Monitoring left ventricular function in small animals

Small animals such as mice and rats are extensively used to investigate the mechanisms and treatment of human cardiac diseases in vivo. The monitoring of left ventricular function is a key factor in this research. The measurement should be rapid, reproducible, and repeatable and allow the detection of subtle differences in function. Currently, echocardiography is most widely used in cardiac research laboratories for measuring left ventricular dimensions and function in small animals. Although the technique is rapid, the reproducibility of the calculations of left ventricular volumes is limited in some circumstances as a result of assumptions that do not necessarily hold true, such as in the setting of dilated, failing ventricles.     

Quantitative gated PET for the assessment of left ventricular function in small animals.

18F-FDG PET can identify areas of myocardial viability and necrosis and provide useful information on the effectiveness of experimental techniques designed to improve contractile function and myocardial vascularization in small animals. The left ventricular volume (LVV) and left ventricular ejection fraction (LVEF) in normal and diseased rats were measured in vivo using the high-resolution avalanche photodiode (APD) small-animal PET scanner of the Université de Sherbrooke. The measurements obtained by PET were compared with those obtained by high-resolution echocardiography and with known values obtained from a small, variable-volume cardiac phantom. METHODS: List-mode gated (18)F-FDG PET studies were performed using the APD PET scanner on 30 rats: 11 healthy, 4 under septic shock, and 15 with heart failure induced by ligature of the left coronary artery. PET images were resized to match human-scale pixels and analyzed using a standard clinical cardiac software program. The LVV and LVEF from the same animals were also evaluated by echocardiography. RESULTS: Agreement was excellent between the endocardial volumes determined by PET and the actual volumes of the cardiac phantom (r(2) = 0.96). Agreement between PET and echocardiography for LVV ranged from good in healthy rats (r(2) = 0.89) to fair in diseased rats (r(2) = 0.49). Agreement was fair between LVEF values measured by the 2 methods (r(2) = 0.56). Normal rats had an average LVEF of 83.2% +/- 8.0% using PET and 81.6% +/- 6.0% using echocardiography. In rats with heart failure, LVEF was 54.6% +/- 15.9% using PET and 54.2% +/- 13.3% using echocardiography. CONCLUSION: Both PET and echocardiography clearly differentiated normal rats from rats with heart failure. Echocardiography is fast and convenient, whereas list-mode PET is also able to assess defect size, myocardial viability, and metabolism.     

Comparison of gated PET with MRI for evaluation of left ventricular function in patients with coronary artery disease.

The aim of this study was to compare left ventricular (LV) volumes and regional wall motion determined by PET with those determined by the reference technique, cardiovascular MRI. METHODS: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured and regional wall motion was scored in 38 patients with chronic coronary artery disease by both gated (18)F-FDG PET and MRI. A 9-segment model was used for PET and MRI to assess regional wall motion. RESULTS: Good correlations were observed between MRI and gated PET for all parameters (r values ranging from 0.91 to 0.96). With PET, there was a significant but small underestimation of LVEDV and LVEF. Mean +/- SD LVEDV, LVESV, and LVEF for MRI were 131 +/- 57 mL, 91 +/- 12 mL, and 33% +/- 12%, respectively, and those for gated PET were 117 +/- 56 mL, 85 +/- 51 mL, and 30% +/- 11%, respectively. For regional wall motion, an agreement of 85% was found, with a kappa-statistic of 0.79 (95% confidence interval, 0.70-0.89; SE, 0.049). CONCLUSION: LV volumes, LVEF, and regional wall motion can be assessed with gated (18)F-FDG PET and correlate well with these parameters assessed by MRI.     

