Abstract

This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter SPECT with 123I-FP-CIT in parkinsonian syndromes. A total of 1306 123I-FP-CIT-SPECT were included retrospectively. Binary classification as ‘reduced’ or ‘normal’ striatal 123I-FP-CIT uptake by an experienced reader served as standard-of-truth. A custom-made 3-dimensional convolutional neural network (CNN) was trained for classification of the SPECT images with 1006 randomly selected images in three different settings: “full image”, “striatum only” (3-dimensional region covering the striata cropped from the full image), “without striatum” (full image with striatal region removed). The remaining 300 SPECT images were used to test the CNN classification performance. Layer-wise relevance propagation (LRP) was used for voxelwise quantification of the relevance for the CNN-based classification in this test set. Overall accuracy of CNN-based classification was 97.0%, 95.7%, and 69.3% in the “full image”, “striatum only”, and “without striatum” setting. Prominent contributions in the LRP-based relevance maps beyond the striatal signal were detected in insula, amygdala, ventromedial prefrontal cortex, thalamus, anterior temporal cortex, superior frontal lobe, and pons, suggesting that 123I-FP-CIT uptake in these brain regions provides clinically useful information for the differentiation of neurodegenerative and non-neurodegenerative parkinsonian syndromes.

Highlights

  • This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter single photon emission computed tomography (SPECT) with 123I-FP-CIT in parkinsonian syndromes

  • A transversal slice through the striatum of the mean relevance maps of the 123I-FP-CIT SPECT images correctly classified by the convolutional neural network (CNN) is shown in Fig. 1, separately for correctly classified normal SPECT and for correctly classified reduced SPECT

  • This study provides further evidence of extrastriatal alterations in 123I-FP-CIT SPECT with typical striatal reduction that might be clinically useful for the differentiation between neurodegenerative and non-neurodegenerative parkinsonian syndromes

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Summary

Introduction

This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter SPECT with 123I-FP-CIT in parkinsonian syndromes. Abbreviations 2d 2-Dimensional 3d 3-Dimensional CBS Corticobasal syndrome CUPS Clinically uncertain parkinsonian syndrome DAT Dopamine transporter DLB Dementia with Lewy bodies 123I-FP-CIT N-ω-Fluoropropyl-2β-carbomethoxy-3β-(4-I-123-iodophenyl)nortropane LRP Layer-wise relevance propagation MSA-P Parkinsonian variant of multiple system atrophy PD Parkinson’s disease PET Positron emission tomography PSP Progressive supranuclear palsy ROC Receiver operating characteristic ROI Region-of-interest SBR Specific binding ratio. Clinical guidelines recommend single photon emission computed tomography (SPECT) with the DAT ligand N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-123I-iodophenyl)nortropane (123I-FP-CIT) for the detection (or exclusion) of relevant DAT loss in the striatum to support the diagnostic workup in patients with clinically uncertain parkinsonian syndrome (CUPS)[3,4]. There is PD-related loss of dopaminergic neurons in the ventral tegmental area that directly project to extrastriatal brain regions including nucleus accumbens, medial prefrontal cortex, hippocampus and ­amygdala[8,9,10,11,12] Degeneration of these dopaminergic pathways most likely contributes to cognitive and behavioral symptoms in PD

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