A three-dimensional in vitro culture model for primary neonatal rat ventricular myocytes

To overcome bad prognosis of patients with heart failure and the lack of organ donors, cardiac tissue engineering has developed as a biomimetic approach to repair, replace, and regenerate the damaged cardiac tissue. During the past decade years, researchers are devoted to find different natural and/or synthetic materials that can build appropriate physical structures to contain and organize implanted cells. In this study, we present a new method for primary neonatal rat cardiomyocytes culture in vitro using alginate/collagen/chitosan hydrogel. To investigate the feasibility of this material as scaffold for cardiac myocytes, neonatal rat ventricular myocytes were isolated and encapsulated in alginate-based beads cross-linked with calcium ion. The growth of cells was evaluated by staining with α-Sarcomeric actin (α-SCA) and Troponin T type 2 (TNNT2), and the viability of cardiomyocytes was studied in vitro by assessing the expression levels of several cardiac ion channels, including CACNL1A1, Connexin 43 and SCN5A. The results showed a significant increase in cardiac myocytes number, and the expression levels of CACNL1A1, Connexin 43 (Cx43) were up-regulated significantly except SCN5A, as compared with two-dimensional cultures. Moreover, extracellular matrix produced by the seeded cells themselves was observed by staining with fibronectin. Taken together, these findings indicate that this alginate/collagen/chitosan hydrogel bead is suitable for supporting the growth and retaining the morphologic and electrophysiologic characteristics of primary cultured rat cardiac muscle cells.     

Characterization of mitochondria isolated from normal and ischemic hearts in rats utilizing atomic force microscopy

Mitochondria play critical roles in both the life and the death of cardiac myocytes. Various factors, such as the loss of ATP synthesis and increase of ATP hydrolysis, impairment in ionic homeostasis, formation of reactive oxygen species (ROS), and release of proapoptotic proteins are related to the generation of irreversible damage. It has been proposed that the release of cytochrome c is caused by a swelling of the mitochondrial matrix triggered by the apoptotic stimuli. However, there is a controversy about whether or not the mitochondria, indeed, swell during apoptosis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopes for bio-imaging include the fact that no special coating and vacuum are required and imaging can be done in all environments--air, vacuum or aqueous conditions. In addition, AFM force-distance curve measurements have become a fundamental tool in the fields of surface chemistry, biochemistry, and material science. In this study, we used AFM to observe the morphological and property changes in heart mitochondria that were isolated from a rat myocardial infarction model. From the shape parameters of the mitochondria in the AFM topographic image, it seemed that myocardial infarction caused the mitochondrial swelling. Also, the results of force-distance measurements showed that the adhesion force of heart mitochondria was significantly decreased by myocardial in infarction. Therefore, we suggested that myocardial infarction might be the cause of mitochondrial swelling and the changes in outer membrane of heart mitochondria.     

A non-contrast CMR index for assessing myocardial fibrosis

PurposeSafe, sensitive, and non-invasive imaging methods to assess the presence, extent, and turnover of myocardial fibrosis are needed for early stratification of risk in patients who might develop heart failure after myocardial infarction. We describe a non-contrast cardiac magnetic resonance (CMR) approach for sensitive detection of myocardial fibrosis using a canine model of myocardial infarction and reperfusion.MethodsSeven dogs had coronary thrombotic occlusion of the left anterior descending coronary arteries followed by fibrinolytic reperfusion. CMR studies were performed at 7 days after reperfusion. A CMR spin-locking T₁ρ mapping sequence was used to acquire T₁ρ dispersion data with spin-lock frequencies of 0 and 511 Hz. A fibrosis index map was derived on a pixel-by-pixel basis. CMR native T₁ mapping, first-pass myocardial perfusion imaging, and post-contrast late gadolinium enhancement imaging were also performed for assessing myocardial ischemia and fibrosis. Hearts were dissected after CMR for histopathological staining and two myocardial tissue segments from the septal regions of adjacent left ventricular slices were qualitatively assessed to grade the extent of myocardial fibrosis.ResultsHistopathology of 14 myocardial tissue segments from septal regions was graded as grade 1 (fibrosis area, < 20% of a low power field, n = 9), grade 2 (fibrosis area, 20–50% of field, n = 4), or grade 3 (fibrosis area, > 50% of field, n = 1). A dramatic difference in fibrosis index (183%, P < 0.001) was observed by CMR from grade 1 to 2, whereas differences were much smaller for T₁ρ (9%, P = 0.14), native T₁ (5.5%, P = 0.12), and perfusion (− 21%, P = 0.05).ConclusionA non-contrast CMR index based on T₁ρ dispersion contrast was shown in preliminary studies to detect and correlate with the extent of myocardial fibrosis identified histopathologically. A non-contrast approach may have important implications for managing cardiac patients with heart failure, particularly in the presence of impaired renal function.     

