Improving the Access of Cardiac Magnetic Resonance in Low-Middle Income Countries to Improve Cardiac Care: Rapid CMR

Non-communicable diseases– cancer and cardiovascular disease - are the leading causes of death in high-income countries (HICs). Cardiovascular disease, however, is increasing in Low-Middle Income Countries (LMICs) and is the emergent primary cause of mortality. Part of the reason is suboptimal therapies– from primary prevention to more advanced tertiary care. Not only are advanced therapies scarce but advanced diagnostic tests which apply to them are not fully available, and so diagnoses could be inaccurate and treatments poorly targeted. Within the portfolio and hierarchy of cardiovascular diagnostic testing, Cardiac Magnetic Resonance (CMR) is a crucial diagnostic imaging test that redefines diagnosis and enables targeted therapies, but is expensive with inadequate training and poor availability in LMICs countries. I demonstrated that CMR could be made fast, easy, and cheap – sufficient for delivery in five LMICs countries in three continents. To achieve this, I developed an abbreviated CMR protocol, focused on the core of CMR - volumes, function, and scar imaging (with selected additions like iron quantification), and by embedding the technical quality protocol within clinical care, training, and mentoring, so it proved to have diagnostic utility and change management, as well being a self-sustaining and essential service. I also used CMR as a research method in LMICs specifically to complement research in areas of a specific need to those countries, exploiting opportunities that were previously unavailable, with one chapter dedicated to evaluating early cardiovascular involvement in treated and non-treated people living with HIV in Peru, and a second chapter of the potential utility of CMR for screening cardiotoxicity and its comparison in precision with other cardiac imaging modalities in the UK, potentially extending the role of rapid CMR in HICs. Unlike traditional PhDs in medicine, my research involved technology adaptation, transfer, and collaboration. The project was multi-layered with political, social, educational, training, and partnership aspects, along with more traditional aspects such as clinical effectiveness and cost-effectiveness analysis. I showed the use of advanced cardiac imaging in LMICs by breaking down barriers, demonstrating that Rapid CMR can be possible in new clinical environments where much need exists

Beta Thalassemia

Beta thalassemia is a common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. This book covers most of the aspects related to this disease and greatly helps in understanding this disease and its complications. Of interest are clinical studies as well as basic and translational research reports regarding pathogenesis, genetics, diagnosis as well as standard and novel therapies. This book intends to provide the reader with a comprehensive overview of today’s practices and tomorrow’s possibilities about beta thalassemia

SMART TECHNIQUES FOR FAST MEDICAL IMAGE ANALYSIS AND PROCESSING

Medical Imaging has become an important transversal applications and re- search field that embraces a great variety of sciences. Imaging is the central science of measurement in diagnosis and treating diseases. The effort of the technological progress has made possible human imaging starting from a single molecule to the whole body. The open challenge is to treat the huge amount of medical informations with the use of smart and fast techniques that allows clinical and images data analysis and processing. In this ph.D. Thesis, many issues have been addressed and a certain amount of improvement in various fields have been produced, such as biom- etry, organs and tissues segmentation, MRI thermometry, medical reports retrieval and classification. The topic prefixed at the beginning of this ph.D. route was to analyze, understand, and give a step over to various kind of problematics related to Medical Images and Data analysis, working closely to radiologist physicians, with specific equipments, and following the common denominator of fast and smart methodologies applied to the medical imaging issue. A series of contribution have been carried out in fields such as: • proposing two different kind of multimodal biometric authentication systems that investigates fingerprint and iris fusion and processing; • applying expert systems to the issue of data validation, comparing and validating data to two different methodologies that assess liver iron overload in thalassemic patients;• addressing and improving non-invasive referenceless thermometry by using Radial Basis Function as interpolator; • applying the multi-seed region growing method to the segmentation of CT liver dataset; • proposing a novel unsupervised voxel-based morphology method for MRI brain segmentation by using k-means clustering and neural net- work classification; • proposing a novel ontology-based algorithm for information retrieval from mammographic text reports. The above work has been developed with the cooperation of the medical staff of the “Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi” and the “Scuola di Specializzazione in Radiodiagnostica" of the Università degli Studi di Palermo. All the proposed contributions show good performance using the stan- dard metrics. Most of them have produced scientific publications in com- puter science venues as well as in radiological venues. In addition, some specific frameworks, such as OsiriX, have been used to improve usability and easiness of the developed systems

