The influence of glucose on the myocardial time-activity curve during 17-iodo-123 heptadecanoic acid scintigraphy

The lipid pools of the heart (i.e. the triglyceride and phospholipid pool) participate in the free fatty acid metabolism. The degree of involvement, for instance will be determined by the available substrate in the blood. Scintigraphy with 17-iodo-123 heptadecanoic acid was performed to study free fatty acid kinetics in the normal human myocardium during control and glucose infusion (n = 9). In both situations the derived time-activity curves, measured during a period of 75 min, obeyed a monoexponential plus a constant curve fitting [A(t) = A(o)exp(-tln2/T1/2)+C]. During glucose infusion the half-time values did not change but the lipid storage increased in favour of the oxidation pool. In the three protocols used, hypoglycaemic responses were observed, therefore these protocols cannot be advocated.     

Effect of doxorubicin on [omega-I-131]heptadecanoic acid myocardial scintigraphy and echocardiography in dogs

The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega-I-131]heptadecanoic acid (I-131 HA), and on global left-ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin-treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg/kg. A significant increase in the myocardial t1/2 of the I-131 HA was observed only at a higher cumulative dose, 10 mg/kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I-131 HA are not the initiating factor in doxorubicin cardiotoxicity.     

Measurement of myocardial fatty acid metabolism: kinetics of iodine-123 heptadecanoic acid in normal dog hearts

To define the potential of iodine-123 heptadecanoic acid (IHA) for the noninvasive assessment of myocardial fatty acid metabolism with gamma camera imaging, the influence of myocardial oxygen consumption (MVO2) and blood flow (MBF) on extraction and half-times of IHA were investigated in dogs. Following IHA injection into the left circumflex coronary artery, extraction fraction and half-times were derived from the peak and slope of the IHA time activity curve, which consisted of a vascular, early, and late phase. Single-pass extraction fraction of IHA averaged 0.53 +/- 0.11 s.d. at control and was not influenced by MVO2 and MBF. The half-time of the early phase (T = 9.3 min +/- 2.8 s.d. in controls) as well as the ratio between the size of the early and late phase increased with MVO2 (r = 0.82, r = 0.87, respectively). Thus, early phase intracellular turnover of IHA increased, yet clearance of 123I activity was slowed by augmented cardiac work. Preliminary data of HPLC and electrophoretic analysis of myocardial arterial and venous blood samples over time indicate that the early phase is characterized by a decreasing washout of IHA and a relative increase of radioiodine washout. The half-time of the late phase (T = 245 min +/- 156 s.d. at control) was not related to MVO2 and MBF. In conclusion, myocardial fatty acid metabolism cannot be measured from the half-time of the early phase but might be analyzed from the ratio between the size of the early and late phase when using IHA.     

Clinical value of phase and amplitude images and left ventricle time-activity curves in assessing patients with acute myocardial infarction

The purpose of this study was to assess the clinical usefulness of phase and amplitude images and of the left ventricle time-activity curve (LVTAC) obtained by equilibrium gated radionuclide ventriculography (EGRV) in patients with acute myocardial infarction (AMI).Fifty-six patients were studied within 4 days of the onset of AMI by EGRV; of these 49 also underwent first-pass (FP) angiocardiography, for comparison with EGRV, and 21 underwent repeated EGRV 3 months after AMI. Phase and amplitude images were obtained by Fourier analysis. LVTAC analysis was performed by a third degree polynomial fitting to determine peak ejection rate (PER) and peak filling rate (PFR).A substantial equivalence of EGRV and FP methods was demonstrated, as regards left ventricle ejection fraction (LVEF), while a sharp superiority of EGRV with Fourier analysis was shown with regard to the sensitivity of RWM abnormality detection. With only one exception all the cases showed RWM abnormalities, while LVEF was normal in 21 of 27 patients with less than three affected segments. The most sensitive global function index was the LVPFR. In the acute phase regional dyskinesis was observed in 14 of 56 patients.About 40% of our cases showed an improvement of the kinetic abnormalities 3 months after AMI. The highest rate of improvement was observed in the group with ECG patterns of limited infarction and with normal LVEF.     

