Diffusivity- and T2 imaging at 3 Tesla for the detection of degenerative changes in human-excised tissue with high resolution: atherosclerotic arteries

RATIONALE AND OBJECTIVES: We investigated whether it is possible to investigate degenerative changes in human tissue on a sub-100-microm resolution scale not only on special high-field small-bore MR-microscopy systems but also on a 3T whole-body MR-scanner. METHODS: Spin-spin relaxation, proton density, and diffusion microimaging were investigated in studying human atherosclerotic arteries. Strong diffusion weighting and high spatial resolution was achieved by means of a strong dedicated gradient system and a small birdcage radiofrequency resonator. RESULTS: Quantitative parameter maps were obtained at voxel sizes down to 73 x 73 x 600 microm3. The morphologic structure and pathology connected to lipid deposits, plaques, small thrombi, and bifurcations were well visualized. CONCLUSION: High-resolution parameter-weighted and parameter-imaging at sub-100-microm pixel resolution can be achieved for excised tissue on a 3.0 T whole body MR system. Perspectives for the characterization of atherosclerotic plaques imply not only cost advantages but also equivalence of contrast, especially as to T(2), for in vivo and high-resolution ex vivo investigations on the same MR scanner.     

Magnetic resonance histology for morphologic phenotyping

Magnetic resonance histology (MRH) images of the whole mouse have been acquired at 100-micron isotropic resolution at 2.0 T with image arrays of 256 x 256 x 1024. Higher resolution (50 x 50 x 50 microns) of limited volumes has been acquired at 7.1T with image arrays of 512 x 512 x 512. Even higher resolution images (20 x 20 x 20 microns) of isolated organs have been acquired at 9.4 T. The volume resolution represents an increase of 625000 x over conventional clinical MRI. The technological basis is summarized that will allow basic scientists to begin using MRH as a routine method for morphologcic phenotyping of the mouse. MRH promises four unique attributes over conventional histology: 1). MRH is non-destructive; 2). MRH exploits the unique contrast mechanisms that have made MRI so successful clinically; 3). MRH is 3-dimensional; and 4). the data are inherently digital. We demonstrate the utility in morphologic phenotyping a whole C57BL/6J mouse.     

In vivo multiple-mouse MRI at 7 Tesla.

We developed a live high-field multiple-mouse magnetic resonance imaging method to increase the throughput of imaging studies involving large numbers of mice. Phantom experiments were performed in 7 shielded radiofrequency (RF) coils for concurrent imaging on a 7 Tesla MRI scanner outfitted with multiple transmit and receive channels to confirm uniform signal-to-noise ratio and minimal ghost artifacts across images from the different RF coils. Grid phantoms were used to measure image distortion in different positions in the coils. The brains of 7 live mice were imaged in 3D in the RF coil array, and a second array of 16 RF coils was used to 3D image the whole bodies of 16 fixed, contrast agent-perfused mice. The images of the 7 live mouse brains at 156 microm isotropic resolution and the 16 whole fixed mice at 100 microm isotropic resolution were of high quality and free of artifacts. We have thus shown that multiple-mouse MRI increases throughput for live and fixed mouse experiments by a factor equaling the number of RF coils in the scanner.     

Effects of luminance and resolution on observer performance with chest radiographs

PURPOSE: To examine the combined effects of image resolution and display luminance on observer performance for detection of abnormalities depicted on posteroanterior chest radiographs. MATERIALS AND METHODS: A total of 529 radiographs were displayed on a specially constructed view box at three luminance levels (770, 260, and 85 cd/m(2)) and three resolutions (100-microm, 200-microm, and 400-microm pixels). Each image was reviewed nine times by six radiologists who participated in this study. The abnormalities included nodule, pneumothorax, interstitial disease, alveolar infiltrates, and rib fracture. Negative (normal) radiographs were also included. RESULTS: Receiver operating characteristic curves indicated that the effect of image luminance was greater than that of resolution. The detection of pneumothorax, interstitial disease, and rib fracture showed statistically significant differences (P <. 05) due to luminance. The detection of pneumothorax was the only abnormality with a statistically significant difference due to resolution. There was no evidence that luminance was related to image resolution for any of the abnormalities. CONCLUSION: At a resolution of 400-microm pixels or higher across the field of view and a luminance of 260 cd/m(2) or more, primary diagnosis with posteroanterior chest radiographs is not likely to be affected by the quality of display.     

