Use of gated 13N-NH3 micro-PET to examine left ventricular function in rats

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Abstract

Introduction

Myocardial perfusion gating techniques offer the possibility of measurement of left ventricular end-systolic (ESV) and end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) in clinical and preclinical trials. The aim of this study was to evaluate left ventricular volumes (LVV) and LVEF with 13N-NH3 in comparison with the reference 18F-FDG in different rat models.

Methods

In this study, 18 male Wistar rats, 12 control rats and 6 rats with myocardial infarction (MI) were imaged with micro-PET. The ratswere scanned with gated 13N-NH3 and 18F-FDG sequentially for the assessment of LVV and LVEF. A validated three-dimensional segmentation algorithm was used to calculate LVV and LVEF.

Results

Mean LVEF measured with 13N-NH3 was 45.6±8.9 and 75.3±9.4%, mean ESV was 0.40±0.12 and 0.14±0.11 ml, and mean EDVwas 0.53±16 and 0.75±0.18 ml for MI and control rats, respectively. Moderate to good correlations were observed between values of 13N-NH3 and 18F-FDG for calculation of ESV [r=0.80, P<.0001, standard error of estimate (SEE)=0.10], EDV (r=0.63, P=.005, SEE=0.14) and LVEF (r=0.84, P<.0001, SEE=9.5). LVEF measured with 13N-NH3 was significantly lower in MI rats in comparison to measurement with 18F-FDG (45.6±8.9 vs 54.9±9.3 %; P=.04).

Conclusion

Correlations were moderate to good for the assessment of ESV, EDV and LVEF between gated 13N-NH3 and 18F-FDG. LVEF was underestimated with gated 13N-NH3 in rats with myocardial infarction. In healthy rats, LV volumes and LVEF can be measured reproducibly with either approach.

Introduction

Animal models are widely used in studies on heart disease and monitoring novel treatment therapies. However, the possibilities of noninvasive assessment of cardiac function in small animals are still limited. Positron emission tomography (PET) has been proven to be a useful and accurate tool for detection of stunning, ischemia and for measuring perfusion [1]. In addition, PET can be used to visualize cardiac perfusion and metabolism and the calculation of left ventricular volumes (LVV) and ejection fraction (LVEF) by the application of cardiac gating techniques and specific PET tracers [2], [3]. A combined measurement of different parameters is a powerful way to monitor in a noninvasive way cardiac function and perfusion. This is helpful in evaluating the effectiveness of various treatment strategies in small animal models mimicking heart disease. Previously, these measurements had to be made sequentially using different tracers, characterized by their own specific properties. PET measurements performed with 13N-NH3 are currently predominantly used as an accurate noninvasive diagnostic technique for quantification of myocardial perfusion in the clinical setting [4]. Simultaneous measurement of myocardial perfusion, LVV and LVEF with 13N-NH3 using a combination of dynamic and ECG-gated acquisition protocols has been reported earlier in human studies, but not in animal studies [5], [6]. Even though clinical results are very promising, cardiac nuclear imaging in small animals remains challenging due to the small size of the animal and consequent small heart volume.

18F-FDG has proven itself to be a reliable tracer for the assessment of LVV and LVEF and myocardial viability, in rats as well as in humans [1], [2], [5], [7], and is therefore the preferred method for these measurements. However, a gated 13N-NH3 PET measurement in small animals has not been evaluated so far. The aim of this study was to evaluate gated 13N-NH3 for the assessment and reproducibility of LVV and LVEF measurements in rats in comparison with the reference method, gated 18F-FDG PET, using micro-PET.

Section snippets

Animals

The study was performed in 18 male Wistar rats (Harlan, The Netherlands). Animals were housed in groups under standard conditions at 12-h light/dark cycle until they reached 12 weeks of age. All animals received standard diet and water ad libitum during the study. At 12 weeks of age, the rats were subjected to myocardial infarction (MI) (n=6) by coronary artery ligation as described before [8]. Twelve controls were included. Approximately 11 weeks after MI surgery, the rats were subjected to

Results

There were no significant differences in body weight (364±94 vs. 423±72 g for control and MI rats, respectively) or heart rates (354±22 vs. 349±49 beats per minute for control and MI rats, respectively) during PET imaging between groups. Mean MI size in the MI group was 37±12%.

Good reproducibility was observed for ESV, EDV and LVEF when control rats were scanned on different days for gated 13N-NH3 as well as 18F-FDG PET (Table 1).

The mean values of LVV and LVEF are presented in Table 2. There

Discussion

In this study, we showed that LV function measurements (ESV, EDV and LVEF) can be obtained with gated 13N-NH3 micro-PET images in rats, both healthy and those with an induced MI. In the total group of rats, a moderate agreementfor ESV and EDV and good agreement for LVEF were observed when comparing the two gated-based imaging methods. Both ESV and EDV obtained from 13N-NH3 images were slightly higher, but not significant, as compared to 18F-FDG-derived values. There was an underestimation of

Conclusion

ECG-gated 13N-NH3 PET correlates with gated 18F-FDG for the assessment of LVV and LVEF in rats. Whereas LV volumes and LVEF in healthy rats can be measured reproducibly with either approach, LVEF in the MI model was slightly underestimated with gated 13N-NH3 PET. The small systematic bias and the limits of agreement are reasonably small enough to justify the conclusion that these methods can be used interchangeably. Dynamic ECG-gated 13N-NH3 PET may provide a novel noninvasive method

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