therapy of pediatric liver tumors. For diagnosis, the PHITT biopsy guidelines emphasize and recommend percutaneous image-guided tumor biopsy. Additionally, both percutaneous and endovascular procedures provide therapeutic alternatives that have been, to this point, only minimally utilized in the pediatric population. Specifically, percutaneous ablation offers a number of cytotoxic technologies that can potentially eradicate disease or downstage children with unresectable disease. Percutaneous portal vein embolization is an additional minimally invasive procedure that might be useful to induce remnant liver hypertrophy prior to extended liver resection in the setting of a primary liver tumor. PHITT offers an opportunity to collect data from children treated with these emerging therapeutic options across the world. The purpose of this manuscript is to describe the potential role of minimally invasive percutaneous transhepatic procedures, as well as review the existing data largely stemming from the adult HCC experience.

Role of interventional radiology in managing pediatric liver tumors : Part 1: Endovascular interventions.

Primary liver malignancies are rare in children. Hepatoblastoma and hepatocellular carcinoma (HCC) together represent the overwhelming majority of cases. Overall survival of hepatoblastoma approaches 80% with multimodal treatment approaches that include chemotherapy, surgery and transplantation. However, there remains a subset of children with hepatoblastoma in whom resection or transplantation is not possible. The 5-year survival for children diagnosed with HCC is less than 30% and remains a significant therapeutic challenge. The poor outcomes for children with primary liver tumors motivate investigation of new therapeutic alternatives. Interventional oncology offers a broad scope of percutaneous and transcatheter endovascular cancer therapies that might provide clinical benefits. Minimally invasive approaches are distinct from medical, surgical and radiation oncologic treatments, and in adults these approaches have been established as the fourth pillar of cancer care. Transarterial chemoembolization is a minimally invasive locoregional treatment option performed by interventional radiologists with level-I evidence as standard of care in adults with advanced liver malignancy; transarterial chemoembolization in adults has served to prolong disease-free progression, downstage and bridge patients for surgical and transplant interventions, and improve overall survival. However, while several groups have reported that transarterial chemoembolization is feasible in children, the published experience is limited primarily to small retrospective case series. The lack of prospective trial evidence has in part limited the utilization of transarterial chemoembolization in the pediatric patient population. The purpose of this article is to provide an overview of the role of interventional radiology in the diagnosis and endovascular management of hepatic malignancies in children.

An oxygen plasma treated poly(dimethylsiloxane) bioscaffold coated with polydopamine for stem cell therapy.

In this study, 3D macroporous bioscaffolds were developed from poly(dimethylsiloxane) (PDMS) which is inert, biocompatible, non-biodegradable, retrievable and easily manufactured at low cost. PDMS bioscaffolds were synthesized using a solvent casting and particulate leaching (SCPL) technique and exhibited a macroporous interconnected architecture with 86 ± 3% porosity and 300 ± 100 µm pore size. As PDMS intrinsically has a hydrophobic surface, mainly due to the existence of methyl groups, its surface was modified by oxygen plasma treatment which, in turn, enabled us to apply a novel polydopamine coating onto the surface of the bioscaffold. The addition of a polydopamine coating to bioscaffolds was confirmed using composition analysis. Characterization of oxygen plasma treated-PDMS bioscaffolds coated with polydopamine (polydopamine coated-PDMS bioscaffolds) showed the presence of hydroxyl and secondary amines on their surface which resulted in a significant decrease in water contact angle when compared to uncoated-PDMS bioscaffolds (35 ± 3%, P < 0.05). Seeding adipose tissue-derived mesenchymal stem cells (AD-MSCs) into polydopamine coated-PDMS bioscaffolds resulted in cells demonstrating a 70 ± 6% increase in viability and 40 ± 5% increase in proliferation when compared to AD-MSCs seeded into uncoated-PDMS bioscaffolds (P < 0.05). In summary, this two-step method of oxygen plasma treatment followed by polydopamine coating improves the biocompatibility of PDMS bioscaffolds and only requires the use of simple reagents and mild reaction conditions. Hence, our novel polydopamine coated-PDMS bioscaffolds can represent an efficient and low-cost bioscaffold platform to support MSC therapies.

Use of blood pool agents with steady-state MRI to assess the vascular system.

Over the past two decades there have been significant advances in the use of magnetic resonance imaging (MRI) to assess the vascular system. New imaging sequences and improvements in magnet design have enabled the creation of higher spatial resolution images. MRI is now a viable alternative imaging modality when compared to both invasive angiography and computed tomographic angiography. The use of blood pool agents has further facilitated the use of MR angiography (MRA); their high molecular weight allows for lower doses of contrast medium administration while their prolonged presence in the blood stream allows for repeated high-quality volumetric imaging of both the arterial and venous circulation. As such, MRA is now no longer constrained by the tight windows for first-pass arterial and venous enhancement, which has resulted in the ability to assess and diagnose a large range of vascular pathologies in both arterial and venous systems. The intent of this review is to highlight MRI findings in common vascular pathologies including peripheral arterial disease (PAD), abnormalities of the abdominal aortic branches, postendovascular aortic aneurysm repair (EVAR) endoleak assessment, popliteal artery entrapment syndrome (PAES), deep venous thrombosis (DVT), vascular thoracic outlet syndrome (TOS), and vascular malformations. In addition, the latest MRI techniques currently used to optimally assess each of these pathologies will be discussed. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1559-1572.

Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2-1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.-Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

Stereotactic body radiotherapy for pediatric hepatocellular carcinoma with central biliary obstruction.

Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma causing central biliary obstruction and persistently elevated bilirubin of 3.0-4.3 mg/dl despite placement of bilateral internal-external biliary drains. The tumor was not resectable, and the patient was not a candidate for liver transplant due to nodal disease, for chemotherapy due to hyperbilirubinemia, or for local therapies aside from stereotactic body radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the management of this patient, and its role in allowing the patient to become a candidate for additional therapies.