Formation of leptofibrils is associated with remodelling of muscle cells and myofibrillogenesis in the border zone of myocardial infarction

Leptofibrils, or leptomeres, remain the least studied cytoskeletal structures in muscle cells, and their function and mechanism of assembly are still poorly understood. Our ultrastructural study of the surviving cardiac myocytes located in the perinecrotic border zone of the infarcted left ventricle in rats revealed intense formation of leptofibrils and leptofibrillar clusters during 4-15 days following experimental myocardial infarction. In the perinecrotic myocytes, leptofibrils developed predominantly in the subsarcolemmal areas, near disassembled intercalated discs and at the sites of intense myofibrillogenesis in the peripheral zones of the sarcoplasm. We found that the development of these structures occurred before or at the time of assembly of myofibrils. In our material, leptofibrils consisted of longitudinally oriented filamentous bundles inserted in electron dense Z-band-like material and periodically crossed by 3-8 bands of this material with the period of cross-striation of 120-210 nm. The presence of leptofibrils in growing cytoplasmic processes and ruffles developing in the border zone in the areas of lost intercellular contacts indicates their formation de novo during post-infarction period. We observed four major morphological types of localization of these structures: (1) direct contact of one end of leptofibrils with Z bands of nascent, mature or disassembling myofibrils; (2) direct contact with the sarcolemma: (a) multifocal attachment of leptofibrils to the sarcolemma through the lateral surfaces of their minute Z band-like structures; (b) attachment of one or both ends of leptofibrils to the sarcolemma without contacts or in contact with myofibrils; (3) attachment of leptofibrils to subsarcolemmal accumulations of electron dense Z-band material in newly formed fasciae adherentes of the remodeled intercalated disks; (4) clustering and contacts of leptofibrils with one another predominantly at the level of their Z bands. Interestingly, most leptofibrils of all four types were topographically associated with the system of T-tubules, the sarcoplasmic reticulum and subsarcolemmal vesicles. Serial sections through the areas containing leptofibrils indicate their spindle-like or nearly cylindrical shape. Thus, we found that leptofibrils assemble in terminally differentiated cardiac myocytes following destabilization of their differentiated state and partial dedifferentiation induced by myocardial infarction. The results of this study demonstrate that formation of leptofibrils, earlier described mainly in the developing and malignant muscle, is temporally associated with adaptive structural remodelling and the activation of myofibrillogenesis in functionally overloaded cardiac myocytes of adult animals. Our findings suggest that re-expression of some structural characteristics of the embryonic muscle appear to represent one of the mechanisms that underlie adaptive plasticity of the myocardium following injury and under conditions of hyperfunction.     

Serial magnetic resonance imaging in patients following acute myocardial infarction.

The detection of serial changes in magnetic resonance (MR) signal intensity of the heart following acute myocardial infarction may provide a useful method of characterizing tissue healing. Fourteen patients with acute Q-wave infarction underwent T2-weighted, spin-echo cardiac imaging during hospitalization, followed by one or more additional MR studies (total 31) over a 6- to 27-wk period (mean: 3 mo). Visual assessment of the images demonstrated a gradual reduction in signal intensity and localization of the bright signal to the subendocardium of the infarction region over the three-mo study period. A quantitative measurement of signal intensity (infarction/normal myocardium) fell from 1.81 +/- 0.42 on the initial study to 1.34 +/- 0.37 (p less than 0.05) at a mean of 14 wk. Two patients had an increase in signal intensity on the follow-up study and both patients had been readmitted with acute coronary syndromes. In summary, characterization of changes in signal intensity may provide a useful method of assessing myocardial healing following acute myocardial infarction. Further studies are indicated to determine the prognostic significance of these parameters.     