Development of a compact mouse MRI using a yokeless permanent magnet.

A compact mouse MRI has been developed using a 1.0T yokeless permanent magnet and portable MRI console. The entire system was installed in a space measuring 2 m x 1 m. The imaging region was the cylindrical volume (35 mm diameter, 50 mm length) at the center of the magnet and was used for whole-brain or body imaging of mice. Whole-brain imaging took less than 90 min for T1- and T2-weighted 3D images with 2-mm slice thickness and 200-microm in-plane resolution. Body imaging took less than 30 min for T1-weighted spin-echo and FLASH 3D images with 0.5- to 1.0-mm slice thickness and 250- to 300-microm in-plane resolution. In addition to the compactness of the system, the mouse MRI has several advantages over high-field superconducting animal MRI systems in its accessibility to the specimen, similarity to clinical MRI in image contrast, capacity for biological isolation, and maintenance. The results obtained demonstrate the potential of this new system for routine imaging in biomedical laboratories.     

Fast retrospectively gated quantitative four-dimensional (4D) cardiac micro computed tomography imaging of free-breathing mice

OBJECTIVE: We sought to demonstrate retrospectively gated dynamic 3D cardiac micro computed tomography (CT) of free-breathing mice. MATERIALS AND METHODS: Five C57Bl6 mice were scanned using a cone-beam scanner with a slip-ring-mounted flat-panel detector. After the injection of an intravascular iodinated contrast agent, projection images were acquired over the course of 50 seconds, while the scanner rotated through 10 complete rotations. The mouse respiratory and electrocardiogram signals were recorder simultaneously with image acquisition. After acquisition, the projection images were retrospectively sorted into projections belonging to different cardiac time points, occurring only during expiration. RESULTS: Dynamic 3D cardiac images, with isotropic 150-microm voxel spacing, were reconstructed at 12-millisecond intervals throughout the cardiac cycle in all mice. The average ejection fraction and cardiac output were 58.2+/-4.6% and 11.4+/-1.3 mL/min, respectively. The measured entrance dose for the entire scan was 28 cGy. Repeat scans of the same animals showed that intrasubject variability was smaller than intersubject variability. CONCLUSIONS: We have developed a high-resolution micro computed tomography method for evaluating the cardiac function and morphology of free-breathing mice in acquisition times shorter than 1 minute.     

Benign and malignant lesions in the human breast depicted with ultrahigh resolution and three-dimensional optical coherence tomography

Institutional review board approval at the participating institutions was obtained. Informed consent was waived for this HIPAA-compliant study. The study purpose was to establish the correspondence of optical coherence tomographic (OCT) image findings with histopathologic findings to understand which features characteristic of breast lesions can be visualized with OCT. Imaging was performed in 119 specimens from 35 women aged 29-81 years with 3.5-microm axial resolution and 6-microm transverse resolution at 1.1-microm wavelength on freshly excised specimens of human breast tissue. Three-dimensional imaging was performed in 43 specimens from 23 patients. Microstructure of normal breast parenchyma, including glands, lobules, and lactiferous ducts, and stromal changes associated with infiltrating cancer were visible. Fibrocystic changes and benign fibroadenomas were identified. Imaging of ductal carcinoma in situ, infiltrating cancer, and microcalcifications correlated with corresponding histopathologic findings. OCT is potentially useful for visualization of breast lesions at a resolution greater than that of currently available clinical imaging methods.     

Imaging brain vasculature with BOLD microscopy: MR detection limits determined by in vivo two-photon microscopy.

