Fast gated EPR imaging of the beating heart: Spatiotemporally resolved 3D imaging of free‐radical distribution during the cardiac cycle

In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided only time‐averaged information. In order to achieve direct gated EPRI, a fast EPR acquisition scheme was developed to decrease EPR projection acquisition time down to 10–20 ms, along with corresponding software and instrumentation to achieve fast gated EPRI of the isolated beating heart with submillimeter spatial resolution in as little as 2–3 min. Reconstructed images display temporal and spatial variations of the free‐radical distribution, anatomical structure, and contractile function within the rat heart during the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Proton electron double resonance imaging (PEDRI) of the isolated beating rat heart.

Proton electron double resonance imaging (PEDRI) is a double resonance technique where proton MRI is performed with irradiation of a paramagnetic solute. A low-field PEDRI system was developed at 20.1 mT suitable for imaging free radicals in biological samples. With a new small dual resonator, PEDRI was applied to image nitroxide free radicals in isolated beating rat hearts. Experiments with phantoms showed maximum image enhancement factors (IEF) of 42 or 28 with TEMPONE radical concentrations of 2-3 mM at EPR irradiation powers of 12W or 6W, respectively. In the latter case, image resolution better than 0.5 mm and radical sensitivity of 5 microM was obtained. For isolated heart studies, EPR irradiation power of 6W provided optimal compromise of modest sample heating with good SNR. Only a small increase in temperature of about 1 degrees C was observed, while cardiac function remained within 10% of control values. With infusion of 3 mM TEMPONE an IEF of 15 was observed enabling 2D or 3D images to be obtained in 27 sec or 4.5 min, respectively. These images visualized the change in radical distribution within the heart during infusion and clearance. Thus, PEDRI enables rapid and high-quality imaging of free radical uptake and clearance in perfused hearts and provides a useful technique for studying cardiac radical metabolism.     

Three-dimensional spatial EPR imaging of the rat heart

While instrumentation capable of performing three-dimensional EPR imaging of free radicals in whole tissues and isolated organs has been developed at L-band, important questions remain regarding the resolution and image quality that can be obtained in practice using the presently available free radical labels. Therefore, studies were performed applying three-dimensional spatial EPR imaging at L-band to image the distribution of free radical labels in the isolated heart and in phantoms of similar size. With nitroxide labels the obtainable resolution is limited by the presence of hyperfine structure in the EPR absorption function that in turn limits the maximum applicable gradient. The authors observed that with the nitroxide labels, resolutions in the range of 1–2 mm are possible, while with a single line glucose char label, resolutions of 0.2 mm are obtained. With the nitroxides, images were of sufficient resolution to resolve the overall global shape of the heart and the location of the left and right ventricular cavities; however, finer structures could not be resolved. With the glucose char much finer resolution could be obtained enabling visualization of the ventricles, aortic root, and proximal coronary arteries.     

In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy

Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 μs, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10–50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques.     

EPR/NMR co-imaging for anatomic registration of free-radical images.

While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free-radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI-derived free-radical images. An approach is reported for whole-body, EPRI-based, free-radical imaging along with proton MRI in mice. EPRI instrumentation with a 750-MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low-field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free-radical images were precisely registered, enabling assignment of the location of the observed free-radical distribution within the organs of the mice. This technique enabled differentiation of the distribution and metabolism of nitroxide radicals within the major organs and body sites of living mice.     

Gated cardiac scanning: canine studies.

Retrospective electrocardiograph gating of data from a rotating detector fan beam computed tomography system was employed to produce end systolic and end diastolic images of the beating heart in a series of normal and experimentally infarcted canines. The gating window was typically less than 20% of the cardiac cycle, and the gated images showed superior spatial resolution compared with ungated images of the same cross section. Comparison of the scans of the normal and of the infarcted animals shows abnormal contrast enhancement of the myocardium in the region of the infarct, and the gating studies demonstrate dyskinetic behavior of the infarct zone.     