In vivo lipid diffusion coefficient measurements in rat bone marrow

The diffusion coefficient of lipids, D_l, within bone marrow, fat deposits and metabolically active intracellular lipids in vivo will depend on several factors including the precise chemical composition of the lipid distribution (chain lengths, degree of unsaturation, etc.) as well as the temperature. As such, D_l may ultimately prove of value in assessing abnormal fatty acid distributions linked to diseases such as cystic fibrosis, diabetes and coronary heart disease. A sensitive temperature dependence of D_l may also prove of value for MR-guided thermal therapies for bone tumors or disease within other fatty tissues like the breast. Measuring diffusion coefficients of high molecular weight lipids in vivo is, however, technically difficult for a number of reasons. For instance, due to the much lower diffusion coefficients compared to water, much higher b factors than those used for central nervous system applications are needed. In addition, the pulse sequence design must incorporate, as much as possible, immunity to motion, susceptibility and chemical shift effects present whenever body imaging is performed. In this work, high b-factor line scan diffusion imaging sequences were designed, implemented and tested for D_l measurement using a 4.7-T horizontal bore animal scanner. The gradient set available allowed for b factors as high as 0.03 μs/nm² (30,000 s/mm²) at echo times as short as 42 ms. The methods were used to measure lipid diffusion coefficients within the marrow of rat paws in vivo, yielding lipid diffusion coefficients approximately two orders of magnitude smaller than typical tissue water diffusion coefficients. Phantom experiments that demonstrate the sensitivity of lipid diffusion coefficients to chain length and temperature were also performed.     

Ⅱ型糖尿病人与大鼠红细胞拉曼光谱学比较

使用激光共聚焦拉曼光谱仪测量正常大鼠红细胞、正常人红细胞、糖尿病STZ造模大鼠红细胞、糖尿病四氧嘧啶造模大鼠红细胞和人Ⅱ型糖尿病红细胞的拉曼光谱,应用主成分分析(principal component analysis,PCA)结合支持向量机(support vector machines,SVM)分类器对数据进行判别分析,然后采用类间距离判断两种造模方法与人Ⅱ型糖尿病的接近程度。结果发现糖尿病红细胞与正常红细胞的拉曼光谱存在明显差异,糖尿病在酰胺 ⅥCO变形振动谱带处峰高显著,并在酰胺ⅤN—H变形振动谱带处谱线出现偏移,属于磷脂的脂酰基C—C骨架1 130 cm-1谱线增强,1 088 cm-1谱线强度减弱,说明糖尿病红细胞膜的通透性增强。PCA结合SVM可以很好地区分以上5类红细胞的拉曼光谱,分类器测试结果表明分类准确度达100%。通过分别计算两种造模方法与人Ⅱ型糖尿病的类间距离,发现STZ造模法更接近人Ⅱ型糖尿病。由此得出结论：拉曼光谱法可以用于糖尿病诊断,大鼠糖尿病STZ造模法更接近人类Ⅱ型糖尿病。     

The extracellular matrix is an important source of ultrasound backscatter from myocardium

Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10-30 microm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from 15.4 +/- 0.8 to 12.6 +/- 1.1dB for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.     

Analysis of serum from type II diabetes mellitus and diabetic complication using surface-enhanced Raman spectra (SERS)

In this paper, we show surface-enhanced Raman spectra (SERS) of serums from type II diabetes mellitus and diabetic complication (coronary disease, glaucoma and cerebral infarction), and analyze the SERS through the multivariate statistical methods of principal component analysis (PCA). In particular, we find that there exist many adenines in these serums, which maybe come from DNA (RNA) damage. The relative intensity of the band at 725±2 cm⁻¹ assigned to adenine is higher for patients than for the healthy volunteers; therefore, it can be used as an important ‘fingerprint’ in order to diagnose these diseases. It is also shown that serums from type II diabetes mellitus group, diabetic complication group and healthy volunteers group can be discriminated by PCA.     

