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Comparison of the beta-hydroxybutyrate, glucose, and lactate concentrations derived from postmortem proton magnetic resonance spectroscopy and biochemical analysis for the diagnosis of fatal metabolic disorders

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Abstract

Purpose

The detection and quantification of metabolites relevant for the diagnosis of fatal metabolic disorders by proton magnetic resonance spectroscopy (1H-MRS) was recently demonstrated. This prospective study aimed to compare the concentrations of beta-hydroxybutyrate (BHB), glucose (GLC), and lactate (LAC) derived from both biochemical analyses and 1H-MRS for the diagnosis of fatal metabolic disorders.

Methods

In total, 20 cases with suspected fatal metabolic disorders were included in the study. For the agreement based on thresholds, the concentrations of BHB and GLC in the vitreous humor (VH) from the right vitreous and in cerebrospinal fluid (CSF) from the right lateral ventricle were derived from 1H-MRS and biochemical analyses. The predefined thresholds for pathological elevations were 2.5 mmol/l for BHB and 10 mmol/l for GLC based on the literature. In addition, concentrations of the same metabolites in white matter (WM) tissue from the corona radiata of the right hemisphere were analyzed experimentally using both methods. To enable the biochemical analysis, a dialysate of WM tissue was produced. For all three regions, the LAC concentration was determined by both methods.

Results

The conclusive agreement based on thresholds was almost perfect between both methods with only one disagreement in a total of 70 comparisons due to the interference of a ferromagnetic dental brace. The differences in the concentrations between both methods showed high standard deviations. Confidence intervals of the bias not including 0 were found in CSF-GLC (− 3.1 mmol/l), WM-GLC (1.1 mmol/l), and WM-LAC (− 6.5 mmol/l).

Conclusion

Despite a considerable total error attributable to both methods, MRS derives the same forensic conclusions as conventional biochemical analyses. An adaptation of the protocol to reduce the detected errors and more data are needed for the long-term validation of MRS for the diagnosis of fatal metabolic disorders. The production of WM dialysates cannot be recommended due to high glycolytic loss.

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Abbreviations

DM1:

Diabetes mellitus type 1

DM2:

Diabetes mellitus type 2

DKA:

Diabetic ketoacidosis

HHS:

Hyperosmolar hyperglycemic state

1H-MRS:

Proton magnetic resonance spectroscopy

BCA:

Biochemical analysis

VH:

Vitreous humor

CSF:

Cerebrospinal fluid

WM:

White matter

BHB:

Beta-hydroxybutyrate

GLC:

Glucose

LAC:

Lactate

AcAc:

Acetoacetate

MM:

Macromolecules

TR:

Repetition time

SD:

Standard deviation

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Acknowledgments

We thank Roger Odermatt for the time-intensive production of the white matter dialysates. The authors express their gratitude to Emma Louise Kessler, MD, for her generous donation to the Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.

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Authors and Affiliations

  1. Institute of Forensic Medicine, Department of Forensic Medicine and Imaging, University of Zurich, Winterthurerstrasse 190/52, CH-8057, Zurich, Switzerland

    Jakob Heimer, Dominic Gascho, Rosa Maria Martinez, Michael J. Thali & Niklaus Zoelch

  2. Institute of Forensic Medicine, Rheinische Friedrich-Wilhelms-University Bonn, Stiftsplatz 12, D-53111, Bonn, Germany

    Burkhard Madea

  3. Institute of Forensic Medicine, Department of Forensic Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190/52, CH-8057, Zurich, Switzerland

    Andrea Steuer

  4. Hospital of Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Lenggstrasse 31, CH-8032, Zurich, Switzerland

    Niklaus Zoelch

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  1. Jakob Heimer
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  2. Dominic Gascho
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Correspondence to Jakob Heimer.

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This article does not contain any studies with live human participants or animals performed by any of the authors. Ethical approval for the publication of case-related data was obtained by the Ethics Committee of the Canton of Zurich, Nr. KEK ZH-Nr. 15-0686.

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Heimer, J., Gascho, D., Madea, B. et al. Comparison of the beta-hydroxybutyrate, glucose, and lactate concentrations derived from postmortem proton magnetic resonance spectroscopy and biochemical analysis for the diagnosis of fatal metabolic disorders. Int J Legal Med 134, 603–612 (2020). https://doi.org/10.1007/s00414-019-02235-6

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