Cardiac imaging using gated magnetic resonance

To overcome the limitations of magnetic resonance (MR) cardiac imaging using nongated data acquisition, three methods for acquiring a gating signal, which could be applied in the presence of a magnetic field, were tested: an air-filled plethysmograph, a laser-Doppler capillary perfusion flowmeter, and an electrocardiographic gating device. The gating signal was used for timing of MR imaging sequences (IS). Application of each gating method yielded significant improvements in structural MR image resolution of the beating heart, although with both plethysmography and laser-Doppler velocimetry it was difficult to obtain cardiac images from the early portion of the cardiac cycle due to an intrinsic delay between the ECG R wave and peripheral detection of the gating signal. Variations in the temporal relationship between the R wave and plethysmographic and laser-Doppler signals produced inconsistencies in the timing of IS. Since the ECG signal is virtually free of these problems, the preferable gating technique is IS synchronization with an electrocardiogram. The gated images acquired with this method provide sharp definition of internal cardiac morphology and can be temporarily referenced to end diastole and end systole or intermediate points.     

Resolution‐recovery for EPR imaging of free radical molecules in mice

A method of post‐processing to enhance the image resolution of the distribution of free radical molecules obtained with continuous‐wave electron paramagnetic resonance (CW‐EPR) imaging is reported. The low spatial resolution of EPR imaging, which has created difficulties in biomedical applications, was overcome by the method of resolution‐recovery for EPR imaging. High spatial resolution images for the distribution of free radical molecules with a very short relaxation time were obtained with this method. The method's two‐step postprocessing consists of conventional deconvolution and filtered back‐projection and a process of iterative deconvolution. The resolution‐recovery method was demonstrated with three‐dimensional (3D) imaging of stable nitroxyl radicals in mouse head. In phantom experiments with a solution of triarylmethyl (TAM) radicals, the spatial resolution was improved by a factor of 7 with the resolution‐recovery method. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

High spatial and temporal resolution cardiac cine MRI from retrospective reconstruction of data acquired in real time using motion correction and resorting

Cine MRI is used for assessing cardiac function and flow and is typically based on a breath‐held, segmented data acquisition. Breath holding is particularly difficult for patients with congestive heart failure or in pediatric cases. Real‐time imaging may be used without breath holding or ECG triggering. However, despite the use of rapid imaging sequences and accelerated parallel imaging, real‐time imaging typically has compromised spatial and temporal resolution compared with gated, segmented breath‐held studies. A new method is proposed that produces a cardiac cine across the full cycle, with both high spatial and temporal resolution from a retrospective reconstruction of data acquired over multiple heartbeats during free breathing. The proposed method was compared with conventional cine images in 10 subjects. The resultant image quality for the proposed method (4.2 ± 0.4) without breath holding or gating was comparable to the conventional cine (4.4 ± 0.5) on a five‐point scale (P = n.s.). Motion‐corrected averaging of real‐time acquired cardiac images provides a means of attaining high‐quality cine images with many of the benefits of real‐time imaging, such as free‐breathing acquisition and tolerance to arrhythmias. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo proton electron double resonance imaging of the distribution and clearance of nitroxide radicals in mice.

Proton electron double resonance imaging (PEDRI) is an emerging technique that utilizes the Overhauser effect to enable in vivo and in vitro imaging of free radicals in biological systems. Nitroxide spin probes enable measurement of tissue redox state based on their reduction to diamagnetic hydroxylamines. PEDRI instrumentation at 0.02 T was applied to assess the ability to image the in vivo distribution, clearance, and metabolism of nitroxide radicals in living mice. Using phantoms of 2,2,5,5-tetramethyl-3-carboxylpyrrolidine-N-oxyl (PCA) in normal saline the dependence of the enhancement on RF power and spin probe concentration was determined. Enhancements of up to -23 were obtained in phantoms with 2 mM levels. Maximum enhancement of -7 was observed in vivo. Coronal images of nitroxide-infused mice enabled visualization of the kinetics of spin probe uptake and clearance in different organs including the great vessels, heart, lungs, kidneys, and bladder with an in-plane spatial resolution of 0.6 mm. PEDRI of living mice was also performed using 3-carbamoyl-proxyl and 2,2,6,6-tetramethyl-4-oxopiperidine-N-oxyl to compare the different rate of clearance and metabolism among different nitroxide probes. PCA, due to its intravascular compartmentalization, provided the sharpest contrast for the vascular system and highest enhancement values in the PEDRI images among the three nitroxides.     

Three-dimensional display of gated cardiac blood-pool studies

There has been little interest in use of single photon tomography in gated cardiac blood-pool imaging. This fact arises most likely from two principal causes: the difficulty associated with interpretation of images presented as series of beating slices, and the formidable computational burdens involved in processing the data. We have addressed both of these issues. A new method, called volume rendering, is used to generate realistic and easily interpreted three-dimensional images of the cardiac blood pool. These images of the beating heart can be displayed in a continuously rotating cine format or viewed in any orientation selected by the observer. Total computation time for a 16-frame gated study, including filtered backprojection, spatial and temporal filtering, and volume rendering, is 82.7 min employing a 32-bit computer and an array processor. With greater use of the array processor it should be possible to reduce the time to approximately 40 min, thus making routine use of these three-dimensional images clinically feasible.     