Enhanced homing of mesenchymal stem cells to the ischemic myocardium by ultrasound-targeted microbubble destruction

In recent years, ultrasound-targeted microbubble destruction (UTMD) has been utilised for the targeted delivery of stem cells. We tested the effects of the myocardial micro-environment changes induced by UTMD on promoting the homing of mesenchymal stem cells (MSCs) to the ischemic myocardium. Dogs were randomly divided into two groups and treated with or without UTMD after the establishment of myocardial infarction models. 4,6-diamino-2-phenyl indole (DAPI) labelled MSCs were transplanted via coronary injections 2 weeks after myocardial infarction in both groups. The results from real-time PCR and western blot analyses indicated that the expression of various cytokines in UTMD-treated dogs was much higher than that observed in non-treated dogs. Histopathological findings demonstrate that ultrasound at a frequency of 1 MHz and an intensity of 1.0 W/cm² provoked inflammatory reactions with mild myocardial damage. Myocardial microenvironment changes caused by UTMD may promote the homing of MSCs to the ischemic myocardium. This non-invasive technique may be a promising method for cardiac cell transplantation therapy.     

Identification of human myocardial infarction in vitro based on the frequency dependence of ultrasonic backscatter.

It has been reported previously that acute and mature myocardial infarction in dogs can be differentiated in vitro and in vivo by ultrasonic tissue characterization based on measurement of the frequency dependence of ultrasonic backscatter. To characterize human infarction with an index of the frequency dependence of backscatter that could be obtained in patients, cylindrical biopsy specimens from 7 normal regions and 12 regions of infarction of 6 fixed, explanted human hearts in 2-deg steps around their entire circumference with a 5-MHz broadband transducer were insonified. One to six consecutive transmural levels were studied for each specimen. The dependence of apparent (uncompensated for attenuation or beam width) backscatter, /B(f)/2, on frequency (f) was computed from spectral analyses of radio-frequency data as /B(f)/2 = afn, where from theoretical considerations the magnitude of n decreases as scatterer size increases. Apparent integrated backscatter was computed as the average of /B(f)/2 from 3 to 7 MHz. The average value for n for normal tissue (0.9 +/- 0.1) exceeded that for tissue from regions of infarction (0.6 +/- 0.1; p less than 0.05). Infarct manifested a significant decrease of n from epicardial to endocardial levels (epi----mid----endo: 0.9----0.7----0.2; p less than 0.05) whereas normal tissue manifested similar values for n at each transmural level (0.8----1.1----0.9; p = NS). Average integrated backscatter across all transmural levels for infarct was significantly greater than for normal tissue (-48.3 +/- 0.5 vs -53.4 +/- 0.4 dB, infarct versus normal; p less than 0.05). The presence of fibrosis was associated with smaller values of n and greater integrated backscatter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac magnetic resonance imaging: infarct size is an independent predictor of mortality in patients with coronary artery disease

Background

Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods to assess infarct size have shown that patients with larger myocardial infarctions have a worse prognosis than those with smaller myocardial infarctions.

Objectives

This study assessed the prognostic significance of infarct size determined by CMR.

Methods

Cine and contrast CMR were performed in 100 patients with coronary artery disease (CAD) undergoing routine cardiac evaluation. Infarct size was determined by planimetry. We used Cox proportional hazards regression analyses (stepwise forward selection approach) to evaluate the risk of all-cause death associated with traditional cardiovascular risk factors, symptoms of heart failure, medication use, left ventricular ejection fraction, left ventricular mass, angiographic severity of CAD and extent of infarct size determined by CMR.

Results

Ninety-one patients had evidence of myocardial infarction by CMR. Mean follow-up was 4.8±1.6 years after CMR, during which time 30 patients died. The significant multivariable predictors of all-cause mortality were extent of myocardial infarction by CMR, extent of left ventricular systolic dysfunction, symptoms of heart failure, and diabetes mellitus (P<.05). The presence of infarct greater than or equal to 24% of left ventricular mass and left ventricular ejection fraction less than or equal to 30% were the most optimal cut-off points for the prediction of death with bivariate adjusted hazard ratios of 2.11 (95% confidence interval 1.02-4.38) and 4.06 (95% confidence interval 1.73-9.54), respectively.

Conclusions

The extent of myocardial infarction determined by CMR is an independent predictor of death in patients with CAD.     

