Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging

Thyroid hormones influence cardiac performance directly and indirectly via changes in peripheral circulation. Little, however, is known about the effect on myocardial oxidative metabolism and its relation to cardiac function and geometry. Patients with a history of thyroidectomy for thyroid cancer present a unique model to investigate the cardiac effects of hypothyroidism. Ten patients without heart disease were investigated in the hypothyroid state and again 4-6 weeks later under euthyroid conditions. Myocardial oxidative metabolism was measured by positron emission tomography with [11C]acetate and the clearance constant k(mono). Cine magnetic resonance imaging was applied to determine left ventricular geometry. A stroke work index (SWI = stroke volume x systolic blood pressure/ventricular mass) was calculated. Then, to estimate myocardial efficiency, a work metabolic index [WMI = SWI x heart rate/k(mono)] was obtained. Compared to hormone replacement, systemic vascular resistance and left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and SWI were significantly lower. Despite an additional reduction of k(mono), the WMI was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease.     

Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner.     

Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.     

Hepatic imaging: positron emission tomography, digital angiography, and nuclear magnetic resonance imaging

Major advances in diagnostic imaging of the human body have been made in recent years. Positron emission tomography, a technique founded on advances in radiopharmaceuticals and radionuclide imaging apparatus, permits imaging regional metabolism, metabolite distribution, and flow. Thus far, its major applications have been in the study of the brain, and to a lesser extent, the heart; however, it is also finding a role in the study of the liver. Digital angiography is being applied to fluoroscopic systems which permits visualization of relatively low doses of intravascular iodinated radiographic contrast media. Imaging of the major arteries is possible using simple intravenously administered contrast media; digital techniques also increase the diagnostic yield in intraarterial studies. Nuclear magnetic resonance (NMR) imaging is an outgrowth of laboratory NMR spectroscopy; the interaction of radiofrequency signals with nuclei in strong magnetic fields permits imaging the distribution and certain chemical properties of various isotopes. Hydrogen NMR imaging is proving most useful for clinical diagnosis. The techniques used to image hydrogen are also being applied to NMR spectroscopy in vivo of various isotopes, including carbon-13, phosphorus-31, and hydrogen-1.     

Preoperative assessment of pancreatic tumors using magnetic resonance imaging, endoscopic ultrasonography, positron emission tomography and laparoscopy.

BACKGROUND: The appropriate preoperative evaluation of a pancreatic tumor remains a matter of debate. METHODS: We retrospectively evaluated an institutional strategy including magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), positron emission tomography (PET) and laparoscopy (LAP) for detection and staging of pancreatic tumors suspected to be malignant. RESULTS: In a consecutive series of 59 patients screened by MRI, PET, EUS and LAP between July 1998 and November 2002, 48 patients were found to bear pancreatic adenocarcinoma and surgery was performed in 27 of them. For tumor detection, the sensitivity of EUS was superior to MRI and PET (98 vs. 87.5 and 87.5%, respectively, p = 0.13). MRI best assessed loco-regional staging, i.e. arterial involvement. For the detection of distant metastases, the sensitivity of all preoperative examinations taken separately was low. When laparotomy was performed with a curative intent according to all four examinations, occult metastasis or carcinomatosis was discovered in 7/27 patients and the overall predictive value of resectability was thus 74%. Five-year and median survival were significantly better in resected vs. non-resected patients (39% and 26 months vs. 0% and 8 months, p = 0.0006). CONCLUSIONS: MRI can be recommended has the first examination in patients bearing pancreatic tumors, complemented by EUS if the findings of MRI are non-conclusive. For detection of distant metastasis, only the combination of all preoperative examination was proved to be more accurate than a single technique.     