Rat brain vasculature was imaged at 9.4T with blood oxygenation level-dependent (BOLD) microscopy. Data were acquired without exogenous contrast agent in <35 min using 3D gradient-echo imaging with 78-microm isotropic resolution. Detailed vascular patterns including intracortical veins and some branches were observed in simple magnitude-contrast data acquired at an experimentally optimized echo time. The venous origin of the dark patterns was confirmed by oxygenation-dependent studies, and when the systemic arterial oxygen saturation level was <80% BOLD microscopy revealed additional intracortical vessels presumed to be of arterial origin. Quantification shows a decrease of intracortical venous density with depth. The full width at half-minimum intensity was 90-190 microm for most intracortical venous vessels identifiable by BOLD venography. Since actual diameters are not directly quantifiable by BOLD, we also measured diameter-dependent intracortical venous density in vivo by two-photon excitation fluorescent microscopy. Density comparisons between the two modalities, along with computer simulations, show that venous vessels as small as approximately 16-30 microm diameter are detectable with 9.4T BOLD microscopy under our experimental conditions.     

In vitro echogenicity characterization of poly[lactide-coglycolide] (plga) microparticles and preliminary in vivo ultrasound enhancement study for ultrasound contrast agent application

OBJECTIVES: This work includes (1) the characterization of a reproducible poly[lactide-coglycolide] (PLGA) microparticle preparation with an optimial mean diameter and size distribution and (2) the preliminary in vivo ultrasonographic investigation of PLGA microparticles. METHODS: A first series of PLGA microparticle preparations (1 to 15 mum) was acoustically characterized on a hydrodynamic device to select the most appropriate for ultrasound contrast agent application. Preparations of 3-microm microparticles were selected, characterized at different doses, and then injected into 20 melanoma grafted mice for contrast-enhanced power Doppler ultrasonography evaluation. RESULTS: The 3-microm microparticles (3.26-microm mean diameter with 0.41-microm standard deviation) led to in vitro enhancement of 18.3 dB at 0.62 mg/mL. In vivo experiments showed 47% enhancement of intratumoral vascularization detection after PLGA injection, significantly correlated (P < 0.0001) with preinjection intravascularization and tumoral volume. No toxicity was histologically observed. CONCLUSION: The 3-microm PLGA microparticles provided significant enhancement in vitro and in vivo without any toxicity.     

High-resolution three-dimensional magnetic resonance imaging of mouse lung in situ

OBJECTIVES: This study establishes a method for high-resolution isotropic magnetic resonance (MR) imaging of mouse lungs using tracheal liquid-instillation to remove MR susceptibility artifacts. METHODS: C57BL/6J mice were instilled sequentially with perfluorocarbon and phosphate-buffered saline to an airway pressure of 10, 20, or 30 cm H2O. Imaging was performed in a 7T MR scanner using a 2.5-cm Quadrature volume coil and a 3-dimensional (3D) FLASH imaging sequence. RESULTS: Liquid-instillation removed magnetic susceptibility artifacts and allowed lung structure to be viewed at an isotropic resolution of 78-90 microm. Instilled liquid and modeled lung volumes were well correlated (R = 0.92; P < 0.05) and differed by a constant tissue volume (220 +/- 92 microL). 3D image renderings allowed differences in structural dimensions (volumes and areas) to be accurately measured at each inflation pressure. CONCLUSION: These data demonstrate the efficacy of pulmonary liquid instillation for in situ high-resolution MR imaging of mouse lungs for accurate measurement of pulmonary airway, parenchymal, and vascular structures.     

Time-resolved contrast-enhanced imaging with isotropic resolution and broad coverage using an undersampled 3D projection trajectory.

Time-resolved contrast-enhanced 3D MR angiography (MRA) methods have gained in popularity but are still limited by the tradeoff between spatial and temporal resolution. A method is presented that greatly reduces this tradeoff by employing undersampled 3D projection reconstruction trajectories. The variable density k-space sampling intrinsic to this sequence is combined with temporal k-space interpolation to provide time frames as short as 4 s. This time resolution reduces the need for exact contrast timing while also providing dynamic information. Spatial resolution is determined primarily by the projection readout resolution and is thus isotropic across the FOV, which is also isotropic. Although undersampling the outer regions of k-space introduces aliased energy into the image, which may compromise resolution, this is not a limiting factor in high-contrast applications such as MRA. Results from phantom and volunteer studies are presented demonstrating isotropic resolution, broad coverage with an isotropic field of view (FOV), minimal projection reconstruction artifacts, and temporal information. In one application, a single breath-hold exam covering the entire pulmonary vasculature generates high-resolution, isotropic imaging volumes depicting the bolus passage.     

Fast spin-echo for multiple mouse magnetic resonance phenotyping.

High-resolution magnetic resonance imaging is emerging as a powerful tool for phenotyping mice in biologic studies of genetic expression, development, and disease progression. In several applications, notably random mutagenesis trials, large cohorts of mice must be examined for abnormalities that may occur in any part of the body. In the aim of establishing a protocol for imaging multiple mice simultaneously in a standardized high-throughput fashion, this study investigates variations of a three-dimensional fast spin-echo sequence that implements driven equilibrium, modified refocusing, and partial excitation pulses. Sequence variations are compared by simulated and experimental measurements in phantoms and mice. Results indicate that when using a short repetition time (TR相似文献   

In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2.

Follow-up T(1)-weighted 3D gradient-echo MRI (2.35 T) of murine brain in vivo (N = 5) at 120 microm isotropic resolution revealed spatially distinct signal increases 6-48 hr after subcutaneous application of MnCl(2) (20 mg/kg). The effects result from a shortening of the water proton T(1) relaxation time due to the presence of unchelated paramagnetic Mn(2+) ions, which access the brain by systemic circulation and crossing of the blood-brain barrier (BBB). A pronounced Mn(2+)-induced signal enhancement was first seen in structures without a BBB, such as the choroid plexus, pituitary gland, and pineal gland. Within 24 hr after administration, Mn(2+) contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and the CA3 subfield of the hippocampus. The affinity of Mn(2+) to various brain systems suggests the neuronal uptake of Mn(2+) ions from the extracellular space and subsequent axonal transport. Thus, at least part of the Mn(2+) contrast reflects a functional brain response of behaving animals, for example, in the olfactory system. In vivo MRI staining of the brain by systemic administration of MnCl(2) may contribute to phenotyping mutant mice with morphologic and functional alterations of the central nervous system.     

Depth-dependent profiles of glycosaminoglycans in articular cartilage by microMRI and histochemistry

PURPOSE: To quantify the distribution profile of glycosaminoglycans (GAGs) in articular cartilage with the magnetic resonance imaging (MRI) gadolinium (Gd) contrast method (the dGEMRIC procedure in clinical MRI) and correlate with histochemical results. MATERIALS AND METHODS: Fresh canine cartilage from seven humeral heads was harvested. Sixteen cartilage specimens were imaged at 13 microm pixel resolution using the microMRI T1-Gd method to generate 2D GAG maps in cartilage. Nineteen cartilage specimens from adjacent locations on the same joints were papain-digested to quantify the bulk GAG content in tissue. In addition, six cartilage specimens were microtomed into 40-microm serial sections that were parallel with the articular surface. These sections were biochemically analyzed individually to determine the depth-dependent profiles of GAG concentration. RESULTS: The GAG concentrations between the microMRI measurement and the bulk biochemical method have statistically significant agreement. The depth-dependent GAG profiles from the histochemical method (40 microm depth resolution) have similar line shapes as that determined by microMRI at 13 microm resolution. CONCLUSION: The GAG concentration as measured by microMRI T1-Gd contrast method provides an accurate account of the macromolecular content in articular cartilage.     

Intracranial arterial wall imaging using three-dimensional high isotropic resolution black blood MRI at 3.0 Tesla

Purpose:

To develop a high isotropic‐resolution sequence to evaluate intracranial vessels at 3.0 Tesla (T).