Post-stress end-systolic left ventricular dilation: a marker of endocardial post-ischemic stunning

Several studies have shown the accuracy of gated single photon emission computed tomography (SPECT) using thallium-201 and technetium tracers in the assessment of myocardial perfusion and function. Gated SPECT has been successfully utilized to detect post-stress left ventricular ejection fraction (LVEF) reduction resulting from post-ischemic stunning in patients with coronary obstruction. The aim of this study was to evaluate whether the post-stress LVEF impairment could be related to the post-stress end-systolic ventricular dilation resulting from post-ischemic endocardial stunning. Two hundred and eighty-two consecutive patients were studied by conventional diagnostic 2 day stress/rest gated SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual-headed SPECT camera. One hundred and forty-seven of these patients (52%) showed reversible perfusion defects, 69 (24%) permanent defects and the remaining 66 (24%) had normal perfusion. One hundred and thirty-eight of these patients had a history of myocardial infarction (MI) and 19% underwent coronary angiography without an intervening cardiac event. Perfusion was analysed on ungated images using 20 segments scored on a five-point scale (0, normal; 4, no uptake), while wall thickening (WT) was assessed visually on stress/rest end-systolic images using a four-point score (0, normal; 3, absence of WT). LVEF and volumes were calculated using an automatic algorithm. The post-stress and rest ratios were determined for both end-diastolic (EDV) and end-systolic (ESV) volume. Normal values for all these parameters were obtained using data from 149 patients with a low likelihood (<5%) of coronary artery disease (CAD). In 50 of the 147 (34%) of patients with reversible perfusion defects, post-stress LVEF was >5% lower than rest values (stunned group), while the remaining 97 patients did not show a significant LVEF change (group 2A). The percentage of patients who developed exercise-induced angina, the percentage of patients who underwent coronary angiography and the segmental summed perfusion and WT scores were significantly higher in the stunned group compared with group 2A. Only ESV increased significantly post-stress, and this increase occurred only in stunned patients. Both EDV and ESV ratios were significantly higher in the stunned group compared with normal controls (P=0.008 and P<0.000001, respectively) and with the subgroup 2A (P=0.011 and P<10(-12), respectively). The ESV stress/rest ratio correlated significantly with the summed WT difference score by univariate analysis in stunned patients. It can be concluded that the post-stress ESV dilation, obtained by stress/rest gated SPECT, seems to be due to endocardial post-ischemic stunning. The stunned patients showed more severe clinical, angiographic, perfusion and function parameters.     

Usefulness of Tl-201 SPECT imaging in evaluation of left ventricular hypertrophy and dilation in patients with previous myocardial infarction.

Using short axis slices of Tl-201 myocardial SPECT images, total left ventricular (LV) mass, perfused LV mass, defect size, defect mass, ratio of total LV area to cavity area (T/C), ratio of radius of total LV area to radius of cavity area (TR/CR), and ratio of wall thickness to radius of cavity area (W/R) were obtained. The left ventricular ejection fraction (LVEF) was calculated using blood pool imaging studies. A total of 33 patients with old myocardial infarctions were studied. The patients were divided into group 1 (n = 16) with no history of heart failure, and group 2 (n = 17) with a history of heart failure. The LVEF (P less than 0.001), T/C (P less than 0.005), TR/CR (P less than 0.005) and W/R (P less than 0.001) were significantly lower, while the total LV mass (P less than 0.001) and perfused LV mass (P less than 0.01) were significantly higher in group 2. In the whole group of 33 patients, there was inverse linear correlation between the total LV mass and LVEF (r = -0.82), perfused LV mass and LVEF (r = -0.67), and defect mass and LVEF (r = -0.59). There was linear correlation between W/R and LVEF (r = 0.64). Nonlinear correlations were found between T/C and LVEF (r = 0.81) and TR/CR and LVEF (r = 0.80). Tl-201 myocardial SPECT imaging is useful for the evaluation of LV hypertrophy and cavity dilation in patients with previous myocardial infarction.     

Discordance between exercise SPECT lung TI-201 uptake and left ventricular transient ischemic dilation in patients with CAD

