Serial evaluation of fatty acid metabolism in rats with myocardial infarction by pinhole SPECT

BACKGROUND: Iodine 123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is mainly trapped in the myocardium as triglyceride, depending on the adenosine triphosphate level. Ten percent to 20% of it is metabolized through alpha-oxidation after beta-oxidation; however, the precise mechanism of the regulatory pathways of BMIPP is yet to be clarified. METHODS AND RESULTS: A brief left coronary artery occlusion (10-30 minutes) was performed in 28 male Wistar-Kyoto rats. Dual single photon emission computed tomography images of BMIPP and thallium 201 were obtained 3 days and 24 days after the operation. The activities of 3-hydroxyacyl-coenzyme A dehydrogenase (HAD), citrate synthase (CS), and alpha-glycerol-phosphate dehydrogenase (GPD) were then measured in both ischemic and nonischemic regions. BMIPP and Tl-201 chloride severity scores were also evaluated conventionally. CS and HAD levels were significantly lower in the ischemic region than in the nonischemic region in the chronic group (CS, 102.9 +/- 28.1 vs 138.7 +/- 33.7 micromol/g/min, respectively, P =.0051; HAD, 54.7 +/- 20.1 vs 78.6 +/- 18.7 micromol/g/min, respectively, P =.0031). There was no difference in GPD between the ischemic and nonischemic regions. The BMIPP severity score had closer inverse relations with HAD (acute, r = -0.82; chronic, r = -0.80) and CS (acute, r = -0.87; chronic, r = -0.81), but not with GPD, than did Tl-201 chloride severity score. CONCLUSIONS: BMIPP imaging correlates well with the activities of HAD and CS, suggesting that a decrease in BMIPP uptake reflects deterioration of both fatty acid metabolism and citrate cycle and shows information other than regional myocardial perfusion.     

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.     

Serial investigation of perfusion disturbances and vasogenic oedema in hypertensive encephalopathy by diffusion and perfusion weighted imaging

Serial MRI including diffusion and perfusion imaging was performed in a patient with hypertensive encephalopathy. At admission, the patient was disorientated and presented with seizures and cortical blindness. Perfusion imaging showed a marked reduction in blood volume and flow, with corresponding vasogenic oedema in the occipital, posterior temporal, and, to a lesser extent, frontal lobes. The clinical symptoms disappeared rapidly following treatment, whereas the disturbed circulation pattern and vasogenic oedema resolved more slowly. A complete normalisation was seen after 1 year.     

Prognostic value of fatty acid imaging in patients with angina pectoris without prior myocardial infarction: comparison with stress thallium imaging

A fatty acid analogue, ¹²³I-labelled -methyl iodophenyl pentadecanoic acid (BMIPP), has been used to identify ischaemic and metabolically impaired myocardium. However, the prognostic value of BMIPP imaging, particularly in relation to stress myocardial perfusion imaging, remains unclear. Data from 167 consecutive patients with angina pectoris but without prior myocardial infarction (MI) who had undergone both BMIPP and stress ²⁰¹Tl (sTL) imaging were analysed. Tracer uptake was graded using a 13-segment, 4-point scoring model. Patients were followed up for 48 months with primary end points (cardiac death, non-fatal MI) as hard cardiac events and with secondary end points (late revascularisation, recurrent angina and heart failure) as soft events. For overall cardiac events (5 hard and 29 soft events), Kaplan-Meier analysis revealed significantly lower event rates in subgroups with normal BMIPP uptake, a summed difference score of sTL (SDS) of <3 or absence of diabetes mellitus when compared to each counterpart. Multivariate Coxs analysis revealed reduced BMIPP uptake, SDS 3, diabetes and reduced ejection fraction to be significant predictors. Negative predictive values of normal BMIPP and SDS <3 for all events were 91% and 84%, respectively. No hard event occurred in 66 patients with normal BMIPP uptake, whereas two patients with SDS <3 but impaired BMIPP uptake had hard events. In conclusion, normal BMIPP imaging is an excellent prognostic sign, independently of stress myocardial perfusion imaging, in patients with angina pectoris without prior MI.     