Cardiac MRI of the normal and hypertrophied mouse heart

With the development of recent transgenic techniques, studies involving mice offer opportunities to increase understanding of cardiac disease. This provides motivation for the current study to perform noninvasive evaluation of the normal and hypertrophied mouse heart with MRI. By acquiring EGG and respiratory signals, the MR image acquisition was gated to both the cardiac and respiratory cycles. Combining a spin-warp imaging sequence with an RF surface coil resulted in short-axis images that allowed quantification of in vivo cardiac mass. Excellent agreement between MRI-determined (y) and postmortem heart weight (x) was obtained: y = 0.991x + 1.43 (r = 0.996). Isoproterenol, at 282 μMmol/kg body weight (BW) and 573 μMmol/kg BW, induced a dose-dependent increase in the ratio of heart weight to BW of 16.8 ± 1.09% and 24.1 ± 1.71 %, respectively, which was accurately measured by MRI. These results demonstrate the ability of MRI to non-invasively monitor cardiac anatomy in the mouse.     

Imaging asynchronous mechanical activation of the paced heart with tagged MRI

A method for imaging the rapid temporal-spatial evolution of myocardial deformations in the paced heart is proposed. High time resolution-tagged MR images were obtained after stimulation of the myocardium with an MR-compatible pacing system. The images were analyzed to reconstruct dynamic models of local 3D strains over the entire left ventricle during systole. Normal canine hearts were studied in vivo with pacing sites on the right atrium, left ventricular free wall and right ventricular apex. This method clearly resolved local variations in myocardial contraction patterns caused by ventricular pacing. Potential applications are noninvasive determination of electrical conduction abnormalities and the evaluation of new pacing therapies.     

冠状动脉多层螺旋CT检查技术及价值初步探讨

目的　初步探讨冠状动脉多层螺旋CT(MSCT)检查技术及临床应用价值。资料与方法　 5 5例心绞痛患者于冠状动脉造影前行MSCT检查 ,用容积重建和曲面重建技术作图像后处理 ,回顾性分析心电门控重建图像质量的重要因素 ,包括心率和心动周期的选择 ,并以冠状动脉造影为金标准对照分析MSCT的检查结果。结果　心率5 1～ 70次 /min病例图像的运动伪影较少 ,显示率依次为左主干、前降支、回旋支和右主干 ,MSCT显示冠状动脉闭塞和 >75 %狭窄准确性较高 ,并可显示冠状动脉变异和邻近脏器病变。结论　冠状动脉MSCT检查结果与冠状动脉造影有较高的一致性 ,有望成为筛选冠状动脉病变的首选无创检查方法     

Simultaneous multislice imaging (SIMUSIM) for improved cardiac imaging

In conventional ECG gated multislice imaging of the heart, slice position and phase in the heart cycle are not independent parameters. This drawback is removed by simultaneous imaging of multiple slices. This paper describes a technique which is based on simultaneous excitation of several slices by multifrequency selective rf pulses. In comparison to conventional cardiac multislice imaging an improved quality of heart images is obtained, because more acquisitions are attributed to the MR signal of the slices. The gain in signal-to-noise ratio per measurement time increases with the square root of the number of slices investigated simultaneously. This is demonstrated using phantom experiments and cardiac images.     

Cardiac imaging: Comparison of two-shot echo-planar imaging with fast segmented k-space and conventional gradient-echo cine acquisitions

We compared the cardiac image quality of multishot echo-planar imaging (EPI), segmented K-space, and conventional cine acquisitions. Three techniques were used to obtain gated multiphase acquisitions of an axial section traversing both ventricles in 10 volunteers: two-shot EPI acquired nonsequentially over two heart beats breath-held segmented K-space cine with eight K-space lines acquired per cardiac trigger over 16 R-R intervals, also breath-held and 24 cine phases obtained over 256 R-R intervals. Intraventricular SNRs with two-shot EPI were superior to segmented K-space cine acquisitions (P <.005) and not statistically different from conventional cine acquisitions (P <. 1). Intraventricular signal was most homogeneous on conventional cine images (P <.05). Coronary artery visualization and myocardial delineation were better on the EPI image set than on segmented K-space cine images (P <.05). Two-shot EPI provides high-quality gated cardiac images with an acquisition time of only 2 seconds.     