BACKGROUND: In patients with coronary artery disease (CAD), the characteristics of those with discordant exercise thallium 201 single photon emission computed tomography (SPECT) lung uptake (lung-to-heart [L/H] ratio) and left ventricular (LV) transient ischemic dilation (LVTID) are not well defined. METHODS AND RESULTS: The population included 310 patients having exercise Tl-201 SPECT and coronary angiography. The population was subclassified into 4 subgroups: increased L/H ratio only, increased LVTID only, both, and neither. The L/H ratio was weakly correlated to LVTID (r = 0.18). The L/H ratio was correlated to the summed difference score (r = 0.26), summed rest score (r = 0.31), summed stress score (r = 0.5), and rest and stress LV volume (r = 0.5 and r = 0.54, respectively). LVTID was only correlated to the summed difference score (r = 0.32) and stress LV volume (r = 0.17). Increased LVTID only was associated with more frequent ischemia and patients with it tended to be more extensively ischemic, as compared with patients with increased L/H ratio only, but had a similar angiographic extent of CAD. These results were independent of prior myocardial infarction variable. CONCLUSIONS: As compared with patients with increased L/H ratio alone, patients with increased LVTID alone are more frequently ischemic but have a similar angiographic extent of CAD. Increased L/H ratio was correlated to both rest and postexercise LV volume, whereas increased LVTID was correlated only to postexercise LV volume.     

Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET.

The aim of this study was to evaluate, whether PET with (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) may be used to monitor noninvasively the antiproliferative effects of tyrosine kinase inhibitors. METHODS: Using a high-resolution small animal scanner, we measured the effect of the ErbB-selective kinase inhibitor PKI-166 on the (18)F-FDG and (18)F-FLT uptake of ErbB1-overexpressing A431 xenograft tumors. RESULTS: Treatment with PKI-166 markedly lowered tumor (18)F-FLT uptake within 48 h of drug exposure; within 1 wk (18)F-FLT uptake decreased by 79%. (18)F-FLT uptake by the xenografts significantly correlated with the tumor proliferation index as determined by proliferating cell nuclear antigen staining (r = 0.71). Changes in (18)F-FLT uptake did not reflect inhibition of ErbB kinase activity itself but, rather, the effects of kinase inhibition on tumor cell proliferation. Tumor (18)F-FDG uptake generally paralleled the changes seen for (18)F-FLT. However, the baseline signal was significantly lower than that for (18)F-FLT. CONCLUSION: These results indicate that (18)F-FLT PET provides noninvasive, quantitative, and repeatable measurements of tumor cell proliferation during treatment with ErbB kinase inhibitors and provide a rationale for the use this technology in clinical trials of kinase inhibitors.     

Assessment of transient dilation of the left ventricular cavity in patients with hypertrophic cardiomyopathy by exercise thallium-201 scintigraphy

Exercise Tl scintigraphy (EX-Tl) provides a noninvasive means of identifying myocardial perfusion abnormalities in patients (pts) with hypertrophic cardiomyopathy (HCM). We have noted that some pts with HCM have a pattern of transient dilation of the left ventricle (LV) on the immediate post exercise images as compared with 3 hour redistribution images. We presumed that left ventricular dilation was caused by subendocardial hypoperfusion. So we studied transient dilation of the LV in 50 pts with HCM and 20 controls (C). Initial and delayed conventional short tomographic images were obtained after reconstruction of 30 projections acquired over 180 degrees. Thirty six radii every 10 degrees were generated from the center of the middle myocardial images of the short axis. An area surrounded by the thirty six points of maximal count on each radius was calculated in initial and delayed images. Transient Dilation Index (TDI) as an index of dilation was determined by dividing an area in initial image by an area in delayed image. TDI in pts with HCM was larger than that in C. Pts with HCM were classified into the two groups, Group A: TDI greater than 1.11 (mean + 2 SD in C), 24 pts, Group B: TDI greater than 1.11, 26 pts. Frequency of pts with history of chest pain in Group A was higher than that in Group B, and frequency of pts with positive exercise ECG in Group A was higher than that in Group B. End diastolic volume in Group B did not change 10 minutes after exercise by radionuclide ventriculography. In conclusion, transient dilation of the LV in pts with HCM by EX-Tl is in appearance, and may reflect subendocardial ischemia.     

The role of left ventricular hypertrophy and diabetes in the presence of transient ischemic dilation of the left ventricle on myocardial perfusion SPECT images.

