Dataset Information

Detection of sympathetic denervation defects in Fabry disease by hybrid [¹¹C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

ABSTRACT:

Background

Myocardial glycosphingolipid accumulation in patients with Fabry disease (FD) causes biochemical and structural changes. This study aimed to investigate sympathetic innervation in FD using hybrid cardiac positron emission tomography (PET)/magnetic resonance imaging (MRI).

Methods and results

Patients with different stages of Fabry disease were prospectively enrolled to undergo routine CMR at 1.5T, followed by 3T hybrid cardiac PET/MRI with [¹¹C]meta-hydroxyephedrine ([11C]mHED). Fourteen patients with either no evidence of cardiac involvement (n = 5), evidence of left ventricular hypertrophy (LVH) (n = 3), or evidence of LVH and fibrosis via late gadolinium enhancement (LGE) (n = 6) were analyzed. Compared to patients without LVH, patients with LVH or LVH and LGE had lower median T1 relaxation times (ms) at 1.5 T (1007 vs. 889 vs. 941 ms, p = 0.003) and 3T (1290 vs. 1172 vs. 1184 p = .014). Myocardial denervation ([11C]mHED retention < 7%·min) was prevalent only in patients with fibrosis, where a total of 16 denervated segments was found in two patients. The respective area of denervation exceeded the area of LGE in both patients (24% vs. 36% and 4% vs. 32%). However, sympathetic innervation defects ([11C]mHED retention ≤ 9%·min) occurred in all study groups. Furthermore, a reduced sympathetic innervation correlated with an increased left ventricular mass (p = .034, rs = - 0.57) and a reduced global longitudinal strain (GLS) (p = 0.023, rs = - 0.6).

Conclusion

Hybrid cardiac PET/MR with [11C]mHED revealed sympathetic innervation defects, accompanied by impaired GLS, in early stages of Fabry disease. However, denervation is only present in patients with advanced stages of FD showing fibrosis on CMR.

SUBMITTER: Gatterer C

PROVIDER: S-EPMC10558396 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Detection of sympathetic denervation defects in Fabry disease by hybrid [<sup>11</sup>C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

Gatterer Constantin C Wollenweber Tim T Pichler Verena V Vraka Chrysoula C Sunder-Plassmann Gere G Lenz Max M Hengstenberg Christian C Hacker Marcus M Loewe Christian C Graf Senta S Beitzke Dietrich D

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20230228 5

<h4>Background</h4>Myocardial glycosphingolipid accumulation in patients with Fabry disease (FD) causes biochemical and structural changes. This study aimed to investigate sympathetic innervation in FD using hybrid cardiac positron emission tomography (PET)/magnetic resonance imaging (MRI).<h4>Methods and results</h4>Patients with different stages of Fabry disease were prospectively enrolled to undergo routine CMR at 1.5T, followed by 3T hybrid cardiac PET/MRI with [<sup>11</sup>C]meta-hydroxyep ...[more]

PMID: 36855009

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Project description:ObjectiveSynaptic loss is an early feature of neurodegenerative disease models, and is severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synaptic density in vivo. This study used [11 C]UCB-J PET in participants with behavioral variant frontotemporal dementia (bvFTD), testing the hypothesis that synaptic loss is severe and related to clinical severity.MethodsEleven participants with clinically probable bvFTD and 25 age- and sex-matched healthy controls were included. Participants underwent dynamic [11 C]UCB-J PET, structural magnetic resonance imaging, and a neuropsychological battery, including the revised Addenbrooke Cognitive Examination, and INECO frontal screening. General linear models compared [11 C]UCB-J binding potential maps and gray matter volume between groups, and assessed associations between synaptic density and clinical severity in patients. Analyses were also performed using partial volume corrected [11 C]UCB-J binding potential from regions of interest (ROIs).ResultsPatients with bvFTD showed severe synaptic loss compared to controls. [11 C]UCB-J binding was reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insular cortex, and medial temporal lobe. Synaptic loss in the frontal and cingulate regions correlated significantly with cognitive impairments. Synaptic loss was more severe than atrophy. Results from ROI-based analyses mirrored the voxelwise results.InterpretationIn accordance with preclinical models, and human postmortem evidence, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to severity. [11 C]UCB-J PET could support translational studies and experimental medicine strategies for new disease-modifying treatments for neurodegeneration. ANN NEUROL 2023;93:142-154.

Dataset Information

Detection of sympathetic denervation defects in Fabry disease by hybrid [¹¹C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

Background

Methods and results

Conclusion

Publications

Detection of sympathetic denervation defects in Fabry disease by hybrid [<sup>11</sup>C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Detection of sympathetic denervation defects in Fabry disease by hybrid [11C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

Background

Methods and results

Conclusion

Publications

Detection of sympathetic denervation defects in Fabry disease by hybrid [<sup>11</sup>C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Detection of sympathetic denervation defects in Fabry disease by hybrid [¹¹C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.