Materials and Methods:

Thirteen healthy volunteers and 4 patients with intracranial stenosis were imaged at 3.0T using 0.5‐mm isotropic‐resolution three‐dimensional (3D) Volumetric ISotropic TSE Acquisition (VISTA; TSE, turbo spin echo), with conventional 2D‐TSE for comparison. VISTA was repeated for 6 volunteers and 4 patients at 0.4‐mm isotropic‐resolution to explore the trade‐off between SNR and voxel volume. Wall signal‐to‐noise‐ratio (SNR_wall), wall‐lumen contrast‐to‐noise‐ratio (CNR_wall‐lumen), lumen area (LA), wall area (WA), mean wall thickness (MWT), and maximum wall thickness (maxWT) were compared between 3D‐VISTA and 2D‐TSE sequences, as well as 3D images acquired at both resolutions. Reliability was assessed by intraclass correlations (ICC).

Results:

Compared with 2D‐TSE measurements, 3D‐VISTA provided 58% and 74% improvement in SNR_wall and CNR_wall‐lumen, respectively. LA, WA, MWT and maxWT from 3D and 2D techniques highly correlated (ICCs of 0.96, 0.95, 0.96, and 0.91, respectively). CNR_wall‐lumen using 0.4‐mm resolution VISTA decreased by 27%, compared with 0.5‐mm VISTA but with reduced partial‐volume‐based overestimation of wall thickness. Reliability for 3D measurements was good to excellent.

Conclusion:

The 3D‐VISTA provides SNR‐efficient, highly reliable measurements of intracranial vessels at high isotropic‐resolution, enabling broad coverage in a clinically acceptable time. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Isotropic submillimeter fMRI in the human brain at 7 T: Combining reduced field-of-view imaging and partially parallel acquisitions

Echo‐planar imaging is the most widely used imaging sequence for functional magnetic resonance imaging (fMRI) due to its fast acquisition. However, it is prone to local distortions, image blurring, and signal voids. As these effects scale with echo train length and field strength, it is essential for high‐resolution echo‐planar imaging at ultrahigh field to address these problems. Partially parallel acquisition methods can be used to improve the image quality of echo‐planar imaging. However, partially parallel acquisition can be affected by aliasing artifacts and noise enhancement. Another way to shorten the echo train length is to reduce the field‐of‐view (FOV) while maintaining the same spatial resolution. However, to achieve significant acceleration, the resulting FOV becomes very small. Another problem occurs when FOV selection is incomplete such that there is remaining signal aliased from the region outside the reduced FOV. In this article, a novel approach, a combination of reduced FOV imaging with partially parallel acquisition, is presented. This approach can address the problems described above of each individual method, enabling high‐quality single‐shot echo‐planar imaging acquisition, with submillimeter isotropic resolution and good signal‐to‐noise ratio, for fMRI at ultrahigh field strength. This is demonstrated in fMRI of human brain at 7T with an isotropic resolution of 650 μm. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Improved preparation of chick embryonic samples for magnetic resonance microscopy.

Previous work demonstrated the power of three-dimensional (3D) magnetic resonance microscopy (MRM) to follow complicated morphologic development in the embryonic cardiovascular system. In this study we describe a new dual-contrast method for specimen preparation that combines perfusion fixation and immersion in fixative with macro- and small molecular gadolinium agents to provide enhanced definition of both the heart wall and chamber. MRM was performed at 9.4 T with image resolutions of 25, 31, and 50 microm isotropic voxels for three stages of chick embryos (day 4, day 5.5, and day 9), and compared to histological sections of the same embryos. The results show considerable improvement of image quality over previous efforts, with better signal-to-noise ratio (SNR) and contrast between the cardiac chamber and myocardial wall. Excellent correlation was shown between the MRM images and histological sections. Thus, 3D high-resolution MRM in combination with the dual-contrast technique is useful for acquiring quantitative 3D morphologic data regarding heart development.     

Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T(1) mapping.