Improving motion estimation by accounting for local image distortion

Cardiac elastography is a useful diagnostic technique for detection of heart function abnormalities, based on analysis of echocardiograms. The analysis of the regional heart motion allows assessing the extent of myocardial ischemia and infarction. In this paper, a new two-stage algorithm for cardiac motion estimation is proposed, where the data is taken from a sequence of 2D echocardiograms. The method combines the advantages of block-matching and optical flow techniques. The first stage employs a standard block-matching algorithm (sum of absolute differences) to provide a displacement estimate with accuracy of up to one pixel. At the second stage, this estimate is corrected by estimating the parameters of a local image transform within a test window. The parameters of the image transform are estimated in the least-square sense. In order to account for typical heart motions, like contraction/expansion, translation and rotation, a local affine model is assumed within the test window. The accuracy of the new algorithm is evaluated using a sequence of 500 grayscale B-mode images, which are generated as distorted, but known copies of an original ROI, taken from a real echocardiogram. The accuracy of the motion estimation is expressed in terms of errors: maximum absolute error, root-mean-square error, average error and standard deviation. The errors of the proposed algorithm are compared with these of the known block-matching technique with cross-correlation and interpolation in the sub-pixel space. Statistical analysis of the errors shows that the proposed algorithm provides more accurate estimates of the heart motion than the cross-correlation technique with interpolation in the sub-pixel space.     

Improving motion estimation by accounting for local image distortion

Cardiac elastography is a useful diagnostic technique for detection of heart function abnormalities, based on analysis of echocardiograms. The analysis of the regional heart motion allows assessing the extent of myocardial ischemia and infarction. In this paper, a new two-stage algorithm for cardiac motion estimation is proposed, where the data is taken from a sequence of 2D echocardiograms. The method combines the advantages of block-matching and optical flow techniques. The first stage employs a standard block-matching algorithm (sum of absolute differences) to provide a displacement estimate with accuracy of up to one pixel. At the second stage, this estimate is corrected by estimating the parameters of a local image transform within a test window. The parameters of the image transform are estimated in the least-square sense. In order to account for typical heart motions, like contraction/expansion, translation and rotation, a local affine model is assumed within the test window. The accuracy of the new algorithm is evaluated using a sequence of 500 grayscale B-mode images, which are generated as distorted, but known copies of an original ROI, taken from a real echocardiogram. The accuracy of the motion estimation is expressed in terms of errors: maximum absolute error, root-mean-square error, average error and standard deviation. The errors of the proposed algorithm are compared with these of the known block-matching technique with cross-correlation and interpolation in the sub-pixel space. Statistical analysis of the errors shows that the proposed algorithm provides more accurate estimates of the heart motion than the cross-correlation technique with interpolation in the sub-pixel space.     

MRI of cardiac pseudoaneurysm and other complications of myocardial infarction

The purpose of this paper is to review the spectrum of pathology revealed by cardiac magnetic resonance (MR) in the evaluation of myocardial infarction. In addition, the paper is intended to provide a concise introduction to the capabilities and limitations of MR in the evaluation of myocardial infarction and its complications. To provide this introductory guide, three cases of infarction are reviewed in detail, including one unusual case of infarction with both true and false ventricular aneurysm formation. A selected review of the literature is included to demonstrate the current role of MR in the work-up and follow-up of acute infarction.     

Motion dependence of myocardial transverse relaxation time in magnetic resonance imaging

We discuss the effects of motion on the computation of the myocardial transverse relaxation time by use of magnetic resonance imaging. Equations describing its behavior are derived and illustrated graphically under different conditions. It is shown that the myocardial transverse relaxation time calculated from magnetic resonance images depends on the actual myocardial transverse relaxation time ex vivo (T2) as well as the phase of the cardiac cycle in which it is computed, heart rate, cardiac wall velocity, choice of spin-echoes used in the calculation, and the spin-echo times employed. In particular, the error in T2 decreases when both the first and third echoes are employed in the calculation, rather than only the first two echoes. However, the myocardial transverse relaxation time is more strongly dependent on heart rate in the former case rather than in the latter. Furthermore, the error in T2, when both the first and second spin echoes are used in the calculation, is seen to increase as the spin-echo time shortens. On the other hand, the error in T2 decreases for shorter spin-echo times when both the first and third spin echoes are used instead. The results are relevant to the noninvasive assessment of ischemia, cardiac transplantation rejection, and other myocardial disorders.     