Computer tomography, positron emission tomography and nuclear magnetic resonance in cardiology

Ultrafast CT scanning, due to short exposure time, high repetition rate and multiple projections, is well-suited for studies of the heart. A typical ultrafast CT study is composed of three different series of images: volume mode, flow mode and motion mode. With the equipment on this service, using volume mode and EKG triggering, a series of eight contiguous 1 cm-thick slices are generated within 240 ms with and without contrast medium. This imaging technique serves for localization of structures. In flow mode, EKG-triggered slices at multiple levels are generated after a bolus injection of contrast dye. Consequently, the passage of the contrast medium can be followed from the right to the left heart and the circulation time can be estimated, the knowledge of which is advantageous for planning of the subsequent motion study. On use of the motion mode, up to 17 slice images per second can be generated at four, six or eight levels during maximal contrast opacification of both ventricles. Possibilities for clinical application of fast CT scanning can be found in diseases of the aorta and pericardium, cardiac tumors and thrombi as well as for use in assessing cardiac chambers and wall thickness, temporal changes in wall thickness, regional wall motion impairment and quantification of cardiac output and shunt flow. Due to the short imaging time, the technique can also be used for exercise studies and to evaluate pharmacological interventions. According to preliminary results, myocardial blood flow can also be reliably quantitated. Coronary bypass grafts can be directly visualized after injection of contrast dye and, through use of the peak arrival time at various levels, information with regard to blood flow velocity as well as estimations of cross-sectional area in the grafts can be obtained. The sensitivity and specificity of assessment of patency of coronary bypass grafts is currently at approximately 95%.     

Imaging of transplanted islets by positron emission tomography,magnetic resonance imaging,and ultrasonography

While islet transplantation is considered a useful therapeutic option for severe diabetes mellitus (DM), the outcome of this treatment remains unsatisfactory. This is largely due to the damage and loss of islets in the early transplant stage. Thus, it is important to monitor the condition of the transplanted islets, so that a treatment can be selected to rescue the islets from damage if needed. Recently, numerous trials have been performed to investigate the efficacy of different imaging modalities for visualizing transplanted islets. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities for this purpose. Some groups, including ours, have also tried to visualize transplanted islets by ultrasonography (US). In this review article, we discuss the recent progress in islet imaging.     

Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart; a non-invasive study using positron emission tomography.

AIMS: To identify functional and metabolic correlates of impaired presynaptic sympathetic innervation in the cardiomyopathic human heart using non-invasive correlative imaging. METHODS AND RESULTS: In 10 patients with idiopathic dilated cardiomyopathy, presynaptic catecholamine uptake sites were quantified by positron emission tomography with C-11 hydroxyephedrine. Oxidative metabolism was measured using C-11 acetate. Global and regional function was assessed by tomographic radionuclide angiography. Left ventricular ejection fraction in patients was 19%+/-10%. Myocardial hydroxyephedrine retention was abnormally low in 58%+/-38% of the left ventricles. Globally and regionally, hydroxyephedrine retention was significantly correlated with ventricular function (r=0.67, P=0.03 with left ventricular ejection fraction; r=0.31, P<0.01 with regional endocardial shortening). Multivariate analysis confirmed hydroxyephedrine retention as the closest independent determinant of left ventricular ejection fraction. Oxidative metabolism was determined by rate pressure product as a measure of workload (r=0.78, P<0.01) and peripheral vascular resistance as a measure of afterload (r=-0.61, P=0.06), but did not correlate with hydroxyephedrine retention (r=0.08 for global, r=0.04 for regional parameters). CONCLUSION: Alterations of presynaptic sympathetic innervation in dilated cardiomyopathy are associated with impaired contractile function, suggesting a common pathogenetic pathway. Overall oxidative metabolism, however, was not directly correlated with these findings. Normal regulatory mechanisms for oxidative metabolism were operational.     

Scar imaging using multislice computed tomography versus metabolic imaging by F-18 FDG positron emission tomography: A pilot study

Introduction

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) FDG PET is an established metabolic imaging technique to assess myocardial viability. Delayed iodinated contrast enhancement (DE) of myocardium on computed tomography (CT) has also been shown to be an anatomical marker of nonviable myocardium. A pilot study was undertaken to determine quantitative and qualitative agreement between metabolic viability imaging and scar imaging using FDG PET and multislice CT respectively.