Noninvasive rapid cardiac magnetic resonance for the assessment of cardiomyopathies in low-middle income countries

INTRODUCTION: Cardiac Magnetic Resonance (CMR) is a crucial diagnostic imaging test that redefines diagnosis and enables targeted therapies, but the access to CMR is limited in low-middle Income Countries (LMICs) even though cardiovascular disease is an emergent primary cause of mortality in LMICs. New abbreviated CMR protocols can be less expensive, faster, whilst maintaining accuracy, potentially leading to a higher utilization in LMICs. AREAS COVERED: This article will review cardiovascular disease in LMICs and the current role of CMR in cardiac diagnosis and enable targeted therapy, discussing the main obstacles to prevent the adoption of CMR in LMICs. We will then review the potential utility of abbreviated, cost-effective CMR protocols to improve cardiac diagnosis and care, the clinical indications of the exam, current evidence and future directions. EXPERT OPINION: Rapid CMR protocols, provided that they are utilized in potentially high yield cases, could reduce cost and increase effectiveness. The adoption of these protocols, their integration into care pathways, and prioritizing key treatable diagnoses can potentially improve patient care. Several LMIC countries are now pioneering these approaches and the application of rapid CMR protocols appears to have a bright future if delivered effectively

How I manage medical complications of beta-thalassemia in adults

The complex pathophysiology in beta-thalassemia can translate to multiple morbidities that affect every organ system. Improved survival due to advances in management meant that patients are exposed to the harmful effects of ineffective erythropoiesis, anemia and iron overload for a longer duration, and we started seeing new or more frequent complications in adult compared with younger patients. In this article, we highlight particular aspects of managing adult patients with beta-thalassemia utilizing our own experience in treating such patients. We cover both transfusion-dependent and non-transfusion-dependent forms of the disease and tackle specific morbidities of highest interest

Blood

This book examines both the fluid and cellular components of blood. After the introductory section, the second section presents updates on various topics in hemodynamics. Chapters in this section discuss anemia, 4D flow MRI in cardiology, cardiovascular complications of robot-assisted laparoscopic pelvic surgery, altered perfusion in multiple sclerosis, and hemodynamic laminar shear stress in oxidative homeostasis. The third section focuses on thalassemia with chapters on diagnosis and screening for thalassemia, high blood pressure in beta-thalassemia, and hepatitis C infection in thalassemia patients

Echocardiography Audit on Patients with Hereditary Haemochromatosis

Background: The European Association for the Study of the Liver (EASL) Guidelines for Hereditary Haemochromatosis (HH) refer specifically to symptomatic Homozygous C282Y patients and provide an algorithm for treating such patients who are predisposed to iron overloading. The British Society of Echocardiography does not make provisions for HH patients per se. Cardiac failure is a known complication of severe iron overload although it is atypical. Aim: To retrospectively investigate if an echocardiogram (echo) was warranted in the HH population at Louth County Hospital (LCH) Venesection Clinic based on the current guidelines. Methods: A cohort of 833 HH patients was reviewed with respect to: Hyperferritinemia (HFE) genotype, echo results, serum ferritin levels, transferrin saturations, patient gender, age at HH diagnosis and co-morbidities. Results: From the cohort investigated, 553 of 833 patients (66 percent) had echoes performed. When reviewing all echo results for these patients (553), 87 percent (480) recorded normal echoes. Consolidating all echoes performed where Serum Ferritin Level data was present (548) and then targeting patients with no co-morbidities only (345), the LCH Venesection Clinic data analysis demonstrates that 92 percent of this cohort’s echoes (319) show normal results. Conclusion: The results proved the thesis hypothesis was valid and a recommendation that the number of patients receiving echoes for Hereditary Haemochromatosis should be reviewed and local policy changed to reflect a lower frequency rate for echoes required, thereby reducing the backlog waiting list

