An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis

doi:10.1007/s12350-021-02715-6

Journal of Nuclear Cardiology

Volume 28, Issue 6, December 2021, Pages 2483-2496

https://doi.org/10.1007/s12350-021-02715-6 Get rights and content

Abstract

Background

In [^99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°).

Methods

In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i.

Results

In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader’s confidence.

Conclusions

Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

Resumen

Antecedentes

En la gammagrafía con [ 99mTc]-DPD para amiloidosis cardiaca ATTR, se recomienda la adquisición de imágenes planares a las 3h p.i y SPECT/CT en modo L. Este estudio investigó si las imágenes planares más tempranas (1h p.i.) tienen beneficios y si la adquisición del SPECT/CT debería preferirse en modo H (ángulo de detección de 180 °) o en modo L (90 °).

Métodos

En las mediciones con el fantoma del SPECT/CT (cámaras de NaI, n= 2; CZT, n=1), la recuperación pico de contraste (CRpico) se derivó de inserciones de esfera o de inserciones miocárdicas (fantoma cardiaco; relación señal-fondo [SBR], 10:1 o 5: 1). En 25 pacientes positivos y 38 negativos (referencia: biopsia endomiocárdica o diagnóstico clínico), el score de Perugini y la relación de cuentas corazón-contralateral (H/CL) se derivaron de imágenes planares a 1h y 3h p.i.

Resultados

En mediciones con el fantoma, la precisión del CRpico miocárdico en SBR 10:1 (modo H, 0.95-0.99) y la reproducibilidad a 5:1 (modo H, 1.02-1.14) fue comparable para el modo H y el modo L. Sin embargo, el modo L mostró una mayor variabilidad de las cuentas de fondo y del CRpico de la esfera en todo el campo de visión que el modo H. En pacientes, la sensibilidad/especificidad fue ≥ 95% para las relaciones H/CL en ambos puntos de tiempo y con un score visual a las 3 h. A 1h, los scores visuales mostraron una especificidad de (89%) y disminución de la confianza del lector.

Conclusiones

Las imágenes tempranas de DPD no proporcionaron ningún valor adicional para el score visual o las relaciones H/CL. En SPECT/CT, se prefiere el modo H sobre el modo L, especialmente si la cuantificación se aplica aparte del miocardio.

摘要

背景

[99mTc]Tc-DPD闪烁显像检查心肌ATTR淀粉样变性时, 建议使用3h p.i.平面图像和L模式SPECT/CT扫描。本研究探讨了早期平面图像(1h p.i.)是否有益, 以及SPECT/CT采集是否应首选H模式(探测器角度180°)或L模式(90°)。

方法

在SPECT/CT模体测量中(NaI相机, n=2;CZT, n=1), 峰值造影剂恢复(CRpeak)来自球体插入物或心肌插入物(心脏模体; 信号与背景比[SBR], 10:1 或5:1)。在25个阳性和38个阴性病人中(参考标准: 心内膜活检或临床诊断), Perugini分数和心脏/对侧 (H / CL)计数比率来自平面图像1 h和3 h p.i.。

结果

在模体测量中, 心肌CRpeak的SBR准确性 10:1 (H-mode, 0.95 - 0.99)和可重复性5:1 (H-mode, 1.02 - 1.14), H模式和L 模式相当。然而, 与H模式相比, L模式在整个视野中表现出更高的背景计数和球形CRpeak变异性。在患者中, 两个时间点的H/CL比值以及3h视觉评分的敏感性/特异性均≥95%。1h时, 视觉评分特异性为89%, 阅读者的信心降低。

结论

DPD早期图像对视觉评分和H/CL比值没有额外的价值。在SPECT/CT中, H模式优于L模式, 特别是心肌之外定量时。

Section snippets

Background

Amyloid transthyretin (ATTR) amyloidosis is a potentially life-threatening cause of heart failure caused by accumulation of liver-derived, misfolded transthyretin. Scintigraphy with bisphosphonates, such as [^99mTc]Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), plays a key role in identifying myocardial involvement.¹ Quantification of myocardial uptake using single photon emission computed tomography/computed tomography (SPECT/CT) might provide prognostic value² or therapy monitoring of

SPECT/CT Phantom Measurements: Phantom Filling

Methods regarding the phantom measurements are described in Online Resource 1. Imaging was performed with three general-purpose SPECT/CT cameras. The NaI cameras were equipped with a low-energy high-resolution (LEHR) collimator (GE Discovery 670 DR Pro, GE Healthcare, Milwaukee, WI, USA; Siemens Symbia T6, Siemens Healthcare, Erlangen, Germany). The CZT camera (GE Discovery 670 CZT) used a wide-energy high-resolution (WEHR45) collimator.

