Imaging Acute Organ Transplant Rejection with [sup(19)]F MRI

Despite advances in immunosuppressive therapies following organ transplantation, acute rejection remains a leading cause of patient morbidity and mortality. Clinical surveillance of acute rejection relies on serial tissue biopsy, which is an invasive procedure and prone to sampling errors. Research in animal models of acute rejection has demonstrated that cellular MRI of graft-infiltrating macrophages may provide an alternative method for acute organ transplant rejection surveillance. In this chapter, we will review cellular MRI studies used to detect kidney and heart allograft acute rejection, including two studies that have utilized PFC labeling and 19F MRI [1, 2]. 6.1 Organ TransplantationOrgan transplantation has become the preferred treatment option for patients facing end-stage organ failure. Solid organs

may be transplanted from a deceased donor, or in some cases from a living donor; for example, individuals can donate a single kidney or part of their liver without losing essential organ function. Although organ transplantation has met with great success, two major problems remain: a shortage of donors and rejection of the transplanted organs. There is an ever-widening gap between the number patients on transplantation waiting lists and the number of donor organs available each year, with some patients not surviving long enough for a suitable donor organ to become available. At the same time, unless the organ is transplanted from a genetically identical donor (e.g., an identical twin), recipients face a lifetime threat of their immune systems destroying the foreign, transplanted organ. While successful transplantation surgery was first reported in the 1950s, outcomes overall have vastly improved over the

years. In 1954, Merrill performed the first successful human kidney transplantation surgery between identical twins [3]. At that time, transplantation from non-identical donors remained challenging, mainly due to ineffective methods for controlling the recipients’ immune response, with patients rarely surviving beyond 30 days [4]. Clinical transplantation of other organs also proved more difficult, taking more than a decade later to demonstrate therapeutic potential. In 1967, Starzl performed the first successful human liver transplantation [5]. In the same year, Barnard [6] achieved some success in heart transplantation; however, early results were poor with few patients surviving past their hospital stay. For a recent review and historical perspective, see ref. [7]. With advances in modern immunosuppressive therapy, organ preservation, and patient monitoring, the survival rates for allograft transplant patients have improved dramatically over the last several decades. As a result, organ transplantation has now become a widespread clinical treatment for organ failure, with thousands of procedures performed each year. According to Scientific Registry of Transplant Recipients in the United States (https://www.srtr.org), current five-year graft survival is nearly 75% following heart transplantation, and nearly 85% for kidney transplantation from a living donor. Nevertheless, allograft rejection, both acute and chronic, are still the leading causes of morbidity and mortality after organ transplantation.