糜酶介导自发性高血压大鼠心肌纤维化的作用机制

目的:观察糜酶对自发性高血压大鼠(SHR)心肌纤维化的影响及作用机制。方法:采用RT-PCR检测心肌组织Ⅰ、Ⅲ型胶原和糜酶mRNA表达,Western blot检测转化生长因子β1(TGF-β1)和过氧化酶体增殖物激活受体α(PPARα)蛋白表达。结果:SHR组和糜酶抑制剂(CHI)组Ⅰ、Ⅲ型胶原mRNA、TGF-β1蛋白高于对照组,PPARα蛋白低于对照组(P<0.01,P<0.05)。SHR组糜酶mRNA高于对照组(P<0.01)。结论:糜酶参与心肌纤维化,其机制与TGF-β1蛋白上调、PPARα蛋白下调有关。     

Serial assessment of myocardial infarction by using gated MR imaging and Gd-DTPA

In order to assess the usefulness of Gd-DTPA in the evaluation of myocardial infarction, 17 patients were examined with gated MR imaging. Scans were made by using a spin-echo pulse sequence before and after IV administration of 0.15 mmol/kg of Gd-DTPA. The images were made at four intervals (average of 5, 12, 30, and 90 days) after the onset of the infarction. Gd-DTPA uptake at the infarcted area was graded as marked, moderate, or no increase in signal intensity by visual inspection. At these four time intervals, an area of increased signal intensity in the infarcted myocardium was detected on T1-weighted images after administration of Gd-DTPA in 14 (82%) of 17 cases, 16 (94%) of 17 cases, six (38%) of 16 cases, and three (21%) of 14 cases, respectively. Markedly increased signal intensity in infarcted areas was shown on T1-weighted images with Gd-DTPA at 5 and 12 days. The ratio of gadolinium uptake in the infarcted area to that in normal myocardium also was evaluated. At 5 and 12 days, the mean increase in signal intensity in the infarcted area was significantly higher than that in a normal area, but not at 30 and 90 days. Increased signal intensity also was apparent on T2-weighted images without Gd-DTPA at 5 and 12 days; however, the use of late echo reduced the signal-to-noise ratio, leading to image degradation. Uptake of Gd-DTPA was a positive marker in acute myocardial infarction, but no significant uptake of Gd-DTPA occurred in chronic myocardial infarction.     

Echo-planar magnetic resonance myocardial perfusion imaging: parametric map analysis and comparison with thallium SPECT

Magnetic resonance (MR) perfusion FLASH imaging has been used for assessing coronary artery disease (CAD). Echo-planar MR techniques have advantages in speed and in making MR perfusion imaging results more clinically accessible through parametric maps, but have not been previously assessed. We implemented a spin-echo, echo-planar MR technique and applied it at rest and during adenosine stress in 26 patients with CAD and abnormal thallium single-photon-emission computed tomography (SPECT), and analyzed the results by using a newly developed parametric map analysis of time to peak, peak intensity, and slope of contrast washin. The results were compared with the results of conventional visual analysis of the perfusion cine series. For detecting abnormal coronary territories, MR and SPECT were comparable for sensitivity, specificity, and accuracy (thallium, 70%, 78%, and 73%; MR, 79% 83%, and 80%; P = NS). There was good agreement between thallium and MR during stress (kappa = 0.49), but defects were larger by MR (2.4 vs. 3.1 segments for slope; P < 0.01). Additional segments were detected at rest by MR (58 for slope vs. 25 for thallium), which correlated with areas that became abnormal with stress in the thallium (sensitivity, 100%; specificity, 63%). The parametric maps were easier and faster to interpret than review of the original first-pass series of images (chi2 = 10.8; P < 0.04). The diagnostic performance of echo-planar perfusion MR and SPECT was similar, and combining the results with parametric mapping was useful for interpretation and considerably improved data display for clinical interpretation. MR, however, was faster and yielded images of higher resolution with no radiation burden. In multislice mode, these new MR techniques may have clinical value.     

Detection of acute myocardial infarction in spontaneously hypertensive rats by 99mTc-pyrrolidino methyl tetracycline

The myocardial infarct induced by isoproterenol in spontaneously hypertensive rats accumulates higher activities of 99mTc-PM tetracycline compared with the cardiac infarct in normotensive rats caused by the same method. The isoproterenol model of the myocardial necrosis was induced in intact rats without opening the thorax and is a convenient method for experimental radioisotope studies.     

Detection of acute myocardial infarction in spontaneously hypertensive rats by 99mTc-pyrrolidino methyl tetracycline

The myocardial infarct induced by isoproternol in spontaneously hypertensive rats accumulates higher activities of ^99mTc-PM tetracycline compared with the cardiac infarct in normotensive rats caused by the same method. The isoproterenol model of the myocardial necrosis was induced in intact rats without opening the thorax and is a convenient method for experimental radioisotope studies.     