Quantitative Magnetic Resonance Imaging of the Liver and Heart In Iron Overload

Systemic iron overload (IO) is considered a principal determinant in the clinical outcome of different forms of IO and in allogeneic hematopoietic stem cell transplantation (alloSCT). However, indirect markers for iron do not provide exact quantification of iron burden, and the evidence of iron-induced adverse effects in hematological diseases has not been established. Hepatic iron concentration (HIC) has been found to represent systemic IO, which can be quantified safely with magnetic resonance imaging (MRI), based on enhanced transverse relaxation. The iron measurement methods by MRI are evolving. The aims of this study were to implement and optimise the methodology of non-invasive iron measurement with MRI to assess the degree and the role of IO in the patients. An MRI-based HIC method (M-HIC) and a transverse relaxation rate (R2*) from M-HIC images were validated. Thereafter, a transverse relaxation rate (R2) from spin-echo imaging was calibrated for IO assessment. Two analysis methods, visual grading and rSI, for a rapid IO grading from in-phase and out-of-phase images were introduced. Additionally, clinical iron indicators were evaluated. The degree of hepatic and cardiac iron in our study patients and IO as a prognostic factor in patients undergoing alloSCT were explored. In vivo and in vitro validations indicated that M-HIC and R2* are both accurate in the quantification of liver iron. R2 was a reliable method for HIC quantification and covered a wider HIC range than M-HIC and R2*. The grading of IO was able to be performed rapidly with the visual grading and rSI methods. Transfusion load was more accurate than plasma ferritin in predicting transfusional IO. In patients with hematological disorders, the prevalence of hepatic IO was frequent, opposite to cardiac IO. Patients with myelodysplastic syndrome were found to be the most susceptible to IO. Pre-transplant IO predicted severe infections during the early post-transplant period, in contrast to the reduced risk of graft-versus-host disease. Iron-induced, poor transplantation results are most likely to be mediated by severe infections.Siirretty Doriast

From data to models : reducing uncertainty in benefit risk assessment : application to chronic iron overload in children

Growing awareness about the relevance of formal evaluation of the efficacy and safety in children has resulted into important changes in the requirements for the approval of medicines for children. In this thesis a model-based approach is proposed to ensure more efficient use of the evidence available from historical data. The work presented provides a quantitative framework for the assessment of the benefit-risk balance prior to drug approval. Three central questions are addressed, which refer to the need to ensure that accurate inferences are made about the safety and efficacy of a therapeutic intervention, especially when considering long-term outcome. In brief, we demonstrate how modelling and simulations can be applied together with multi-criteria decision analysis to address essential clinical, scientific and regulatory questions. Focus is given to the opportunity for optimising experimental protocol design (evidence generation) and integrating existing knowledge about the drug and the disease in the target population (evidence synthesis). These concepts are illustrated by real-life examples on the treatment of transfusion-dependent haemoglobinopathies, but the proposed framework can be extrapolated to a broader range of diseases and conditions. We anticipate that some of the meta-analytical elements presented here will become embedded into daily practice in pharmaceutical R&D.UBL - phd migration 201

Sickle Hemoglobin-Related Nephropathy: an Overview on Pathophysiology, Diagnosis, and Treatment

AbstractSickle cell disease (SCD) is a common hemoglobinopathy in the world with progressive multi organ failure. Many organs have been affected in this disease, but sickle cell nephropathy (SCN) is a major complication which affects the quality of life in these patients. SCN has a wide range of renal manifestations such as asymptomatic microalbuminuria, hyposthenuria, hematuria, frank proteinuria, nephrotic syndrome and end stage renal disease (ESRD). Nowadays novel biomarkers such as N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and transforming growth factor β (TGF-β) has allowed the early detection of the kidney involvement in sickle cell disease. The angiotensin converting enzyme (ACE) inhibitor drugs such as captopril or enalapril and also ACE receptor blockers (losartan) have beneficial effects in albuminuria or proteinuria. Also endothelin-1 (ET-1) receptor antagonists have a promising role in glomerular injury in SCD. In sickle patients who develop ESRD, renal replacement therapy can be life- saving. In recent years, kidney transplantation is the only curative treatment for advanced chronic kidney disease in these patients. Keywords: Sickle cell; Nephropathy; Kidney