Journal of Nuclear Cardiology

, Volume 25, Issue 6, pp 2096–2111 | Cite as

Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A preclinical study

  • Hassan Mohy-ud-Din
  • Nabil E. Boutagy
  • John C. Stendahl
  • Zhen W. Zhuang
  • Albert J. Sinusas
  • Chi Liu
Original Article



Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs).


Dual-gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts.


The estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ΔIMBV. Estimates of IMBV and ΔIMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 ≥ 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias.


Non-invasive quantification of IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.


Intramyocardial blood volume partial volume correction SPECT-CT imaging microCT coronary microcirculation cardio-respiratory motion correction 



Single photon emission computed tomography/computed tomography


Contrast-enhanced CT


Non-contrast CT for attenuation correction


Cardiovascular disease


Coronary microvascular disease


Coronary artery disease


Left ventricle, right ventricle


Intramyocardial blood volume


Cycle-dependent change in IMBV

CLV-blp, Cmyo

99mTc-RBC uptake in the LV blood pool or myocardium



The authors wish to thank Dr. Eva Romito, Dr. Attila Feher, Dr. Jing Wu, Sharon Wang, Tsa Shelton, and Christi Hawley for their help in conducting the experiments.


Hassan Mohy-ud-Din, Nabil E. Boutagy, John C. Stendahl, Zhen W. Zhuang, Albert J. Sinusas, and Chi Liu claim no potential conflict of interests.

Ethical approval

All experiments were performed in accordance with Yale University Institutional Animal Care and Use Committee standards and approval.

Supplementary material

12350_2017_970_MOESM1_ESM.pptx (677 kb)
Supplementary material 1 (PPTX 677 kb)


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Copyright information

© American Society of Nuclear Cardiology 2017

Authors and Affiliations

  • Hassan Mohy-ud-Din
    • 1
    • 3
  • Nabil E. Boutagy
    • 2
  • John C. Stendahl
    • 2
  • Zhen W. Zhuang
    • 2
  • Albert J. Sinusas
    • 1
    • 2
  • Chi Liu
    • 1
  1. 1.Department of Radiology and Biomedical ImagingYale UniversityNew HavenUSA
  2. 2.Section of Cardiovascular Medicine, Department of MedicineYale University School of MedicineNew HavenUSA
  3. 3.Shaukat Khanum Memorial Cancer Hospital and Research CenterLahorePakistan

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