Radionuclide assessment of myocardial fatty acid metabolism by PET and SPECT

Although fatty acid is a major energy source in the normal myocardium, fatty acid oxidation is easily suppressed in a variety of cardiac disorders. Therefore assessment of fatty acid metabolism may hold an important role for early detection of myocardial abnormalities and provide insights into cardiac pathologic states. C-11 palmitate is a well-established PET tracer to probe myocardial fatty acid metabolism. On the other hand, a variety of iodinated fatty acid compounds have been introduced for assessment of fatty acid metabolism with conventional gamma cameras. These include straight-chain, such as iodopheyl pentadecanoic acid (IPPA), and branch-chain fatty acid compounds, such as beta-methyl iodopheyl pentadecanoic acid (BMIPP). This review article includes the characterization of these tracers and clinical experiences with these tracers for detection and characterizing patients with ischemic heart disease and cardiomyopathy.     

定量门控心肌显像评价局部室壁运动

目的　探讨定量门控99Tcm 甲氧基异丁基异腈 (MIBI)、2 0 1 Tl和99Tcm tetrofosmin心肌显像评价局部室壁运动的可靠性。方法　对 30 1例左室功能受检者行门控99Tcm MIBI(n =15 8)、2 0 1 Tl(n =113)和99Tcm tetrofosmin(n=30 )心肌显像 ,采用QGSPECT程序评价左室总体和各区域局部室壁运动。并与二维超声心动图进行比较。结果　①左室总体局部室壁运动 :定量门控99Tcm MIBI心肌显像评价室壁运动与超声心动图的结果基本符合 (Kappa =0 6 3,P <0 0 1) ,定量门控2 0 1 Tl(Kappa =0 5 2 ,P <0 0 1)和99Tcm tetrofosmin(Kappa =0 5 4 ,P <0 0 1)心肌显像评价室壁运动与超声心动图的结果中等符合。②左室各区域局部室壁运动 :定量门控99Tcm MIBI和99Tcm tetrofosmin心肌显像能较准确评价左室前壁、前侧壁、后侧壁、下壁、前间壁、后间壁和后壁局部室壁运动 (Kappa =0 4 6～ 0 89,P <0 0 1) ;而定量门控2 0 1 Tl心肌显像只能较准确评价左室前壁、下壁和后壁局部室壁运动 (Kappa=0 6 5～ 0 72 ,P <0 0 1) ,其侧壁和间壁的可靠性低于前者 (Kappa =0 2 7～ 0 39)。结论　定量门控99Tcm MIBI、2 0 1 Tl和99Tcm tetro fosmin心肌显像能较准确评价局部室壁运动。     

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.     

Serial change of myocardial fatty acid metabolism in a case with severe myocardial ischemia

A 66-year-old-man was admitted to our hospital because of chest pain on effort in October 1999. The initial images of 123I-BMIPP myocardial SPECT (BM) showed moderately decreased tracer uptake in the apex and the delayed images revealed redistribution in the apex. Coronary angiography revealed 99% stenosis in the proximal portion of the left anterior descending artery. Since sudden onset anaphylactic shock induced by contrast media developed, so percutaneous transluminal coronary angioplasty was not performed. The patient's symptoms were improved with medical treatment. On BM in March 2000, the initial images indicated slightly reduced uptake in the apico-anteroseptal region and the delayed images revealed mildly redistribution in the same area. BM in September 2000, the initial images showed moderately reduced uptake in the apico-anteroseptal region and the delayed images revealed high washout in the same area. The patient's symptoms markedly deferiorrated in March 2001, and BM initial images revealed slightly reduced uptake in the apico-anteroseptal region and the delayed images revealed redistribution in the same area again. During the clinical course, electrocardiography and 99mTc-tetrofosmin myocardial SPECT revealed no marked changes. We consider that 123I-BMIPP myocardial SPECT is useful in estimating myocardial ischemia.     

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: Comparison with rest-redistribution thallium 201 imaging

Background

This study examined the ability of dynamic ¹²³I-labeled iodophenylpentade-canoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease.

Methods and Results

Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi ¹²³I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34%±11%). The segmental uptake was compared with that of rest-redistribution ²⁰¹Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11±5 vs 10±5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (κ=0.78±0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (κ=0.54±0.04). However, there were more reversible IPPA defects than reversible thallium defects (7±4 vs 3±4 segments/patient; p=0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33%±11% to 39%±12% (p=0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10±4 vs 5±4 segments/patient; p=0.075).

Conclusions

¹²³I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.     

