Efficient and Comprehensive Advanced Magnetic Resonance Imaging of Hereditary Hemorrhagic Telangiectasia Vascular Malformations (AVIATOR)
Abstract
Background and Rationale: Patients with the genetic disease hereditary hemorrhagic telangiectasia (HHT) are at risk for vascular malformations in multiple organs, including the brain, lungs, liver, nose, and gastrointestinal (GI) tract. Each of these vascular malformations has different risk for clinical complications: intracranial bleeding for brain arteriovenous malformations (AVMs), transit of clots from leg veins through lung AVMs causing ischemic strokes when clots lodge in the brain, heart failure due to high blood flow through large liver AVMs, and anemia due to bleeding from nasal and GI vascular malformations. Current clinical guidelines for vascular malformation screening in HHT include contrast-enhanced brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA), chest computed tomography angiography (CTA) or echocardiogram (cardiac ultrasound) with agitated saline injection, and liver ultrasound (US). Because new vascular malformations can form over time, lung screening studies are repeated every 5 years in adulthood. When vascular malformations are diagnosed in any of these organs, follow-up detailed diagnostic exams include invasive catheter digital subtraction x-ray cerebral angiography (DSA), chest computed tomography (CT) angiography and liver MRI or invasive right heart catheterization. Given the complexity of vascular malformations and their clinical complications in patients with HHT, improvements are needed both in the efficiency of multi-organ screening and the sensitivity of organ-specific focused imaging exams. We propose to improve HHT care by developing advanced non-invasive MRI techniques. Hypotheses: Hypothesis 1: We hypothesize the improved contrast resolution of ferumoxytol (an iron oxide nanoparticle medication) will enable a single head-to-abdomen screening MRI exam for AVMs that can replace three separate standard MRI, CT, and US exams. Hypothesis 2: We hypothesize new fast MRI techniques will improve evaluation of AVMs in the liver as compared to standard ultrasound and will enable long-term monitoring of clinically significant pulmonary AVMs (PAVMs) without the use of ionizing radiation as is needed in standard-of-care CTA. Hypothesis 3: We hypothesize the improved spatial resolution of ultra-high-magnetic-field-strength (7 Tesla) MRI will non-invasively detect features of brain AVMs (BAVMs) better than standard 3 Tesla MR and will approach gold standard invasive DSA. Specific Aims and Objectives: SA1: Develop an efficient multi-organ screening 3 Tesla MRI/MRA examination for new patients with possible or definite HHT. We will improve and combine ferumoxytol-enhanced flow and structural imaging from the head through the liver. Hypothesis: in a single rapid MR examination of </=60 minutes we will image the brain, lungs, heart, and liver at a resolution to detect clinically significant vascular malformations and their complications. Metrics for success are detection of: BAVM >/=2mm, BAVM-related microhemorrhage, PAVM-related prior strokes, PAVM >/=2mm, and enlarged heart (an indirect sign of abnormally high flow through a liver AVM LAVM), and LAVM itself. Results will be compared to standard clinical imaging in the same patients. SA2: Develop advanced organ-specific focused diagnostic 3 Tesla MRI/MRA examinations for HHT patients with known AVMs involving the lungs and liver. In order to follow patients’ vascular malformations and their complications over time, advanced imaging techniques will be developed. Metrics for success: MRI/MRA will be more sensitive and specific than US in liver AVM-related right heart failure and high blood flow in the liver. MRI/MRA will detect at least 90% of PAVMs as compared to CTA but will not require the ionizing radiation of CTA. SA3: Develop 7T brain MRI/MRA techniques to evaluate the detailed angioarchitecture of brain AVMs in HHT and non-HHT patients. A novel noninvasive 7 Tesla MRI/MRA exam will be compared
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210178
Entities
People
- Steven Hetts
Organizations
- United States Army
- University of California, San Francisco