Methods

Fifteen patients with coronary artery disease and left ventricular dysfunction were recruited in the study. All patients underwent same day FDG PET and DECT to evaluate myocardial viability. The images were analyzed quantitatively and qualitatively using a 17 segment model.

Results

DECT diagnosed viability in 57% (146/255) whilst PET in 51% (129/255) of segments. The per-segment agreement between DECT and FDG PET on qualitative analysis was 70% (Kappa: 0.40). The agreement in quantitative measurements between the two techniques for viability showed modest correlation [Pearson ρ: 0.63; P < 0.0001] on scatter plot and the Passing–Bablok regression analysis. Higher agreement (70 vs 77%; P = 0.051; Kappa: 0.40 vs 0.53) was obtained with quantitative compared to qualitative DECT.

Conclusions

DECT may be useful in characterizing myocardial scar, and preliminary results correlate modestly with metabolic FDG PET, both qualitatively and quantitatively. Although in our study quantitative analysis offered superior agreement compared to qualitative with DECT, further studies are needed to determine its incremental value.     

Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography

OBJECTIVES: The study compared flow reserve indices by magnetic resonance imaging (MRI) with quantitative measures of coronary angiography and positron emission tomography (PET). BACKGROUND: The noninvasive evaluation of myocardial flow by MRI has recently been introduced. However, a comparison to quantitative flow measurement as assessed by PET has not been reported in patients with coronary artery disease (CAD). METHODS: Two groups of healthy volunteers and 25 patients with angiographically documented CAD were examined by MRI and PET at rest and during adenosine stress. Dynamic MRI was performed using a multi-slice ultra-fast hybrid sequence and a rapid gadolinium-diethylenetriaminepenta-acetic acid bolus injection (0.05 mmol/l). Upslope and peak-intensity indices were regionally determined from first-pass signal intensity curves and compared to N-13 ammonia PET flow reserve measurements. RESULTS: In healthy volunteers, the upslope analysis showed a stress/rest index of 2.1 plus minus 0.6, which was higher than peak intensity (1.5 plus minus 0.3), but lower than flow reserve by PET (3.9 plus minus 1.1). Localization of coronary artery stenoses (> 75%, MRI < 1.2), based on the upslope index, yielded sensitivity, specificity and diagnostic accuracy of 69%, 89% and 79%, respectively. Upslope index correlated with PET flow reserve (r = 0.70). A reduced coronary flow reserve (PET < 2.0, MRI < 1.3) was detected by the upslope index with sensitivity, specificity and diagnostic accuracy of 86%, 84% and 85%, respectively. CONCLUSIONS: Magnetic resonance imaging first-pass perfusion measurements underestimate flow reserve values, but may represent a promising semi-quantitative technique for detection and severity assessment of regional CAD.     

Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography.

Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult. Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning. Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence. Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole. The myocardium was divided into nine segments for direct comparison of perfusion with wall motion. Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion. After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects. The site of wall motion deterioration was always the site of a reversible thallium defect. Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging. There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole. There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments. In nine patients the change was apparent visually and it was maximal in the subendocardial region. Magnetic resonance imaging of reversible wall motion abnormalities in patients with coronary artery disease is feasible during pharmacological stress with dipyridamole and may be associated with a reduced magnetic resonance signal. The failure to show wall motion abnormalities in all cases of reversible thallium defects may be because the defect was small or because dipyridamole caused perfusion defects in the absence of myocardial ischaemia.     

Cardiac magnetic resonance imaging and computed tomography: anatomic fundamentals

Due to lack of appropriate anatomic visualization using fluoroscopy, radiological scans such as computed tomography and magnetic resonance imaging are increasingly used to provide detailed anatomy of cardiac structures. Furthermore, these imaging modalities are now being used to integrate images with other modalities to navigate catheters in real time on the detailed depicted anatomy. This review details the anatomic fundamentals of these modalities.     

Novel non-invasive assessment of upper airway inflammation in obstructive sleep apnea using positron emission tomography/magnetic resonance imaging

Purpose

To develop a novel non-invasive technique to quantify upper airway inflammation using positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with obstructive sleep apnea (OSA).