Patients: Characteristics

Between 05/2019 and 08/2020, 69 patients were referred

Myocardial CRpeak

At signal-to-background ratio (SBR) of 10:1, CRpeak of the myocardial compartment was similar between H-mode (0.99 ± 0.07) vs L-mode (1.00; single measurement, P = 0.84) for the DR Pro camera, for the CZT camera (0.95 ± 0.05 vs 1.01, P = 0.17) and for the Symbia camera (0.96 ± 0.08 vs 1.01 ± 0.02, P = 0.35).

At SBR of 5:1 (DR Pro and CZT camera only), the DR Pro and CZT showed similar myocardial CRpeak for H-mode vs L-mode (DR Pro, 1.09 ± 0.1 vs 1.11, P = 0.76; CZT, 1.14 ± 0.13 vs 1.15, P =

Discussion

This study examined a comprehensive imaging protocol for [^99mTc]Tc-DPD scintigraphy in patients with suspicion for cardiac ATTR amyloidosis.

Applying the visual score for planar images initially proposed by Perugini et al.,⁸ sensitivity at the early time point at 1 hour p.i. (100%) was comparable to 3 hour p.i. (96%). The slightly lower specificity at the early time point (89% vs 95%) might be caused by high blood pool activity of DPD at 1 hour p.i. This is underlined by the observation that

New Knowledge Gained

To ensure accurate and reproducible quantification of cardiac SPECT/CT in patients with ATTR amyloidosis, the proposed workflow of optimized image acquisition (H-mode) and image reconstruction (based on the myocardial CRpeak in a cardiac phantom) can be employed. This facilitates comparable quantitative accuracy for myocardial uptake between different general-purpose SPECT/CT cameras (NaI and CZT detectors). Early planar images may be safely omitted with [^99mTc]Tc-DPD for a convenient

Conclusions

Early planar images (1 hour p.i.) can be omitted for [^99mTc]Tc-DPD as they provided no additional value for Perugini scoring or H/CL ratios compared to the reference at 3 hour p.i. In SPECT/CT phantom measurements, both H-mode and L-mode acquisition accurately quantified myocardial [^99mTc]Tc-DPD uptake using the CRpeak. However, L-mode would impair quantitative accuracy in localizations other than the heart. These results suggest that H-mode acquisition with automated body contouring is

Acknowledgements

JMMR is participant in the BIH-Charité Digital Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin, the Berlin Institute of Health, and the German Research Foundation (DFG).

Funding

Open Access funding enabled and organized by Projekt DEAL.

Disclosures

Imke Schatka and Holger Amthauer received project-specific funding from Pfizer Pharmaceuticals for a different project. David Frumkin received project related research funding from Pfizer as well as speaker fee or reimbursement of costs as

