MRI is used both for clinical and scientific purposes. This is possible because of the many different pulse sequences that each result in different imaging contrast and information (e.g. anatomical versus physiological image, but also functional MRI). The development environments for these sequences are, however, protected by vendors and only accessible under non-disclosure agreements. Education on MR Physics, implementation of new sequences and transparency and reproducibility or research is unnecessary complicated. In this project, we continue our work on a Philips-driver for an open pulse programming environment and demonstrate this with an advanced sequence on Philips, GE and Siemens scanners.

Hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia, are among the most frequent lethal gene disorders in humans causing abnormalities in erythrocytes due to mutations in the β-globin gene locus. To-date, severe forms of hemoglobinopathies are treated with lifelong blood-transfusions with iron chelation, which cause dramatic side effects and with the best care provide the patient with a life expectance of 30-40 years. Novel treatments are needed, as the only cure of hemoglobinopathies involve transplantation of donor hematopoietic stem cells (HSCs) or gene therapy of the patients HSCs. The first is associated with high mortality; and despite promising results, gene therapy is costly and is not available in developing countries where the disease is most common. I propose that the development of a targeted gene therapy will overcome the disadvantage of current gene therapies and maximize its strengths. The key objective is to develop a targeted form of in-vivo gene therapy for the treatment of SCD and β-thalassemia based on CRISPR/Cas9 and targeted delivery to reactivate transcription of fetal hemoglobin (HbF) in erythrocytes. CRISPR guide-RNAs and Cas9 endonuclease will be encapsulated in biodegradable polymers of lactic and glycolic acid (PLGA)-nanoparticles (NPs) guided by anti-CD34 or anti-Gpr56 antibody to target HSCs (erythrocyte precursor) in the blood and bone marrow. PLGA-NPs improve the stability and delivery of CRISPR/Cas9 and allow long-term storage, while the antibodies ensure specific targeting to HSCs; key factors that facilitate the use of this gene therapy in the clinic and greatly reduce costs. We will test the gene editing capacity of the targeting CRISPR/Cas9-PLGA-NPs in-vitro in a human erythrocyte cell line, ex-vivo in human HSCs and in-vivo in a humanized mouse model. The impact of targeted gene therapy in HSCs via CRISPR/Cas9-PLGA-NPs is very broad and has other non-SCD/β-thalassemia applications.

Every organ, and especially our brain, depends on a constant blood supply. The rate of blood supply, (perfusion) can be interrupted, or delayed by diseases of the blood vessels. MRI scans are used to measure how well and fast the brain receives blood. Unfortunately these scans are rarely used because they take too long, and the scans don’t properly present the information that the doctors need. In this proposal a new and quicker version of perfusion MRI scans will be developed, helping doctors to see the rate (strength and speed) of their patient’s blood supply.

Every minute counts: a mobile brain scan to recognize stroke in the ambulance and trauma helicopter Acute brain injuries, such as stroke and brain trauma, are the most common cause of disabilities and a major cause of death. Due to the vulnerability of our brain, enormous amounts of healthy life is lost due to delays in diagnosis and treatment selection. Therefore, this research project investigates if a mobile magnetic detection technology will enable us to quickly determine brain injury outside of the hospital, enabling faster and more efficient treatment.