Methods

Patients with treatment naïve moderate-to-severe OSA underwent [18F]-fluoro-2-deoxy-d-glucose (FDG) PET/MRI. Three readers independently performed tracings of the pharyngeal soft tissue on MRI. Standardized uptake values (SUV) were generated from region of interest (ROI) tracings on corresponding PET images. Background SUV was measured from the sternocleidomastoid muscle. SUV and target-to-background (TBR) were compared across readers using intraclass correlation coefficient (ICC) analyses. SUV from individual image slices were compared between each reader using Bland–Altman plots and Pearson correlation coefficients. All tracings were repeated by one reader for assessment of intra-reader reliability.

Results

Five participants completed our imaging protocol and analysis. Median age, body mass index, and apnea–hypopnea index were 41 years (IQR 40.5–68.5), 32.7 kg/m² (IQR 28.1–38.1), and 30.7 event per hour (IQR 19.5–48.1), respectively. The highest metabolic activity regions were consistently localized to palatine or lingual tonsil adjacent mucosa. Twenty-five ICC met criteria for excellent agreement. The remaining three were TBR measurements which met criteria for good agreement. Head-to-head comparisons revealed strong correlation between each reader.

Conclusions

Our novel imaging technique demonstrated reliable quantification of upper airway FDG avidity. This technology has implications for future work exploring local airway inflammation in individuals with OSA and exposure to pollutants. It may also serve as an assessment tool for response to OSA therapies.

     

Clinical impact of 11C-Pittsburgh compound-B positron emission tomography in addition to magnetic resonance imaging and single-photon emission computed tomography on diagnosis of mild cognitive impairment to Alzheimer's disease

This study aimed to evaluated the clinical impact of adding [¹¹C] Pittsburgh compound-B (¹¹C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer''s disease (AD) dementia.Twenty six (mean age 78.5 ± 5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent ¹¹C-PiB-PET, MRI, and SPECT scanning. ¹¹C-PiB-PET was compared with MRI and SPECT for clinical impact.¹¹C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for ¹¹C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. ¹¹C-PiB-PET accuracy was significantly higher than that of SPECT.¹¹PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.     

Cardiac anatomy, function and metabolism in elite cyclists assessed by magnetic resonance imaging and spectroscopy

We investigated whether left ventricular hypertrophy in elitecyclists is associated with functional changes or abnormal energymetabolism. Left ventricular hypertrophy is a powerful risk factor for suddencardiac death with different prognostic significance among thevarious geometric forms. Cyclists may have a combination ofmixed eccentric and concentric hypertrophy. Magnetic resonance imaging was used to define left ventricularmass, geometry and function. Thirteen highly trained male cyclistsand 12 healthy controls were investigated. Proton-decoupledphosphorus-31 cardiac spectroscopy was performed to assess parametersof myocardial high-energy phosphate metabolism. Left ventricularmass and end-diastolic volumes normalized for body surface areawere significantly higher in cyclists (124·1 ±9·4 g. m^–2 and 106·2 ± 11·4ml. m^–2, respectively) than in controls (85·9 ±9·3 g. m^–2 and 79·1 ± 11·6ml. m^–2, respectively), (both P<0·0001). Theleft ventricular mass to end-diastolic volume ratio, as a parameterof left ventricular geometry, was not significantly increasedin cyclists compared to controls. Resting left ventricular ejectionfraction, cardiac index, and systolic wall stress in cyclistsdid not differ significantly from those of controls. The phosphocreatineto adenosine triphosphate ratio was not significantly differentbetween cyclists and controls (2·2 ± 0·34vs 2·2 ± 0·17, ns). Cyclists show prominent left ventricular hypertrophy with normalgeometry. The finding that the hypertrophic hearts of the cyclistshad normal left ventricular function and a normal phosphocreatineto adenosine triphosphate ratio suggests that sport-inducedleft ventricular hypertrophy is a physiological adaptation ratherthan a pathophysiological response.