Limitations of stimulated echo acquisition mode (steam) techniques in cardiac applications

Stimulated echoes are widely used for imaging functional tissue parameters such as diffusion coefficient, perfusion, and flow rates. They are potentially interesting for the assessment of various cardiac functions. However, severe limitations of the stimulated echo acquisition mode occur, which are related to the special dynamic properties of the beating heart and flowing blood. To the well-known signal decay due to longitudinal relaxation and through-plane motion between the preparation and the read-out period of the stimulated echoes, additional signal loss is often observed. As the prepared magnetization is fixed with respect to the tissue, this signal loss is caused by the tissue deformation during the cardiac cycle, which leads to a modification of the modulation frequency of the magnetization. These effects are theoretically derived and corroborated by phantom and in vivo experiments.     

Comparison of 16-frame and 8-frame gated SPET imaging for determination of left ventricular volumes and ejection fraction

Electrocardiographic (ECG) gated single-photon emission tomography (SPET) allows for simultaneous assessment of myocardial perfusion and left ventricular (LV) function. Presently 8-frame per cardiac cycle ECG gating of SPET images is standard. The aim of this study was to compare the effect of 8-frame and 16-frame gated SPET on measurements of LV volumes and to evaluate the effects of the presence of myocardial perfusion defects and of radiotracer dose administered on the calculation of LV volumes. A total of 86 patients underwent technetium-99m SPET myocardial perfusion imaging using 16-frame per cardiac cycle acquisition. Eight-frame gated SPET images were generated by summation of contiguous frames. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated from the 16-frame and 8-frame data sets. The patients were divided into groups according to the administered dose of the radiotracer and the size of the perfusion defect. Results. Sixteen frame per cardiac cycle acquisition resulted in significantly larger EDV (122±72 ml vs 115±68 ml, P<0.0001), smaller ESV (64±58.6 ml vs 67.6±59.5 ml, P<0.0001), and higher LVEF (55.3%±18% vs 49%±17.4%, P<0.0001) as compared to 8-frame SPET imaging. This effect was seen regardless of whether a high or a low dose was administered and whether or not significant perfusion defects were present. This study shows that EDV, ESV and LVEF determined by 16-frame gated SPET are significantly different from those determined by 8-frame gated SPET. The radiotracer dose and perfusion defects do not affect estimation of LV parameters by 16-frame gated SPET.Disclosure: Frans J.T. Wackers and Yi-Hwa Liu, through an arrangement with Yale University School of Medicine (New Haven, Conn.), receive royalties from the sale of Wackers-Liu CQ software.     

Evaluation of the dose distribution gradient in the close vicinity of brachytherapy seeds using electron paramagnetic resonance imaging

Electron paramagnetic resonance (EPR) spectroscopy has been successfully employed to determine radiation dose using alanine. The EPR signal intensity reflects the number of stable free radicals produced, and provides a quantitative measurement of the absorbed dose. The aim of the present study was to explore whether this principle can be extended to provide information on spatial dose distribution using EPR imaging (EPRI). Lithium formate was selected because irradiation induces a single EPR line, a characteristic that is particularly convenient for imaging purposes. ¹²⁵I‐brachytherapy seeds were inserted in tablets made of lithium formate. Images were acquired at 1.1 GHz. Monte Carlo (MC) calculations were used for comparison. The dose gradient can be determined using two‐dimensional (2D) EPR images. Quantitative data correlated with the dose estimated by the MC simulations, although differences were observed. This study provides a first proof‐of‐concept that EPRI can be used to estimate the gradient dose distribution in phantoms after irradiation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Slice-selective images of free radicals in mice with modulated field gradient electron paramagnetic resonance (EPR) imaging.

Continuous wave (CW) electron paramagnetic resonance (EPR) imaging can be used to obtain slice-selective images of free radicals without measuring three-dimensional (3D) projection data. A method that incorporated a modulated magnetic field gradient (MFG) was combined with polar field gradients to select a slice in the subject noninvasively. The slice-selective in vivo EPR imaging of triarylmethyl radicals in the heads of live mice is reported. 3D surface-rendered images were successfully obtained from slice-selective images. In the experiment in mice, a slice thickness of 1.8 mm was achieved.