Transient ischemic dilation of the left ventricle found on SPECT myocardial perfusion imaging (MPI) is an accepted marker of severe and extensive coronary artery disease (CAD) and poor prognosis. The influence of other clinical variables on the incidence of transient ischemic dilation is less certain. The aim of this study was to investigate clinical factors that may influence the incidence of transient ischemic dilation. In particular, we looked at factors that may independently affect subendocardial perfusion, such as left ventricular hypertrophy (LVH) and diabetes. METHODS: MPI studies of 103 consecutive patients who had undergone recent coronary angiography (< or =6 mo) and transthoracic echocardiography within a year of stress electrocardiography-gated MPI were retrospectively analyzed. Transient ischemic dilation was assessed quantitatively using a software program. A ratio cutoff of > or =1.22 was considered to represent transient ischemic dilation. Summed stress score and summed difference score (ischemia score) were determined using the standard 17-segment 5-point scoring system to quantify myocardial ischemia. LVH was defined as a left ventricular wall thickness of >11 mm on M-mode echocardiography. Severe CAD was defined as severe stenosis (> or =90%) of either the left anterior descending artery or both the right coronary and lateral circumflex arteries. RESULTS: Nineteen (18%) of the 103 patients had transient ischemic dilation, 19 (18%) had LVH, and 23 (22%) were diabetic. A high percentage had severe CAD (46/103 [45%]), whereas 57 of 103 (55%) had less severe CAD (30/103 [29%]) or nonsignificant CAD (26/103 [25%]). Severe CAD (P < 0.001), diabetes (P < 0.0001), LVH (P < 0.003), and the ischemia score (P < 0.023) were independent predictors of transient ischemic dilation by multivariate logistic regression. In patients with severe CAD, the effect of LVH on the incidence of transient ischemic dilation was additive, increasing the incidence from 21% (8/38) without LVH to 75% (6/8) with LVH (P < 0.006). Likewise, with severe CAD, the incidence of transient ischemic dilation rose from 21% (7/33) in patients without diabetes to 54% (7/13) in those with diabetes (P < 0.04). CONCLUSION: The presence of transient ischemic dilation on myocardial perfusion SPECT is associated with the presence of severe CAD, but this association is modified by the presence of LVH and diabetes.     