The alterations of magnetic resonance relaxation parameters in excised myocardial tissue during NMR spectroscopy: the effects of time, environmental exposure and TTC staining

To investigate the potential impact of air exposure, time delay and vital tissue staining on the MR relaxation parameters in normal and pathological heart tissues, myocardial samples from a canine model of myocardial infarction were subject to (a) air exposure for up to 20 hours or (b) wrapping in Parafilm for up to 20 hours; immersion in (c) full strength pathological stain consisting of triphenyl tetrazolium chloride (TTC), or (d) half strength TTC, or (e) normal saline for 30 minutes. We found that (a) exposure to air produced rapid change in both T1 and T2 such that there is a reduction of T1 by 12.2% and T2 by 14.4% (p less than 0.001) in one hour; (b) airtight wrapping attenuated dramatically these changes, but T1 still was reduced by 2.9% and T2 by 4.8% in one hour (p less than 0.01). These changes followed similar but non-linear changes of tissue water content. T1 did not change significantly after exposure to full strength TTC, but did increase significantly after exposure to half strength TTC, and increased even further after exposure to saline. T2 on the other hand increased significantly with all of these test solutions. We conclude that the in vitro processing of excised myocardial tissues should be done by wrapping in an airtight container with T1 and T2 parameters measured within one hour, if possible. All tissue processing, including stains and saline exposure, should be done after spectrometer measurements.     

Synchronization of low-frequency oscillations in the cardiovascular system: Application to medical diagnostics and treatment

We investigate synchronization between the low-frequency oscillations of heart rate and blood pressure having in humans a basic frequency close to 0.1?Hz. A quantitative estimation of this synchronization based on calculation of relative time of phase synchronization of oscillations is proposed. We show that assessment of synchronization between the considered oscillations can be useful for selecting an optimal dose of beta-blocker treatment in patients after acute myocardial infarction. It is found out that low value of synchronization between the low-frequency rhythms in heart rate and blood pressure at the first week after acute myocardial infarction is a sensitive marker of high risk of mortality during the subsequent 5 years.     

Fibroblasts alter spiral wave stability

We consider a three-domain model of cardiac tissue consisting of fibroblasts, myocytes, and extracellular space. We show in the one dimensional case that the fibroblasts with different resting potentials may alter restitution properties of tissue. On this basis we demonstrated that in two dimensional slice of cardiac tissue, a spiral wave break up can be caused purely by the influence of fibroblasts and, vice-versa, initially unstable spiral can be stabilized by fibroblasts depending on the value of their resting potential.     

Preliminary quantitative analysis of myocardial fatty acid metabolism from fluorescent X‐ray computed tomography imaging

Fluorescent X‐ray computed tomography (FXCT) using synchrotron radiation reveals the cross‐sectional distribution of specific elements in biomedical objects. The aim of this study was to investigate the feasibility of FXCT imaging to assess the myocardial metabolic state quantitatively. Hearts labelled with non‐radioactive iodine myocardial fatty acid agent 15‐p‐(iodophenyl)‐3‐methylpentadecanoic acid (BMIPP) from cardiomyopathic and normal hamsters were imaged. FXCT images were compared with optical microscope images. Myocardial fatty acid metabolism enhanced with BMIPP was clearly depicted by FXCT, which showed an almost homogeneous image for normal and a heterogeneous image for cardiomyopathic hearts. Morphological structures of the heart such as the left ventricle and myocardial wall were also visualized by FXCT. Optical microscopy showed no fibrosis in normal and slight interstitial fibrosis in cardiomyopathic hearts. In the case of cardiomyopathy, the area of significantly reduced BMIPP uptake was 39% in the short axis of the mid‐left ventricle in the FXCT image, whereas a slight interstitial fibrosis of around 12% was recognized by optical microscopy for the same slice. This result indicated that reduced BMIPP uptake was caused by the myocardial fatty acid metabolic abnormality, not by the fibrosis in cardiomyopathy. Thus, FXCT images might be used to assess the quantitative metabolic analysis in small animal models of heart diseases.