There has been growing interest in using manganese-enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn(2+) produces a very wide range of T(1) change. In particular, in neuronal tract tracing experiments the site of Mn(2+) injection can have very short T(1) while distant regions have small T(1) reductions, primarily due to dilution of Mn(2+). Most MEMRI studies use T(1)-weighted sequences, which can only give optimal contrast for a narrow range of T(1) changes. To improve sensitivity to the full extent of Mn(2+) concentrations and to optimize detection of low concentrations of Mn(2+), a fast T(1) mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T(1) compared to more conventional T(1) measurements. Using center-out segmented EPI, whole-brain 3D T(1) maps with 200-microm isotropic resolution were obtained in 2 h from rat brain. Mn(2+) transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T(1). With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn(2+) used.     

Free-breathing 3D coronary MRA: the impact of "isotropic" image resolution

During conventional x-ray coronary angiography, multiple projections of the coronary arteries are acquired to define coronary anatomy precisely. Due to time constraints, coronary magnetic resonance angiography (MRA) usually provides only one or two views of the major coronary vessels. A coronary MRA approach that allowed for reconstruction of arbitrary isotropic orientations might therefore be desirable. The purpose of the study was to develop a three-dimensional (3D) coronary MRA technique with isotropic image resolution in a relatively short scanning time that allows for reconstruction of arbitrary views of the coronary arteries without constraints given by anisotropic voxel size. Eight healthy adult subjects were examined using a real-time navigator-gated and corrected free-breathing interleaved echoplanar (TFE-EPI) 3D-MRA sequence. Two 3D datasets were acquired for the left and right coronary systems in each subject, one with anisotropic (1.0 x 1.5 x 3.0 mm, 10 slices) and one with "near" isotropic (1.0 x 1.5 x 1.0 mm, 30 slices) image resolution. All other imaging parameters were maintained. In all cases, the entire left main (LM) and extensive portions of the left anterior descending (LAD) and the right coronary artery (RCA) were visualized. Objective assessment of coronary vessel sharpness was similar (41% +/- 5% vs. 42% +/- 5%; P = NS) between in-plane and through-plane views with "isotropic" voxel size but differed (32% +/- 7% vs. 23% +/- 4%; P < 0.001) with nonisotropic voxel size. In reconstructed views oriented in the through-plane direction, the vessel border was 86% more defined (P < 0.01) for isotropic compared with anisotropic images. A smaller (30%; P < 0.001) improvement was seen for in-plane reconstructions. Vessel diameter measurements were view independent (2.81 +/- 0.45 mm vs. 2.66 +/- 0.52 mm; P = NS) for isotropic, but differed (2.71 +/- 0.51 mm vs. 3.30 +/- 0.38 mm; P < 0.001) between anisotropic views. Average scanning time was 2:31 +/- 0:57 minutes for anisotropic and 7:11 +/- 3:02 minutes for isotropic image resolution (P < 0.001). We present a new approach for "near" isotropic 3D coronary artery imaging, which allows for reconstruction of arbitrary views of the coronary arteries. The good delineation of the coronary arteries in all views suggests that isotropic 3D coronary MRA might be a preferred technique for the assessment of coronary disease, although at the expense of prolonged scan times. Comparative studies with conventional x-ray angiography are needed to investigate the clinical utility of the isotropic strategy.     

Aperture correction with an asymmetrically trimmed Gaussian weight in SPECT with a fan-beam collimator

Objectives

The aim of the study is to improve the spatial resolution of SPECT images acquired with a fan-beam collimator.

Methods

The aperture angle of a hole in the fan-beam collimator depends on the position of the collimator. To correct the aperture effect in an iterative image reconstruction, an asymmetrically trimmed Gaussian weight was used for a model. To confirm the validity of our method, point source phantoms and brain phantom were used in the simulation, and we applied the method to the clinical data.

Results

The results of the simulation showed that the spatial resolution of point sources improved from about 6 to 2 pixels full width at half maximum, and the corrected point sources were isotropic. The results of the simulation with the brain phantom showed that our proposed method could improve the spatial resolution of the phantom, and our method was effective for different fan-beam collimators with different focal lengths. The results of clinical data showed that the quality of the reconstructed image was improved with our proposed method.

Conclusions

Our proposed aperture correction method with the asymmetrically trimmed Gaussian weighting function was effective in improving the spatial resolution of SPECT images acquired with the fan-beam collimator.