Monitoring proton therapy with PET

Protons are being used in radiation therapy because of typically better dose conformity and reduced total energy deposited in the patient as compared with photon techniques. Both aspects are related to the finite range of a proton beam. The finite range also allows advanced dose shaping. These benefits can only be fully utilized if the end of range can be predicted accurately in the patient. The prediction of the range in tissue is associated with considerable uncertainties owing to imaging, patient set-up, beam delivery, interfractional changes in patient anatomy and dose calculation. Consequently, a significant range (of the order of several millimetres) is added to the prescribed range in order to ensure tumour coverage. Thus, reducing range uncertainties would allow a reduction of the treatment volume and reduce dose to potential organs at risk.To understand the true uncertainties and to reduce delivery errors, in vivo verification of the delivered dose or range would be highly desirable. The obvious choice is the use of in vivo dosimetry detectors that would allow real-time dose reporting.¹ However, this approach is only feasible for very few indications, such as prostate cancer, where detectors could be placed on the rectal balloon used for immobilization. A more promising approach is the use of imaging methods. To use imaging devices in order to monitor treatment delivery is common practice in photon therapy where each beam penetrates the patient so that the exit dose can be measured. Protons on the other hand stop in the patient, and thus imaging can only be based on secondary radiation that is being created by the primary beam. Various methods have been proposed. For instance, MRI can be used to monitor tissue changes owing to radiation, which could potentially allow dosimetric verification.² The downside of this method is that it cannot be used for online verification because the changes appear days or even months after treatment.The two most promising methods for online verification are based on the fact that protons undergo nuclear interactions in tissue.³ These interactions can lead to photons that are energetic enough to penetrate the patient. For example, nuclei can be left in an excited state, which leads to high-energy (MeV) γ-radiation emitted shortly after the interaction of the primary proton with the nucleus. This radiation is thus called prompt γ-radiation. This method is very promising for the future but is currently not practical because of the lack of appropriate systems to detect these γ-rays with high efficiency and spatial resolution in a clinical setting. Thus, substantial research is still needed before this approach can find its way into clinical practice (see below).The currently more practical approach is the use of positron emission tomography (PET) imaging. The idea to use PET for proton range verification dates back to the 1970s^3,4 but was initially mentioned in pion therapy.⁵ Nuclear interactions of the proton beam in tissue can result in positron-emitting isotopes.⁶ Thus, the acquired PET images are taken without any radiotracers utilizing the activation of the patient by the treatment beam. The positron emitters of main interest are ¹¹C and ¹⁵O with half-lives of approximately 20 and 2 min, respectively. Their β+ decay leads to coincident γ-rays resulting from the annihilation of emitted positrons with electrons, which can be used to reconstruct a three dimensional distribution of positron emitters in the patient. The main purpose is to verify the range of the proton beam and not necessarily the entire dose distribution because the PET activation is not directly correlated to the dose distribution as protons lose their energy mainly via electromagnetic interactions.Because the image reconstructed by a PET camera cannot be directly compared with the dose distribution, a different reference has to be created. For this purpose, Monte Carlo codes that are capable of not only simulating the dose but also the frequency and location of nuclear interactions are used. Such simulations create an expected PET image in the patient that can be compared (in terms of the distal signal fall-off) with the measured and reconstructed image.⁶ The threshold energies in the nuclear interaction cross-sections for the production of β+ isotopes are typically at a few MeV so that the Bragg peak position and the distal dose fall-off appears at a greater depth compared with the fall-off of the PET activity distribution. Nevertheless, the difference in the fall-off position between the simulated and the measured PET distribution resembles the difference in the distal dose fall-off (unless the tissue at the fall-off positions is vastly different between simulation and treatment).Various obstacles limit the accuracy with which range can be verified with this method.⁷ One issue is the accuracy of the Monte Carlo simulation. The relevant cross-sections for isotope production in tissues are not known to sufficient accuracy because of (a) uncertainties in converting CT Hounsfield units into material compositions in tissue⁸ and (b) because experiments at physics laboratories typically focus on thin targets rather than thick targets (i.e. the patient) where a wide proton energy distribution has to be considered.⁹ Furthermore, the simulation results need to be corrected for biological washout because the activity in perfused tissues changes over time.^10,11 Other correction factors consider that the activity is time dependent owing to the half-lives of the isotopes and that the efficiency of the detector system affects the activity distribution.⁸Range verification using PET-based activity measurements has been carried out clinically in various pilot studies. Imaging can be performed either “online”,^12,13 i.e. during the treatment, or “offline”,^10,14,15 i.e. after the treatment has been completed. Measurements performed offline have the advantage that a PET detector is not required in the room but pose the problem of rapid decrease of the signal owing to decay and biological washout. Images taken offline predominantly show activity from radioisotopes whose half-life is longer than the time it takes to transfer the patient to the PET scanner, i.e. it reduces the signal to mainly ¹¹C. Furthermore, patient set-up performed separately for treatment and post-treatment imaging can add an additional source of uncertainty. The main issue with online methods is the background radiation in the treatment room and the potential limited angle coverage. There is also a hybrid approach whereby a PET scanner on wheels can be moved into the treatment room shortly after the treatment has been finished (i.e. within 1–2 min).¹⁶ In order to obtain an image with reasonable statistical resolution, patients have to be scanned for a few minutes which, when online methods are being used, affects the clinical workflow. The different approaches with their pros and cons have been compared in a review.¹⁷Range verification using PET activity is currently at a cross-road. The performance shown clinically so far is typically not sufficient to suggest that a routine clinical use, both offline or online, would add significant benefit. Certainly, clinically relevant information beyond range verification might be extracted, but a range verification accuracy of 1–2 mm has been shown only in favourable locations of patients with head and neck tumours close to bony structures where co-registration of the PET image with CT can be performed very accurately.¹⁰ Generally, only accuracies in range verification of the order of 3–5 mm have been achieved.¹¹Several research approaches are currently under way to improve the accuracy of PET-based range verification. The use of PET/CT instead of PET solutions avoids errors owing to image registration but does add some imaging dose to patients. A mobile PET/CT on wheels has recently been introduced at Massachusetts General Hospital for in-room proton range verification. The addition of dual-energy CT information also has potential to improve the conversion of CT information to the material composition needed for the PET simulations.¹⁸ Furthermore, image resolution could be improved by in-beam time-of-flight PET detectors.¹⁹ Time of flight also offers the possibility of partial ring in-beam PET detectors without artefacts. In-beam detectors are able to collect data earlier, before significant radiological or biological decay. Experiments in animal systems are being conducted to improve the prediction of the biological washout that would allow a more accurate prediction of the PET signal using Monte Carlo simulations.^20,21 Additional experimental data in particular for the ¹⁶O(p,3p3n)¹¹C reaction are required to further reduce the uncertainties in Monte Carlo simulations.²²In summary, PET monitoring of proton therapy remains a promising approach and the only one currently clinically viable and actively explored by several manufacturers in new proton therapy suites. However, currently, the achievable accuracy of PET scanner-based in vivo range verification is still limited to several millimetres owing to the several issues discussed above. Nevertheless, most of these problems can be overcome in ongoing research efforts focusing on high-resolution, high-sensitivity PET that captures the biological washout following treatment. In particular, a kinetic modelling approach is being developed to derive washout-free PET activity production maps using built-in time–activity information contained in dynamic PET data.¹⁹A possible alternative approach for in vivo range verification is using prompt γ-rays. This technique is based on the detection of prompt γ-radiation emitted after nuclear excitation by the proton beam.^23,24 The latter offers distinct advantages compared with PET because of the much higher count rate at production²⁵ and the lack of biological washout. In combination with a high-efficiency detector, the expected count rate could theoretically even allow real-time range verification. Another advantage of PET-based imaging is that the maximum in the nuclear interaction cross-sections leading to prompt γ-rays appears at a lower energy compared with the production of positron emitters. The consequence is that the prompt γ-ray fall-off is closer to the Bragg peak depth compared with the PET activity fall-off.²⁵ There are also many disadvantages of the prompt γ-ray method, such as the absence of a coincidence signal (i.e. it is essentially a single photon emission CT method) and most importantly the absence of a suitable detector at this time. These issues, however, are to a large extent dependent on engineering aspects that can be solved. PET imaging involves biological phenomena that may be more difficult to tackle, although it can also be improved with the development of in-beam dynamic PET imaging.     

