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Published on: July 28, 2013
Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of
L Y Cai1, C Tanase2, A W Anderson3,4,5
1From the Department of Biomedical Engineering (L.Y.C., A.W.A., B.A.L.) leon.y.cai@vanderbilt.edu.
Insights
Type 1 diabetes in children is linked to neuroaxonal loss in brain white matter, particularly with diabetic ketoacidosis history. Magnetic Resonance Spectroscopic Imaging (MRSI) can detect these changes, highlighting the impact of complications on brain health.
Area of Science:
- Neuroimaging
- Pediatric Endocrinology
- Metabolic Disorders
Background:
- Type 1 diabetes (T1D) affects over 200,000 US children, increasing cognitive dysfunction risk.
- Previous studies suggest reduced NAA/Cr (neuroaxonal loss marker) in T1D, but differences across complications and brain tissues are unclear.
- Multisite pilot study to investigate T1D's impact on brain tissue using Magnetic Resonance Spectroscopic Imaging (MRSI).
Purpose of the Study:
- To assess if MRSI can differentiate brain tissue (white matter and deep gray matter) based on NAA/Cr levels in children with T1D.
- To investigate associations between NAA/Cr and T1D disease severity markers like hemoglobin A1c (HbA1c) and diabetic ketoacidosis (DKA).
- To explore the differential impact of chronic hyperglycemia and DKA on neuroaxonal integrity in pediatric T1D.
Main Methods:
- Acquired T1WI and 2D MRSI data from 25 children (6-14 years) with T1D across 3 sites.
- Quantified tissue-weighted NAA/Cr in white matter (WM) and deep gray matter (GM).
- Modeled NAA/Cr against study covariates including HbA1c and DKA history, using phantom studies for calibration.
Main Results:
- MRSI successfully differentiated WM and deep GM by NAA/Cr at the individual level.
- Significant negative associations found between WM NAA/Cr and both HbA1c (P<.005) and DKA history (P<.05).
- A statistical interaction (P<.05) indicated DKA history may have a greater impact on neuroaxonal loss than chronic hyperglycemia; no associations were found in deep GM.
Conclusions:
- MRSI can differentiate WM and deep GM NAA/Cr in children with T1D.
- Disease complications, particularly DKA, may cause neuroaxonal loss in WM.
- Further research is needed to understand how DKA and hyperglycemia affect brain health and cognition in pediatric T1D.
Background And Purpose:
Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study.
Materials And Methods:
In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates.
Results:
We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM.
Conclusions:
Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.