Fatty acid myocardial imaging using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP): comparison of myocardial perfusion and fatty acid utilization in canine myocardial infarction (occlusion and reperfusion model)

To evaluate the relationship between myocardial perfusion and fatty acid metabolism in canine myocardial infarction, 16 dogs were studied using thallium and 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP). Eight dogs (group A) had left anterior coronary arterial occlusion (6 h ligation), 6 dogs (group B) had reperfusion (3 h ligation and 1 h reperfusion) and 2 dogs served as the normal control. Myocardial imaging with BMIPP was excellent, owing to its higher uptake and longer retention in myocardium and rapid blood disappearance in addition to diminished liver and lung uptake. The mean half time value which was generated from the BMIPP myocardial washout curve, was significantly larger in the reperfused myocardium. The gamma camera imaging showed uncoupling of BMIPP and thallium (BMIPP uptake greater than thallium uptake) in five dogs in group B. On the other hand, all dogs in group A had a persistent defect in BMIPP and thallium uptake. Our findings indicate that the combination of BMIPP and thallium for myocardial imaging supply different information about the zone of infarction and ischemia, which may be useful for the assessment of myocardial viability.     

Dual tracer autoradiographic study of beta-methyl-(1-14C) heptadecanoic acid and 15-p-(131I)-iodophenyl-beta-methylpentadecanoic acid in normotensive and hypertensive rats

The myocardial distribution of 15-p-[131I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMPDA) and 1[14C]-3-(R,S)-methylheptadecanoic acid (BMHDA) was compared in normotensive and hypertensive rats using quantitative dual tracer autoradiographic techniques. The myocardial distribution of carbon-14 [14C] BMHDA and iodine-131 [131I] BMPDA was nearly homogeneous in the normotensive rats, while both tracers showed similar, though very heterogeneous, distribution in hypertensive hearts with decreased uptake in the endocardial region. Our data demonstrate that myocardial distribution of [131I]BMPDA was essentially the same as [14C]BMHDA, and thus single photon emission computed tomographic imaging with 123I-labeled BMPDA could be useful for the detection of regional changes of myocardial fatty acid uptake in patients with prolonged and severe hypertension.     

Comparison of open- and closed-chest canine model for quantification of coronary stenosis severity by myocardial contrast echocardiography

RATIONALE AND OBJECTIVES: The objective of the present study was to compare the data regarding the ability of real-time myocardial contrast echocardiography (MCE) to assess altered myocardial blood flow produced by graded coronary stenoses between open- and closed-chest canine models. MATERIALS AND METHODS: Three grades of left anterior descending coronary artery stenosis and occlusion were created in 6 open- and 6 closed-chest canine models. MCE used FS-069 infusion and real-time imaging. Myocardial signal intensity versus time plots were fitted to a 1-exponential function to obtain the peak signal intensity (A) and rate of signal intensity rise (b) for quantification of myocardial blood flow. RESULTS: The value of b obtained from closed-chest canine models (without stenosis = 0.995 +/- 0.087, mild stenosis = 0.968 +/- 0.076, moderate stenosis = 0.569 +/- 0.077, severe stenosis = 0.288 +/- 0.032, occlusion = 0.085 +/- 0.031) was not significantly different from that obtained from open-chest canine models (without stenosis = 1.028 +/- 0.107, mild stenosis = 0.998 +/- 0.098, moderate stenosis = 0.601 +/- 0.055, severe stenosis = 0.321 +/- 0.029, occlusion = 0.079 +/- 0.028) at any grade of stenosis (P = 0.09, 0.08, 0.44, 0.11, 0.74, respectively). CONCLUSIONS: In myocardial regions where attenuation of the ultrasound beam and artifacts produced by the chest wall are minimal, the data from transthoracic MCE in the closed-chest model may show values similar to those from MCE in the open-chest model.     