Absolute quantitation of left ventricular wall and cavity parameters using ECG-gated PET

BACKGROUND: Electrocardiography (ECG)-gated scintigraphy demonstrates promising results for the simultaneous assessment of myocardial glucose metabolism and contractile function. In this study a method was evaluated for absolute quantitation of left ventricular wall and cavity parameters with the use of fluorine 18 fluorodeoxyglucose (FDG) ECG-gated positron emission tomography (PET). METHODS AND RESULTS: A previously developed 2-dimensional mathematical model was implemented for computer-automated identification of endocardial and pericardial borders. The accuracy and precision were tested in a heart phantom and in healthy subjects. Twelve healthy men aged 64 +/- 8 years were studied by use of cine magnetic resonance imaging (MRI) and ECG-gated FDG-PET during euglycemic glucose-insulin clamp. At increasing image noise levels, the estimated cavity volume of the heart phantom was within 2 mL of the actual volume, and no significant difference was found between actual and estimated wall thicknesses. Endocardial wall motion as assessed by ECG-gated PET in the healthy subjects was systematically underestimated compared with MRI. This underestimation correlated linearly with endocardial excursion during PET end diastole as measured by MRI. Myocardial end-diastolic wall thickness was systematically overestimated by PET, whereas end-systolic thickness deviated less than 1 mm from MRI. Cavity volumes measured by PET correlated linearly with MRI, with a tendency toward an underestimation of end-diastolic cavity volumes by PET. CONCLUSIONS: Absolute measures of cardiac structure and function may be obtained with a reasonable degree of accuracy by use of ECG-gated PET imaging. However, a high ECG-gating frequency appears to be required to obtain measurements comparable to what may be achieved by MRI.     

Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET.

