ABSTRACT
Recently, myocardial blood flow quantitation with dynamic SPECT has been validated to enhance the detection of multivessel coronary artery disease (CAD) and conclude equivocal SPECT myocardial perfusion study. This advance opened an important clinical application to utilize the tool in guiding CAD management for area where myocardial perfusion tracers for PET are unavailable or unaffordable. We present a clinical patient with ongoing recursive angina who underwent multiple nuclear stress tests for a sequence of CAD evaluation in 26 months and demonstrated that SPECT myocardial blood flow quantitation properly guided CAD management to warrant patient outcome.
Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , Coronary Circulation , Tomography, Emission-Computed, Single-Photon , Coronary Artery Disease/therapy , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: This study investigated the performance of SPECT myocardial blood flow (MBF) quantitation lacking full physical corrections (All Corr) in dynamic SPECT (DySPECT) images. METHODS: Eleven healthy normal volunteers (HVT) and twenty-four patients with angiography-documented CAD were assessed. All Corr in 99mTc-sestamibi DySPECT encompassed noise reduction (NR), resolution recovery (RR), and corrections for scatter (SC) and attenuation (AC), otherwise no correction (NC) or only partial corrections. The performance was evaluated by quality index (R 2) and blood-pool spillover index (FBV) in kinetic modeling, and by rest flow (RMBF) and stress flow (SMBF) compared with those of All Corr. RESULTS: In HVT group, NC diminished 2-fold flow uniformity with the most degraded quality (15%-18% reduced R 2) and elevated spillover effect (45%-50% increased FBV). Consistently higher RMBF and SMBF were discovered in both groups (HVT 1.54/2.31 higher; CAD 1.60/1.72; all P < .0001). Bland-Altman analysis revealed positive flow bias (HVT 0.9-2.6 mL/min/g; CAD 0.7-1.3) with wide ranges of 95% CI of agreement (HVT NC -1.9-7.1; NR -0.4-4.4; NR + SC -1.1-4.3; NR + SC + RR -0.7-2.5) (CAD NC -1.2-3.8; NR -1.0-2.8; NR + SC -1.0-2.5; NR + SC + RR -1.1-2.6). CONCLUSIONS: Uncorrected physical interference in DySPECT images can extensively impact the performance of MBF quantitation. Full physical corrections should be considered to warrant this tool for clinical utilization.
Subject(s)
Coronary Circulation , Tomography, Emission-Computed, Single-Photon/methods , Adult , Aged , Aged, 80 and over , Coronary Artery Disease/diagnostic imaging , Humans , Middle AgedABSTRACT
Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD.
Subject(s)
Cell Survival/genetics , Dopaminergic Neurons/metabolism , Gene Expression Regulation , Nerve Degeneration/metabolism , Protein Serine-Threonine Kinases/metabolism , Substantia Nigra/metabolism , Animals , Dopaminergic Neurons/pathology , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 , Levodopa/pharmacology , Mice , Mice, Transgenic , Motor Activity/drug effects , Motor Activity/genetics , Nerve Degeneration/genetics , Nerve Degeneration/pathology , Neurogenesis/genetics , Protein Serine-Threonine Kinases/genetics , Substantia Nigra/pathologyABSTRACT
Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.
