Magnetic Resonance Imaging/Angiography Findings in Adult Patients with Sickle Cell Disease: Correlation with Transcranial Color Doppler Sonography
Authors: Graziadei Giovanna , Casoni Francesca Marta , Costa Antonella , Marcon Alessia , Triulzi Fabio , Cappellini Maria Domenica , Annoni Federico 
Published: October 2019

Abstract
Introduction. Stroke is a severe complication of Sickle Cell Disease (SCD). Ischemic strokes are more frequent among patients younger than 20 years of age, whereas older patients experience hemorrhagic strokes. At present few data are available in adult patients.
Aim. To evaluate Magnetic Resonance Imaging/Angiography (MRI/MRA) findings and to correlate with Transcranial Color Doppler Sonography (TCCD) in adult SCD patients.
Patients and methods. Fifty-one adult patients with SCD (median age 36.2 years, range 17-69 years; M:F 19:32) were enrolled, including 15 Sickle Cell Anemia (SCA), 24 Sickle Cell Thalassemia (HbS-βThal) and 12 HbS/HbC, all followed in a single tertiary Rare Disease Center in Milan, Italy. The study was approved by Ethic Committee and all subjects gave written informed consent. Clinical history and hematological tests were collected. 3.0 T MRI/MRA was performed to detect cerebral parenchyma lesions and vessels abnormalities. Color and Duplex Doppler Sonography (CDDS) and TransCranial Color Doppler (TCCD) following the STOP protocol but with angle correction were performed by the same physician to evaluate mean Peak Systolic Velocity (PSV) and Pulsatility Index (PI) of the extracranial vessels (ICA and VA) and middle (MCA), anterior (ACA), posterior (PCA) cerebral arteries, carotid siphon (SIPH), vertebral (VA intracranial) and basilar (BAS) arteries.
Results. In overall SCD adult patients median Hb levels were 9.9±1.7 g/dL, Hct 28.5±4.5%, HbS% 60±18.5% (range 5.5-90.2%), HbF% 8.5±8.6% (range 0.9-33.8%); 68.6% SCD patients had <4 crises/year, 27.5% >4 crises/year, while 3.9% were completely asymptomatic; 37.3% SCD patients were treated with Hydroxycarbamide (HU); 49% were transfused <4 RBCs Units /year and 19.6% >4 RBCs Units/year, while 31.4% had never been transfused; 21.6% were splenectomized. No patient experienced stroke nor ischemic, neither hemorrhagic, despite history of sickle crises. Out of 51 SCD patients, 51% showed cerebral parenchimal lesions, 33.3% aneurisms of the intracranial vessels, 96.1% vessel tortuosity (25.5% mild and 70.6% severe). In only 2 patients (4%) mild focal stenosis were detected. Comparing the three SCD subgroups, in SCA patients the percentage of cerebral parenchimal lesions (60%), aneurisms (53%) and tortuosity vessels (100%, 13.3% mild and 86.7 severe) were significantly higher than in HbS-βThal and HbS/HbC patients (p<0.01), where cerebral parenchimal lesions were respectively 45.8% and 50%, aneurisms 20.8% and 33.3%, and vessels tortuosity 92.6% (33.3% mild and 58.3% severe) and 100% (25% mild and 75% severe). Considering SCD patients with cerebral parenchimal lesions, MCA TAMM and PSV values were lower (87.30±16.88 cm/sec, p <0.002; 123.32±22.36, p <0.013 respectively) then in SCD group without lesions. SCD patients with aneurism showed lower MCA TAMM and PSV values (87.55±16 cm/sec, p <0.049; 123.02±22.2, p <0.08 respectively) then SCD group without lesions, as well. Same correlations were found in SCA, HbS-βThal and HbS/HbC patients. No statistical differences between PI, Hb, HT and HbS and the overall MRI/MRA abnormalities were found. Considering the other intracranic vessels studied, no correlations were found between TCCD blood flow velocities and MRI/MRA cerebral findings.
Conclusions. In the studied group of SCD adult patients MRI/MRA findings are characterized by aneurismal enlargement and tortuosity of cerebral vessels, probably due to age-related brain endothelial damage. MCA TAMM and PSV values were lower in SCD adult patients with cerebral parenchimal lesions and aneurisms, in comparison with ones without, indicating a consequent reduced blood flow velocity. According to our data, we could suggest as potentially pathological cut off MCA TAMM <100 cm/sec and MCA PSV value <125 cm/s, measurement close to the normal, but lower than ones found in SCD adult patients. These threshold intracranial blood flow velocities could be an indication to perform MRI/MRA to evaluate vessel tortuosity and mainly life-threatening aneurysms The correlations observed between TCCD values and MRI/MRA findings require further investigations.

Disclosures
Cappellini: Novartis, Shire, Cellgene, Sanofi: Advisory board Other.