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Absolute quantification of myocardial uptake of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR)
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Determinar la contribución diagnóstica de la cuantificación absoluta del depósito miocárdico de ^99mTc-DPD en pacientes con amiloidosis cardiaca por depósitos de transtiretina (ATTR).
Se realizó SPECT/TC a 41 pacientes con resultado gammagráfico positivo para amiloidosis cardiaca ATTR. Se dividió a los pacientes en dos grupos (grados 2 y 3 de Perugini) y se calcularon los SUVmax a nivel del hueso y de ambos ventrículos y el porcentaje de dosis calculado en estas áreas. Se empleó la prueba t de Student para comparar resultados y se calculó el área bajo la curva (AUC) para evaluar la eficacia diferencial y establecer unos puntos de corte discriminatorios entre ambos grupos de pacientes.
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La cuantificación absoluta de la captación miocárdica de ^99mTc-DPD en las imágenes SPECT/TC de pacientes con sospecha de amiloidosis cardiaca por depósitos de transtiretina supone una nueva herramienta diagnóstica que permite una adecuada clasificación de los pacientes, acorde a la escala de gradación visual de Perugini.
To determine the diagnostic contribution of the absolute quantification of the myocardial deposit of ^99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR).
SPECT/CT was performed on 41 patients with positive scintigraphic results for ATTR cardiac amyloidosis. The patients were divided into two groups (Perugini grades 2 and 3) and the SUVmax at the level of the bone and both ventricles and the percentage of dose calculated in these areas were calculated. Student's t-test was used to compare results and the area under the curve (AUC) was calculated to assess differential efficacy and establish discriminatory cut-off points between both groups of patients.
Statistically significant differences were observed in all the study variables, with the exception of SUVmax bone. The differences with the greatest statistical power were observed in the variables SUVmax_RV and the percentage of dose in both ventricles (P < .001). The cut-off point obtained for the variable SUVmax_LV was 8.620 (sensitivity 87.9% and specificity 100%; AUC: 0.966), while that of the variable SUVmax_RV was 6.195 (sensitivity 81.8% and specificity 100%; AUC: 0.955).
The absolute quantification of myocardial uptake of ^99mTc-DPD in the SPECT/CT images of patients with suspected cardiac amyloidosis due to transthyretin deposits represents a new diagnostic tool that allows an adequate classification of patients, according to the visual grading scale of Perugini.
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Bone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging.
The geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i..
Total counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i..
Cardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.
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We investigated quantitative ^99mTc-pyrophosphate (PYP) SPECT/CT reproducibility and accuracy for diagnosing cardiac transthyretin amyloidosis (ATTR), and whether SPECT/CT improved visual and quantitative results compared to SPECT-only.
Data were reviewed for 318 patients with suspected ATTR who underwent PYP SPECT/CT. Myocardial-to-blood pool count (MBP) ratios were computed and repeated independently > 1 month later. A physician independently scored LV myocardial-to-rib uptake on SPECT/CT as: 0 (negative), 1 < rib (equivocal), 2 = rib (positive) or 3 > rib (positive), and the image quality as: 1 (poor), 2 (adequate), and 3 (good). SPECT-only MBP ratios and visual scores were assessed separately for a subgroup of the first sequential 191 patients.
25% of patients had positive myocardial uptake (myocardial-to-rib uptake score of ≥ 2). SPECT/CT MBP ratios were reproducible (1.35 ± .68 vs 1.33 ± .74, p = .09) and corresponded with visual scores ≥ 2 (ROC AUC = 99 ± 1%) more accurately than SPECT-only MBPs (93 ± 3%, p = .02). SPECT/CT image quality was better than that of SPECT-only (2.7 ± .5 vs 2.1 ± .5, p < .0001) with fewer equivocal results (2.6% vs 22.5%, p < .0001).
SPECT/CT produces MBP ratios that are reproducible and accurately identify a positive scan, with better image quality and fewer equivocal cases than SPECT-only.
SPECT/CT SUV-based metrics: A promising diagnostic tool in classifying patients with suspected transthyretin cardiac amyloidosis among the different Perugini grades?
2023, Hellenic Journal of Nuclear Medicine
Reliability and feasibility of visual grading systems and quantitative indexes on [99mTc]Tc-DPD imaging for cardiac amyloidosis
2022, Scientific Reports
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Julian M. M. Rogasch and Christoph Wetz have contributed equally to this work.

The publication is on behalf of the Amyloidosis Center Charité Berlin (ACCB).

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Original ArticleAn optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis

Abstract

Background

Methods

Results

Conclusions

Resumen

Antecedentes

Métodos

Resultados

Conclusiones

摘要

背景

方法

结果

结论

Section snippets

Background

SPECT/CT Phantom Measurements: Phantom Filling

Patients: Characteristics

Myocardial CRpeak

Discussion

New Knowledge Gained

Conclusions

Acknowledgements

Funding

Disclosures

JACC Cardiovasc Imaging

J Cardiac Fail

J Am Coll Cardiol

J Cardiac Fail

JACC Cardiovasc Imaging

JACC Cardiovasc Imaging

Comput Med Imaging Graph

J Nucl Cardiol

Nonbiopsy diagnosis of cardiac transthyretin amyloidosis

Circulation

Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy

N Engl J Med

Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis

N Engl J Med

Inotersen treatment for patients with hereditary transthyretin amyloidosis

N Engl J Med

Multicenter study of planar technetium 99m Pyrophosphate cardiac imaging: Predicting survival for patients with ATTR cardiac amyloidosis

JAMA Cardiol

Forming inferences about some intraclass correlation coefficients

Psychol Methods

Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instrument in psychology

Psychol Assess

(99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses

Circ Cardiovasc Imaging

Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis

Amyloid

Original Article
An optimized imaging protocol for [^99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis