Clinical 3.0 T Magnetic Resonance Scanner to Be Used for Imaging of Mouse Atherosclerotic Lesions

Magnetic resonance imaging (MRI) is a useful tool for non-invasive identification and characterization of atherosclerotic plaques in both basic science and clinical practice. To date, the reported studies on in vivo vascular MRI of small animals, such as mice and rats, are mainly performed on high-field micro-MR scanners, which are not always available in many academic institutions and basic research units. This study aimed to explore the possibility of generating high-resolution MR images of the atherosclerotic aortic walls/plaques of mice using a clinical 3.0 T MR scanner with a dedicated solenoid mouse coil. An atherosclerotic mouse model was first generated by feeding 8 ApoE⁻/⁻ mice an atherogenic diet. MR images of the ascending aortas of these mice were then achieved using a three-dimensional black-blood turbo spin-echo sequence (repetition time TR = 4 heart echo time TE = 10 ms). The MRI displayed a clear view of the aortic lumens and the atherosclerotic lesions, which correlated significantly well with subsequent histological confirmations (linear regression analysis, r = 0.73, P = 0.04). This study demonstrated that a clinical 3.0 T MR scanner can be used for high-resolution imaging of mouse atherosclerotic lesions to some extent.     

High-resolution ultrahigh-field MRI of stroke

BACKGROUND: Ultrahigh-field MRI at 8 T offers unprecedented resolution for imaging brain structures and microvasculature. OBJECTIVE: The aim of this study is to apply high-resolution MRI for stroke imaging and to characterize findings at 1.5 and 8 T. METHODS: Seventeen subjects with minor ischemic infarcts were studied using T2-weighted gradient echo (GE) and rapid acquisition with relaxation enhancement (RARE) images at 8 T with resolution up to 200 microm. In 10 subjects, T1- and T2-weighted fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR) images were also acquired at 1.5-T MRI. RESULTS: The 8-T images showed infarcts as sharply demarcated areas of high-signal intensity (n=21) and revealed more infarctions than 1.5-T images (n=14) (P<.003). The low-signal intensity areas that surrounded infarctions were suggestive of hemosiderin deposits. The 8-T characteristics of microvessels terminating within the infractions were distinct from normal vasculature. The 8-T images revealed an angioma at the site of a second stroke, not apparent on 1.5-T images. CONCLUSIONS: Ultrahigh-field MRI at 8 T is feasible for stroke imaging. The 8-T MRI visualized infarcts and microvasculature with high resolution, revealing infarcts and vascular pathologies that were not apparent at 1.5 T.     

Investigation of atherosclerotic plaques with MRI at 3 T using ultrasmall superparamagnetic particles of iron oxide

This study aims to investigate the uptake of the experimental ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agent DDM43/34 (Schering AG, Berlin, Germany) by aortic atherosclerotic plaques using magnetic resonance imaging (MRI) at 3 T. Six Watanabe heritable hyperlipidemic rabbits were injected with USPIO at doses of 0.1–1.0 mmol/kg Fe. Parasagittal magnetic resonance angiography (MRA) scans were acquired using 3D gradient-echo sequences before and after USPIO administration, then again after 6 h, 1 day, 2 days and 5 days. At later time points, when the USPIO concentration was too low to enhance blood signal, additional MRA scans were acquired during the infusion of gadopentate dimeglumine (Magnevist; Schering AG). In the images, widespread susceptibility artifacts demonstrated readily detectable USPIO uptake in the liver, bone marrow and lymphatic vessels. Surprisingly, however, no such effects could be associated specifically with the aortic vessel wall, in contrast to previous studies that showed strong uptake with similar pulse sequences. Histological analysis was performed on aortic slices from two animals, demonstrating that aortic plaques were active but showed very little USPIO uptake, consistent with MRI findings. We conclude that, despite the exciting potential of plaque detection using USPIO, some caution is advised since the absence of susceptibility effects does not necessarily imply the absence of plaque, even at 3 T, which offers increased sensitivity to susceptibility. Future work will investigate the dependence of such results on stage of plaque development, magnetic field strength and choice of contrast agent.     

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (tau=40 ms) versus stable plaques (tau=400 ms) and normal aorta (tau=500 ms) . These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.     

Optimized 3D bright blood MRI of aortic plaque at 3 T

PURPOSE: To evaluate the feasibility of an optimized bright blood MRI protocol at 3 T in combination with contrast agent administration for the detection and characterization of aortic high-risk plaques for the improved workup of acute stroke patients. MATERIALS AND METHODS: ECG synchronized T1-weighted 3D gradient echo MRI was performed in 45 acute stroke patients. Data were acquired with high near isotropic spatial resolution (approximately 1 mm(3)) covering the entire thoracic aorta. To compensate for breathing and vessel motion artifacts, images were collected using respiratory navigator gating in combination with short diastolic data acquisition windows adjusted on a patient-by-patient basis. In patients with aortic plaques > or =3 mm in thickness, gadolinium contrast agent was administered and both pre- and post-contrast T1-weighted 3D measurements with identical vessel coverage were performed. RESULTS: Bright blood 3D MRI detected 33 high-risk plaques with an average maximum plaque thickness of 4.2+/-1.0 mm in 23 of 45 acute stroke patients. The availability of pre- and post-contrast images acquired within the same session enhanced the identification of calcified plaque components in 77% of all analyzed plaques: post-contrast MRI clearly improved the delineation of hypointense plaque cores in 23 of 30 cases and assisted in the classification of core shape and of core fraction. CONCLUSION: 3D bright blood MRI at 3 T was feasible for the detection of aortic high-risk sources and may help to improve the detection of causes of cerebral embolism in acute stroke patients.     

新型Gd基T2造影剂的制备和应用

设计并合成了结构为TPP-Lys（Acp-DOTA-Gd）-COOH（简称Gd-DOTA-TPP）的小分子磁共振探针,通过电转染的方式用探针标记人源脐带间充质干细胞（hMSCs）.11.7 T磁共振成像（MRI）扫描结果表明,Gd-DOTA-TPP标记的hMSCs在细胞内Gd含量为9×10⁹ Gd/cell时,T₂加权信号强度即可低至背景信号强度,呈现较强暗信号.将Gd-DOTA-TPP标记的hMSCs移植入小鼠脑室,可明显提高移植干细胞在MRI设备上的检测灵敏度,检测限可低至10³个细胞.     

Photoacoustic characteristics of lipid-rich plaques under ultra-low temperature and formaldehyde treatment

Photoacoustic imaging(PAI) has been used to characterize the spatial and quantitative features of lipid-rich atherosclerotic plaques with high sensitivity and specificity. In this Letter, we first validate that the ultra-low temperature and formaldehyde treatment have no effect on photoacoustic characteristics of the artery samples.Comparative experiments between the PAI and histological results demonstrate that the ultra-low temperature or formaldehyde treatment has few effects on the PAI of the lipid-rich atherosclerotic plaques; the lipid relative concentration and the lipid percentage by PAI hold high correlation with histology.     

MR signal change in venous thrombus relates organizing process and thrombolytic response in rabbit

Venous thrombus is subsequently organized and replaced by fibrous connective tissue. However, the sequential changes in venous thrombi are not reliably detected by current noninvasive diagnostic techniques. The purpose of this study is to reveal whether magnetic resonance (MR) can detect venous thrombus, define thrombus age and predict thrombolytic responses. Thrombus in the rabbit jugular vein was imaged with a 1.5-T MR system at 4 h and at 1, 2 and 4 weeks using three-dimensional (3D) fast asymmetric spin echo T2-weighted (T2W) and 3D-gradient echo T1-weighted (T1W) sequences. The jugular veins were histologically assessed at each time point. Magnetic resonance imaging (MRI) was also performed in vivo before and 30 min after tissue plasminogen activator (t-PA) administration. The thrombi in MRI were comparable in size to histological sections. The signal intensity (SI) of thrombi at 4 h was heterogeneously high or low on T2W or T1W images, respectively. The SI of thrombi on T2W images decreased time-dependently, but increased on T1W images at 1 and 2 weeks. Morphological analysis showed time-dependent decreases in erythrocyte, platelet and fibrin areas and time-dependent increases in smooth muscle cell, macrophage, collagen and iron areas. The t-PA administration significantly decreased thrombus volume at 4 h but not at 1, 2 and 4 weeks. Venous thrombosis can be reliably and noninvasively detected by MRI. Measurement of SI might support assessments of thrombus age and thrombolytic response.     

Cardiovascular applications of magnetic resonance imaging

Magnetic resonance imaging (MRI) is a completely noninvasive modality that has shown significant promise for the evaluation of the cardiovascular system. Our imaging technique employed electrocardiographic (ECG) gating, which resulted in well-resolved images of the cardiac structures. Patients and animals with a variety of cardiovascular abnormalities were also assessed with this technique; the abnormalities included acute and remote myocardial infarctions and their sequelae, atherosclerotic plaques, hypertrophic cardiomyopathy, pericardial diseases, and aneurysms. The diagnostic utility of MRI includes direct tissue characterization, and such utility may be further extended by the use of paramagnetic contrast media. In addition, metabolic imaging of elements other than hydrogen may further increase the clinical potential of MRI for assessment of the cardiovascular system.     

Optimised in vivo visualisation of cortical structures in the human brain at 3 T using IR-TSE

The primary visual cortex in humans can be identified using magnetic resonance imaging (MRI) in vivo by detection of the stria of Gennari. To fully characterize this area, high spatial resolution is essential, including the use of very thin image slices to avoid loss of definition due to partial volume effects. A three-dimensional magnetization-prepared turbo spin-echo sequence, with appropriate parameter optimization, provided high-resolution imaging (0.4 x 0.4 x 0.5 mm3) on a clinical 3-T scanner with adequate contrast to noise ratio. These images allowed visualisation of the stria of Gennari in every slice of a volume covering most of the occipital cortex, in each of six healthy volunteers. The effective longitudinal relaxation time was measured with the isotropic resolution turbo spin echo sequence and found to be substantially shorter than values measured with a dedicated relaxometric sequence. The shortening was attributed to magnetization transfer effects, as supported by the investigation of its slab and turbo-factor dependence.     

MRI methodological development of intervertebral disc degeneration: a rabbit in vivo study at 9.4 T

Intervertebral disc (IVD) degeneration is a complex process characterized by biochemical and structural changes in both the nucleus pulposus and the anulus fibrosus. In this study, we were able to obtain in vivo magnetic resonance (MR) images of the rabbit spine, with several MR imaging (MRI) contrasts (ρ, T₁ and T₂). We quantified several parameters (T₂, apparent diffusion coefficient, disc height and area) to differentiate between healthy and degenerative IVDs and to characterize the degeneration process. To our knowledge, there has not been any previous in vivo study of rabbit IVDs at high-field MRI (9.4 T).A custom radio frequency (RF) coil for 9.4 T was designed to match rabbit IVD morphology, to study the degeneration in vivo on a model of human lumbar disease. Our new probe, a custom half-birdcage-type coil, obtains the necessary exploration depth while meeting the requirements for signal homogeneity and sensitivity of the study. This design addresses some of the difficulties with constructing RF coils at high field strengths.     

Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.     

MRI-based biomechanical imaging: initial study on early plaque progression and vessel remodeling

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.     

MRI of tarantulas: morphological and perfusion imaging

This paper describes a study performed to evaluate the feasibility of using a 1.5-T whole-body magnetic resonance imaging (MRI) equipment, in combination with pharmacokinetic modeling, to obtain in vivo information about the morphology and perfusion of tarantulas (Eurypelma californicum). MRI was performed on three tarantulas using spin-echo sequences for morphological imaging and a rapid spoiled gradient-echo sequence for dynamic imaging during and after contrast medium (CM; Gd-DTPA) injection. Signal enhancement in dynamic measurements was evaluated with a pharmacokinetic two-compartment model. Spin-echo images showed morphological structures well. Dynamic images were of sufficient quality and allowed a model analysis of CM kinetics, which provides information about regional perfusion. In conclusion, morphological and dynamic contrast-enhanced MRI of tarantulas is feasible with a conventional clinical scanner. Studies of this kind are therefore possible without a dedicated high-field animal scanner.     

19F Magnetic resonance imaging of perfluorooctanoic acid encapsulated in liposome for biodistribution measurement

The tissue distribution of perfluorooctanoic acid (PFOA), which is known to show unique biological responses, has been visualized in female mice by (19)F magnetic resonance imaging (MRI) incorporated with the recent advances in microimaging technique. The chemical shift selected fast spin-echo method was applied to acquire in vivo (19)F MR images of PFOA. The in vivo T(1) and T(2) relaxation times of PFOA were proven to be extremely short, which were 140 (+/- 20) ms and 6.3 (+/- 2.2) ms, respectively. To acquire the in vivo (19)F MR images of PFOA, it was necessary to optimize the parameters of signal selection and echo train length. The chemical shift selection was effectively performed by using the (19)F NMR signal of CF(3) group of PFOA without the signal overlapping because the chemical shift difference between the CF(3) and neighbor signals reaches to 14 kHz. The most optimal echo train length to obtain (19)F images efficiently was determined so that the maximum echo time (TE) value in the fast spin-echo sequence was comparable to the in vivo T(2) value. By optimizing these parameters, the in vivo (19)F MR image of PFOA was enabled to obtain efficiently in 12 minutes. As a result, the time course of the accumulation of PFOA into the mouse liver was clearly pursued in the (19)F MR images. Thus, it was concluded that the (19)F MRI becomes the effective method toward the future pharmacological and toxicological studies of perfluorocarboxilic acids.     

An automatic cerebellum extraction method in T1-weighted brain MR images using an active contour model with a shape prior

Purpose

The objective of this paper was to automatically segment the cerebellum from T1-weighted human brain magnetic resonance (MR) images.

Materials and Methods

The proposed method constructs a cerebellum template using five sets of 3-T MR imaging (MRI) data, which are used to determine the initial position and the shape prior of the cerebellum for the active contour model. Our formulation includes the active contour model with shape prior, which thereby maintains the shape of the template. The proposed active contour model is sequentially applied to sagittal-, coronal- and transverse-view images. To evaluate the proposed method, it is applied to BrainWeb data and a 3-T MRI data set and compared with FreeSurfer with respect to performance assessment metrics.

Results

The segmented cerebellum was compared with the results from FreeSurfer. Using the manually segmented cerebellum as reference, we measured the average Jaccard coefficients of the proposed method, which were 0.882 and 0.885 for the BrainWeb data and 3-T MRI data set, respectively.

Conclusion

We presented the active contour model with shape prior for extracting the cerebellum from T1-weighted brain MR images. The proposed method yielded a robust and accurate segmentation result.     

Initial in vivo rodent sodium and proton MR imaging at 21.1 T

The first in vivo sodium and proton magnetic resonance (MR) images and localized spectra of rodents were attained using the wide bore (105 mm) high resolution 21.1-T magnet, built and operated at the National High Magnetic Field Laboratory (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats (∼250 g) were acquired with custom designed radiofrequency probes at frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging resolutions of ∼0.125 μl for mouse and rat heads were achieved by using a 3D back-projection pulse sequence. A gain in SNR of ∼3 for sodium and ∼2 times for proton were found relative to corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton mouse images (50×50×50 μm³) were acquired in 90 min and corresponding rat images (100×100×100 μm³) within a total time of 120 min. Both in vivo large rodent MR imaging and localized spectroscopy at the extremely high field of 21.1 T are feasible and demonstrate improved resolution and sensitivity valuable for structural and functional brain analysis.     

Behavior of Atherosclerotic Plaque Components After in Vitro Angioplasty and Atherectomy Studied by High Field MR Imaging

Aims: Using magnetic resonance imaging (MRI), we developed in vitro models to image the response of fatty, fibrous, and calcified plaques to in vitro models of angioplasty and atherectomy, and tested the resistance of collagenous cap and lipid core to radial compression. Methods and Results: We studied the effects of balloon compression on 10 fibrous plaques with a complete collagenous cap (group A), 6 fatty plaques without cap (group B), and 5 calcified plaques (group C). Atherectomy was performed on nine other fibrous lesions (group D). In group A, fibrous cap, lipid core, and plaque did not change after radial compression despite a decrease in luminal obstruction due to medial stretching. In group B, a reduction of plaque (−30%) and lipid core (−35%) were observed. Compression dissected calcified plaques at the shoulder level. In group D, atherectomy reduced collagenous cap by 54%, and plaque by 35%. Conclusions: In these models, MRI shows 1) the high resistance of collagenous caps to radial compression, 2) a stretching effect of compression on disease-free walls, enlarging lumen in case of fibrous plaque, but a reduction and redistribution of lipid cores in case of fatty plaques, 3) the rupture of calcified arteries at the plaque shoulder, and 4) the reduction of fibrous components by atherectomy but not by angioplasty. By characterizing plaque composition, MRI may allow a predictable response of atherosclerotic arteries to interventional procedures.     

Brain Imaging with Slotted Hybridized Magnetic Metamaterial Hat at 7-T MRI

Study of human pathologies and acquisition of anatomical images without any surgical intervention inside human body is possible because of magnetic resonance imaging (MRI), which is the keystone technique to characterize the psychology and neurochemistry of human body. However, for clinical trials, the study and cure of human diseases are followed by medical investigations of different animal anatomies. By employing different imaging techniques to animal anatomical models during their clinical trials yielded in exceptional image acquisition without any surgical invasion in the model, which resulted in noninvasive technique as compared to surgical invasion and opened the possibility to study human pathologies more precisely. This work exploits the notable properties of unique combination of multi-circular hybridized surface coils which can be used as hybridized magnetic metamaterial hat (HMMH). HMMH not only strengthens the uniformity of radio frequency (RF) rotational symmetry around its axis but also improves the signal-to-noise ratio (SNR) for rat’s brain imaging at 7-T MRI. We analyzed a periodic array of strongly coupled circular copper coils attached on circular coil shaped printed circuit board (PCB) substrate. In the design, some copper coils were inspired by the slot cavity loaded with parametric elements (capacitor and inductor). In addition, coils in the form of HMMH exploited the advantages of the hybrid modes which exhibited better and deeper RF sensitivity into the region of interest (ROI) as compared to single loop RF coil by exciting two Eigen modes simultaneously which resulted in homogenized magnetic field (B-field) and enhanced SNR at ROI. At resonance, the value of relative negative permeability, μ _r  = ?7 + j11 was achieved at 300 MHz for 7-T MRI. Furthermore, image quality at ROI was optimized by varying rat’s head position under magnetic resonance (MR) coil of MRI apparatus and in the presence or absence of HMMH. Design configuration and circuit model analysis were also done.     

Discrimination of components in atherosclerotic plaques from human carotid endarterectomy specimens by magnetic resonance imaging ex vivo

Specific MRI techniques have been used to determine the dimensional and compositional properties of atherosclerotic lesions in carotid endarterectomy tissues. A quantitative comparison of areas of specific features in typical tissue segments was performed using MR images and histologic images. The mean difference for the measurements by the two methods was 4.5% for the total vessel, 5.3% for the internal carotid artery lumen, and 5.0% for the external carotid lumen. For other less abundant components, the mean difference was 14.2%. For direct characterization, individual tissue components were isolated by microdissection and their T1 and T2 relaxation times measured. Highly calcified areas typically had rather short T1 (452-837 ms) and short T2 (10.4-18.4 ms). In contrast, regions enriched in lipid had much longer T1 (1,380-1,480 ms) and longer T2 (35.3-49.0 ms). Other components such as thrombus had intermediate T1 (1,180 ms) and short T2 (15.4 ms). T2 parametric imaging was used as a complementary approach for segmentation and quantitation of tissue components. In fresh tissue, several different components exhibited different T2 ranges: calcified/solid lipid (13-18 ms). cellular/ECM (9-30 ms), fluid lipid (35-40 ms): fibrous (50-60 ms). These results demonstrate the utility of MRI for identifying and quantifying specific components of atherosclerotic plaque ex vivo, and suggest its value for these measurements in vivo as well.