Prognostic validation of an algorithm to convert myocardial perfusion SPECT imaging data from a 12-segment model to a 17-segment model

Background  A 17-segment model has become the standard for interpreting myocardial perfusion single-photon emission computed tomography (SPECT). Methods for converting pre-existing databases from 12-segment models to the 17-segment model are needed for ongoing prognostic studies. Methods and Results  To develop the conversion algorithm, 150 consecutive SPECT studies (82 abnormal) were read by both a 12-segment and the standard 17-segment models. Summed stress scores (SSSs) were calculated from a 17-segment model derived from the 12-segment data and compared to those of the standard 17-segment model. The effect of the conversion algorithm on prognostic data derived from the 12-segment model was evaluated in 25,876 patients from the Duke Nuclear Cardiology Database, including a sample of 3,205 patients with known covariates for adjusted analysis. The derived 17-segment SSS from the 12-segment model was highly correlated (R = 0.99) to the SSS from the standard 17-segment model. In both unadjusted and adjusted analysis, there was no difference in the prognostic information. Conclusions  An algorithm for conversion of 12-segment perfusion scores to 17-segment scores has been developed which is highly correlated to visual interpretation by the 17-segment model with nearly identical prognostic information.     

The determination of myocardial viability using Gd-DTPA in a canine model of acute myocardial ischemia and reperfusion

The partition coefficient of Gd-DTPA was thought to vary with the amount of cellular membrane damage after an acute myocardial infarction. The relationship between the partition coefficient of Gd-DTPA (λ) and the uptake of ²⁰¹TI (as a marker of tissue viability) was studied 2 h to 3 weeks after reperfusion of a 2-h occlusion to the left anterior descending coronary artery in a canine model. Gd-DTPA was infused as a bolus followed by a prolonged constant infusion, and this infusion protocol was optimized such that the concentration of Gd-DTPA was directly related to λ. After this infusion, MR images of excised hearts showed regions of increased signal intensity corresponding to increased Gd-DTPA concentration. At all time points, λ and ²⁰¹TI uptake were strongly negatively correlated indicating that λ is an accurate indicator of myocardial viability. Furthermore, λ in the infarcted regions was increased relative to normal regions after 2 h of reperfusion and stayed elevated up to 3 weeks. At all time points, λ in the infarcted and normal regions were significantly different. As well, this data showed a trend that λ in infarcted regions decreased monotonically from 1 day to 3 weeks. This trend was confirmed with MR imaging by examining the change in signal intensity of in vivo images from 4 days to 3 weeks in two animals. These results suggest that MRI with Gd-DTPA could be used to measure the extent of myocardial damage after an acute myocardial infarction.     

Comparison of hot contrast material and hot saline for renal ablation in a canine model

Renal ablation was performed in eight dogs with either 76% diatrizoate for normal saline. Both fluids were heated to 100 degrees C before injection. Coagulation necrosis and tubular atrophy were seen with both agents, indicating that much of the effectiveness of hot contrast material is due to heat. Diatrizoate also caused glomerular sclerosis, probably due to its inherent nephrotoxicity. Hot diatrizoate is probably more effective for renal ablation, but may not have an advantage over hot normal saline outside the kidney. Because of the risk of infection, prophylactic antibiotics are advised when renal ablation is performed with hot fluids.     

Comparison study of intraarticular and intravenous gadolinium-enhanced magnetic resonance imaging of cartilage in a canine model

Background: Magnetic resonance (MR) imaging and measurement of glycosaminoglycan (GAG) have potential for characterization of hyaline articular cartilage. Recently, some reports have demonstrated the potential of direct administration of contrast media for MR imaging of cartilage.

Purpose: To prove the feasibility of intraarticular gadolinium-enhanced MR imaging of cartilage (iGEMRIC) and T1 relaxation mapping of the articular cartilage in vivo with intraarticular injection of Gd-DTPA^2-.

