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Hematopoietic stem cell transplantation reverses white matter injury measured by diffusion-tensor imaging (DTI) in sickle cell disease patients

Bone Marrow Transplantation volume 56, pages 2705–2713 (2021)Cite this article

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Abstract

Brain injury in sickle cell disease (SCD) comprises a wide spectrum of neurological damage. Neurocognitive deficits have been described even without established neurological lesions. DTI is a rapid, noninvasive, and non-contrast method that enables detection of normal-appearing white matter lesions not detected by conventional magnetic resonance imaging (MRI). The aim of the study was to evaluate if stem cell transplantation can revert white matter lesions in patients with SCD. Twenty-eight SCD patients were evaluated with MRI and DTI before and after allogeneic hematopoietic stem cell transplantation (HSCT), compared with 26 healthy controls (HC). DTI metrics included fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity maps, global efficiency, path length, and clustering coefficients. Compared to HC, SCD patients had a lower FA (p = 0.0086) before HSCT. After HSCT, FA increased and was not different from healthy controls (p = 0.1769). Mean MD, RD, and AD decreased after HSCT (p = 0.0049; p = 0.0029; p = 0.0408, respectively). We confirm previous data of white matter lesions in SCD and present evidence that HSCT promotes recovery of brain injury with potential improvement of brain structural connectivity.

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Fig. 1: Evaluation of diffusion scales.
Fig. 2: Brain network analysis.
Fig. 3: Fractional anysotropy in SCD patients and in healthy controls.
Fig. 4: Diffusivity measures (MD, RD, AD) and network properties (global efficiency, path length and clustering coefficient) in SCD patients.

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Acknowledgements

The authors acknowledge the patients and their families, the medical and multidisciplinary bone marrow transplantation team, the blood center group for their support and Hans-Kolb for reviewing this paper. This study was supported by the São Paulo Research Foundation (Center for Cell-Based Research, CTC-CEPID-FAPESP, Process 2013/08.135-2), by INCTC (CNPq Process number 465.539/2014-9) and by the Ribeirão Preto Medical School—University of São Paulo (FMRP-USP)

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Author notes

  1. These authors contributed equally: Thalita Cristina de Mello Costa, Rodolfo Chiari-Correia

  2. These authors jointly supervised this work: Antônio Carlos Santos, Belinda P. Simões

Authors and Affiliations

  1. Department of Medical Imaging, Hematology and Clinical Oncology, Clinical Hospital of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Thalita Cristina de Mello Costa, Rodolfo Chiari-Correia, Fabiano Pieroni, Juliana B. E. Dias, Renato Guerino-Cunha, Antônio Carlos Santos & Belinda P. Simões

  2. Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    Thalita Cristina de Mello Costa, Maria Carolina Oliveira, Renato Guerino-Cunha & Belinda P. Simões

  3. Department of Physics, Faculty of Philosophy, Sciences and Letters, University of São Paulo, Ribeirão Preto, Brazil

    Carlos Ernesto G. Salmon

  4. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    Luiz Guilherme Darrigo-Junior, Carlos Eduardo S. Grecco & Joana Teresa B. Faria

  5. Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    Ana Beatriz P. L. Stracieri, Daniela Aparecida de Moraes & Maria Carolina Oliveira

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Contributions

BPS and ACS designed the study; TMC, RDC, and MCO performed data analysis; TMC, LGDJ, CESG, JTBF, JBED, RC, FP, and ABPLS provided protocol support; TMC and RDC wrote the paper; and BPS, ACS, MCO, and CEGS reviewed the paper.

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Correspondence to Thalita Cristina de Mello Costa.

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Costa, T.C.d.M., Chiari-Correia, R., Salmon, C.E.G. et al. Hematopoietic stem cell transplantation reverses white matter injury measured by diffusion-tensor imaging (DTI) in sickle cell disease patients. Bone Marrow Transplant 56, 2705–2713 (2021). https://doi.org/10.1038/s41409-021-01365-z

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