Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter,NeuroImage: Clinical

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Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter
NeuroImage: Clinical ( IF 4.2 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.nicl.2020.102428
Ellen van der Plas ₁ , T Leigh Spencer Noakes ₂ , Darci T Butcher ₃ , Rosanna Weksberg ₄ , Laura Galin-Corini ₅ , Elizabeth A Wanstall ₆ , Patrick Te ₇ , Laura Hopf ₈ , Sharon Guger ₈ , Brenda J Spiegler ₉ , Johann Hitzler ₁₀ , Russell J Schachar ₁₁ , Shinya Ito ₁₂ , Brian J Nieman ₁₃

Affiliation

Department of Psychiatry, University of Iowa Hospital & Clinics, Iowa City, IA, USA.
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Genetics & Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Genetics & Genome Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada; Clinical and Metabolic Genetics, Hospital for Sick Children Research Institute, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Psychology, York University, Toronto, ON, Canada.
Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, ON, Canada.
Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada; Psychiatry Research, Hospital for Sick Children, Toronto, ON, Canada.
Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, ON, Canada; Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Introduction

Cure rates for pediatric acute lymphoblastic leukemia (ALL) have reached an all-time high (>90%); however, neurocognitive difficulties continue to affect quality of life in at least a subset of survivors. There are relatively few quantitative neuroimaging studies in child and adolescent ALL survivors treated with chemotherapy only. Use of different outcome measures or limited sample sizes restrict our ability to make inferences about patterns of brain development following chemotherapy treatment. In this study, we used magnetic resonance imaging (MRI) to evaluate brain outcomes in ALL survivors, comparing against a group of typically developing, cancer free peers.

Materials and methods

Participants included 71 ALL survivors, on average 8 years after diagnosis and 8–18 years of age, and 83 typically developing controls. Anatomical MRI was performed to evaluate brain structure; diffusion and magnetization transfer MRI were used to examine brain tissue microstructure.

Results

Successful MRI scans were acquired in 67 survivors (94%) and 82 controls (99%). Structurally, ALL survivors exhibited widespread reductions in brain volume, with 6% less white matter and 5% less gray matter than controls (p = 0.003 and 0.0006 respectively). Much of the brain appeared affected – 71 of 90 evaluated structures showed smaller volume – with the most notable exception being the occipital lobe, where no significant differences were observed. Average full-scale IQ in the survivor and control groups were 95 (CI 92–99) and 110 (CI 107–113), respectively. Using data from the NIH Pediatric MRI Data Repository, we evaluated the extent to which elevated IQ in the control group might affect the structural differences observed. We estimated that two thirds of the observed brain differences were attributable to ALL and its treatment. In addition to the structural changes, survivors showed, on average, globally lower white matter fractional anisotropy (-3%) and higher radial diffusivity (+5%) (p < 10⁻⁶), but no differences in magnetization transfer ratio.

Conclusions

Neuroanatomical alterations in late childhood and adolescent ALL survivors treated with chemotherapy-only protocols are widespread, with white matter being somewhat more affected than gray matter. These MRI results indicate brain development is altered in ALL survivors and highlight the need to examine how these alterations emerge.

中文翻译：

儿童和青少年白血病幸存者的MRI定量结果：灰质和白质整体改变的证据

介绍

小儿急性淋巴细胞白血病（ALL）的治愈率已达到历史最高（> 90％）；然而，神经认知障碍继续影响至少一部分幸存者的生活质量。仅使用化学疗法治疗的儿童和青少年ALL幸存者中，定量神经影像学研究相对较少。使用不同的结果指标或有限的样本量会限制我们对化学疗法治疗后大脑发育模式进行推断的能力。在这项研究中，我们使用磁共振成像（MRI）评估了所有幸存者的大脑结局，并与一组通常正在发展的无癌同伴进行了比较。

材料和方法

参与者包括71名ALL幸存者，平均诊断后8年，年龄为8-18岁，另有83名典型的发展中的对照组。进行了解剖MRI以评估大脑结构；扩散和磁化转移MRI用于检查脑组织的微观结构。

结果

67名幸存者（94％）和82名对照（99％）获得了成功的MRI扫描。从结构上讲，所有幸存者均表现出大脑体积的广泛减少，与对照组相比，白质减少了6％，白质减少了5％（分别为p = 0.003和0.0006）。大部分大脑似乎都受到了影响-90个评估结构中的71个显示体积较小-最值得注意的例外是枕叶，未观察到明显差异。幸存者和对照组的平均全面智商分别为95（CI 92–99）和110（CI 107–113）。使用来自NIH儿科MRI数据存储库的数据，我们评估了对照组智商升高可能影响所观察到的结构差异的程度。我们估计观察到的三分之二的大脑差异可归因于ALL及其治疗。^-6），但磁化传递比没有差异。