Identifying Renal Microstructural and Blood Flow Changes in Sickle Cell Disease Using Quantitative MRI Techniques
Authors: Piccone Connie M. , Lu Lan , Donnola Shannon , Dell Katherine , Little Jane A. , Flask Chris 
Published: October 2019

Abstract
BACKGROUND: In patients with sickle cell disease (SCD), renal disease is strikingly high, with up to one third of adults developing chronic kidney disease. Renal disease is associated with considerable morbidity and mortality although it has not been as well studied as other SCD-related complications. Studies which could provide insight into clinically silent renal injury are limited. To date, no large studies of functional or structural renal changes have been published, particularly in the context of sickle cell crises. Magnetic Resonance Imaging (MRI) is safe and capable of providing quantitative assessments of disease without ionizing radiation. Clinically available MRI techniques have already been used to assess both acute and chronic kidney disease. This is the first study to evaluate these MRI techniques in SCD renal disease.
OBJECTIVE: The objective of this pilot study was to evaluate the capability of quantitative MRI techniques to assess both structural changes and renal blood flow in patients with SCD.
METHODS: Pediatric and adult patients were recruited to an IRB approved study from the Sickle Cell Anemia Centers at UH Rainbow Babies & Children’s Hospital and University Hospitals Case Medical Center. Six pediatric patients (age 12-18 years, 1 male, 5 female, eGFR 110-185 mL/min/1.73m2) have been recruited to date. Healthy controls were also recruited. Diffusion (DTI) and Arterial Spin Labeling (ASL) scans were performed to assess medullary microstructure and cortical perfusion (non-contrast), respectively. Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) maps were calculated using established methods. Mean renal T2* was measured to assess iron burden. A Student’s t-test was performed to compare the mean renal DTI and ASL results between subjects and healthy controls.
RESULTS: In the six pediatric subjects, medullary FA values were decreased, suggesting degradation of medullary microstructure. Both cortical ADC and medullary FA were significantly reduced, indicative of microstructural changes in SCD subjects compared to controls. ASL perfusion maps, likewise, showed reduced cortical perfusion for SCD subjects in comparison to controls. Preliminary differences in blood flow and microstructure were seen between SCD subjects on hydroxyurea (HU) and those not on HU. Analysis of the T2* data showed increased renal iron deposition that did not appear to correlate with serum ferritin.
CONCLUSIONS: Our results suggest that quantitative diffusion and ASL MRI are sensitive to medullary microstructural and cortical blood flow changes in pediatric patients with SCD. Preliminarily, iron deposition in the kidney appears to relate to chronic hemolysis rather than transfusional iron. These sensitive techniques may be useful in assessing the impact of therapeutic interventions, such as HU, on renal function in children. There may also be utility in assessing the impact of acute hemolysis/sickling on renal microstructure and perfusion.

Disclosures
Piccone: Novartis Pharmaceuticals Cooperation: Speakers Bureau.