Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study.

Alwin Tubben; Niek H J Prakken; Oleksandra V Ivashchenko; Hendrea S A Tingen; Andor W J M Glaudemans; Walter Noordzij; Hans L A Nienhuis; Peter van der Meer; Riemer H J A Slart

doi:10.1016/j.nuclcard.2025.102146

Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study.

Alwin Tubben, Niek H J Prakken, Oleksandra V Ivashchenko, Hendrea S A Tingen, Andor W J M Glaudemans, Walter Noordzij, Hans L A Nienhuis, Peter van der Meer, Riemer H J A Slart

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

PURPOSE: Cardiac sympathetic neuronal dysfunction is an early marker in wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM). [ 123I]-MIBG imaging evaluates cardiac sympathetic innervation but lacks volumetric activity quantification in current methods. This study aims to quantify cardiac sympathetic neuronal dysfunction in ATTRwt-CM using [ 123I]-MIBG SPECT/CT and correlate findings with functional and structural cardiac parameters from echocardiogram and cardiac magnetic resonance imaging (CMR).

METHODS: We conducted a single-center, descriptive, cross-sectional study to quantify absolute myocardial sympathetic function in ATTRwt-CM using [ 123I]-MIBG SPECT/CT. Retrospective reconstruction allowed for absolute tracer-uptake quantification of the left ventricle, overall and segmented, in kBq/mL, SUV and percentage of the injected dose (%ID). Echocardiography, CMR, and bone scintigraphy were performed according to clinical standards. Segmented [ 123I]-MIBG SPECT/CT values were correlated with global longitudinal strain (GLSS) on echocardiography, native-T1, and extracellular volume (ECV) on CMR using SPECT/CT fused with CMR.

RESULTS: Twenty-nine ATTRwt-CM patients (75.8±6.6 years, 90% male) were prospectively included. All exhibited cardiac sympathetic neuronal dysfunction, with a median late heart-to-mediastinum ratio of 1.69[1.45-1.89] and a washout rate of 22.7% (16.4-27.3%). SUV mean, SUV peak, SUV max and %ID were 1.80 ± 0.78, 3.84 ± 1.41, 4.46 ± 1.68 and 0.46 ± 0.18 respectively, correlating with semi-quantitative [ 123I]-MIBG measures. No correlations were found with GLSS on echocardiography or native T1 and ECV on CMR.

CONCLUSION: The current study demonstrates the feasibility of volumetric quantification of [ 123I]-MIBG SPECT/CT in ATTRwt-CM. SUV mean, SUV peak, SUV max and %ID correlate with semi-quantitative measures but not with key cardiac parameters on echocardiography or CMR. This confirms the sensitivity of [ 123I]-MIBG SPECT/CT to different aspects of cardiac function or pathology.

TRIAL REGISTRATION: EudraCT ref. 2020-003350-72, retrospectively registered 20 March 2023. https://classic.

CLINICALTRIALS: gov/ct2/show/NCT05776212.

Original language	English
Article number	102146
Number of pages	14
Journal	Journal of Nuclear Cardiology
Volume	45
Early online date	3-Feb-2025
DOIs	https://doi.org/10.1016/j.nuclcard.2025.102146
Publication status	Published - Mar-2025

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Tubben, A., Prakken, N. H. J., Ivashchenko, O. V., Tingen, H. S. A., Glaudemans, A. W. J. M., Noordzij, W., Nienhuis, H. L. A., van der Meer, P., & Slart, R. H. J. A. (2025). Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study. Journal of Nuclear Cardiology, 45, Article 102146. https://doi.org/10.1016/j.nuclcard.2025.102146

@article{fbb1e91a957b4a4da413a225af23a781,

title = "Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study.",

abstract = "PURPOSE: Cardiac sympathetic neuronal dysfunction is an early marker in wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM). [ 123I]-MIBG imaging evaluates cardiac sympathetic innervation but lacks volumetric activity quantification in current methods. This study aims to quantify cardiac sympathetic neuronal dysfunction in ATTRwt-CM using [ 123I]-MIBG SPECT/CT and correlate findings with functional and structural cardiac parameters from echocardiogram and cardiac magnetic resonance imaging (CMR). METHODS: We conducted a single-center, descriptive, cross-sectional study to quantify absolute myocardial sympathetic function in ATTRwt-CM using [ 123I]-MIBG SPECT/CT. Retrospective reconstruction allowed for absolute tracer-uptake quantification of the left ventricle, overall and segmented, in kBq/mL, SUV and percentage of the injected dose (\%ID). Echocardiography, CMR, and bone scintigraphy were performed according to clinical standards. Segmented [ 123I]-MIBG SPECT/CT values were correlated with global longitudinal strain (GLSS) on echocardiography, native-T1, and extracellular volume (ECV) on CMR using SPECT/CT fused with CMR. RESULTS: Twenty-nine ATTRwt-CM patients (75.8±6.6 years, 90\% male) were prospectively included. All exhibited cardiac sympathetic neuronal dysfunction, with a median late heart-to-mediastinum ratio of 1.69[1.45-1.89] and a washout rate of 22.7\% (16.4-27.3\%). SUV mean, SUV peak, SUV max and \%ID were 1.80 ± 0.78, 3.84 ± 1.41, 4.46 ± 1.68 and 0.46 ± 0.18 respectively, correlating with semi-quantitative [ 123I]-MIBG measures. No correlations were found with GLSS on echocardiography or native T1 and ECV on CMR. CONCLUSION: The current study demonstrates the feasibility of volumetric quantification of [ 123I]-MIBG SPECT/CT in ATTRwt-CM. SUV mean, SUV peak, SUV max and \%ID correlate with semi-quantitative measures but not with key cardiac parameters on echocardiography or CMR. This confirms the sensitivity of [ 123I]-MIBG SPECT/CT to different aspects of cardiac function or pathology. TRIAL REGISTRATION: EudraCT ref. 2020-003350-72, retrospectively registered 20 March 2023. https://classic.CLINICALTRIALS: gov/ct2/show/NCT05776212.",

author = "Alwin Tubben and Prakken, \{Niek H J\} and Ivashchenko, \{Oleksandra V\} and Tingen, \{Hendrea S A\} and Glaudemans, \{Andor W J M\} and Walter Noordzij and Nienhuis, \{Hans L A\} and \{van der Meer\}, Peter and Slart, \{Riemer H J A\}",

year = "2025",

month = mar,

doi = "10.1016/j.nuclcard.2025.102146",

language = "English",

volume = "45",

journal = "Journal of Nuclear Cardiology",

issn = "1071-3581",

publisher = "Springer",

}

Tubben, A , Prakken, NHJ , Ivashchenko, OV , Tingen, HSA , Glaudemans, AWJM , Noordzij, W , Nienhuis, HLA, van der Meer, P & Slart, RHJA 2025, 'Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study.', Journal of Nuclear Cardiology, vol. 45, 102146. https://doi.org/10.1016/j.nuclcard.2025.102146

Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study. / Tubben, Alwin ; Prakken, Niek H J ; Ivashchenko, Oleksandra V et al.
In: Journal of Nuclear Cardiology, Vol. 45, 102146, 03.2025.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT

T2 - the I-NERVE study.

AU - Tubben, Alwin

AU - Prakken, Niek H J

AU - Ivashchenko, Oleksandra V

AU - Tingen, Hendrea S A

AU - Glaudemans, Andor W J M

AU - Noordzij, Walter

AU - Nienhuis, Hans L A

AU - van der Meer, Peter

AU - Slart, Riemer H J A

PY - 2025/3

Y1 - 2025/3

N2 - PURPOSE: Cardiac sympathetic neuronal dysfunction is an early marker in wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM). [ 123I]-MIBG imaging evaluates cardiac sympathetic innervation but lacks volumetric activity quantification in current methods. This study aims to quantify cardiac sympathetic neuronal dysfunction in ATTRwt-CM using [ 123I]-MIBG SPECT/CT and correlate findings with functional and structural cardiac parameters from echocardiogram and cardiac magnetic resonance imaging (CMR). METHODS: We conducted a single-center, descriptive, cross-sectional study to quantify absolute myocardial sympathetic function in ATTRwt-CM using [ 123I]-MIBG SPECT/CT. Retrospective reconstruction allowed for absolute tracer-uptake quantification of the left ventricle, overall and segmented, in kBq/mL, SUV and percentage of the injected dose (%ID). Echocardiography, CMR, and bone scintigraphy were performed according to clinical standards. Segmented [ 123I]-MIBG SPECT/CT values were correlated with global longitudinal strain (GLSS) on echocardiography, native-T1, and extracellular volume (ECV) on CMR using SPECT/CT fused with CMR. RESULTS: Twenty-nine ATTRwt-CM patients (75.8±6.6 years, 90% male) were prospectively included. All exhibited cardiac sympathetic neuronal dysfunction, with a median late heart-to-mediastinum ratio of 1.69[1.45-1.89] and a washout rate of 22.7% (16.4-27.3%). SUV mean, SUV peak, SUV max and %ID were 1.80 ± 0.78, 3.84 ± 1.41, 4.46 ± 1.68 and 0.46 ± 0.18 respectively, correlating with semi-quantitative [ 123I]-MIBG measures. No correlations were found with GLSS on echocardiography or native T1 and ECV on CMR. CONCLUSION: The current study demonstrates the feasibility of volumetric quantification of [ 123I]-MIBG SPECT/CT in ATTRwt-CM. SUV mean, SUV peak, SUV max and %ID correlate with semi-quantitative measures but not with key cardiac parameters on echocardiography or CMR. This confirms the sensitivity of [ 123I]-MIBG SPECT/CT to different aspects of cardiac function or pathology. TRIAL REGISTRATION: EudraCT ref. 2020-003350-72, retrospectively registered 20 March 2023. https://classic.CLINICALTRIALS: gov/ct2/show/NCT05776212.

AB - PURPOSE: Cardiac sympathetic neuronal dysfunction is an early marker in wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM). [ 123I]-MIBG imaging evaluates cardiac sympathetic innervation but lacks volumetric activity quantification in current methods. This study aims to quantify cardiac sympathetic neuronal dysfunction in ATTRwt-CM using [ 123I]-MIBG SPECT/CT and correlate findings with functional and structural cardiac parameters from echocardiogram and cardiac magnetic resonance imaging (CMR). METHODS: We conducted a single-center, descriptive, cross-sectional study to quantify absolute myocardial sympathetic function in ATTRwt-CM using [ 123I]-MIBG SPECT/CT. Retrospective reconstruction allowed for absolute tracer-uptake quantification of the left ventricle, overall and segmented, in kBq/mL, SUV and percentage of the injected dose (%ID). Echocardiography, CMR, and bone scintigraphy were performed according to clinical standards. Segmented [ 123I]-MIBG SPECT/CT values were correlated with global longitudinal strain (GLSS) on echocardiography, native-T1, and extracellular volume (ECV) on CMR using SPECT/CT fused with CMR. RESULTS: Twenty-nine ATTRwt-CM patients (75.8±6.6 years, 90% male) were prospectively included. All exhibited cardiac sympathetic neuronal dysfunction, with a median late heart-to-mediastinum ratio of 1.69[1.45-1.89] and a washout rate of 22.7% (16.4-27.3%). SUV mean, SUV peak, SUV max and %ID were 1.80 ± 0.78, 3.84 ± 1.41, 4.46 ± 1.68 and 0.46 ± 0.18 respectively, correlating with semi-quantitative [ 123I]-MIBG measures. No correlations were found with GLSS on echocardiography or native T1 and ECV on CMR. CONCLUSION: The current study demonstrates the feasibility of volumetric quantification of [ 123I]-MIBG SPECT/CT in ATTRwt-CM. SUV mean, SUV peak, SUV max and %ID correlate with semi-quantitative measures but not with key cardiac parameters on echocardiography or CMR. This confirms the sensitivity of [ 123I]-MIBG SPECT/CT to different aspects of cardiac function or pathology. TRIAL REGISTRATION: EudraCT ref. 2020-003350-72, retrospectively registered 20 March 2023. https://classic.CLINICALTRIALS: gov/ct2/show/NCT05776212.

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DO - 10.1016/j.nuclcard.2025.102146

M3 - Article

C2 - 39909199

SN - 1071-3581

VL - 45

JO - Journal of Nuclear Cardiology

JF - Journal of Nuclear Cardiology

M1 - 102146

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Tubben A , Prakken NHJ , Ivashchenko OV , Tingen HSA , Glaudemans AWJM , Noordzij W et al. Feasibility of the Absolute Quantification and Left Ventricular Segmentation of Cardiac Sympathetic Innervation in Wild-type Transthyretin Amyloidosis Cardiomyopathy with [123I]-MIBG SPECT/CT: the I-NERVE study. Journal of Nuclear Cardiology. 2025 Mar;45:102146. Epub 2025 Feb 3. doi: 10.1016/j.nuclcard.2025.102146