MRI detection of brain abnormality in sickle cell disease

ABSTRACT

Introduction: Over the past decades, neuroimaging studies have clarified that a significant proportion of patients with sickle cell disease (SCD) have functionally significant brain abnormalities. Clinically, structural magnetic resonance imaging (MRI) sequences (T2, FLAIR, diffusion-weighted imaging) have been used by radiologists to diagnose chronic and acute cerebral infarction (both overt and clinically silent), while magnetic resonance angiography and venography have been used to diagnose arteriopathy and venous thrombosis. In research settings, imaging scientists are increasingly applying quantitative techniques to shine further light on underlying mechanisms.

Areas covered: From a June 2020 PubMed search of ‘magnetic’ or ‘MRI’ and ‘sickle’ over the previous 5 years, we selected manuscripts on T1-based morphometric analysis, diffusion tensor imaging, arterial spin labeling, T2-oximetry, quantitative susceptibility, and connectivity.

Expert Opinion: Quantitative MRI techniques are identifying structural and hemodynamic biomarkers associated with risk of neurological and neurocognitive complications. A growing body of evidence suggests that these biomarkers are sensitive to change with treatments, such as blood transfusion and hydroxyurea, indicating that they may hold promise as endpoints in future randomized clinical trials of novel approaches including hemoglobin F upregulation, reduction of polymerization, and gene therapy. With further validation, such techniques may eventually also improve neurological and neurocognitive risk stratification in this vulnerable population.

KEYWORDS:

• Sickle cell
• mri
• neuroimaging
• neuroradiology
• biomarkers

Article highlights

• Neurological pathologies detectable on radiological MRI, including vasculopathy and overt and silent stroke, are among the most common, but poorly understood, manifestations of sickle cell disease (SCD).

• Whilst there are radiological evidence-based strategies for stroke prevention in children with SCD, the specificity of screening is poor, treatment is often burdensome, and many patients continue to suffer progressive vasculopathy and/or recurrent insults.

• In recent years, evidence has emerged indicating that pathologies observable on radiological MRI may represent only the tip of the iceberg in terms of the causes of neurological morbidity in SCD.

• Quantitative MRI studies have identified cerebral hemodynamic, metabolic, volumetric and microstructural abnormalities that may be more prevalent, widespread, and potentially also more functionally significant, but no risk-stratification or treatment approaches exist for these pathologies.

• With further validation, quantitative MRI techniques may hold promise not only in providing clinically significant endpoints for trials of novel treatment approaches but also in improving risk stratification and individualized treatment options for precision medicine.

Declaration of interest

H Stotesbury received funding from Action Medical Research [GN2509]; J Kawadler received funding from Great Ormond Street Children’s Charity [V4615]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Hanne Stotesbury was funded by Action Medical Research (GN2509). Jamie Kawadler was funded by Great Ormond Street hospital Children’s Charity (V4615). The work is supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Children’s hospital NHS Foundation Trust and UCL Institute of Child Health (IS-BRC-1215-20012).