Impaired myocardial fatty acid metabolism detected by123I-BMIPP in patients with unstable angina pectoris: Comparison with perfusion imaging by99mTc-sestamibi

The present study was undertaken to determine the potential diagnostic value of¹²³I-BMIPP scintigraphy for the detection of altered myocardial fatty acid metabolism in patients with unstable angina. Both myocardial metabolic imaging with¹²³I-BMIPP and perfusion imaging with^99mTcsestamibi were performed at rest in 28 patients with unstable angina in the pain-free state. The regional uptakes of¹²³I-BMIPP or^99mTc-sestamibi were scored semiquantitatively (0 = normal, 4 = no activity) and compared with the coronary arteriographic findings. Decreased uptakes of¹²³I-BMIPP were observed in 18 patients, and 11 patients had abnormal^99mTc-sestamibi images. Defect scores of¹²³I-BMIPP were larger than those of^99mTc-sestamibi (7.8 ± 2.1 vs. 5.2 + 1.9, p < 0.01). The sensitivity for the detection of patients with unstable angina was higher in¹²³I-BMIPP than in^99mTc-sestamibi (77% vs. 45%, p < 0.01). The site of the decreased¹²³I-BMIPP uptake corresponded to the most stenotic coronary artery lesion in all patients. Fatty acid metabolic imaging with¹²³I-BMIPP was more sensitive for detecting myocardial ischemia than perfusion imaging with^99mTc-sestamibi.¹²³I-BMIPP may be a clue to define the culprit lesion in unstable angina and be helpful to decide the best treatment and guide coronary angioplasty.     

Inappropriate utilization of SPECT myocardial perfusion imaging on the USA-Mexico border

Background

The American College of Cardiology/American Society of Nuclear Cardiology published revised appropriate use criteria (AUC) for SPECT MPI in 2009. We assessed adherence to these guidelines and factors associated with inappropriate utilization at the University Medical Center.

Methods

The AUC was applied retrospectively to 420 SPECT MPI studies. Two-sample t test, Fisher’s exact test, and multivariable logistic regression models were used for analysis.

Results

There were 322 appropriate (86%) and 54 (14%) inappropriate studies. The odds of having an inappropriate test increased with younger age (P < .001) and female gender (P < .001). Subjects with diabetes (P = .007) and chest pain (P < .001) were less likely to have an inappropriate test. Academic outpatients were three times more likely to have an inappropriate study (P = .123), while community PCPs were 5.6 times (P = .011) and community cardiologists eight times more likely to order inappropriate tests (P = .031).

Conclusions

Inappropriate SPECT MPI in low risk younger women is an important issue on the USA-Mexico border. Initiatives to reduce inappropriate SPECT MPI should focus on a few indications and evaluation of cardiovascular symptoms in younger age women in outpatient/community practices.     

Bradycardia progressing to cardiac arrest during adenosine thallium myocardial perfusion imaging in occult sino-atrial disease

Adenosine is used increasingly as an alternative to dynamic exercise during myocardial perfusion imaging because it is a powerful coronary vasodilator with a short half-life. Minor side-effects are common but life-threatening events are rare. We report two cases of provocation by adenosine infusion of profound sinus bradycardia progressing to atrial and ventricular asystole. Despite discontinuation of the infusion, asystole persisted for up to 1 min in one case and was accompanied by a grand mal seizure. Normal sinus rhythm returned spontaneously in both cases without long-term sequelae. Sino-atrial disease was later suggested in both cases by 24-h electrocardiographic monitoring. We conclude that patients to whom adenosine is given may have occult sino-atrial disease and may be susceptible to life-threatening arrhythmias. Significant sinus bradycardia during the infusion may provide a warning of its presence.     

Simultaneous dual-isotope imaging based on an artificial neural network for evaluating myocardial perfusion and fatty acid metabolism

Background

We contrived a scatter correction method based on an artificial neural network (ANN) and applied it to the simultaneous evaluation of myocardial perfusion and fatty acid metabolism in single-photon emission computed tomography (SPECT).

Methods

The count data of three energy windows were used as inputs of the ANN. The count ratios of the estimated primary-to-total photons for ^99mTc and ¹²³I, which were used to reconstruct ^99mTc and ¹²³I images, were calculated using the ANN. In a phantom study, single- and dual-isotope imaging with ^99mTc/¹²³I and ²⁰¹Tl/¹²³I was performed by means of a cardiac phantom simulating patients with and without obesity. In a human study, five normal volunteers and ten patients with myocardial infarction underwent myocardial perfusion and fatty acid metabolism imaging with single and dual SPECT with combinations of ^99mTc-methoxyisobutylisonitrile/¹²³I-beta-methyl(p-iodophenyl)pentadecanoic acid (BMIPP) and ²⁰¹Tl/¹²³I-BMIPP as tracers.

Results

Technetium-99m yielded more homogeneous images than ²⁰¹Tl because of the lower degree of photon attenuation, especially in the condition of obese patients, resulting in clearer visualization of the perfusion-metabolism mismatch. Dual ^99mTc/¹²³I SPECT offered comparable images with single SPECT in assessing myocardial damage.

Conclusions

The method effectively separated ^99mTc and ¹²³I primary photons and proved applicable to ^99mTc/¹²³I dual-isotope myocardial SPECT.