Material and Methods: Five healthy beagle dogs underwent MR imaging and T1 relaxation mapping of the knee joints of both hind legs. The delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) and iGEMRIC techniques were interchanged with MR imaging. For dGEMRIC, a double routine dose of Gd-DTPA^2- (0.2 mM/kg) was administered intravenously. For iGEMRIC, 2.5 and 1.25 mmol/l saline-diluted Gd-DTPA^2- solutions were separately injected into the right and left knee joints, respectively, prior to MR imaging. Color-coded T1 maps of 20 femoral condyles were obtained from the dGEMRIC and iGEMRIC images. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and glycosaminoglycan (GAG) delineation of articular cartilage were compared between the dGEMRIC and iGEMRIC techniques.

Results: The mean SNR was higher with dGEMRIC than with iGEMRIC, but the difference was not statistically significant (P = 0.174). The mean (±SD) CNR was higher with iGEMRIC (-11.6±3.4) than with dGEMRIC (-16.7±4.0; P = 0.000), although the absolute value of the CNR was higher with dGEMRIC. The layering and gradient distribution of GAG were more clearly visualized on the iGEMRIC images. The mean scores of GAG delineation with dGEMRIC and iGEMRIC were 0.7±0.6 and 2.2±1.7, respectively. The iGEMRIC method better visualized GAG distribution (P = 0.001).

Conclusion: Although the SNR did not differ significantly between the iGEMRIC and dGEMRIC techniques, the color-coded T1 map produced with iGEMRIC allowed better cartilage evaluation. Thus, iGEMRIC exhibits the useful features of both MR arthrography and dGEMRIC, and provides a color-coded T1 map that is useful for diagnosing early articular cartilage damage.     

Tracer kinetics of 15-(ortho-123/131I-phenyl)-pentadecanoic acid (oPPA) and 15-(para-123/131I-phenyl)-pentadecanoic acid (pPPA) in animals and man

The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta-oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double-labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle.     

Significance of myocardial uptake of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid: Comparison with kinetics of carbon 11-labeled palmitate in positron emission tomography

Background

A radioactively labeled beta-methyl branched fatty acid analog,¹²³I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP), has been developed to probe regional myocardial fatty acid metabolism. However, the significance of BMIPP uptake in the myocardium remains unclear.

Methods and Results

To evaluate the significance of BMIPP uptake, single-photon emission computed tomography was performed 30 minutes after injection of BMIPP, and²⁰¹Tl-labeled single-photon emission computed tomography was taken on a separate day in 10 patients. Findings of BMIPP and²⁰¹Tl-labeled imaging were compared with the data obtained from positron emission tomography with¹¹C-labeled palmitate. The BMIPP uptake (percent of maximum) was significantly correlated with the early uptake (percent) and delayed uptake (percent) of¹¹C-labeled palmitate (r=0.659 andr=0.687, respectively) (p<0.01 each), whereas it was not significantly correlated with the residual fraction (r=0.205) or the clearance half-time of the early component (r=0.138) of¹¹C-labeled palmitate as a marker of β-oxidation of the fatty acid.

Conclusions

These data indicate that, although the myocardial uptake of BMIPP may not directly reflect β-oxidation of fatty acids, its uptake may reflect both regional myocardial blood flow and fatty acid extraction.     

双源CT心肌灌注碘成像与核素心肌灌注显像诊断犬急性心肌梗死的研究

目的 评价双源CT(DSCT)心肌灌注碘成像诊断犬实验性急性心肌梗死的可行性和准确性.方法 6只犬开胸结扎冠状动脉左前降支(LAD)建立心肌梗死模型,另3只仅开胸而不结扎LAD作为对照组,分别于术前及术后3 h行DSCT心肌灌注碘成像扫描,然后行99Tcm-甲氧基异丁异腈(MIBI)SPECT静息态心肌灌注检查.检查结...     

