Introduction
In pediatric patients with sickle cell anemia (SCA), stroke is a major cause of morbidity and mortality with an estimated 1.9-11% risk of stroke by the age of 20 (1-7). Specific screening and treatment guidelines aimed at both primary and secondary prevention have successfully reduced the incidence of overt strokes in this high-risk population (4). The Stroke Prevention Trial in Sickle Cell Anemia (STOP) trial showed significant primary stroke prevention by reducing the risk of first stroke by 90% with chronic transfusions in those patients at increased risk as determined by Transcranial Doppler (TCD) (4). This study lead to a national recommendation to conduct annual TCD screening for all children with SCA between the ages of 2-16 years (8).
Patients with SCA who have conditional or abnormal TCDs or neurologic symptoms may undergo regular neuroimaging with Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiogram (MRA) to confirm cerebral vasculopathy and stratify stroke risk. Risk stratification using MRA is recommended by the American Society of Hematology in selection of a stroke prevention treatment plan (9). Current recommendations based on the multicenter, randomized controlled trial TWiTCH (TCD with Transfusions Changing to Hydroxyurea) suggest that a child aged 2-16 with abnormal TCD results who has been receiving transfusion therapy for at least 1 year with low-risk MRA imaging can be transitioned off transfusions and onto hydroxyurea treatment (9, 10). Determination of low-risk or high-risk requires MRA grading of vasculopathy, highlighting the importance of accurate MRA assessment.
Standard non-contrast MRA is accomplished with a 3-dimensional time of flight technique and allows assessment of the patency and caliber of intracerebral arterial vessels (11). Technical artifacts can influence the appearance of arterial structures on MRA (12), especially in regions of arterial tortuosity or bifurcation, sites commonly affected in patients with SCA. These technical artifacts can lead to the erroneous interpretation of arterial stenosis, and thereby lead to inappropriate risk stratification and treatment selection for primary stroke prevention, such as initiation or continuation of chronic transfusion therapy or transition to hydroxyurea. While chronic transfusion therapy can significantly lower stroke risk (13), it has notable risks including iron overload, alloimmunization, and infection (14-16).
Investigators in the Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) trial developed standardized scanning protocols for their entry and exit brain MRI, MRA, and TCD studies. The SWiTCH MRA scanning protocol specified an echo time of <5 msec (12). Echo time or TE, describes the time between application of radiofrequency excitation pulse and peak of the signal induced in the coil, measured in milliseconds (msec). While SWiTCH primary objective was to compare standard transfusion therapy to hydroxyurea in preventing recurrent stroke and quantitative liver iron content (12), the standardized imaging scanning protocols developed provide an opportunity for further study of flow artifact and its clinical importance. These MRA scanning protocols were also utilized in the TWiTCH trial to grade vasculopathy as low and high risk and guide treatment decisions. The generalizability and real-world application of the results of the TWiTCH trial could potentially depend on close adherence to study MRA protocols. Few reports have mentioned minimizing TE to <5 msec to limit flow-related artifact (5, 6, 17), however, no prior studies have reported the clinical implications of these protocols.
The primary objective of our study was to document any change in stroke prevention therapy, particularly discontinuation of chronic transfusions, that could be attributed to the implementation of the standardized MRA scanning protocol based on the SWiTCH protocol. We hypothesized that the implementation of a standardized MRA protocol would lead to re-classification of the level of cerebral stenosis and impact treatment plan for a subset of patients.