The purpose of this study was to evaluate myocardial electrocardiography (ECG)-gated 13N-ammonia (13N-NH3) PET for the assessment of cardiac end-diastolic volume (EDV), cardiac end-systolic volume (ESV), left ventricular (LV) myocardial mass (LVMM), and LV ejection fraction (LVEF) with gated 18F-FDG PET as a reference method. METHODS: ECG-gated 13N-NH3 and 18F-FDG scans were performed for 27 patients (23 men and 4 women; mean+/-SD age, 55+/-15 y) for the evaluation of myocardial perfusion and viability. For both 13N-NH3 and 18F-FDG studies, a model-based image analysis tool was used to estimate endocardial and epicardial borders of the left ventricle on a set of short-axis images and to calculate values for EDV, ESV, LVEF, and LVMM. RESULTS: The LV volumes determined by 13N-NH3 and 18F-FDG were 108+/-60 mL and 106+/-63 mL for ESV and 175+/-71 mL and 169+/-73 mL for EDV, respectively. The LVEFs determined by 13N-NH3 and 18F-FDG were 42%+/-13% and 41%+/-13%, respectively. The LVMMs determined by 13N-NH3 and 18F-FDG were 179+/-40 g and 183+/-43 g, respectively. All P values were not significant, as determined by paired t tests. A significant correlation was observed between 13N-NH3 imaging and 18F-FDG imaging for the calculation of ESV (r=0.97, SEE=14.1, P<0.0001), EDV (r=0.98, SEE=15.4, P<0.0001), LVEF (r=0.9, SEE=5.6, P<0.0001), and LVMM (r=0.93, SEE=15.5, P<0.0001). CONCLUSION: Model-based analysis of ECG-gated 13N-NH3 PET images is accurate in determining LV volumes, LVMM, and LVEF. Therefore, ECG-gated 13N-NH3 can be used for the simultaneous assessment of myocardial perfusion, LV geometry, and contractile function.     

Non-invasive measurement of stroke volume and left ventricular ejection fraction. Radionuclide cardiography compared with left ventricular cardioangiography

The stroke volume (SV) was determined by first passage radionuclide cardiography and the left ventricular ejection fraction (LVEF) by multigated radionuclide cardiography in 20 patients with ischemic heart disease. The results were evaluated against those obtained by the invasive dye dilution or thermodilution and left ventricular cardioangiographic techniques. In a paired comparison the mean difference between the invasive and radionuclide SV was -1 ml (SED 3.1) with a correlation coefficient of 0.83 (p less than 0.01). Radionuclide LVEF values also correlated well with cardioangiographic measurements, r = 0.93 (p less than 0.001). LVEF determined by multigated radionuclide cardiography was, however, significantly lower than when measured by cardioangiography, the mean difference being 6 per cent (p less than 0.001). These findings suggest that radionuclide determinations of SV and LVEF are reliable. The discrepancy between the non-invasive and invasive LVEF values raises the question, whether LVEF is overestimated by cardioangiography or underestimated by radionuclide cardiography.     

Right and left ventricular uptake with Rb-82 PET myocardial perfusion imaging: Markers of left main or 3 vessel disease

Background

Relative myocardial perfusion imaging may underestimate severity of coronary disease (CAD), particularly in cases of balanced ischemia. Can quantification of peak left (LV) and right (RV) ventricular Rb-82 uptake measurements identify patients with left main or 3 vessel disease?

Methods

Patients (N = 169) who underwent Rb-82 PET MPI and coronary angiography were categorized as having no significant coronary stenosis (n = 60), 1 or 2 vessel disease (n = 81), or left main disease/3 vessel disease (n = 28), based on angiography. Maximal LV and RV ventricular myocardial Rb-82 uptake was measured during stress and rest.

Results

Failure to augment LV uptake by ≥ 8500 Bq/cc at stress, predicted left main or 3 vessel disease with a sensitivity of 93% and specificity of 61% (area under curve = 0.83). A ≥10% increase in RV: LV uptake ratios with stress over rest was 93% specific (area under curve = 0.74) for left main or 3 vessel disease. These indices incrementally predicted left main or 3 vessel disease compared to models including age, gender, cardiac risk factors, and summed stress and difference scores.

Conclusion

Quantifying maximal rest and stress LV and RV uptake with PET myocardial perfusion imaging may independently and incrementally identify patients with left main or 3 vessel disease.

     

18F-FDG PET心肌代谢显像对左心室室壁瘤患者长期预后的价值

目的 评估18F-脱氧葡萄糖(FDG)PET心肌代谢显像对左心室室壁瘤患者长期预后的价值.方法 对70例左心室室壁瘤患者[超声心动图示左心室射血分数(LVEF)为(36±8)%]行99Tcm-甲氧基异丁基异腈(MIBI)SPECT心肌灌注显像和18F-FDG PET心肌代谢显像,对经冠状动脉造影确诊的左心室室壁瘤患者进行随访,计算室壁瘤部位、非室壁瘤部位以及左心室心肌灌注和代谢积分,以及灌注-代谢不匹配分(MMS).MMS≥2.0为心肌存活.室壁瘤部位心肌不存活者中,药物治疗为组1,手术治疗为组2;室壁瘤部位心肌存活者中,药物治疗为组3,手术治疗为组4.心源性死亡和心脏事件为随访终点.以Kaplan-Meier方法获得生存曲线,并用Log-rank法比较率的差异.结果 组1至组4患者例数分别为14,23,10和23例.随访1～105(72±32)个月,16例患者发生心源性死亡.组3的心源性年死亡率为11.6%,高于组4的1.5%(X2=12.87,P<0.0001),也高于组1的4.8%(X2=4.13,P<0.05)和组2的2.2%(χ2=10.46,P=0.001).Cox回归多因素分析显示室壁瘤部位的MMS[风险比(HR)1.40,95%可信区间(CI)为1.11～1.75,P=0.003]和血运重建术(HR 0.35,95%CI为0.18～0.69,P=0.002)是预测心源性死亡的独立危险因子.结论 18F-FDG PET心肌代谢显像和99Tcm-MIBI SPECT心肌灌注显像对于室壁瘤患者的治疗方案制定及长期预后估测有重要意义.     

射血分数保留的心力衰竭左心室舒张功能的影像学评价

射血分数保留的心力衰竭发病率在逐年上升。准确测量左室舒张功能有利于对该病的临床评价。目前可采用超声心动图、心脏MRI(CMRI)及其他多种检查方法评价左室舒张功能,并对舒张功能的病生理机制、舒张功能障碍分级有提示作用。其中CMRI技术的作用日益突出,包括舒张期容积-时间曲线、二尖瓣血流与肺静脉血流成像、心肌标记及其他CMRI技术。     

Transient left ventricular dilation at quantitative stress-rest sestamibi tomography: Clinical, electrocardiographic, and angiographic correlates

BACKGROUND: Few data are available regarding the incidence and significance of transient left ventricular (LV) dilation on stress sestamibi single photon emission computed tomography (SPECT), which is different from thallium-201 studies because images are acquired late after tracer injection. METHODS: We studied 234 patients with ischemic heart disease and interpretable electrocardiograms undergoing stress-rest sestamibi SPECT on separate days. Sestamibi uptake defect extent was quantified on SPECT polar maps. Epicardial and endocardial transient dilation indexes (TDI) were also calculated. RESULTS: According to our normal TDI values, 148 patients (63%) had no dilation and 86 patients (37%) had abnormal endocardial TDI; a global LV dilation (abnormal endocardial and epicardial TDI) was observed in 19 patients (8%). ST-segment depression was more frequent in patients with transient LV dilation (55%) than in those without (36%; P < .01), as were the extent of stress hypoperfusion (13% +/- 12% vs 6% +/- 7% in patients with no dilation; P < .001) and the angiographic severity score (11.4 +/- 5.9 vs 9.2 +/- 3.7; P < .05). At multivariate analysis, stress hypoperfusion was the sole predictor of transient LV dilation. CONCLUSIONS: Transient LV cavity dilation is frequent on stress sestamibi SPECT. Ventricular cavity dilation is more common than global dilation and suggests subendocardial ischemia. It is related to a greater amount of jeopardized myocardium and is strongly associated with electro-cardiographic signs of ischemia.