Comparison of FAIR perfusion kinetics with DSC-MRI and functional histology in a model of transient ischemia.

Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive method for perfusion imaging. It has been shown that the FAIR signal may depend on hemodynamic parameters other than perfusion, the most important one being transit delays of labeled spins to the observed tissue. These parameters are expected to change with ischemia. The goal of this study was to assess the effect of these changes on the interpretation of FAIR results in the case of altered perfusion. This was investigated in a rat model of transient cerebral ischemia. It was shown that the ratio of FAIR signal in the infarct compared to the contralateral side was lower at short inflow times, which suggests that transit times affected the effective FAIR signal. The FAIR results were compared with those from functional histology and dynamic susceptibility contrast MRI, and the findings indicated that the altered kinetics of the FAIR signal were related to reduced and delayed inflow in the infarct region--not to a decrease in the number of functional vessels.     

Assessment of myocardial function and perfusion in a canine model of non-occlusive coronary artery stenosis using fast magnetic resonance imaging

Magnetic resonance (MR) functional and perfusion imaging were employed in a canine model of coronary artery stenosis (n = 6) for the quantification of functional and perfusion deficits before and after dipyridamole administration. Left anterior descending and circumflex (LCX) coronary blood flow were measured continuously after placing Doppler flowmeters. Inversion recovery gradient echo images during the transit of MR contrast medium gadolinium-benzyloxypropionictetraacetate dimeglumine (Gd-BOPTA/Dimeg) and fast breath-hold cine MR images were acquired at baseline, during LCX stenosis in basal state, and during LCX stenosis with vasodilation (dipyridamole 0.5 mg/kg). The extent of the functional defect and perfusion defect was expressed as percent of left ventricle (LV) circumference. During stenosis (LCX flow: 62.6 +/- 5.6% of baseline) the extent of the functional defect was slightly larger than the perfusion defect (11.0 +/- 1.8% versus 6.3 +/- 1.70% of LV circumference, respectively; P < 0.01). During vasodilation the extent of the functional defect was considerably smaller than the perfusion defect (25.3 +/- 2.5% versus 35.3 +/- 3.5%; P < 0.01). Thus, the sizes of ischemic regions displayed by MR perfusion defect and functional defect differ from each other.     

Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart

Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.     

Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart

Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two ¹²⁵I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue: albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.     

Assessment of myocardial oxygen extraction fraction and perfusion reserve with BOLD imaging in a canine model with coronary artery stenosis

PURPOSE: To determine the feasibility of T2-weighted BOLD imaging for estimating regional myocardial oxygen extraction fraction (OEF) and approximating perfusion reserve (MPR) simultaneously in a canine model with moderate coronary artery stenosis. MATERIALS AND METHODS: Eight mongrel dogs with moderate coronary artery stenosis underwent BOLD imaging at rest and during dipyridamole-induced hyperemia, using a turbo spin echo (TSE) sequence. Based on a two-compartment model, myocardial OEF(hyperemia) was calculated with the corresponding T2. MPR could be approximated based on Fick's law. RESULTS: During responsive hyperemia, a regional hypointensity was observed in the abnormally perfused myocardium, reflecting a relatively smaller myocardial T2 increase (3.06% +/- 2.74%, in contrast to 10.19% +/- 4.12% in the normal region). The average OEFs in the normally and abnormally perfused myocardial territories were 0.21 +/- 0.11 and 0.43 +/- 0.12, respectively. For the MPR approximated from the BOLD imaging, a strong correlation (R = 0.9) in the normal myocardium and a good correlation (R = 0.6) distal to the stenosis were obtained compared to microsphere results. CONCLUSION: In a canine model with moderate coronary artery stenosis, TSE-based BOLD imaging can quantitatively estimate the regional OEF(hyperemia) and approximate the MPR, and can distinguish segments perfused by defected coronary artery.